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Publicaciones científicas más recientes (desde 2010)

Autores: Chahuan, B. , (Autor de correspondencia); Soza-Ried, C. ; Farina, A.; et al.
Revista: BREAST JOURNAL
ISSN 1075-122X  Vol. 26  Nº 8  2020  págs. 1603-1605
Autores: Fastner, G. , (Autor de correspondencia); Gaisberger, C. ; Kaiser, J.; et al.
Revista: RADIOTHERAPY AND ONCOLOGY
ISSN 0167-8140  Vol. 149  2020  págs. 150 - 157
The aim of this review is to provide a comprehensive overview of the role of intraoperative radiation therapy with electrons (IOERT) in breast conserving therapy (BCT), both as partial breast irradiation (PBI) as well as anticipated boost ("IOERT-Boost"). For both applications, the criteria for patient selection, technical details/requirements, physical aspects and outcome data are presented. IOERT as PBI: The largest evidence comes from Italian studies, especially the ELIOT randomized trial. Investigators showed that the rate of in-breast relapses (IBR) in the IOERT group was significantly greater than with whole breast irradiation (WBI), even when within the pre-specified equivalence margin. Tumour sizes >2 cm, involved axillary nodes, Grade 3 and triple negative molecular subtypes emerged as statistically significant predictors of IBR. For patients at low risk for in-breast recurrence (ASTRO/ESTRO recommendations), full dose IOERT was isoeffective with standard WBI. Hence, several national guidelines now include this treatment strategy as one of the standard techniques for PBI in carefully selected patients. IOERT Boost: The largest evidence for boost IOERT preceding WBI comes from pooled analyses performed by the European Group of the International Society of Intraoperative Radiation Therapy (ISIORT Europe), where single boost doses (mostly around 10 Gy) preceded whole-breast irradiation (WBI) with 50 Gy (conventional fractionation). At median follow-up periods up to ten years, local recurrence rates around 1% were observed for low risk tumours. Higher local relapse rates were described for grade 3 tumours, triple negative breast cancer as well as for patients treated after primary systemic therapy for locally advanced tumours. Even in this settings, long-term (>5y) local tumour control rates beyond 95% were achieved. These encouraging results are interpreted as being attributable to utmost precision in dose delivery (by avoiding a "geographic and/or temporal miss"), and the possible radiobiological superiority of a single high dose fraction, compared to the conventionally fractionated boost. IOERT also showed favourable results in terms of cosmetic outcome, assumedly thanks to the small treated volumes combined with complete skin sparing. (C) 2020 Elsevier B.V. All rights reserved.
Autores: Garcia-Vazquez, V., (Autor de correspondencia); Calvo Manuel, Felipe; Ledesma-Carbayo, M. J.; et al.
Revista: PLOS ONE
ISSN 1932-6203  Vol. 15  Nº 1  2020 
In intraoperative electron radiation therapy (IOERT) the energy of the electron beam is selected under the conventional assumption of water-equivalent tissues at the applicator end. However, the treatment field can deviate from the theoretic flat irradiation surface, thus altering dose profiles. This patient-based study explored the feasibility of acquiring intraoperative computed tomography (CT) studies for calculating three-dimensional dose distributions with two factors not included in the conventional assumption, namely the air gap from the applicator end to the irradiation surface and tissue heterogeneity. In addition, dose distributions under the conventional assumption and from preoperative CT studies (both also updated with intraoperative data) were calculated to explore whether there are other alternatives to intraoperative CT studies that can provide similar dose distributions. The IOERT protocol was modified to incorporate the acquisition of intraoperative CT studies before radiation delivery in six patients. Three studies were not valid to calculate dose distributions due to the presence of metal artefacts. For the remaining three cases, the average gamma pass rates between the doses calculated from intraoperative CT studies and those obtained assuming water-equivalent tissues or from preoperative CT studies were 73.4% and 74.0% respectively. The agreement increased when the air gap was included in the conventional assumption (98.1%) or in the preoperative CT images (98.4%). Therefore, this factor was the one mostly influencing the dose distributions of this study. Our experience has shown that intraoperative CT studies are not recommended when the procedure includes the use of shielding discs or surgical retractors unless metal artefacts are removed. IOERT dose distributions calculated under the conventional assumption or from preoperative CT studies may be inaccurate unless the air gap (which depends on the surface irregularities of the irradiated volume and on the applicator pose) is included in the calculations.
Autores: Goswami, S. S.; Ortuno, J. E.; Santos, A. ; et al.
Revista: IEEE ACCESS
ISSN 2169-3536  Vol. 8  2020  págs. 137501 - 137516
A new workflow is proposed to update the intraoperative electron radiotherapy (IOERT) planning refreshing the position and orientation (pose) of a virtual applicator with respect to the preoperative computed tomography (CT) with the actual pose during surgery. The workflow proposed relies on a robust registration of the preoperative CT and intraoperative projection radiographs acquired with a C-arm system. The workflow initially performs a geometric calibration of the C-arm using fiducials placed on the applicator. In the next step, a point-based 2D-3D registration based on fiducials positioned on the patient's skin is performed, followed by an intensity-based registration that refines the point-based registration result. The performance of the workflow has been evaluated using a realistic physical phantom consisting of a pig lower limb and its corresponding CT and 7 C-arm projections at different poses. The accuracy has been measured with respect to the applicator origin and axis before and after the registration refinement process. A feasibility study with human data is also included. Error analysis revealed angular accuracy of 0.9 +/- 0.7 degrees and translational accuracy of 1.9 +/- 1 mm. Our experiments demonstrated that the proposed workflow can achieve subdegree angular accuracy in locating the applicator with respect to the preoperative CT to update and supervise the IOERT planning right before radiation delivery. The proposed workflow could be easily implementable in a routine, corresponding to a significant improvement in quality assurance during IOERT procedures.
Autores: Calvo Manuel, Felipe (Autor de correspondencia); Asencio, J. M. ; Roeder, F. ; et al.
Revista: CLINICAL AND TRANSLATIONAL RADIATION ONCOLOGY
ISSN 2405-6308  Vol. 23  2020  págs. 91 - 99
Radiation therapy (RT) is a valuable component of multimodal treatment for localized pancreatic cancer. Intraoperative radiation therapy (IORT) is a very precise RT modality to intensify the irradiation effect for cancer involving upper abdominal structures and organs, generally delivered with electrons (IOERT). Unresectable, borderline and resectable disease categories benefit from dose-escalated chemoradiation strategies in the context of active systemic therapy and potential radical surgery. Prolonged preoperative treatment may act as a filter for selecting patients with occult resistant metastatic disease. Encouraging survival rates have been documented in patients treated with preoperative chemoradiation followed by radical surgery and IOERT (>20 months median survival, >35% survival at 3 years). Intensive preoperative treatment, including induction chemotherapy followed by chemoradiation and an IOERT boost, appears to prolong long-term survival within the subset of patients who remain relapse-free for>2 years (>30 months median survival; >40% survival at 3 years). Improvement of local control through higher RT doses has an impact on the survival of patients with a lower tendency towards disease spread. IOERT is a well-accepted approach in the clinical scenario (maturity and reproducibility of results), and extremely accurate in terms of dose-deposition characteristics and normal tissue sparing. The technique can be adapted to systemic therapy and surgical progress. International guidelines (National Comprehensive Cancer Network or NCCN guidelines) currently recommend use of IOERT in cases of close surgical margins and residual disease. We hereby report the ESTRO/ACROP recommendations for performing IOERT in borderline-resectable pancreatic cancer. (C) 2020 The Author(s). Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology.
Autores: Calvo Manuel, Felipe (Autor de correspondencia); Krengli, M.; Asencio, J. M.; et al.
Revista: RADIOTHERAPY AND ONCOLOGY
ISSN 0167-8140  Vol. 148  2020  págs. 57 - 64
Radiation therapy (RT) is a valuable component of multimodal treatment for localized pancreatic cancer. Intraoperative radiation therapy (IORT) is a very precise sub-component of RT that can intensify the irradiation effect for cancer involving an anatomically well-defined volume, generally delivered with electrons (IOERT). Unresectable disease categories benefit from dose-escalated chemoradiation strategies in the context of active systemic therapy and potential radical surgery. Prolonged preoperative treatment may act as a filter for selecting patients with occult resistant metastatic disease. Long-term survivors were observed among unresected patients treated with external beam RT and an IOERT boost (OS 6% at 3 years; 3% >5 years). Improvement of local control through higher RT doses has an impact on the survival of patients with a lower tendency towards disease spread. IOERT is a well-accepted asset in the clinical scenario (maturity and reproducibility of results, albeit of low official level of evidence) and extremely accurate in terms of dose-deposit characteristics and normal tissue sparing. It is a technique that can be integrated with systemic therapy and surgical progress. International guidelines (National Comprehensive Cancer Network or NCCN guidelines) currently recommend the use of IOERT in cases of close surgical margins and residual disease. We report the ESTRO/ACROP recommendations for performing IOERT in unresected pancreatic cancer. (C) 2020 Elsevier B.V. All rights reserved.
Autores: Marijnen, C. A. M.; Peters, F. P.; Rodel, C. ; et al.
Revista: RADIOTHERAPY AND ONCOLOGY
ISSN 0167-8140  Vol. 148  2020  págs. 213 - 215
Autores: Rodríguez Ruiz, María Esperanza (Autor de correspondencia); Rodriguez, I.; Leaman, O.; et al.
Revista: PHARMACOLOGY AND THERAPEUTICS
ISSN 0163-7258  Vol. 196  2019  págs. 195 - 203
Radiotherapy of cancer has been traditionally considered as a local therapy without noticeable effects outside the irradiated fields. However, ionizing radiation exerts multiple biological effects on both malignant and stromal cells that account for a complex spectrum of mechanisms beyond simple termination of cancer cells. In the era of immunotherapy, interest in radiation-induced inflammation and cell death has considerably risen, since these mechanisms lead to profound changes in the systemic immune response against cancer antigens. Immunotherapies such as immunomodulatory monoclonal antibodies (anti-PD-1, anti-CTLA-4, anti-CD137, anti-OX40, anti-CD40, anti-TGF beta), TLR-agonists, and adoptive T-cell therapy have been synergistically combined with radiotherapy in mouse models. Importantly, radiation and immunotherapy combinations do not only act against the irradiated tumor but also against distant non-irradiated metastases (abscopal effects). A series of clinical trials are exploring the beneficial effects of radioimmunotherapy combinations. The concepts of crosspriming of tumor neoantigens and immunogenic cell death are key elements underlying this combination efficacy. Proinflamatory changes in the vasculature of the irradiated lesions and in the cellular composition of the leukocyte infiltrates in the tumor microenvironment contribute to raise or dampen cancer immunogenicity. It should be stressed that not all effects of radiotherapy favor antitumor immunity as there are counterbalancing mechanisms such as TGF beta, and VEGFs that inhibit the efficacy of the antitumor immune response, hence offering additional therapeutic targets to suppress. All in all, radiotherapy and immunotherapy are compatible and often synergistic approaches against cancer that jointly target irradiated and non-irradiated malignant lesions in the same patient. (C) 2018 Published by Elsevier Inc.
Autores: Mattiucci, G. C.; Morganti, A. G.; Cellini, F., (Autor de correspondencia); et al.
Revista: TRANSLATIONAL ONCOLOGY
ISSN 1936-5233  Vol. 12  Nº 1  2019  págs. 1 - 7
BACKGROUND: Presurgical carbohydrate antigen 19-9 (CA19-9) level predicts overall survival (OS) in resected pancreatic adenocarcinoma (PaC). The aim of this pooled analysis was to evaluate if presurgical CA19-9 level can also predict local control (LC) and distant metastasis-free survival (DMFS). METHODS: Seven hundred patients with PaC from eight institutions who underwent surgical resection +/- adjuvant treatment between 2000 and 2014 were analyzed. Patients were divided based on four presurgical CA19-9 level cutoffs (5, 37, 100, 353 U/ml). Weibull regression model to identify independent predictors of OS on 404 patients with complete information was fitted. RESULTS: Median follow-up was 17 months (range: 2-225 months). Univariate analysis showed a better prognosis in pT1-2, pN0, diameter <30 mm, or grade 1 tumors and in patients undergoing R0 resection, distal pancreatectomy, or adjuvant chemotherapy and with lower CA19-9 levels. Five-year OS, LC, and DMFS were as follows: CA19-9 <5.0: 5.7%, 47.2%, 17.0%; CA19-9 5.1-37.0: 37.9%, 63.3%, 46.0%; CA19-9 37.1-100.0: 27.1%, 59.4%, 39.0%; CA19-9 100.1-353.0: 17.4%, 43.4%, 26.7%; CA19-9 >353.1: 10.9%, 50.2%, and 23.4%, respectively. At multivariate analysis, CA19-9 >100 and <353 level (P=.002), CA19-9 >= 353.1 (P<.001) level, G3 tumor (P=.002), and tumor diameter >30 mm (P<.001) correlated with worse OS. Patients treated with postoperative chemoradiation doses >50.0 Gy showed improved OS (P<.001). CONCLUSION: Presurgical CA19-9 predicts both OS and pattern of failure. Therefore, CA19-9 should be included in predictive models in order to customize treatments based on prognostic factors. Moreover, future studies should stratify patients according to presurgical CA19-9 level.
Autores: Rodríguez Ruiz, María Esperanza (Autor de correspondencia); Rodriguez, I.; Mayorga Ortiz, Lina Paola; et al.
Revista: MOLECULAR CANCER THERAPEUTICS
ISSN 1535-7163  Vol. 18  Nº 3  2019  págs. 621 - 631
Radiotherapy can be synergistically combined with immunotherapy in mouse models, extending its efficacious effects outside of the irradiated field (abscopal effects). We previously reported that a regimen encompassing local radiotherapy in combination with anti-CD137 plus anti-PD-1 mAbs achieves potent abscopal effects against syngeneic transplanted murine tumors up to a certain tumor size. Knowing that TGF beta expression or activation increases in irradiated tissues, we tested whether TGF beta blockade may further enhance abscopal effects in conjunction with the anti-PD-1 plus anti-CD137 mAb combination. Indeed, TGF beta blockade with 1D11, a TGF beta-neutralizing mAb, markedly enhanced abscopal effects and overall treatment efficacy against subcutaneous tumors of either 4T1 breast cancer cells or large MC38 colorectal tumors. Increases in CD8 T cells infiltrating the nonirradiated lesion were documented upon combined treatment, which intensely expressed Granzyme-B as an indicator of cytotoxic effector capability. Interestingly, tumor tissue but not healthy tissue irradiation results in the presence of higher concentrations of TGF beta in the nonirradiated contralateral tumor that showed smad2/3 phosphorylation increases in infiltrating CD8 T cells. In conclusion, radiotherapy-induced TGF beta hampers abscopal efficacy even upon combination with a potent immunotherapy regimen. Therefore, TGF beta blockade in combination with radioimmunotherapy results in greater efficacy.
Autores: Chiva de Agustín, Luis; Chacon Cruz, Enrique Maria; Carriles Rivero, Isabel; et al.
Revista: INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER
ISSN 1048-891X  Vol. 29  Nº Supl. 4  2019  págs. A20 - A21
Autores: Chacon Cruz, Enrique Maria; Alcázar Zambrano, Juan Luis; Mínguez Milio, José Ángel; et al.
Revista: INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER
ISSN 1048-891X  Vol. 29  Nº Supl. 4  2019  págs. A450 - A451
Autores: Martin-Aragon, T., (Autor de correspondencia); Serrano, J. ; Benedi, J.; et al.
Revista: JOURNAL OF GASTROINTESTINAL ONCOLOGY
ISSN 2078-6891  Vol. 9  Nº 4  2018  págs. 631 - 640
Background: To evaluate, in a context of innovative multidisciplinary clinical practice, the efficacy of oxaliplatin in adjuvant administration (chemotherapy, CT) in relation to the total administered dose, in terms of prognosis with other clinical and therapeutic factors, in the heterogeneous model of locally advanced rectal cancer (LARC), which is characterized by a risk pattern of dominant systemic progression. Methods: Observational-analytical, retrospective, unicentric, non-randomized study of two cohorts of patients receiving FOLFOX-4 induction CT in neoadjuvancy, radiochemotherapy and surgery, differing in that one cohort did not receive any adjuvant post-surgical treatment and the other one received adjuvant CT with FOLFOX-4 cycles. A total of 212 patients from the Radiotherapy Oncology Service at the University Hospital Gregorio Maranon were studied: the neoadjuvant CT treatment group with oxaliplatin consisted of 110 patients and adjuvant CT treatment group with oxaliplatin consisted of 102 patients. The median follow-up time for the whole study population was 72 months (6 years). Results: The sociodemographic, clinical and diagnostic characteristics were very similar in both cohorts of patients, but with a pattern of therapeutic selection towards elements of adversity in pathological post-neoadjuvant staging. The dose of oxaliplatin in adjuvance (postoperative) superior to 6 cycles was positively associated with the locoregional control (LRC) at 5 years (P=0.012) and with the overall survival (OS) (P=0.048) at 5 years. In the responders to neoadjuvance with oxaliplatin [patients with tumor regression grade (TRG 3-4)], the dose of oxaliplatin greater than 5 cycles in adjuvance (postoperative) was positively associated with OS (P=0.06). And the dose of oxaliplatin in the range of 4-5 cycles in adjuvance (postoperative) was positively associated with distant metastasis-free survival (DMFS) and disease-free survival (DFS) in the cohort of responding patients (P=0.015 and 0.004, respectively). Conclusions: The contribution of adjuvant oxaliplatin in the oncological evolution shows a favorable effect of LRC, DMFS, DFS and OS in the subgroups of patients that exhibit elements of response to neoadjuvant oxaliplatin (categories TRG 3-4, and pN0, downstaging T, downstaging N). Therefore, this neoadjuvant response profile with oxaliplatin, measured with highly reliable methodology (validated microscopic pathological response scales), defines a population of oxaliplatin-sensitive patients who benefits significantly from the administration of adjuvant oxaliplatin in sufficient cumulative doses (more of 5 cycles).
Autores: Arenas, M. , (Autor de correspondencia); Sabater, S.; Biete, A.; et al.
Revista: JOURNAL OF CANCER EDUCATION
ISSN 0885-8195  Vol. 33  Nº 2  2018  págs. 352 - 358
The relevance of radiation oncology (RO) teaching in the Faculty of Medicine Degree Plan is justified by the high number of cancer patients who will require it at some point in their evolution of radiotherapy (RT). About 40 % of the population who will suffer cancer will be cured by RT alone or other related treatment modalities. Therefore, cancer education and RT teaching needs to have an in depth impact in the undergraduate medicine programmes. This education component is highly variable, not only among countries but also within each country, in terms of content (theory and practical training), number of credits and departmental affiliation of the teachers. Our aim is to take a snapshot of the situation of the teaching of RO in undergraduate university education in Spain. We have analysed 40 Spanish universities about specific aspects related to the teaching of RT. Information was obtained by mail or telephone contact throughout 2015. We have analysed the elements involved in teaching performance. In universities with various instructional units, we have taken the average of them. Among the Universities consulted in Spain, during the period of the medical degree, the average time allocated to RT lectures is 12 h (range, 0-36), the mean time allocated to seminars is 4 h (range, 0-22), and the mean time assigned to practices is 11 h (range, 0-38). The subject is mainly taught by a radiation oncologist and 80 % of Spanish universities have at least one radiation oncologist on staff. Undergraduate radiation oncology teaching in Spain shows structural heterogeneity. The Spanish Society of Radiation Oncology (SEOR) University Forum has identified new opportunities and elaborated a proposal to improve undergraduate education in oncology.
Autores: Garcia-Vazquez, V., (Autor de correspondencia); Sese-Lucio, B.; Calvo Manuel, Felipe; et al.
Revista: RADIATION ONCOLOGY
ISSN 1748-717X  Vol. 13  2018 
BackgroundDose calculations in intraoperative electron radiation therapy (IOERT) rely on the conventional assumption of water-equivalent tissues at the applicator end, which defines a flat irradiation surface. However, the shape of the irradiation surface modifies the dose distribution. Our study explores, for the first time, the use of surface scanning methods for three-dimensional dose calculation of IOERT.MethodsTwo different three-dimensional scanning technologies were evaluated in a simulated IOERT scenario: a tracked conoscopic holography sensor (ConoProbe) and a structured-light three-dimensional scanner (Artec). Dose distributions obtained from computed tomography studies of the surgical field (gold standard) were compared with those calculated under the conventional assumption or from pseudo-computed tomography studies based on surfaces.ResultsIn the simulated IOERT scenario, the conventional assumption led to an average gamma pass rate of 39.9% for dose values greater than 10% (two configurations, with and without blood in the surgical field). Results improved when considering surfaces in the dose calculation (88.5% for ConoProbe and 92.9% for Artec).ConclusionsMore accurate three-dimensional dose distributions were obtained when considering surfaces in the dose calculation of the simulated surgical field. The structured-light three-dimensional scanner provided the best results in terms of dose distributions. The findings obtained in this specific experimental setup warrant further research on surface scanning in the IOERT context owing to the clinical interest of improving the documentation of the actual IOERT scenario.
Autores: Jullien-Petrelli, A. C. ; Garcia-Sabrido, J. L.; Orue-Echebarria, M. I.; et al.
Revista: SPINE JOURNAL
ISSN 1529-9430  Vol. 18  Nº 4  2018  págs. 632 - 638
BACKGROUND CONTEXT: Sacral chordoma is a rare entity with high local recurrence rates when complete resection is not achieved. To date, there are no series available in literature combining surgery and intraoperative radiotherapy (IORT). PURPOSE: The objective of this study was to report the experience of our center in the management of sacral chordoma combining radical resection with both external radiotherapy and IORT. STUDY DESIGN: This is a retrospective case series. PATIENT SAMPLE: The patient sample included 15 patients with sacral chordoma resected in our center from 1998 to 2015. OUTCOME MEASURES: The outcome measures were overall survival (OS), disease-free survival (DFS), and rates of local and distant recurrences. METHODS: We retrospectively reviewed the records of all the patients with sacral chordoma resected in our center from 1998 to December 2015. Overall survival, DFS, and rates of local and distant recurrences were calculated. Results between patients treated with or without IORT were compared. RESULTS: A total of 15 patients were identified: 8 men and 7 women. The median age was 59 years (range 28-77). Intraoperative radiotherapy was applied in nine patients and six were treated with surgical resection without IORT. In 13 patients, we performed the treatment of the primary tumor, and in two patients, we performed the treatment of recurrence disease. A posterior approach was used in four patients. Wide surgical margins (zero residue) were achieved in six patients, marginal margins (microscopic residue) were achieved in seven patients, and there were no patients with intralesional (R2) margins. At a median follow-up of 38 months (range 11-209 months), the 5-year OS in the IORT group was 100% versus 53% in the group of non-IORT (p=.05). The median DFS in the IORT group was 85 months, and that in the non-IORT group was 41 months. In the group without IORT, two patients died and nobody died during the follow-up in the group treated with IORT. High-sacrectomy treated patients had a median survival of 41 months, and low-sacrectomy treated patients had a median survival of 90 months. Disease-free survival in patients without gluteal involvement was 100% at 5 years, and that in patients with gluteal involvement was 40%. All patients with a recurrence in our study had gluteal involvement. CONCLUSIONS: Multidisciplinary management of sacral chordoma seems to improve local control. The use of IORT, in our experience, is associated with an increase in OS and DFS. The level of resection and gluteal involvement seems to affect survival. The posterior approach is useful in selected cases. Multicenter studies should be performed to confirm the utility of IORT. (C) 2017 Elsevier Inc. All rights reserved.
Autores: Cambeiro Vázquez, Felix Mauricio (Autor de correspondencia); Calvo Manuel, Felipe
Revista: ARCHIVOS ESPAÑOLES DE UROLOGIA
ISSN 0004-0614  Vol. 71  Nº 3  2018  págs. 298 - 305
OBJECTIVES: We elaborate the bases and rationale for the application of multimodal extended treatment including local radiotherapy in patients with oligometastatic prostate cancer (omPCa). We performed a bibliographic review on the state of the art in this field and propose a therapeutic strategy that incorporates ablative radiotherapy of the primary tumor +/- oligometastatic lesions. METHODS: We performed a comprehensive literature review consulting different sources that include data bases (Pubmed/Medline), and international treatment guidelines ((NCCN, NCI, EUA). Search criteria: Locally advanced prostate cancer, oligometastatic, disseminated and radiotherapy, ablative or stereotactic radiotherapy (SBRT). RESULTS: The most accepted definition for oligometastatic prostate cancer or oligotopic prostatic neoplasia is when we recognize at least 3 non-visceral metastatic lesions in an extrapelvic location. Whole body MRI and PET scan (Choline/PSMA) are non conventional useful tests for staging in the workup for oligometastatic disease. From a clinical point of view, omPCa behaves as an intermediate entity between locally advanced and disseminated or multimetastatic prostate cancer. Androgen deprivation therapy (ADT) represents the base of treatment for castration sensitive PCs. To date there is no biological marker/genetic sign identified that differentiate aggressiveness profiles in omPca. Most evidence on the use of radiotherapy for this entity comes from retrospective studies, showing a benefit in control and prevention of local symptoms. To date, the survival benefit derived from the application of local treatment to the primary tumor with demonstrable metastatic disease is uncertain, and it has not been shown in the available randomized prospective clinical trials. CONCLUSIONS: Primary tumor radiotherapy in omPca positively influences local control and prevention of local symptoms progression. The level of evidence to recommend prostatic radiotherapy as a therapeutic variable with impact on survival on omPca is limited (Level 2B-3 Category). Research lines in omPca deserve the inclusion of a multimodal systemic treatment including ADT, ablative radiotherapy for the tumor and consolidation radiotherapy in metastatic distant lesions.
Autores: Roeder, F., (Autor de correspondencia); de Paoli, A.; Saleh-Ebrahimi, L.; et al.
Revista: ANNALS OF SURGICAL ONCOLOGY
ISSN 1068-9265  Vol. 25  Nº 13  2018  págs. 3833 - 3842
IntroductionWe report a pooled analysis evaluating the combination of gross complete limb-sparing surgery, intraoperative electron radiation therapy (IOERT), and external beam radiation therapy (EBRT) in patients with extremity soft tissue sarcoma (STS).MethodsIndividual data of 259 patients (median follow-up 63months) with extremity STS from three European expert centers were pooled. Median age was 55years and median tumor size was 8cm. Eighty percent of patients presented with primary disease, mainly located in the lower limb (81%). Union for International Cancer Control 7th edition stage at presentation was as follows: stage I: 9%; stage II: 47%; stage III: 39%; stage IV: 5%. Most patients showed high-grade lesions (91%), predominantly liposarcoma (31%). Median IOERT dose was 12Gy, preceeded (17%) or followed (83%) by EBRT, with a median dose of 45Gy.ResultsSurgery resulted in R0 resections in 71% of patients and R1 resections in 29% of patients. The 5-year local control (LC) rate was 86%, and significant factors in univariate analysis were disease status and resection margin. Only margin remained significant in multivariate analysis. The 5-year distant control rate was 69%, and significant factors in univariate analysis were histology, grading, resection margin, and metastases prior to/at IOERT. Only grading and metastases remained significant in multivariate analysis. Actuarial 5-year rates of freedom from treatment failure and OS were 61% and 78%, respectively. Significant factors for OS were grading and metastases prior to/at IOERT (univariate, multivariate). Limb preservation and good functional outcome were achieved in 95% and 81% of patients.ConclusionsOur pooled analysis confirmed prior reports of encouraging LC and survival, with excellent rates of preserved limb function with this treatment approach. Resection margin remained the most important factor for LC, while grading and metastases prior to/at IOERT mainly predicted survival.
Autores: Terlizzi, M.; Rapeaud, E.; Le Pechoux, C.; et al.
Revista: INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
ISSN 0360-3016  Vol. 102  Nº 3  2018  págs. E369 - E370
Autores: Calvo Manuel, Felipe (Autor de correspondencia)
Revista: RADIATION ONCOLOGY
ISSN 1748-717X  Vol. 12  2017 
Intraoperative irradiation was implemented 4 decades ago, pioneering the efforts to improve precision in local cancer therapy by combining real-time surgical exploration/resection with high single dose radiotherapy (Gunderson et al., Intraoperative irradiation: techniques and results, 2011). Clinical and technical developments have led to very precise radiation dose deposit. The ability to deliver a very precise dose of radiation is an essential element of contemporary multidisciplinary individualized oncology. This issue of Radiation Oncology contains a collection of expert review articles and updates with relevant data regarding intraoperative radiotherapy. Technology, physics, biology of single dose and clinical results in a variety of cancer sites and histologies are described and analyzed. The state of the art for advanced cancer care through medical innovation opens a significant opportunity for individualize cancer management across a broad spectrum of clinical practice. The advantage for tailoring diagnostic and treatment decisions in an individualized fashion will translate into precise medical treatment.
Autores: Marinetto, E., (Autor de correspondencia); Victores, J. G.; Garcia-Sevilla, M.; et al.
Revista: MEDICAL PHYSICS
ISSN 0094-2405  Vol. 44  Nº 10  2017  págs. 5061 - 5069
Purpose: Intraoperative electron radiation therapy (IOERT) involves the delivery of a high radiation dose during tumor resection in a shorter time than other radiation techniques, thus improving local control of tumors. However, a linear accelerator device is needed to produce the beam safely. Mobile linear accelerators have been designed as dedicated units that can be moved into the operating room and deliver radiation in situ. Correct and safe dose delivery is a key concern when using mobile accelerators. The applicator is commonly fixed to the patient's bed to ensure that the dose is delivered to the prescribed location, and the mobile accelerator is moved to dock the applicator to the radiation beam output (gantry). In a typical clinical set-up, this task is time-consuming because of safety requirements and the limited degree of freedom of the gantry. The objective of this study was to present a navigation solution based on optical tracking for guidance of docking to improve safety and reduce procedure time. Method: We used an optical tracker attached to the mobile linear accelerator to track the prescribed localization of the radiation collimator inside the operating room. Using this information, the integrated navigation system developed computes the movements that the mobile linear accelerator needs to perform to align the applicator and the radiation gantry and warns the physician if docking is unrealizable according to the available degrees of freedom of the mobile linear accelerator. Furthermore, we coded a software application that connects all the necessary functioning elements and provides a user interface for the system calibration and the docking guidance. Result: The system could safeguard against the spatial limitations of the operating room, calculate the optimal arrangement of the accelerator and reduce the docking time in computer simulations and experimental setups. Conclusions: The system could be used to guide docking with any commercial linear accelerator. We believe that the docking navigator we present is a major contribution to IOERT, where docking is critical when attempting to reduce surgical time, ensure patient safety and guarantee that the treatment administered follows the radiation oncologist's prescription. (C) 2017 American Association of Physicists in Medicine
Autores: Garcia-Vazquez, V. , (Autor de correspondencia); Marinetto, E.; Guerra, P. ; et al.
Revista: ZEITSCHRIFT FUR MEDIZINISCHE PHYSIK
ISSN 0939-3889  Vol. 27  Nº 3  2017  págs. 218 - 231
Intraoperative electron radiation therapy (IOERT) involves irradiation of an unresected tumour or a post resection tumour bed. The dose distribution is calculated from a preoperative computed tomography (CT) study acquired using a CT simulator. However, differences between the actual IOERT field and that calculated from the preoperative study arise as a result of patient position, surgical access, tumour resection and the IOERT set-up. Intraoperative CT imaging may then enable a more accurate estimation of dose distribution. In this study, we evaluated three kilovoltage (kV) CT scanners with the ability to acquire intraoperative images. Our findings indicate that current IOERT plans may be improved using data based on actual anatomical conditions during radiation. The systems studied were two portable systems ("O-arm", a cone-beam CT [CBCT] system, and "BodyTom", a multislice CT [MSCT] system) and one CBCT integrated in a conventional linear accelerator (LINAC) ("TrueBeam"). TrueBeam and BodyTom showed good results, as the gamma pass rates of their dose distributions compared to the gold standard (dose distributions calculated from images acquired with a CT simulator) were above 97% in most cases. The O-arm yielded a lower percentage of voxels fulfilling gamma criteria owing to its reduced field of view (which left it prone to truncation artefacts). Our results show that the images acquired using a portable CT or even a LINAC with on-board kV CBCT could be used to estimate the dose of IOERT and improve the possibility to evaluate and register the treatment administered to the patient.
Autores: Sole, C. V. ; Calvo Manuel, Felipe (Autor de correspondencia); Alvarez, E.; et al.
Revista: EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
ISSN 1619-7070  Vol. 43  Nº 8  2016  págs. 1444 - 1452
Purpose Vascular endothelial growth factor receptor-2 (VEGFR-2), epidermal growth factor receptor-1 (EGFR) and cyclooxygenase-2 (COX-2) stimulate key processes involved in tumour progression and are important targets for cancer therapeutics. F-18-FDG maximum standardized uptake value (SUVmax) on PET/CT is a marker of tumour metabolic activity. The purpose of this study was to measure percentage reductions in SUVmax (a dagger SUVmax%), VEGFR-2 (a dagger VEGFR-2%), EGFR (a dagger EGFR%) and COX-2 (a dagger COX-2%) in patients with locally advanced rectal cancer (LARC) after preoperative treatment, and to correlate the changes in these markers of response with pathological response in terms of tumour regression grade (TRG) using Rodel's scale and long-term clinical outcome. Methods VEGFR-2, EGFR and COX-2 were measured using a quantitative and qualitative compound immunohistochemistry analysis (immunoreactive score) of the pretreatment endoscopic biopsy and definitive surgical specimens. Composite indexes using a dagger SUVmax% and the three molecules were developed to differentiate patients with metabolic and molecular responses from nonresponders. Cox proportional hazards model was used to explore associations between the tumour markers, disease-free survival (DFS) and overall survival (OS). Results The analysis included 38 patients with a median follow-up of 86 months (range 5 - 113 months). The a dagger VEGFR-2%/a dagger SUVmax% index correctly identified 13 of 19 pathological responders (TRG 3 and 4) and 17 of 19 nonresponders (TRG 0 - 2) (sensitivity 68 %, specificity 89 %, accuracy 79 %, positive predictive value 87 %, negative predictive value 74 %). In multivariate analysis, only the a dagger VEGFR-2%/a dagger SUVmax% index was associated with DFS (HR 0.11, p = 0.001) and OS (HR 0.15, p = 0.02). Conclusion In patients with LARC the a dagger VEGFR-2%/a dagger SUVmax% response index is associated with outcome. Determination of the optimal diagnostic cut-off level for this novel biomarker association should be explored. Evaluation in a clinical trial is required to determine whether selected patients could benefit from treatment with a VEGFR-targeted therapeutic agent.
Autores: Zapatero, A. , (Autor de correspondencia); Guerrero, A.; Maldonado, X. ; et al.
Revista: INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
ISSN 0360-3016  Vol. 96  Nº 2  2016  págs. 341 - 348
Purpose: To present data on the late toxicity endpoints of a randomized trial (DART 01/05) conducted to determine whether long-term androgen deprivation (LTAD) was superior to short-term AD (STAD) when combined with high-dose radiation therapy (HDRT) in patients with prostate cancer (PCa). Patients and Methods: Between November 2005 and December 2010, 355 eligible men with cT1c-T3aN0M0 PCa and intermediate-risk and high-risk factors (2005 National Comprehensive Cancer Network criteria) were randomized to 4 months of AD combined with HDRT (median dose, 78 Gy) (STAD) or the same treatment followed by 24 months of AD (LTAD). Treatment-related complications were assessed using European Organization for Research and Treatment of CancereRadiation Therapy Oncology Group and Common Terminology Criteria for Adverse Events v3.0 scoring schemes. Multivariate analyses for late toxicity were done using the Fine-Gray method. Results: The 5-year incidence of grade >= 2 rectal and urinary toxicity was 11.1% and 8.2% for LTAD and 7.6% and 7.3% for STAD, respectively. Compared with STAD, LTAD was not significantly associated with a higher risk of late grade >= 2 rectal toxicity (hazard ratio [HR] 1.360, 95% confidence interval [CI] 0.660-2.790, P=. 410) or urinary toxicity (HR 1.028, 95% CI 0.495-2.130, P=. 940). The multivariate analysis showed that a baseline history of intestinal comorbidity (HR 3.510, 95% CI 1.560-7.930, P=. 025) and the rectal volume receiving > 60 Gy (Vr60) (HR 1.030, 95% CI 1.001-1.060, P=. 043) were the only factors significantly correlated with the risk of late grade >= 2 rectal complications. A history of previous surgical prostate manipulations was significantly associated with a higher risk of grade >= 2 urinary complications (HR 2.427, 95% CI 1.051-5.600, P=. 038). Long-term AD (HR 2.090; 95% CI 1.170-3.720, P=. 012) and a history of myocardial infarction (HR 2.080; 95% CI 1.130-3.810, P=. 018) were significantly correlated with a higher probability of cardiovascular events. Conclusion: Long-term AD did not significantly impact urinary or rectal radiationinduced toxicity, although it was associated with a higher risk of cardiovascular events. Longer follow-up is needed to measure the impact of AD on late morbidity and nonPCa mortality. (C) 2016 Elsevier Inc. All rights reserved.
Autores: Sole, C. V. , (Autor de correspondencia); Calvo Manuel, Felipe; Alvarez, E. ; et al.
Revista: RADIOTHERAPY AND ONCOLOGY
ISSN 0167-8140  Vol. 119  Nº 1  2016  págs. 30 - 34
Purpose: To assess long-term outcomes and toxicity of adjuvant radiotherapy in the post-surgical management of patients with resected high-grade skeletal osteosarcomas. Methods and materials: Seventy-two patients with primary resected osteosarcomas underwent adjuvant radiotherapy after neoadjuvant chemotherapy from December 1984 to December 2008. Local control (LC), overall survival (OS) and disease-free survival (DFS) were estimated using Kaplan-Meier methods. For survival outcomes potential associations were assessed in univariate and multivariate analyses using the Cox proportional hazards model. Results: After a median follow-up of 174 months (range, 33-363 months), 10-year LC, DFS, and OS rates were 82%, 58%, and 73%, respectively. In the multivariate analysis only R1 margin status (p = 0.02) remained significantly associated with LC. Patients with tumor necrosis <90% (p = 0.04) and RI resection margin (p = 0.05) remained at a significantly higher risk of mortality on multivariate analysis. Six patients (8%) developed grade >= 3 treatment-related chronic toxicity events. No grade 5 toxicities were reported. Conclusions: A multimodal radiotherapy-containing approach is a well-tolerated component of treatment for patients with osteosarcomas undergoing programed resection, allowing low toxicity rates while maintaining high local control rates. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
Autores: Zapatero, A.; Guerrero, A. D.; Maldonado, J.; et al.
Revista: INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
ISSN 0360-3016  Vol. 96  Nº 2  2016  págs. S139 - S140
Autores: Roeder, F.; De Paoli, A. ; Alldinger, I. ; et al.
Revista: STRAHLENTHERAPIE UND ONKOLOGIE
ISSN 0179-7158  Vol. 192  2016  págs. 26 - 26
Autores: Valdivieso-Casique, M. F. ; Rodriguez, R. ; Rodriguez-Bescos, S.; et al.
Revista: TRANSLATIONAL CANCER RESEARCH
ISSN 2218-676X  Vol. 4  Nº 2  2015  págs. 196 - 209
In the last decades accumulated clinical evidence has proven that intra-operative radiation therapy (IORT) is a very valuable technique. In spite of that, planning technology has not evolved since its conception, being outdated in comparison to current state of the art in other radiotherapy techniques and therefore slowing down the adoption of IORT. RADIANCE is an IORT planning system, CE and FDA certified, developed by a consortium of companies, hospitals and universities to overcome such technological backwardness. RADIANCE provides all basic radiotherapy planning tools which are specifically adapted to IORT. These include, but are not limited to image visualization, contouring, dose calculation algorithms-Pencil Beam (PB) and Monte Carlo (MC), DVH calculation and reporting. Other new tools, such as surgical simulation tools have been developed to deal with specific conditions of the technique. Planning with preoperative images (preplanning) has been evaluated and the validity of the system being proven in terms of documentation, treatment preparation, learning as well as improvement of surgeons/radiation oncologists (ROs) communication process. Preliminary studies on Navigation systems envisage benefits on how the specialist to accurately/safely apply the pre-plan into the treatment, updating the plan as needed. Improvements on the usability of this kind of systems and workflow are needed to make them more practical. Preliminary studies on Intraoperative imaging could provide an improved anatomy for the dose computation, comparing it with the previous pre-plan, although not all devices in the market provide good characteristics to do so. DICOM.RT standard, for radiotherapy information exchange, has been updated to cover IORT particularities and enabling the possibility of dose summation with external radiotherapy. The effect of this planning technology on the global risk of the IORT technique has been assessed and documented as part of a failure mode and effect analysis (FMEA). Having these technological innovations and their clinical evaluation (including risk analysis) we consider that RADIANCE is a very valuable tool to the specialist covering the demands from professional societies (AAPM, ICRU, EURATOM) for current radiotherapy procedures.
Autores: Sole, C. V., (Autor de correspondencia); Calvo Manuel, Felipe; Lizarraga, S.; et al.
Revista: ANNALS OF SURGICAL ONCOLOGY
ISSN 1068-9265  Vol. 22  2015  págs. S1247 - S1255
Purpose. The aim of this study was to analyze long-term outcomes and prognostic factors associated with survival in patients with locoregional oligo-recurrent (LROR) pelvic malignancies treated in a multimodal protocol. Methods. Patients with an histologic diagnosis of LROR pelvic cancer (rectal 50 %, gynecological 50 %) with absence of distant metastases, undergoing surgery with radical intent and intraoperative radiotherapy (median dose 12.5 Gy) were considered eligible for participation in this study. Additionally, 48 % received external beam radiotherapy (EBRT) (median dose 50 Gy). Results. From 1995 to 2012, a total of 143 patients from a single institution were analyzed. With a median follow-up time of 48 months (range 2-189), 5-year locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) were 53, 44, and 46 %, respectively. On multivariate analysis, no EBRT treatment to the locoregional (p <= 0.001), R1 margin status (p = 0.03), time interval from primary tumor diagnosis to LROR <24 months (p = 0.05), and fragmentation in the resected specimen (p = 0.004) retained significance in relation to LRC. On multivariate analysis we found that only R1 margin status (p = 0.003), primary tumor diagnosis to LROR <24 months (p = 0.02), and high histological grade (p = 0.02) were significantly associated with OS. Conclusions. From this analysis emerges the fact that EBRT influences local control but, given the high risk of distant metastases, DFS remains modest. Margin status, tumor fragmentation, no EBRT to the LR, and time interval from primary tumor diagnosis to LROR are the dominant factors for subsequent locoregional recurrence (LRR). Accordingly, future prospective studies might be designed which adapt treatment according to the predicted risk of subsequent LRR.
Autores: Mattiucci, G. C., (Autor de correspondencia); Falconi, M. ; Van Stiphout, R. G. P. M.; et al.
Revista: ANTICANCER RESEARCH
ISSN 0250-7005  Vol. 35  Nº 6  2015  págs. 3441 - 3446
Aim: To determine the impact of postoperative chemoradiation (POCR) on overall survival (OS) after resection of pancreatic adenocarcinoma (PAC) in elderly (>= 75 years) patients. Materials and Methods: A multi-center retrospective review of 1248 patients who underwent complete resection with macroscopically negative margins (R0-1) for invasive PAC was performed. Exclusion criteria included age <75 years, metastatic or unresectable disease at surgery, macroscopic residual disease (R2), treatment with intraoperative radiotherapy (IORT) and postoperative death. Results: A total of 98 patients were included in the analysis (males=39.8%, females=60.2%; R1 resections=33.7%; pN1=61.2%); 63 patients received POCR and 26 patients received adjuvant chemotherapy alone. The median follow-up was 25.6 months. The mean age for the entire cohort of patients was 78.1+/-2.9 (SD) years. No differences were observed between patients receiving or not receiving POCR in terms of age (p=0.081), tumor diameter (p=0.412), rate of R1 resection (p=0.331) and incidence of lymph node-positive disease (p=0.078). The only factor predicting an improved OS was POCR. The median OS was 69.0 months in patients treated by POCR and 23.0 months in patients treated without POCR (p=0.008). Even by Cox multivariate analysis, the only significant predictor of OS was POCR (hazard ratio=0.449; 95% confidence interval=0.212-0.950; p=0.036). Conclusion: The study represents the first comparative approach on POCR in elderly patients after resection of PAC. OS was higher in patients who received POCR. Further analyses are warranted to evaluate the toxicity rate/grade and the impact of POCR on patient quality of life.
Autores: Maas, M.; Nelemans, P. J.; Valentini, V.; et al.
Revista: INTERNATIONAL JOURNAL OF CANCER
ISSN 0020-7136  Vol. 137  Nº 1  2015  págs. 212 - 220
Recent literature suggests that the benefit of adjuvant chemotherapy (aCT) for rectal cancer patients might depend on the response to neoadjuvant chemoradiation (CRT). Aim was to evaluate whether the effect of aCT in rectal cancer is modified by response to CRT and to identify which patients benefit from aCT after CRT, by means of a pooled analysis of individual patient data from 13 datasets. Patients were categorized into three groups: pCR (ypT0N0), ypT1-2 tumour and ypT3-4 tumour. Hazard ratios (HR) for the effect of aCT were derived from multivariable Cox regression analyses. Primary outcome measure was recurrence-free survival (RFS). One thousand seven hundred and twenty three (1723) (52%) of 3,313 included patients received aCT. Eight hundred and ninety eight (898) patients had a pCR, 966 had a ypT1-2 tumour and 1,302 had a ypT3-4 tumour. For 122 patients response, category was missing and 25 patients had ypT0N+. Median follow-up for all patients was 51 (0-219) months. HR for RFS with 95% CI for patients treated with aCT were 1.25(0.68-2.29), 0.58(0.37-0.89) and 0.83(0.66-1.10) for patients with pCR, ypT1-2 and ypT3-4 tumours, respectively. The effect of aCT in rectal cancer patients treated with CRT differs between subgroups. Patients with a pCR after CRT may not benefit from aCT, whereas patients with residual tumour had superior outcomes when aCT was administered. The test for interaction did not reach statistical significance, but the results support further investigation of a more individualized approach to administer aCT after CRT and surgery based on pathologic staging. What's new? Most patients with locally advanced rectal cancer receive adjuvant chemotherapy after neoadjuvant treatment and surgery. Based on a pooled analysis of individual patient data from 13 datasets, this study however shows that the benefit of adjuvant chemotherapy differs between subgroups, based on the response of patients to previous neoadjuvant chemoradiation. Patients with a complete response after chemoradiation may not benefit from adjuvant chemotherapy, whereas patients with residual tumour have superior outcomes when adjuvant chemotherapy was administered. The results support further investigation of a more individualized approach based on pathologic staging for the administration of adjuvant chemotherapy after chemoradiation and surgery.
Autores: Cambeiro Vázquez, Felix Mauricio (Autor de correspondencia); Aristu Mendioroz, José Javier; Moreno Jiménez, Marta; et al.
Revista: BRACHYTHERAPY
ISSN 1538-4721  Vol. 14  Nº 1  2015  págs. 62 - 70
PURPOSE: To assess the toxicity and efficacy of salvage wide resection (SWR) with intraoperative electron beam radiation therapy (IOERT) or perioperative high-dose-rate brachytherapy (PHDRB) in previously unirradiated patients (PUP) vs. previously irradiated patients (PIP) with isolated local recurrence of soft tissue sarcomas (STS) of the extremities and the superficial trunk. METHODS AND MATERIALS: PUP received SWR and IOERT/PHDRB with external beam radiation therapy. PIP received SWR and IOERT/PHDRB only. RESULTS: Fifty patients were analyzed retrospectively. PUP (n = 24; 48%) received IOERT (n = 13) or PHDRB (n = 11). PIP (n = 26; 52%) received IOERT (n = 10) or PHDRB (n = 16). Reintervention because of complications was not required in PUP. Nine of 26 (34%) PIP required reintervention (p = 0.01). After a median followup of 3.7 years (range, 0.2-18.3), the 5-year rates of locoregional control, distant control, and overall survival were 54%, 66%, and 56%, respectively. Five-year locoregional control was higher in PUP than in PIP (81% vs. 26%, p = 0.01) and in the extremity locations compared with trunk locations (68% vs. 28%, p = 0.001). Five-year overall survival was superior in unifocal vs. multifocal presentations (70% vs. 36%, p = 0.03) and for tumor sizes <4 vs. >= 4 cm (74% vs. 50%, p = 0.05). CONCLUSIONS: Prior irradiation is the main determinant of locoregional control in patients with isolated local recurrence of STS. The locoregional control rates in PUP were similar to those described in primary STS. In PIP, SWR + IOERT/PHDRB reirradiation yielded modest locoregional control rates and was associated with significant morbidity, especially in PHDRB cases. (C) 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.
Autores: Sole, C. V., (Autor de correspondencia); Calvo Manuel, Felipe; Polo, A.; et al.
Revista: INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
ISSN 0360-3016  Vol. 92  Nº 5  2015  págs. 1069 - 1076
Purpose: To assess long-term outcomes and toxicity of intraoperative electron-beam radiation therapy (IOERT) in the management of pediatric patients with Ewing sarcomas (EWS) and rhabdomyosarcomas (RMS). Methods and Materials: Seventy-one sarcoma (EWS n=37, 52%; RMS n=34, 48%) patients underwent IOERT for primary (n=46, 65%) or locally recurrent sarcomas (n=25, 35%) from May 1983 to November 2012. Local control (LC), overall survival (OS), and disease-free survival were estimated using Kaplan-Meier methods. For survival outcomes, potential associations were assessed in univariate and multivariate analyses using the Cox proportional hazards model. Results: After a median follow-up of 72 months (range, 4-310 months), 10-year LC, disease-free survival, and OS was 74%, 57%, and 68%, respectively. In multivariate analysis after adjustment for other covariates, disease status (P=.04 and P=.05) and R1 margin status (P<.01 and P=.04) remained significantly associated with LC and OS. Nine patients (13%) reported severe chronic toxicity events (all grade 3). Conclusions: A multimodal IOERT-containing approach is a well-tolerated component of treatment for pediatric EWS and RMS patients, allowing reduction or substitution of external beam radiation exposure while maintaining high local control rates. (C) 2015 Elsevier Inc. All rights reserved.
Autores: Calvo Manuel, Felipe; Sole, C. V., (Autor de correspondencia); Marsiglia, H. ; et al.
Revista: CURRENT ONCOLOGY REPORTS
ISSN 1523-3790  Vol. 17  Nº 1  2015 
The integration of intraoperative radiotherapy (IORT) into the multimodal treatment of gastrointestinal cancer is feasible and leads to high rates of local control. In-field tumoral control using IORT-containing strategies can be achieved in over 90 % of most cases, regardless of the site or status of the tumor (primary or recurrent). Electron beam IORT, or intraoperative electron radiation therapy, is the dominant technology used in institutions reporting data in publications the 21st century. Neither surgery nor systemic therapy is compromised by the integration of IORT-containing radiotherapy.
Autores: Zapatero, A., (Autor de correspondencia); Guerrero, A.; Maldonado, X. ; et al.
Revista: LANCET ONCOLOGY
ISSN 1470-2045  Vol. 16  Nº 3  2015  págs. 320 - 327
Background The optimum duration of androgen deprivation combined with high-dose radiotherapy in prostate cancer remains undefined. We aimed to determine whether long-term androgen deprivation was superior to short-term androgen deprivation when combined with high-dose radiotherapy. Methods In this open-label, multicentre, phase 3 randomised controlled trial, patients were recruited from ten university hospitals throughout Spain. Eligible patients had clinical stage T1c-T3b N0M0 prostate adenocarcinoma with intermediate-risk and high-risk factors according to 2005 National Comprehensive Cancer Network criteria. Patients were randomly assigned (1: 1) using a computer-generated randomisation schedule to receive either 4 months of androgen deprivation combined with three-dimensional conformal radiotherapy at a minimum dose of 76 Gy (range 76-82 Gy; short-term androgen deprivation group) or the same treatment followed by 24 months of adjuvant androgen deprivation (long-term androgen deprivation group), stratified by prostate cancer risk group (intermediate risk vs high risk) and participating centre. Patients assigned to the short-term androgen deprivation group received 4 months of neoadjuvant and concomitant androgen deprivation with subcutaneous goserelin (2 months before and 2 months combined with high-dose radiotherapy). Anti-androgen therapy (flutamide 750 mg per day or bicalutamide 50 mg per day) was added during the first 2 months of treatment. Patients assigned to long-term suppression continued with the same luteinising hormone-releasing hormone analogue every 3 months for another 24 months. The primary endpoint was biochemical disease-free survival. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT02175212. Findings Between Nov 7, 2005, and Dec 20, 2010, 178 patients were randomly assigned to receive short-term androgen deprivation and 177 to receive long-term androgen deprivation. After a median follow-up of 63 months (IQR 50-82), 5-year biochemical disease-free survival was significantly better among patients receiving long-term androgen deprivation than among those receiving short-term treatment (90% [95% CI 87-92] vs 81% [78-85]; hazard ratio [HR] 1.88 [95% CI 1.12-3.15]; p=0.01). 5-year overall survival (95% [ 95% CI 93-97] vs 86% [83-89]; HR 2.48 [95% CI 1.31-4.68]; p=0.009) and 5-year metastasis-free survival (94% [95% CI 92-96] vs 83% [80-86]; HR 2.31 [95% CI 1.23-3.85]; p=0.01) were also significantly better in the long-term androgen deprivation group than in the short-term androgen deprivation group. The effect of long-term androgen deprivation on biochemical disease-free survival, metastasis-free survival, and overall survival was more evident in patients with high-risk disease than in those with low-risk disease. Grade 3 late rectal toxicity was noted in three (2%) of 177 patients in the long-term androgen deprivation group and two (1%) of 178 in the short-term androgen deprivation group; grade 3-4 late urinary toxicity was noted in five (3%) patients in each group. No deaths related to treatment were reported. Interpretation Compared with short-term androgen deprivation, 2 years of adjuvant androgen deprivation combined with high-dose radiotherapy improved biochemical control and overall survival in patients with prostate cancer, particularly those with high-risk disease, with no increase in late radiation toxicity. Longer follow-up is needed to determine whether men with intermediate-risk disease benefit from more than 4 months of androgen deprivation.
Autores: Sole, C. V.; Calvo Manuel, Felipe (Autor de correspondencia); Ferrer, C.; et al.
Revista: EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
ISSN 1619-7070  Vol. 42  Nº 2  2015  págs. 186 - 196
Purpose It has long been debated whether human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) are associated with rectal cancer. The gene products of HCMV and EBV contribute to cell-cycle progression, mutagenesis, angiogenesis and immune evasion. The aim of this prospective study was to analyse the association between infection of a tumour by HCMV and EBV and clinical, histological, metabolic (F-18-FDG uptake), volumetric (from CT) and molecular (KRAS status) features and long-term outcomes in a homogeneously treated group of patients with locally advanced rectal cancer. Methods HCMV and EBV were detected in pretreatment biopsies using polymerase chain reaction (PCR). The Cox pro-portional hazards regression model was used to explore associations between viral infection and disease-free survival (DFS) and overall survival (OS). Results We analysed 37 patients with a median follow-up of 74 months (range 5-173 months). Locoregional control, OS and DFS at 5 years were 93 %, 74 % and 71 %, respectively. Patients with HCMV/EBV coinfection had a significantly higher maximum standardized uptake value than patients without viral coinfection (p=0.02). Significant differences were also observed in staging and percentage relative reduction in tumour volume between patients with and without HCMV infection (p<0.01) and EBV infection (p<0.01). KRAS wildtype status was significantly more frequently observed in patients with EBV infection (p<0.01) and HCMV/EBV co-infection (p=0.04). No significant differences were observed in OS or DFS between patients with and without EBV infection (p=0.88 and 0.73), HCMV infection (p=0.84 and 0.79), and EBV/CMV coinfection (p=0.24 and 0.39). Conclusion This pilot study showed that viral infections were associated with metabolic staging differences, and differences in the evolution of metabolic and volumetric parameters and KRAS mutations. Further findings of specific features will help determine the best candidates for metabolic and volumetric staging and restaging. Further toxicity profile findings will help to determine the best candidates for specific supportive treatment during pelvic chemoradiotherapy in patients with locally advanced rectal cancer.
Autores: Cambeiro Vázquez, Felix Mauricio (Autor de correspondencia); Calvo Manuel, Felipe; Aristu Mendioroz, José Javier; et al.
Revista: RADIOTHERAPY AND ONCOLOGY
ISSN 0167-8140  Vol. 116  Nº 2  2015  págs. 316 - 322
Purpose To evaluate the influence of equivalent dose (EQD2) in clinical outcomes of patients with isolated locally recurrent tumors (ILRT), treated with salvage surgery and intra-operative electron beam radiation therapy (IOERT). Methods and materials We retrospectively reviewed 128 patients with non-metastatic ILRT of different tissues (soft tissue sarcomas, head and neck, uterine, and colorectal). Patients had received salvage surgery (R0/R1/R2) and IOERT. Previously not irradiated patients had received additional external beam radiation therapy (EBRT). Results IOERT was delivered at a median dose of 15 Gy (range, 5-25 Gy). Seventy-five patients (60.9%) received additional EBRT of 46 Gy. Median EQD2 of salvage program was 62 Gy and median EQD2 of exclusive IORT was 31.2 Gy. Median follow-up was 19.2 months (range: 1.3-220). Thirty-one patients (24.2%) developed severe (grade 3-5) complications. New locoregional recurrence was documented in 86 (67.2%) of the 123 cases. Five-year rates were 31% for locoregional control, 57% for distant metastasis-free and 31% for overall survival. On multivariate analysis, R0-1 vs. R2 resection (HR 2.2, 95 CI: 1.2-4.1) was statistically significant for locoregional recurrence and EQD2 ¿62 Gy for survival (HR 2.2, 95 CI: 1.1-4.1). Conclusions Surgical radicality (gross macroscopic resection) and radiation dose (EQD2 ¿62 Gy in radiation salvage program) are the dominant prognostic factors beside ILRT histology. Modest rates of long-term disease control are expected when both factors are fulfilled.
Autores: Sole, C. V., (Autor de correspondencia); Calvo Manuel, Felipe; Atahualpa, F. ; et al.
Revista: STRAHLENTHERAPIE UND ONKOLOGIE
ISSN 0179-7158  Vol. 191  Nº 1  2015  págs. 17 - 25
Background To analyze prognostic factors associated with long-term outcomes in patients with resected pancreatic cancer treated with chemotherapy (CT) and surgery with or without external beam radiotherapy (EBRT). Patients and methods From January 1995 to December 2012, 95 patients with adenocarcinoma of the pancreas and locoregional disease [clinical stage IB-IIA (n = 45; 47 %), IIB-IIIC (n = 50; 53 %)] were treated with curative resection [R0 (n = 52; 55 %), R1 (n = 43, 45 %)] and CT with (n = 60; 63 %) or without (n = 35; 37 %) EBRT (45-50.4 Gy). Additionally, 29 patients (48 %) also received a pre-anastomosis IOERT boost (applicator diameter size, 7-10 cm; dose, 10-15 Gy; beam energy, 9-18 MeV). Results With a median follow-up of 17.2 months (range, 1-182), 2-year overall survival (OS), disease-free survival (DFS), and locoregional control were 28, 20, and 53 %, respectively. Univariate analyses showed that IIB-IIIC stage (HR, 2.23; p = 0.04), R1 margin resection status (HR, 2.09; p = 0.04), no vascular resection (HR, 0.42; p = 0.02), and not receiving external beam radiotherapy (HR, 2.70; p = 0.004) were associated with locoregional recurrence. In the multivariate analysis, only R1 margin resection status (HR, 2.63; p = 0.009) and not receiving EBRT (HR, 2.91; p = 0.002) retained significance with regard to locoregional recurrence. We observed no difference in toxicity between patients treated with or without EBRT (p = 0.44). Overall treatment mortality was 3 %. No long-term treatment-related death occurred. Conclusions Although adjuvant CT is still the standard of care for resected pancreatic tumors, OS remains modest owing to the high risk of distant metastases. Locoregional treatment needs to be tested in the context of more efficient systemic therapy.
Autores: Mattiucci, G. C. ; Morganti, A. G. ; Falconi, M.; et al.
Revista: INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
ISSN 0360-3016  Vol. 93  Nº 3  2015  págs. E154 - E154
Autores: Maidment, B. W. ; Mattiucci, G. C.; Falconi, M. ; et al.
Revista: INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
ISSN 0360-3016  Vol. 93  Nº 3  2015  págs. E149 - E149
Autores: Sole, C. V., (Autor de correspondencia); Calvo Manuel, Felipe
Revista: INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
ISSN 0360-3016  Vol. 89  Nº 4  2014  págs. 932 - 933
Autores: Calvo Manuel, Felipe; Sole, C. V., (Autor de correspondencia); Polo, A.; et al.
Revista: STRAHLENTHERAPIE UND ONKOLOGIE
ISSN 0179-7158  Vol. 190  Nº 10  2014  págs. 891 - 898
Background or purpose. A joint analysis of data from three contributing centres within the intraoperative electron-beam radiation therapy (IOERT) Spanish program was performed to investigate the main contributions of IORT to the multidisciplinary treatment of high-risk extremity soft tissue sarcoma (STS). Methods and materials. Patients with an histologic diagnosis of primary extremity STS, with absence of distant metastases, undergoing limb-sparing surgery with radical intent, external beam radiotherapy (median dose 45 Gy) and IOERT (median dose 12.5 Gy) were considered eligible for participation in this study. Results. From 1986-2012, a total of 159 patients were analysed in the study from three Spanish institutions. With a median follow-up time of 53 months (range 4-316 years), 5-year local control (LC) was 82 %. The 5-year IOERT in-field control, disease-free survival (DFS) and overall survival (OS) were 86, 62 and 72 %, respectively. On multivariate analysis, only microscopically involved margin (R1) resection status retained significance in relation to LC (HR 5.20, p < 0.001). With regard to IOERT in-field control, incomplete resection (HR 4.88, p = 0.001) and higher IOERT dose (>= 12.5 Gy; HR 0.32, p = 0.02) retained a significant association in multivariate analysis. Conclusion. From this joint analysis emerges the fact that an IOERT dose >= 12.5 Gy increases the rate of IOERT in-field control, but DFS remains modest, given the high risk of distant metastases. Intensified local treatment needs to be tested in the context of more efficient concurrent, neo- and adjuvant systemic therapy.
Autores: Sole, C. V., (Autor de correspondencia); Calvo Manuel, Felipe; Ferrer, C. ; et al.
Revista: STRAHLENTHERAPIE UND ONKOLOGIE
ISSN 0179-7158  Vol. 190  Nº 12  2014  págs. 1111 - 1116
To analyze the performance and quality of intraoperative radiation therapy (IORT) publications identified in medical databases during a recent period in terms of bibliographic metrics. A bibliometric search was conducted for IORT papers published in the PubMed database between 1997 and 2013. Publication rate was used as a quantity indicator; the 2012 Science Citation Index Impact Factor as a quality indicator. Furthermore, the publications were stratified in terms of study type, scientific topic reported, year of publication, tumor type and journal specialty. We performed a one-way analysis of variance (ANOVA) to determine differences between the means of the analyzed groups. Among the total of 207 journals, articles were reported significantly more frequently in surgery (n = 399, 41 %) and radiotherapy journals (n = 273, 28 %; p < 0.01). The highest impact factor was achieved by clinical oncology journals (p < 0.01). The majority of identified articles were retrospective cohort reports (n = 622, 64 %), followed by review articles (n = 204, 21 %; p < 0.001). Regarding primary topic, reports on cancer outcome following specific tumor therapy were most frequently published (n = 661, 68 %; p < 0.001) and gained the highest mean impact factor (p < 0.01). Gastrointestinal tumor reports were represented most frequently (n = 456, 47 %; p < 0.001) and the mean superior impact factor was earned by breast and gynecologic publications (p < 0.01). We identified a consistent and sustained scientific productivity of international IORT expert groups. Most publications appeared in journals with surgical and radiooncological content. The highest impact factor was achieved by medical oncology journals.
Autores: Sole, C. V., (Autor de correspondencia); Calvo Manuel, Felipe; Serrano, J.; et al.
Revista: RADIOTHERAPY AND ONCOLOGY
ISSN 0167-8140  Vol. 112  Nº 1  2014  págs. 52 - 58
Background: Patients with locally advanced rectal cancer (LARC) have a dismal prognosis. We investigated outcomes and risk factors for locoregional recurrence (LRR) in patients treated with preoperative chemoradiotherapy (CRT), surgery and IOERT. Methods: A total of 335 patients with LARC [>= cT3 93% and/or cN+ 69%) were studied. In multivariate analyses, risk factors for LRR, IFLR and OFLR were assessed. Results: Median follow-up was 72.6 months (range, 4-205). In multivariate analysis distal margin distance <= 10 mm [HR 2.46, p = 0.03], R1 resection [HR 5.06, p = 0.02], tumor regression grade 1-2 [HR 2.63, p = 0.05] and tumor grade 3 [HR 7.79, p < 0.001] were associated with an increased risk of LRR. A risk model was generated to determine a prognostic index for individual patients with LARC. Conclusions: Overall results after multimodality treatment of LARC are promising. Classification of risk factors for LRR has contributed to propose a prognostic index that could allow us to guide risk-adapted tailored treatment. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
Autores: Calvo Manuel, Felipe; Sole, C. V. , (Autor de correspondencia); Serrano, J. ; et al.
Revista: STRAHLENTHERAPIE UND ONKOLOGIE
ISSN 0179-7158  Vol. 190  Nº 2  2014  págs. 149 - 157
Background and purpose. It has been previously reported that a short FOLFOX-4 induction significantly improves pathologic complete response in locally advanced rectal cancer (LARC) patients treated with preoperative chemoradiation (CRT). In a larger and updated patient series, we analyzed FOLFOX-4 efficacy in terms of sphincter preservation and long-term outcomes. Patients and methods. From January 1995 to December 2010, 335 LARC patients were treated with preoperative chemoradiation (4500-5040 cGy). Starting in May 2001, 207 consecutive patients additionally received induction FOLFOX-4. Surgery was performed 6 weeks (range 3-12 weeks) after chemoradiation. Results. Incidence of total tumor (63 vs. 54 %, p = 0.02) and nodal downstaging (60 vs. 43 %, p = 0.002) was significantly increased by induction FOLFOX-4. In an analysis of tumors located below 5 cm from the anal verge (n = 114, 34 %), sphincter preservation was feasible in 30 % in the FOLFOX-4 versus 13 % in the upfront CRT group (p = 0.04). Median follow-up time for the entire cohort of patients was 72.6 months (range 4-205 months). FOLFOX-4 was not associated with superior locoregional control (HR 0.88, p = 0.78), disease-free survival (HR 0.83, p = 0.55), distant metastases-free survival (HR 0.94, p = 0.81), or cancer-specific survival (HR 0.70, p = 0.15). Conclusion. Short-intense induction FOLFOX-4 significantly improves downstaging and sphincter preservation in low rectal tumors. Long-term outcomes were not improved in the FOLFOX-4 group of patients.
Autores: Krengli, M. , (Autor de correspondencia); Sedlmayer, F.; Calvo Manuel, Felipe; et al.
Revista: TRANSLATIONAL CANCER RESEARCH
ISSN 2218-676X  Vol. 3  Nº 1  2014  págs. 48 - 58
Purpose: Data from centers active in intraoperative radiotherapy (IORT) were collected within the International Society of Intraoperative Radiation Therapy (ISIORT)-Europe program. The purpose of the present study was to analyze and report the main clinical and technical variables of IORT performed by the participating centers. Materials and methods: Since 2007, ISIORT-Europe centers were invited to record data of IORT procedures in a common database. Other centers worldwide joined this initiative over time. Collected data included demographic, clinical and technical information. Results: Thirty-one centers participated in the survey and data of 7,196 IORT procedures have been recorded to 2013. Median age of patients was 60.6 years (range, 5 months-94 years). Gender was female in 80.2% of cases and male in 19.8%. Treatment intent was curative in 7,054 cases (98%) and 1,587 patients (22.1%) were included in study protocols. The most frequent tumor was breast cancer with 5,654 cases (78.6%) followed by rectal cancer with 641 cases (8.9%), soft-tissue and bone sarcoma with 257 cases (3.6%), prostate cancer with 128 cases (1.8%), pancreatic cancer with 87 cases (1.2%), gastric cancer with 65 cases (0.9%), and esophageal cancer with 53 cases (0.7%). Treatment chronology shows how IORT number of recorded cases increased according with the interest in the ISIORT project. Conclusions: This report gives an overview of patient selection and treatment modalities for the main tumor types effectively treated in a large group of active and experienced international centers using IORT. This data can be a basis for further surveys and for prospective studies devoted to analyze in depth IORT containing multimodal cancer treatment approaches.
Autores: Paly, J. J. ; Hallemeier, C. L.; Biggs, P. J. ; et al.
Revista: INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
ISSN 0360-3016  Vol. 88  Nº 3  2014  págs. 618 - 623
Purpose/Objective(s): This study aimed to analyze outcomes in a multi-institutional cohort of patients with advanced or recurrent renal cell carcinoma (RCC) who were treated with intraoperative radiation therapy (IORT). Methods and Materials: Between 1985 and 2010, 98 patients received IORT for advanced or locally recurrent RCC at 9 institutions. The median follow-up time for surviving patients was 3.5 years. Overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) were estimated with the Kaplan-Meier method. Chained imputation accounted for missing data, and multivariate Cox hazards regression tested significance. Results: IORT was delivered during nephrectomy for advanced disease (28%) or during resection of locally recurrent RCC in the renal fossa (72%). Sixty-nine percent of the patients were male, and the median age was 58 years. At the time of primary resection, the T stages were as follows: 17% T1, 12% T2, 55% T3, and 16% T4. Eighty-seven percent of the patients had a visibly complete resection of tumor. Preoperative or postoperative external beam radiation therapy was administered to 27% and 35% of patients, respectively. The 5-year OS was 37% for advanced disease and 55% for locally recurrent disease. The respective 5-year DSS was 41% and 60%. The respective 5-year DFS was 39% and 52%. Initial nodal involvement (hazard ratio [HR] 2.9-3.6, P < .01), presence of sarcomatoid features (HR 3.7-6.9, P < .05), and higher IORT dose (HR 1.3, P < .001) were statistically significantly associated with decreased survival. Adjuvant systemic therapy was associated with decreased DSS (HR 2.4, P = .03). For locally recurrent tumors, positive margin status (HR 2.6, P = .01) was associated with decreased OS. Conclusions: We report the largest known cohort of patients with RCC managed by IORT and have identified several factors associated with survival. The outcomes for patients receiving IORT in the setting of local recurrence compare favorably to similar cohorts treated by local resection alone suggesting the potential for improved DFS with IORT. (C) 2014 Elsevier Inc.
Autores: Lopez-Tarjuelo, J., (Autor de correspondencia); Bouche-Babiloni, A.; Santos-Serra, A.; et al.
Revista: RADIOTHERAPY AND ONCOLOGY
ISSN 0167-8140  Vol. 113  Nº 2  2014  págs. 283 - 289
Background and purpose: Industrial companies use failure mode and effect analysis (FMEA) to improve quality. Our objective was to describe an FMEA and subsequent interventions for an automated intraoperative electron radiotherapy (IOERT) procedure with computed tomography simulation, pre-planning, and a fixed conventional linear accelerator. Material and methods: A process map, an FMEA, and a fault tree analysis are reported. The equipment considered was the radiance treatment planning system (TPS), the Elekta Precise linac, and TN-502RDM-H metal-oxide-semiconductor-field-effect transistor in vivo dosimeters. Computerized order-entry and treatment-automation were also analyzed. Results: Fifty-seven potential modes and effects were identified and classified into 'treatment cancellation' and 'delivering an unintended dose'. They were graded from 'inconvenience' or 'suboptimal treatment' to 'total cancellation' of 'potentially wrong' or 'very wrong administered dose', although these latter effects were never experienced. Risk priority numbers (RPNs) ranged from 3 to 324 and totaled 4804. After interventions such as double checking, interlocking, automation, and structural changes the final total RPN was reduced to 1320. Conclusions: FMEA is crucial for prioritizing risk-reduction interventions. In a semi-surgical procedure like IOERT double checking has the potential to reduce risk and improve quality. Interlocks and automation should also be implemented to increase the safety of the procedure. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
Autores: Calvo Manuel, Felipe; Morillo, V. ; Santos, M., (Autor de correspondencia); et al.
Revista: JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
ISSN 0171-5216  Vol. 140  Nº 10  2014  págs. 1651 - 1660
The optimal waiting period between neoadjuvant treatment completion and surgery in locally advanced rectal cancer (LARC) is controversial. The specific purpose of this study was to evaluate the effect of prolonging this interval on the pathologic response, postoperative morbidity, and long-term oncologic outcomes. Retrospective data analysis is reported from LARC patients who had been treated with chemoradiation followed by surgery and intra-operative radiotherapy, between February 1995 and December 2012. In total, two groups were studied, according to the time elapsed between neoadjuvant treatment and surgery: conventional interval (CI; < 6 weeks) and delayed interval (DI; a parts per thousand yen6 weeks). Clinicopathological data related to tumor response, postoperative morbidity, and oncologic outcomes were compared. This study included 335 consecutive LARC patients. There was a higher proportion of patients with clinical staging nodal involvement (cN+) in the DI group (76.6 vs. 64.1 %; p = 0.01). The pathologic complete response (pCR) was not significantly different among groups (8.8 vs. 12.1 %; p = 0.34). Longer intervals did not affect complication incidence or severity or hospital admission length. Certain postneoadjuvant tumor effect parameters were significantly increased in the DI group, including N-downstaging and T-downsizing. After a median follow-up of 71 months, patients in the DI group presented with superior 5-year overall survival (OS) (55.9 vs. 70.4 %, p = 0.014); however, no statistically significant differences were observed in 5-year disease-free survival (DFS) or 5-year local control (LC) (69.9 vs. 74.9 %, p = 0.223; 90.4 vs. 94.5 %, p = 0.123, respectively). A modest surgical interval delay (a parts per thousand yen6 weeks) did not increase postoperative complications and was identified as a favorable prognostic factor for OS, although no differences were observed in pCR, LC, or DFS. Innovative multidisciplinary strategies incorporating further time extension of the surgical interval can be safely explored.
Autores: Sole, C. V., (Autor de correspondencia); Calvo Manuel, Felipe; de Sierra, P. A.; et al.
Revista: JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
ISSN 0171-5216  Vol. 140  Nº 7  2014  págs. 1239 - 1248
To analyze prognostic factors and long-term outcomes in patients with locally recurrent pelvic cancer (LRPC) treated with a multidisciplinary approach. From January 1995 to December 2011, 81 patients [rectal (47 %); gynecologic (39 %); retroperitoneal sarcoma (14 %)] underwent extended surgery [multiorgan (58 %), bone (35 %), vascular (9 %), soft tissue (63 %)] and intraoperative electron beam radiation therapy (IOERT) to treat recurrent tumors in the pelvic region. Thirty-five patients (43 %) received external beam radiotherapy (EBRT). Survival was estimated using the Kaplan-Meier method, and risk factors were identified using univariate and multivariate analysis. Median follow-up was 39 months (6-189 months); the 1- 3- and 5-year rates of locoregional control (LRC) were 83, 53, and 41 %, respectively. Univariate Cox proportional hazard analysis revealed worse LRC in patients who did not receive integrated EBRT as rescue treatment of pelvic recurrence (p = 0.003) or underwent non-radical resection (p = 0.01). In the multivariate analysis EBRT, non-radical resection, and tumor fragmentation retained significance (p = 0.002, p = 0.004, and p = 0.05, respectively). Radical resection, absence of tumor fragmentation and addition of EBRT for rescue are associated with improved LRC in patients with LRPC. Our results suggest that this group can benefit from EBRT combined with extended surgical resection and IOERT.
Autores: Calvo Manuel, Felipe; Sole, C. V., (Autor de correspondencia); Cambeiro Vázquez, Felix Mauricio; et al.
Revista: INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
ISSN 0360-3016  Vol. 88  Nº 1  2014  págs. 143 - 150
Background: A joint analysis of data from centers involved in the Spanish Cooperative Initiative for Intraoperative Electron Radiotherapy was performed to investigate long-term outcomes of locally recurrent soft tissue sarcoma (LR-STS) patients treated with a multidisciplinary approach. Methods and Materials: Patients with a histologic diagnosis of LR-STS (extremity, 43%; trunk wall, 24%; retroperitoneum, 33%) and no distant metastases who underwent radical surgery and intraoperative electron radiation therapy (IOERT; median dose, 12.5 Gy) were considered eligible for participation in this study. In addition, 62% received external beam radiation therapy (EBRT; median dose, 50 Gy). Results: From 1986 to 2012, a total of 103 patients from 3 Spanish expert IOERT institutions were analyzed. With a median follow-up of 57 months (range, 2-311 months), 5-year local control (LC) was 60%. The 5-year IORT in-field control, disease-free survival (DFS), and overall survival were 73%, 43%, and 52%, respectively. In the multivariate analysis, no EBRT to treat the LR-STS (P = .02) and microscopically involved margin resection status (P = .04) retained significance in relation to LC. With regard to IORT in-field control, only not delivering EBRT to the LR-STS retained significance in the multivariate analysis (P = .03). Conclusion: This joint analysis revealed that surgical margin and EBRT affect LC but that, given the high risk of distant metastases, DFS remains modest. Intensified local treatment needs to be further tested in the context of more efficient concurrent, neoadjuvant, and adjuvant systemic therapy. (C) 2014 Elsevier Inc.
Autores: Sole, C. V., (Autor de correspondencia); Calvo Manuel, Felipe; Polo, A. ; et al.
Revista: INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
ISSN 0360-3016  Vol. 90  Nº 1  2014  págs. 172 - 180
Purpose: To perform a joint analysis of data from 3 contributing centers within the intraoperative electron-beam radiation therapy (IOERT)-Spanish program, to determine the potential of IOERT as an anticipated boost before external beam radiation therapy in the multidisciplinary treatment of pediatric extremity soft-tissue sarcomas. Methods and Materials: From June 1993 to May 2013, 62 patients (aged <21 years) with a histologic diagnosis of primary extremity soft-tissue sarcoma with absence of distant metastases, undergoing limb-sparing grossly resected surgery, external beam radiation therapy (median dose 40 Gy) and IOERT (median dose 10 Gy) were considered eligible for this analysis. Results: After a median follow-up of 66 months (range, 4-235 months), 10-year local control, disease-free survival, and overall survival was 85%, 76%, and 81%, respectively. In multivariate analysis after adjustment for other covariates, tumor size >5 cm (P = .04) and R1 margin status (P = .04) remained significantly associated with local relapse. In regard to overall survival only margin status (P = .04) retained association on multivariate analysis. Ten patients (16%) reported severe chronic toxicity events (all grade 3). Conclusions: An anticipated IOERT boost allowed for external beam radiation therapy dose reduction, with high local control and acceptably low toxicity rates. The combined radiosurgical approach needs to be tested in a prospective trial to confirm these results. (C) 2014 Elsevier Inc.
Autores: Guerra, P., (Autor de correspondencia); Udias, J. M.; Herranz, E. ; et al.
Revista: PHYSICS IN MEDICINE AND BIOLOGY
ISSN 0031-9155  Vol. 59  Nº 23  2014  págs. 7159 - 7179
This work analysed the feasibility of using a fast, customized Monte Carlo (MC) method to perform accurate computation of dose distributions during pre- and intraplanning of intraoperative electron radiation therapy (IOERT) procedures. The MC method that was implemented, which has been integrated into a specific innovative simulation and planning tool, is able to simulate the fate of thousands of particles per second, and it was the aim of this work to determine the level of interactivity that could be achieved. The planning workflow enabled calibration of the imaging and treatment equipment, as well as manipulation of the surgical frame and insertion of the protection shields around the organs at risk and other beam modifiers. In this way, the multidisciplinary team involved in IOERT has all the tools necessary to perform complex MC dosage simulations adapted to their equipment in an efficient and transparent way. To assess the accuracy and reliability of this MC technique, dose distributions for a monoenergetic source were compared with those obtained using a general-purpose software package used widely in medical physics applications. Once accuracy of the underlying simulator was confirmed, a clinical accelerator was modelled and experimental measurements in water were conducted. A comparison was made with the output from the simulator to identify the conditions under which accurate dose estimations could be obtained in less than 3 min, which is the threshold imposed to allow for interactive use of the tool in treatment planning. Finally, a clinically relevant scenario, namely early-stage breast cancer treatment, was simulated with pre- and intraoperative volumes to verify that it was feasible to use the MC tool intraoperatively and to adjust dose delivery based on the simulation output, without compromising accuracy. The workflow provided a satisfactory model of the treatment head and the imaging system, enabling proper configuration of the treatment planning system and providing good accuracy in the dosage simulation.
Autores: Morganti, A. G. ; Falconi, M. ; van Stiphout, R. G. P. M.; et al.
Revista: INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
ISSN 0360-3016  Vol. 90  Nº 4  2014  págs. 911 - 917
Purpose: To determine the impact of chemoradiation therapy (CRT) on overall survival (OS) after resection of pancreatic adenocarcinoma. Methods and Materials: A multicenter retrospective review of 955 consecutive patients who underwent complete resection with macroscopically negative margins (R0-1) for invasive carcinoma (T1-4; N0-1; M0) of the pancreas was performed. Exclusion criteria included metastatic or unresectable disease at surgery, macroscopic residual disease (R2), treatment with intraoperative radiation therapy (IORT), and a histological diagnosis of no ductal carcinoma, or postoperative death (within 60 days of surgery). In all, 623 patients received postoperative radiation therapy (RT), 575 patients received concurrent chemotherapy (CT), and 462 patients received adjuvant CT. Results: Median follow-up was 21.0 months. Median OS after adjuvant CRT was 39.9 versus 24.8 months after no adjuvant CRT (P < .001) and 27.8 months after CT alone (P < .001). Five-year OS was 41.2% versus 24.8% with and without postoperative CRT, respectively. The positive impact of CRT was confirmed by multivariate analysis (hazard ratio [HR] = 0.72; confidence interval [ CI], 0.60-0.87; P = .001). Adverse prognostic factors identified by multivariate analysis included the following: R1 resection (HR = 1.17; CI = 1.07-1.28; P < .001), higher pT stage (HR = 1.23; CI = 1.11-1.37; P < .001), positive lymph nodes (HR = 1.27; CI = 1.15-1.41; P < .001), and tumor diameter >20 mm (HR = 1.14; CI = 1.05-1.23; P = .002). Multivariate analysis also showed a better prognosis in patients treated in centers with >10 pancreatic resections per year (HR = 0.87; CI = 0.78-0.97; P = .014) Conclusion: This study represents the largest comparative study on adjuvant therapy in patients after resection of carcinoma of the pancreas. Overall survival was better in patients who received adjuvant CRT. (C) 2014 Elsevier Inc.
Autores: Dzhugashvili, M. ; Luengo-Gil, G. ; Garcia, T.; et al.
Revista: INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
ISSN 0360-3016  Vol. 90  Nº 3  2014  págs. 595 - 602
Purpose: To investigate whether polymorphisms of genes related to inflammation are associated with pathologic response (primary endpoint) in patients with rectal cancer treated with primary chemoradiation therapy (PCRT). Methods and Materials: Genomic DNA of 159 patients with locally advanced rectal cancer treated with PCRT was genotyped for polymorphisms rs28362491 (NFKB1), rs1213266/rs5789 (PTGS1), rs5275 (PTGS2), and rs16944/rs1143627 (IL1B) using TaqMan single nucleotide polymorphism genotyping assays. The association between each genotype and pathologic response (poor response vs complete or partial response) was analyzed using logistic regression models. Results: The NFKB1 DEL/DEL genotype was associated with pathologic response (odds ratio [OR], 6.39; 95% confidence interval [CI], 0.78-52.65; P =. 03) after PCRT. No statistically significant associations between other polymorphisms and response to PCRT were observed. Patients with the NFKB1 DEL/DEL genotype showed a trend for longer disease-free survival (log-rank test, P =. 096) and overall survival (P =. 049), which was not significant in a multivariate analysis that included pathologic response. Analysis for 6 polymorphisms showed that patients carrying the haplotype rs28362491-DEL/rs1143627-A/rs1213266-G/rs5789-C/rs5275-A/rs16944-G (13.7% of cases) had a higher response rate to PCRT (OR, 8.86; 95% CI, 1.21-64.98; P =. 034) than the reference group (rs28362491-INS/rs1143627-A/rs1213266-G/rs5789-C/rs5275-A/rs16944-G). Clinically significant (grade >= 2) acute organ toxicity was also more frequent in patients with that same haplotype (OR, 4.12; 95% CI, 1.11-15.36; P =. 037). Conclusions: Our results suggest that genetic variation in NFKB-related inflammatory pathways might influence sensitivity to primary chemoradiation for rectal cancer. If confirmed, an inflammation-related radiogenetic profile might be used to select patients with rectal cancer for preoperative combined-modality treatment. (C) 2014 Elsevier Inc.
Autores: Nowak, F.; Calvo Manuel, Felipe
Revista: ONCOLOGIE
ISSN 1292-3818  Vol. 16  2014  págs. HS58 - HS60
Thanks to the initiative of the 28 molecular genetics centres, France has developed a specific structure for performing molecular analyses of tumours for all patients in France in need of it. However, the increasing number of molecular abnormalities to be screened or of tumors to be analyzed in order to guide treatments requires major technical and organisational developments. To this end, the Cancer Plan 2014-2019 advocates as a first step to implement nationwide next-generation sequencing techniques (NGS) for a limited number of genes, and then, as a second step, the conditions for comprehensive analysis of tumor genomes.
Autores: Sole, C. V., (Autor de correspondencia); Calvo Manuel, Felipe; Lozano, M. A.; et al.
Revista: STRAHLENTHERAPIE UND ONKOLOGIE
ISSN 0179-7158  Vol. 190  Nº 2  2014  págs. 171 - 180
Purpose. The goal of the present study was to analyze prognostic factors in patients treated with external-beam radiation therapy (EBRT), surgical resection and intraoperative electron-beam radiotherapy (IOERT) for oligorecurrent gynecological cancer (ORGC). Patients and methods. From January 1995 to December 2012, 61 patients with ORGC [uterine cervix (52 %), endometrial (30 %), ovarian (15 %), vagina (3 %)] underwent IOERT (12.5 Gy, range 10-15 Gy), and surgical resection to the pelvic (57 %) and paraaortic (43 %) recurrence tumor bed. In addition, 29 patients (48 %) also received EBRT (range 30.6-50.4 Gy). Survival outcomes were estimated using the Kaplan-Meier method, and risk factors were identified by univariate and multivariate analyses. Results. Median follow-up time for the entire cohort of patients was 42 months (range 2-169 months). The 10-year rates for overall survival (OS) and locoregional control (LRC) were 17 and 65 %, respectively. On multivariate analysis, no tumor fragmentation (HR 0.22; p = 0.03), time interval from primary tumor diagnosis to locoregional recurrence (LRR) < 24 months (HR 4.02; p = 0.02) and no EBRT at the time of pelvic recurrence (HR 3.95; p = 0.02) retained significance with regard to LRR. Time interval from primary tumor to LRR < 24 months (HR 2.32; p = 0.02) and no EBRT at the time of pelvic recurrence (HR 3.77; p = 0.04) showed a significant association with OS after adjustment for other covariates. Conclusion. External-beam radiation therapy at the time of pelvic recurrence, time interval for relapse a parts per thousand yenaEuro parts per thousand 24 months and not multi-involved fragmented resection specimens are associated with improved LRC in patients with ORGC. As suggested from the present analysis a significant group of ORGC patients could potentially benefit from multimodality rescue treatment.
Autores: Sole, C. V. , (Autor de correspondencia); Calvo Manuel, Felipe
Revista: CLINICAL ONCOLOGY
ISSN 0936-6555  Vol. 26  Nº 2  2014  págs. 122 - 123
Autores: Arias, F.; Herruzo, I.; Contreras, J.; et al.
Revista: JOURNAL OF CLINICAL ONCOLOGY
ISSN 0732-183X  Vol. 32  Nº 15  2014 
Autores: Zapatero, A.; Guerrero, A. ; Maldonado, J.; et al.
Revista: INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
ISSN 0360-3016  Vol. 90  2014  págs. S1 - S1
Autores: Zapatero, A.; Guerrero, A.; Maldonado, X. ; et al.
Revista: JOURNAL OF CLINICAL ONCOLOGY
ISSN 0732-183X  Vol. 32  Nº 15  2014 
Autores: Macias, V. M. ; Calvo Manuel, Felipe; Serrano, J. ; et al.
Revista: INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
ISSN 0360-3016  Vol. 90  2014  págs. S383 - S383
Autores: Calvo Manuel, Felipe; Sole, C. V., (Autor de correspondencia); Lozano, M. A.; et al.
Revista: GYNECOLOGIC ONCOLOGY
ISSN 0090-8258  Vol. 130  Nº 3  2013  págs. 537 - 544
Objective. To analyze prognostic factors in patients treated with intraoperative electrons containing resective surgical rescue of locally recurrent gynecological cancer (LRGC). Methods. From January 1995 to December 2012, 35 patients with LRGC [uterine cervix (57%), endometrial (20%), ovarian (17%), vagina (6%)] underwent extended [multiorgan (54%), bone (9%), soft tissue (54%), vascular (14%)] surgery and intraoperative electron-beam radiation therapy [IOERT (10-15 Gy)] to the pelvic recurrence tumor bed. Sixteen (46%) patients also received external beam radiation therapy [EBRT (30.6-50.4 Gy)]. Survival outcomes were estimated using the Kaplan-Meier method, and risk factors were identified by univariate and multivariate analyses. Results. Median follow-up time for the entire cohort of patients was 46 months (range, 3-169). Ten-year rates for locoregional control (LRC) and overall survival (OS) were 58 and 16%, respectively. On multivariate analysis non-EBRT at the time of pelvic re-recurrence [HR 4.15; p = 0.02], no tumor fragmentation [HR 0.13; p = 0.05] and time interval from primary tumor to LRR < 24 months [HR 5.16; p = 0.01], retained significance with regard to LRR. Non-EBRT at the time of pelvic re-recurrence [HR 4.18; p = 0.02] and time interval from primary tumor to LRR < 24 months [HR 6.67; p = 0.02] showed a significant association with OS after adjustment for other covariates. Conclusions. EBRT treatment integrated for rescue, time interval for relapse >= 24 months, and not multi-involved fragmented resection specimens are associated with improved LRC in patients with LRGC in the pelvis. Present results suggest that a significant group of patients may benefit from EBRT treatment integrated with extended surgery and IOERT. (C) 2013 Elsevier Inc. All rights reserved.
Autores: Calvo Manuel, Felipe (Autor de correspondencia); Sole, C. V. ; Martinez-Monge, R.; et al.
Revista: STRAHLENTHERAPIE UND ONKOLOGIE
ISSN 0179-7158  Vol. 189  Nº 2  2013  págs. 129 - 136
We report the outcomes of a multimodality treatment approach combining maximal surgical resection and intraoperative electron radiotherapy (IOERT) with or without external beam radiation therapy (EBRT) in patients with locoregionally (LR) recurrent renal cell carcinoma (RCC) after radical nephrectomy or LR advanced primary RCC. From 1983 to 2008, 25 patients with LR recurrent (n = 10) or LR advanced primary (n = 15) RCC were treated with this approach. Median patient age was 60 years (range, 16-79 years). Fifteen patients (60%) received perioperative EBRT (median dose, 44 Gy). Surgical resection was R0 (negative margins) in 6 patients (24%) and R1 (residual microscopic disease) in 19 patients (76%). The median dose of IOERT was 14 Gy (range, 9-15). Overall survival (OS) and relapse patterns were calculated using the Kaplan-Meier method. Median follow-up for surviving patients was 22.2 years (range, 3.6-26 years). OS and DFS at 5 and 10 years were 38% and 18% and 19% and 14%, respectively. LR control (tumor bed or regional lymph nodes) and distant metastases-free survival rates at 5 years were 80% and 22%, respectively. The death rate within 30 days of surgery and IOERT was 4% (n = 1). Six patients (24%) experienced acute or late toxicities of grade 3 or higher according to the National Cancer Institute Common Toxicity Criteria (NCI-CTCAE) v4. In patients with LR recurrent or LR advanced primary RCC, a multimodality approach consisting of maximal surgical resection and IOERT with or without adjuvant EBRT yielded encouraging local control results, justifying further evaluation.
Autores: Garrido, P. , (Autor de correspondencia); Rosell, R.; Arellano, A.; et al.
Revista: LUNG CANCER
ISSN 0169-5002  Vol. 81  Nº 1  2013  págs. 84 - 90
The optimal schedule and regimen of chemotherapy (CT) in association with chemoradiation has not been established in stage III non-small-cell lung cancer (NSCLC). We have compared three schedules of non-platinum-based cr plus either radiotherapy or chemoradiation. From May 2001 to June 2006, 158 patients with unresectable stage III NSCLC were enrolled in a randomized phase II trial with overall response rate (ORR) as the primary endpoint. The initial design included three arms: sequential CT followed by thoracic radiation (TRT); concurrent CT/TRT followed by consolidation CT; and induction CT followed by concurrent CT/TRT. However, based on the preliminary results of the RTOG 9410 trial, the sequential arm was closed when 19 patients had been enrolled. All patients received two cycles of docetaxel 40 mg/m(2) days 1 and 8 plus gemcitabine 1200 mg/m(2) days 1 and 8, as either induction or consolidation therapy. Concurrent CT/TRT consisted of docetaxel 20 mg/m(2) and carboplatin AUC 2 weekly plus 60 Gy TRT. No differences were found in ORR between the two arms (56% and 57%). Hematological toxicity was mild but significantly superior with consolidation Cl'; the esophagitis rate was similar in both arms (16% and 15%). Wlth a median follow-up of 57 months, no differences were found in median survival (13.07 and 13.8 months) or 5-year survival (16.4% and 22%). This regimen cannot be recommended as an alternative to platinum-based CT/TRT although it has an acceptable toxicity profile and encouraging long-term survival data (ClinicalTrials.gov NCT01652820). (C) 2013 Elsevier Ireland Ltd. All rights reserved.
Autores: Calvo Manuel, Felipe (Autor de correspondencia); Sole, C. V.; Obregon, R.; et al.
Revista: ANNALS OF SURGICAL ONCOLOGY
ISSN 1068-9265  Vol. 20  Nº 6  2013  págs. 1962 - 1969
To report feasibility, tolerance, anatomical topography of locoregional recurrence (LRR), and long-term outcome for esophageal and esophagogastric (EG) cancer patients treated with preoperative chemoradiation (CRT) and surgery with or without a radiation boost of intraoperative electron beam radiotherapy (IOERT). From January 1995 to December 2010, 53 patients with primary esophageal (n = 26; 44 %) or EG carcinoma (n = 30; 56 %), and disease confined to locoregional area [clinical stage: IIb (n = 30; 57 %), IIIa (n = 14; 26 %), IIIb (n = 6; 11 %), IIIc (n = 3; 6 %)], were treated with preoperative CRT, curative (R0) resection with an extended (two-field) lymph node dissection in all cases. Thirty-seven patients also received a preanastomotic reconstruction IOERT boost (applicator diameter size 6-9 cm, dose 10-15 Gy, beam energy 6-15 MeV) over the tumor bed in the mediastinum and upper abdominal lymph node area. With a median follow-up time of 27.9 months (range, 0.2-148), LRR rate was 15 % (n = 8). Five-year overall survival (OS) and disease-free survival was 48 and 36 %, respectively. Univariate log-rank analyses showed that receiving IOERT was associated with lower risk of LRR (p = 0.004). On multivariate analysis, only the IOERT group retained significance in relation to LRR (odds ratio, 0.08; 95 % confidence interval, 0.01-0.48; p = 0.01). Postoperative mortality and perioperative complications were 11 % (n = 6) and 30 % (n = 16). Local control is high in the radiation-boosted area, but OS remains modest, given the high risk of distant metastases. Intensified locoregional treatment needs to be tested in the context of more efficient concurrent, neo-, and adjuvant systemic therapy.
Autores: Calvo Manuel, Felipe; Sole, C. V., (Autor de correspondencia); de la Mata, D.; et al.
Revista: EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
ISSN 1619-7070  Vol. 40  Nº 5  2013  págs. 657 - 667
To prospectively evaluate the usefulness of F-18-FDG PET/CT) imaging for predicting histopathological response and long-term clinical outcomes in locally advanced rectal cancer (LARC). This prospective study included 38 patients with a confirmed diagnosis of LARC (cT3-4 or cN+) who underwent F-18-FDG PET/CT before and after neoadjuvant therapy (NAT). Total mesorectal excision was scheduled 6 weeks after NAT and was followed by an expert histopathological analysis of the surgical specimen. Baseline variables and previously identified maximum FDG standardized uptake value (SUVmax) cut-off values before NAT (SUVmax(PRE) a parts per thousand yen6) and after NAT (SUVmax(POST) a parts per thousand yen2), and the absolute and percentage reductions from baseline SUVmax (a dagger SUVmax < 4 and a dagger SUVmax% < 65 %, respectively) were applied to differentiate patients showing a metabolic tumour response from nonresponders. These features were correlated with tumour regression grade (TRG), disease-free survival (DFS) and overall survival (OS). Significantly higher 5-year DFS and OS were seen in 19 responders (TRG 3 or 4) than in 19 nonresponders (TRG 0-2; 94.4 vs. 48.8 %, p = 0.001; 94.7 vs. 63.2 %, p = 0.02, respectively). In multivariate analysis the only PET/CT SUVmax-based parameter significantly correlated with the likelihood of recurrence and survival was a dagger SUV% < 65 % (HR = 5.95, p = 0.02, for DFS; HR = 5.26, p = 0.04, for OS) This prospective study proved that F-18-FDG PET/CT is a valuable imaging tool for assessing rectal cancer TRG and long-term prognosis, and could potentially serve as an intermediate endpoint in treatment optimization research and rectal cancer patient care.
Autores: Calvo Manuel, Felipe; Sole, C. V., (Autor de correspondencia); Serrano, J.; et al.
Revista: JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
ISSN 0171-5216  Vol. 139  Nº 11  2013  págs. 1825 - 1833
In selected patients with rectal cancer, laparoscopic surgery is as safe as open surgery, with similar resection margins and completeness of resection. In addition, recovery is faster after laparoscopic surgery. We analyzed long-term outcomes in a group of patients with locally advanced rectal cancer (LARC) treated with preoperative therapy followed by laparoscopic surgery and intraoperative electron-beam radiotherapy (IOERT). From June 2005 to December 2010, 125 LARC patients were treated with 2 induction courses of FOLFOX-4 (oxaliplatin 85 mg/m(2)/d1, intravenous leucovorin at 200 mg/m(2)/d1-2, and an intravenous bolus of 5-fluorouracil 400 mg/m(2)/d1-2) and preoperative chemoradiation (4,500-5,040 cGy) followed by total mesorectal excision (laparoscopic, 35 %; open surgery, 65 %) and a presacral boost with IOERT. Patients in the laparoscopic surgery group lost less blood (median 200 vs 350 mL, p < 0.01) and had a shorter hospital stay (7 vs 11 days; p = 0.02) than those in the open surgery group. Laparoscopic procedures were shorter than open surgery procedures (270 vs 302 min; p = 0.67). Postoperative morbidity (32 vs 44 %; p = 0.65), RTOG grade a parts per thousand yen3 acute toxicity (25 vs 25 %; p = 0.97), and RTOG grade a parts per thousand yen3 chronic toxicity (7 vs 9 %; p = 0.48) were similar in the laparoscopy and open surgery groups. The median follow-up time for the entire cohort of patients was 59.5 months (range 7.8-90); no significant differences were observed between the groups in locoregional control (HR 0.91, p = 0.89), disease-free survival (HR 0.80, p = 0.65), and overall survival (HR 0.67, p = 0.52). Postchemoradiation laparoscopically assisted IOERT is feasible, with an acceptable risk of postoperative complications, shorter hospital stay, and similar long-term outcomes when compared to the open surgery approach.
Autores: Calvo Manuel, Felipe; Sole, C. V., (Autor de correspondencia); Atahualpa, F.; et al.
Revista: PANCREATOLOGY
ISSN 1424-3903  Vol. 13  Nº 6  2013  págs. 576 - 582
Background/objectives: To analyze prognostic factors associated with long-term outcomes in patients with pancreatic cancer treated with chemoradiation therapy (CRT) and surgery with or without intraoperative electron beam radiotherapy (IOERT). Patients and methods: From January 1995 to December 2012, 60 patients with adenocarcinoma of the pancreas and locoregional disease (clinical stage IB [n = 13; 22%], IIA [n = 16; 27%], IIB [n = 22; 36%], IIIC [n = 9; 15%]) were treated with CRT (45-50.4 Gy before surgery [n = 19; 32%] and after surgery [n = 41; 68%]) and curative resection (R0 [n = 34; 57%], R1 [n = 26, 43%]). Twenty-nine patients (48%) also received a pre-anastomosis IOERT boost (applicator diameter size, 7-10 cm; dose, 10-15 Gy; beam energy, 9-18 MeV). Results: With a median follow-up of 15.9 months (range, 1-182), 5-year overall survival (OS), disease-free survival (DFS), and locoregional control were 20%, 13%, and 58%, respectively. Univariate analyses showed that R1 margin resection status (HR, 3.17; p = 0.04), not receiving IOERT (HR, 7.33; p = 0.01), and postoperative CRT (HR, 5.12; p = 0.04) were associated with a higher risk of locoregional recurrence. In the multivariate analysis, only margin resection status (HR, 3.0; p = 0.05) and not receiving IOERT (HR, 6.75; p = 0.01) retained significance with regard to locoregional recurrence. Postoperative mortality and perioperative complications were 3% (n = 2) and 43% (n = 26). Conclusions: Although local control is good in the radiation-boosted area, OS remains modest owing to high risk of distant metastases. Intensified locoregional treatment needs to be tested in the context of more efficient systemic therapy. Copyright (C) 2013, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. All rights reserved.
Autores: Garcia-Vazquez, V. , (Autor de correspondencia); Marinetto, E. ; Santos-Miranda, J. A.; et al.
Revista: PHYSICS IN MEDICINE AND BIOLOGY
ISSN 0031-9155  Vol. 58  Nº 24  2013  págs. 8769 - 8782
Intra-operative electron radiation therapy (IOERT) combines surgery and ionizing radiation applied directly to an exposed unresected tumour mass or to a post-resection tumour bed. The radiation is collimated and conducted by a specific applicator docked to the linear accelerator. The dose distribution in tissues to be irradiated and in organs at risk can be planned through a pre-operative computed tomography (CT) study. However, surgical retraction of structures and resection of a tumour affecting normal tissues significantly modify the patient's geometry. Therefore, the treatment parameters (applicator dimension, pose (position and orientation), bevel angle, and beam energy) may require the original IOERT treatment plan to be modified depending on the actual surgical scenario. We propose the use of a multi-camera optical tracking system to reliably record the actual pose of the IOERT applicator in relation to the patient's anatomy in an environment prone to occlusion problems. This information can be integrated in the radio-surgical treatment planning system in order to generate a real-time accurate description of the IOERT scenario. We assessed the accuracy of the applicator pose by performing a phantom-based study that resembled three real clinical IOERT scenarios. The error obtained (2 mm) was below the acceptance threshold for external radiotherapy practice, thus encouraging future implementation of this approach in real clinical IOERT scenarios.
Autores: Calvo Manuel, Felipe; Sole, C. V. , (Autor de correspondencia); de Sierra, P. A.; et al.
Revista: INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
ISSN 0360-3016  Vol. 86  Nº 5  2013  págs. 892 - 900
Purpose: To analyze prognostic factors associated with survival in patients after intraoperative electrons containing resective surgical rescue of locally recurrent rectal cancer (LRRC). Methods and Materials: From January 1995 to December 2011, 60 patients with LRRC underwent extended surgery (n = 38: multiorgan [43%], bone [28%], soft tissue [38%]) or nonextended (n = 22) surgical resection, including a component of intraoperative electron-beam radiation therapy (IOERT) to the pelvic recurrence tumor bed. Twenty-eight (47%) of these patients also received external beam radiation therapy (EBRT) (range, 30.6-50.4 Gy). Survival outcomes were estimated by the Kaplan-Meier method, and risk factors were identified by univariate and multivariate analyses. Results: The median follow-up time was 36 months (range, 2-189 months), and the 1-year, 3year, and 5-year rates for locoregional control (LRC) and overall survival (OS) were 86%, 52%, and 44%; and 78%, 53%, 43%, respectively. On multivariate analysis, R1 resection, EBRT at the time of pelvic rerecurrence, no tumor fragmentation, and non-lymph node metastasis retained significance with regard to LRR. R1 resection and no tumor fragmentation showed a significant association with OS after adjustment for other covariates. Conclusions: EBRT treatment integrated for rescue, resection radicality, and not involved fragmented resection specimens are associated with improved LRC in patients with locally recurrent rectal cancer. Additionally, tumor fragmentation could be compensated by EBRT. Present results suggest that a significant group of patients with LRRC may benefit from EBRT treatment integrated with extended surgery and IOERT. (C) 2013 Elsevier Inc.
Autores: Sole, C. V. , (Autor de correspondencia); Calvo Manuel, Felipe; Alvarez, E. ; et al.
Revista: EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
ISSN 1619-7070  Vol. 40  Nº 11  2013  págs. 1635 - 1644
Purpose Vascular endothelial growth factor receptor-2 (VEGFR-2), epidermal growth factor receptor-1 (EGFR), and cyclooxygenase-2 (COX-2) stimulate key processes involved in tumor progression and are important targets for cancer drugs. F-18-FDG maximum standardized uptake value (SUVmax) is a marker of tumor metabolic activity. The purpose of this study was to measure SUVmax combined with VEGFR-2, EGFR and COX-2 proteins in pretreatment tumor biopsies from patients with locally advanced rectal cancer receiving intensive neoadjuvant treatment and to correlate the findings with clinical outcome. VEGFR-2, EGFR and COX-2 were measured using the immunoreactive score (IRS). SUVmax (median 8.4) was quantified in tumors with molecular overexpression (IRS a parts per thousand yen3 + SUVmax a parts per thousand yen 8.4 indicating active tumors; SUVmax < 8.4 indicating inactive tumors). The Cox proportional hazards model was used to explore associations between tumor markers, disease-free survival (DFS) and overall survival (OS). The study group comprised 38 patients with a median follow-up of 69.3 months (range 4.5 - 92 months). Multivariate analysis showed that active tumors (overexpressing VEGFR-2, high SUVmax) were associated with worse DFS (HR 4.73, 95 % CI 1.18 - 22.17; p = 0.04) and OS (HR 4.28, 95 % CI 1.04 - 20.12; p = 0.05). Active tumors overexpressing VEGFR-2 are associated with a worse overall outcome in patients with rectal cancer treated with induction chemotherapy followed by pelvic chemoradiation and surgery. The optimal diagnostic cut-off level for this novel biomarker association should be investigated. Evaluation in a clinical trial is required to determine whether selected patients could benefit from a VEGFR-targeting drug.
Autores: Krengli, M., (Autor de correspondencia); Calvo Manuel, Felipe; Sedlmayer, F.; et al.
Revista: STRAHLENTHERAPIE UND ONKOLOGIE
ISSN 0179-7158  Vol. 189  Nº 9  2013  págs. 729 - 737
A joint analysis of clinical data from centres within the European section of the International Society of Intraoperative Radiation Therapy (ISIORT-Europe) was undertaken in order to define the range of intraoperative radiotherapy (IORT) techniques and indications encompassed by its member institutions. In 2007, the ISIORT-Europe centres were invited to record demographic, clinical and technical data relating to their IORT procedures in a joint online database. Retrospective data entry was possible. The survey encompassed 21 centres and data from 3754 IORT procedures performed between 1992 and 2011. The average annual number of patients treated per institution was 42, with three centres treating more than 100 patients per year. The most frequent tumour was breast cancer with 2395 cases (63.8 %), followed by rectal cancer (598 cases, 15.9 %), sarcoma (221 cases, 5.9 %), prostate cancer (108 cases, 2.9 %) and pancreatic cancer (80 cases, 2.1 %). Clinical details and IORT technical data from these five tumour types are reported. This is the first report on a large cohort of patients treated with IORT in Europe. It gives a picture of patient selection methods and treatment modalities, with emphasis on the main tumour types that are typically treated by this technique and may benefit from it.
Autores: Peeters, K. ; Maas, M. ; Valentini, V.; et al.
Revista: EUROPEAN JOURNAL OF CANCER
ISSN 0959-8049  Vol. 49  2013  págs. S537 - S537
Autores: Sole, C.; Calvo Manuel, Felipe; Alvarez, E.; et al.
Revista: EUROPEAN JOURNAL OF CANCER
ISSN 0959-8049  Vol. 49  2013  págs. S564 - S564
Autores: Polo, A.; Alvarez, A. ; Montero, A. ; et al.
Revista: INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
ISSN 0360-3016  Vol. 87  Nº 2  2013  págs. S166 - S166
Autores: Zapatero, A.; Guerrero, A.; Maldonado, X. ; et al.
Revista: INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
ISSN 0360-3016  Vol. 87  Nº 2  2013  págs. S105 - S105
Autores: Sole, C. V.; Calvo Manuel, Felipe; Munoz, M. ; et al.
Revista: INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
ISSN 0360-3016  Vol. 87  Nº 2  2013  págs. S337 - S337
Autores: Sole, C. ; Calvo Manuel, Felipe; Serrano, J.; et al.
Revista: EUROPEAN JOURNAL OF CANCER
ISSN 0959-8049  Vol. 49  2013  págs. S529 - S529
Autores: De La Mata, M. ; Calvo Manuel, Felipe; Espi, M. G. ; et al.
Revista: INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
ISSN 0360-3016  Vol. 87  Nº 2  2013  págs. S339 - S339
Autores: Paly, J. J. ; Hallemeier, C. L.; Biggs, P. J.; et al.
Revista: JOURNAL OF CLINICAL ONCOLOGY
ISSN 0732-183X  Vol. 31  Nº 6  2013 
Autores: Calvo Manuel, Felipe (Autor de correspondencia); Gonzalez, M. E.; Gonzalez-San Segundo, C.; et al.
Revista: EJSO
ISSN 0748-7983  Vol. 38  Nº 10  2012  págs. 955 - 961
Purpose: To evaluate the feasibility and long-term outcome of surgery combined with intraoperative electron radiotherapy (IOERT) as rescue treatment in patients with recurrent and/or metastatic oligotopic extrapelvic cancer. Methods and materials: From April 1996 to April 2010, we treated 28 patients using 34 IOERT procedures. The main histopathology findings were adenocarcinoma (39%) and squamous cell carcinoma (29%). The original cancer sites were gynecologic (67%), urologic (14%) and colorectal (14%). The location of recurrence was the para-aortic region in 53.5% of patients. Results: Median follow-up was 39 months (1-84 months), during which time 14% of patients experienced local recurrence and 53.5% developed distant metastasis. Overall survival at 2 and 5 years was 57% and 35% respectively. At the time of the analysis, 13 patients were alive, 6 for more than 55 months of follow-up. Local control was not significantly affected by the following histopathologic characteristics of the resected surgical specimen: number of fragments submitted for pathology study (1 to >6), maximal tumor dimension (<= 2 to >= 6 cm), rate of involved nodes (0-100%) and involved resection margin (local recurrence 23% vs 7%; p = 0.21). Local recurrence was significantly affected by microscopic cancer in more than 50% of specimen fragments (38% vs 9%, p = 0.02). Conclusions: IOERT for recurrence of oligotopic extrapelvic cancer incresead long-term survival in patients with controlled cancer and appears to compensate for some adverse prognostic features in local control. Individualized treatment strategies for this heterogeneous category of patients with recurrent cancer will make it possible to optimize results. (C) 2012 Elsevier Ltd. All rights reserved.
Autores: Pascau, J. , (Autor de correspondencia); Miranda, J. A. S. ; Calvo Manuel, Felipe; et al.
Revista: INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
ISSN 0360-3016  Vol. 83  Nº 2  2012  págs. E287 - E295
Purpose: Intraoperative electron beam radiation therapy (IOERT) involves a modified strategy of conventional radiation therapy and surgery. The lack of specific planning tools limits the spread of this technique. The purpose of the present study is to describe a new simulation and planning tool and its initial evaluation by clinical users. Methods and Materials: The tool works on a preoperative computed tomography scan. A physician contours regions to be treated and protected and simulates applicator positioning, calculating isodoses and the corresponding dose-volume histograms depending on the selected electron energy. Three radiation oncologists evaluated data from 15 IOERT patients, including different tumor locations. Segmentation masks, applicator positions, and treatment parameters were compared. Results: High parameter agreement was found in the following cases: three breast and three rectal cancer, retroperitoneal sarcoma, and rectal and ovary monotopic recurrences. All radiation oncologists performed similar segmentations of tumors and high-risk areas. The average applicator position difference was 1.2 +/- 0.95 cm. The remaining cancer sites showed higher deviations because of differences in the criteria for segmenting high-risk areas (one rectal, one pancreas) and different surgical access simulated (two rectal, one Ewing sarcoma). Conclusions: The results show that this new tool can be used to simulate IOERT cases involving different anatomic locations, and that preplanning has to be carried out with specialized surgical input. (C) 2012 Elsevier Inc.
Autores: de la Vega, F. A., (Autor de correspondencia); Contreras, J. ; de las Heras, M.; et al.
Revista: ANNALS OF ONCOLOGY
ISSN 0923-7534  Vol. 23  Nº 4  2012  págs. 1005 - 1009
Background: Standard treatment of advanced squamous cell carcinoma of the head and neck (SCCHN) is concurrent chemoradiation. Erlotinib is an oral tyrosine kinase inhibitor of epidermal growth factor receptor, which has shown activity in SCCHN. Phase I study aims to determine the maximum tolerated dose and dose-limiting toxicity (DLT) of adding erlotinib to chemoradiation therapy in patients with surgically resected locally advanced SCCHN. Patients and methods: Inclusion criteria-SCCHN patients with T3 or T4 primary lesion (except T3N0 with negative resection margins); pathologic N2-N3 disease; poor prognostic findings; age 18-70 years; Eastern Cooperative Oncology Group performance status of zero to one; no evidence of metastasis; adequate organic function and written informed consent. Study design-dose-escalating phase I study with three cohorts of three to six patients each that received increasing doses of erlotinib (100-150 mg/day p.o.) and cisplatin (30-40 mg/m(2) i.v., day 1) for 7 weeks. Radiotherapy-standard regimen of 1.8 Gy daily (5 fractions/week) to a maximum total dose of 63 Gy in 7 weeks. Results: Thirteen male (median age: 57 years) were enrolled. Overall, the regimen was well tolerated. Two of three patients treated at dose level III (erlotinib: 150 mg/day; cisplatin: 40 mg/m(2)) developed DLT consisting of grade 3 infection and grade 3 mucositis. Other toxic effects included diarrhea, asthenia, and rash. Recommended dose for additional studies: erlotinib 150 mg/day p.o.; cisplatin 30 mg/m(2)/week i.v. Conclusion: Erlotinib can be safely combined with chemoradiation without requiring dose reduction of chemo- or radiotherapy in this postsurgical population.
Autores: Marquez-Rodas, I., (Autor de correspondencia); Lopez-Trabada, D.; Blanco, A. B. R.; et al.
Revista: ONCOLOGY
ISSN 0030-2414  Vol. 82  Nº 1  2012  págs. 30 - 34
Introduction: Identification of patients at risk of hereditary cancer is an essential component of oncology practice, since it enables clinicians to offer early detection and prevention programs. However, the large number of hereditary syndromes makes it difficult to take them all into account in daily practice. Consequently, the National Cancer Institute (NCI) has suggested a series of criteria to guide initial suspicion. Objective: It was the aim of this study to assess the perception of the risk of hereditary cancer according to the NCI criteria in our medical oncology service. Methods: We retrospectively analyzed the recordings of the family history in new cancer patients seen in our medical oncology service from January to November 2009, only 1 year before the implementation of our multidisciplinary hereditary cancer program. Results: The family history was recorded in only 175/621 (28%) patients. A total of 119 (19%) patients met 1 or more NCI criteria (1 criterion, n = 91; 2 criteria, n = 23; 3 criteria, n = 4; and 4 criteria, n = 1), and only 14 (11.4%) patients were referred to genetic counseling. Conclusion: This study shows that few clinicians record the family history. The perception of the risk of hereditary cancer is low according to the NCI criteria in our medical oncology service. These findings can be explained by the lack of a multidisciplinary hereditary cancer program when the study was performed Copyright (C) 2012 S. Karger AG, Basel
Autores: Sole, C. V. , (Autor de correspondencia); Calvo Manuel, Felipe
Revista: REVISTA MEDICA DE CHILE
ISSN 0034-9887  Vol. 140  Nº 10  2012  págs. 1369 - 1370
Autores: Sole, C. V.; Lopez, J.; Matute, R. ; et al.
Revista: JOURNAL OF THORACIC ONCOLOGY
ISSN 1556-0864  Vol. 7  Nº 9  2012  págs. S333 - S334
Autores: Calvo Manuel, Felipe
Revista: BREAST
ISSN 0960-9776  Vol. 21  2012  págs. S3 - S4
Autores: Marquez-Rodas, I. ; Ramirez, S. P. ; Podesta, M. C.; et al.
Revista: JOURNAL OF CLINICAL ONCOLOGY
ISSN 0732-183X  Vol. 30  Nº 15  2012 
Autores: Paly, J. J. ; Hallemeier, C. L.; Biggs, P. J.; et al.
Revista: INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
ISSN 0360-3016  Vol. 84  Nº 3  2012  págs. S424 - S425
Autores: Santos, M. ; Guerra, J. L. L.; Gordillo, M. J. O.; et al.
Revista: VALUE IN HEALTH
ISSN 1098-3015  Vol. 15  Nº 7  2012  págs. A354 - A354
Autores: dos Santos, M. A. , (Autor de correspondencia); de Salcedo, J. B. P. ; Diaz, J. A. G.; et al.
Revista: INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
ISSN 0360-3016  Vol. 81  Nº 5  2011  págs. 1436 - 1441
Purpose: Patients with cavernous sinus meningiomas (CSM) have an elevated risk of surgical morbidity and mortality. Recurrence is often observed after partial resection. Stereotactic radiosurgery (SRS), either alone or combined with surgery, represents an important advance in CSM management, but long-term results are lacking. Methods and Materials: A total of 88 CSM patients, treated from January 1991 to December 2005, were retrospectively reviewed. The mean follow-up was 86.8 months (range, 17.1-179.4 months). Among the patients, 22 were followed for more than 10 years. There was a female predominance (84.1%). The age varied from 16 to 90 years (mean, 51.6). In all, 47 patients (53.4%) received SRS alone, and 41 patients (46.6%) had undergone surgery before SRS. A dose of 14 Gy was prescribed to isodose curves from 50% to 90%. In 25 patients (28.4%), as a result of the proximity to organs at risk, the prescribed dose did not completely cover the target. Results: After SRS, 65 (73.8%) patients presented with tumor volume reduction; 14 (15.9%) remained stable, and 9 (10.2%) had tumor progression. The progression-free survival was 92.5% at 5 years, and 82.5% at 10 years. Age, sex, maximal diameter of the treated tumor, previous surgery, and complete target coverage did not show significant associations with prognosis. Among the 88 treated patients, 17 experienced morbidity that was related to SRS, and 6 of these patients spontaneously recovered. Conclusions: SRS is an effective and safe treatment for CSM, feasible either in the primary or the postsurgical setting. Incomplete coverage of the target did not worsen outcomes. More than 80% of the patients remained free of disease progression during long-term follow-up. (C) 2011 Elsevier Inc.
Autores: dos Santos, M. A. , (Autor de correspondencia); de Salcedo, J. B. P.; Diaz, J. A. G. ; et al.
Revista: STEREOTACTIC AND FUNCTIONAL NEUROSURGERY
ISSN 1011-6125  Vol. 89  Nº 4  2011  págs. 220 - 225
Background: Stereotactic radiosurgery (SRS) is one option for treatment of trigeminal neuralgia, after unsuccessful conservative approaches. Objectives: The objective of this study was to retrospectively evaluate our institutional results in the management of patients with idiopathic trigeminal neuralgia treated with linear accelerator SRS. Methods: Fifty-two patients were treated between January 1998 and December 2009 and were followed for more than 6 months (median: 26.6 months). Forty-seven patients (90%) had undergone previous surgery before SRS. The target dose ranged from 50 to 80 Gy. Results: After SRS, 9 patients presented complete remission of the pain, and 21 were pain free but still under medication. Eleven patients reported a relief of more than 50% in crisis frequency. In 9 patients, no significant improvements were seen, and 2 presented an exacerbation of the pain. After an average period of 20 months, 15 patients reported pain recurrence. Results were better in patients older than 60 years (p = 0.019). Nineteen patients presented facial numbness after SRS, with a trend toward favorable treatment response (p = 0.06). Conclusion: SRS is an effective alternative to the treatment of essential trigeminal neuralgia, with long-lasting pain relief in more than 50% of the patients. Better results were seen with patients aged more than 60 years. Copyright (C) 2011 S. Karger AG, Basel
Autores: Pascau, J. ; Santos-Miranda, J.; San-Segundo, C. G.; et al.
Revista: INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
ISSN 0360-3016  Vol. 81  Nº 2  2011  págs. S90 - S90
Autores: Sanchez, E. V. ; Garcia-Sabrido, J. L. ; Calvo Manuel, Felipe; et al.
Revista: RADIOTHERAPY AND ONCOLOGY
ISSN 0167-8140  Vol. 99  2011  págs. S10 - S10
Autores: Blanco, J. A. ; Alvarez, A.; Lozano, M. A. ; et al.
Revista: RADIOTHERAPY AND ONCOLOGY
ISSN 0167-8140  Vol. 99  2011  págs. S17 - S17
Autores: Usychkin, S.; Calvo Manuel, Felipe; Santos, M. ; et al.
Revista: RADIOTHERAPY AND ONCOLOGY
ISSN 0167-8140  Vol. 99  2011  págs. S241 - S241
Autores: Miranda, J. A. S.; Pascau, J.; Lardies, M. D.; et al.
Revista: RADIOTHERAPY AND ONCOLOGY
ISSN 0167-8140  Vol. 99  2011  págs. S246 - S246
Autores: Usychkin, S.; Calvo Manuel, Felipe; Samblas, J.; et al.
Revista: RADIOTHERAPY AND ONCOLOGY
ISSN 0167-8140  Vol. 99  2011  págs. S8 - S8
Autores: Miranda, J. A. S. ; Pascau, J.; de Lucas, R. H.; et al.
Revista: RADIOTHERAPY AND ONCOLOGY
ISSN 0167-8140  Vol. 99  2011  págs. S14 - S14
Autores: Zapatero, A.; Guerrero, A. ; Maldonado, X.; et al.
Revista: JOURNAL OF CLINICAL ONCOLOGY
ISSN 0732-183X  Vol. 29  Nº 15  2011 
Autores: Krengli, M.; Sedlmayer, F. ; Calvo Manuel, Felipe; et al.
Revista: RADIOTHERAPY AND ONCOLOGY
ISSN 0167-8140  Vol. 99  2011  págs. S10 - S11
Autores: Calvo Manuel, Felipe
Revista: EUROPEAN JOURNAL OF CANCER
ISSN 0959-8049  Vol. 47  2011  págs. S48 - S48
Autores: Pascau, J.; Miranda, J. A. S.; Gonzalez-San Segundo, C. ; et al.
Revista: RADIOTHERAPY AND ONCOLOGY
ISSN 0167-8140  Vol. 99  2011  págs. S15 - S15
Autores: Calvo Manuel, Felipe; Serrano, J.; Lozano, M. A. ; et al.
Revista: RADIOTHERAPY AND ONCOLOGY
ISSN 0167-8140  Vol. 99  2011  págs. S18 - S18
Autores: Marquez-Rodas, I. ; Trabada, D. L.; Cabello, S. C.; et al.
Revista: EUROPEAN JOURNAL OF CANCER
ISSN 0959-8049  Vol. 47  2011  págs. S258 - S258
Autores: Navarro, F. R. ; Calvo Manuel, Felipe; Espi, M. G.;
Revista: INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
ISSN 0360-3016  Vol. 81  Nº 2  2011  págs. S369 - S370
Autores: Serrano, J.; Calvo Manuel, Felipe; Gomez-Espi, M.; et al.
Revista: RADIOTHERAPY AND ONCOLOGY
ISSN 0167-8140  Vol. 99  2011  págs. S18 - S18
Autores: Calvo Manuel, Felipe (Autor de correspondencia); Cabezon, L. ; Gonzalez, C. ; et al.
Revista: RADIOTHERAPY AND ONCOLOGY
ISSN 0167-8140  Vol. 97  Nº 2  2010  págs. 212 - 216
Objective: To evaluate efficacy of F-18-FDG PET(CT) in the staging and re staging of patients with locally advanced rectal cancer, its potential role in predicting pathological response to neoadjuvant therapy. Patients and methods: Patients with confirmed diagnosis of rectal cancer (T2-4 or N+) were prospectively studied with F-18-FDG PET before and after neoadjuvant therapy. Surgery was programmed 4-6 weeks after treatment followed by an expert histological analysis of the surgical specimen. Response to neoadjuvant treatment was assessed using two specific variables: difference ins SUV (difSUV) pre/post-neoadjuvant treatment and response index (RI). Results: A total of 64 patients were enrolled for pathologicla and bio-metabolic response assessment. Compared to cNo, cN+ Patients had a higher SUV1 mean value (6.5 vs. 7.6. p = 0.04) and ypN+ patients had higher SUV2 mean values (2.4 vs 3.5, P = 0.06), difSUV values of >= 4 was the most efficient diagnositic parameter (sensitivity = 45.8%, specificity = 86.2%, positive predictive value (PPV) = 73.3%, negative predictive value(NPV) = 65.7%). With an RI of 66.6%, and NPV = 57.8%. Patients who experienced disease progression had an RI <= 66% and a difSUV <= 4. Conclusion: F-18-FDG PET has proven to be an accurate diagnostic technique for assessing rectal cancer response to neoadjuvant therapy. The results in terms of sensitivity, specificity, PPV and NPV were similar, if not superior, to those reported with other diagnositc imaging techniques. (C) Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 97 (2010) 212-216
Autores: Kusters, M. ; Valentini, V.; Calvo Manuel, Felipe; et al.
Revista: ANNALS OF ONCOLOGY
ISSN 0923-7534  Vol. 21  Nº 6  2010  págs. 1279 - 1284
Background: The purpose of this study is to analyze the pooled results of multimodality treatment of locally advanced rectal cancer (LARC) in four major treatment centers with particular expertise in intraoperative radiotherapy (IORT). Patients and methods: A total of 605 patients with LARC who underwent multimodality treatment up to 2005 were studied. The basic treatment principle was preoperative (chemo) radiotherapy, intended radical surgery, IORT and elective adjuvant chemotherapy (aCT). In uni- and multivariate analyses, risk factors for local recurrence (LR), distant metastases (DM) and overall survival (OS) were studied. Results: Chemoradiotherapy lead to more downstaging and complete remissions than radiotherapy alone (P < 0.001). In all, 42% of the patients received aCT, independent of tumor-node-metastasis stage or radicality of the resection. LR rate, DM rate and OS were 12.0%, 29.2% and 67.1%, respectively. Risk factors associated with LR were no downstaging, lymph node (LN) positivity, margin involvement and no postoperative chemotherapy. Male gender, preoperatively staged T4 disease, no downstaging, LN positivity and margin involvement were associated with a higher risk for DM. A risk model was created to determine a prognostic index for individual patients with LARC. Conclusions: Overall oncological results after multimodality treatment of LARC are promising. Adding aCT to the treatment can possibly improve LR rates.
Autores: Maas, M. ; Nelemans, P. J.; Valentini, V. ; et al.
Revista: LANCET ONCOLOGY
ISSN 1470-2045  Vol. 11  Nº 9  2010  págs. 835 - 844
Background Locally advanced rectal cancer is usually treated with preoperative chemoradiation. After chemoradiation and surgery, 15-27% of the patients have no residual viable tumour at pathological examination, a pathological complete response (pCR). This study established whether patients with pCR have better long-term outcome than do those without pCR. Methods In PubMed, Medline, and Embase we identified 27 articles, based on 17 different datasets, for long-term outcome of patients with and without pCR. 14 investigators agreed to provide individual patient data. All patients underwent chemoradiation and total mesorectal excision. Primary outcome was 5-year disease-free survival. Kaplan-Meier survival functions were computed and hazard ratios (HRs) calculated, with the Cox proportional hazards model. Subgroup analyses were done to test for effect modification by other predicting factors. Interstudy heterogeneity was assessed for disease-free survival and overall survival with forest plots and the Q test. Findings 484 of 3105 included patients had a pCR. Median follow-up for all patients was 48 months (range 0-277). 5-year crude disease-free survival was 83.3% (95% CI 78.8-87-0) for patients with pCR (61/419 patients had disease recurrence) and 65.6% (63.6-68.0) for those without pCR (747/2263; HR 0.44, 95% CI 0.34-0.57; p<0.0001). The Q test and forest plots did not suggest significant interstudy variation. The adjusted HR for pCR for failure was 0.54 (95% CI 0.40-0.73), indicating that patients with pCR had a significantly increased probability of disease-free survival. The adjusted HR for disease-free survival for administration of adjuvant chemotherapy was 0.91 (95% CI 0.73-1.12). The effect of pCR on disease-free survival was not modified by other prognostic factors. Interpretation Patients with pCR after chemoradiation have better long-term outcome than do those without pCR. pCR might be indicative of a prognostically favourable biological tumour profile with less propensity for local or distant recurrence and improved survival.
Autores: Mattiucci, G.; Valentini, V.; van Stiphout, R. G. P. M.; et al.
Revista: INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
ISSN 0360-3016  Vol. 78  Nº 3  2010  págs. S101 - S101
Autores: Rodriguez, J. R. ; Lopez-Tarjuelo, J.; Bouche-Babiloni, A. ; et al.
Revista: MEDICAL PHYSICS
ISSN 0094-2405  Vol. 37  Nº 6  2010 
Autores: Kusters, M.; Valentini, V.; Calvo Manuel, Felipe; et al.
Revista: ANNALS OF ONCOLOGY
ISSN 0923-7534  Vol. 21  2010  págs. I15 - I16
Autores: Calvo Manuel, Felipe; De la Mata, M. D. ; Gonzalez, M. ; et al.
Revista: ANNALS OF ONCOLOGY
ISSN 0923-7534  Vol. 21  2010  págs. I25 - I25
Autores: Gonzalez-Domingo, M. ; Calvo Manuel, Felipe; Garcia-Sabrido, J. L.; et al.
Revista: RADIOTHERAPY AND ONCOLOGY
ISSN 0167-8140  Vol. 96  2010  págs. S285 - S285
Autores: Calvo Manuel, Felipe; De La Mata, M. ; Espi, M. G.; et al.
Revista: JOURNAL OF CLINICAL ONCOLOGY
ISSN 0732-183X  Vol. 28  Nº 15  2010 
Autores: Gonzalez-Domingo, M. ; Calvo Manuel, Felipe; Garcia-Sabrido, J. L.; et al.
Revista: RADIOTHERAPY AND ONCOLOGY
ISSN 0167-8140  Vol. 96  2010  págs. IX - IX
Autores: Calvo Manuel, Felipe; Gomez-Espi, M. ; Rivas, F.;
Revista: RADIOTHERAPY AND ONCOLOGY
ISSN 0167-8140  Vol. 96  2010  págs. S287 - S287
Autores: de la Vega, F. A. ; Herruzo, I.; de las Heras, M. ; et al.
Revista: JOURNAL OF CLINICAL ONCOLOGY
ISSN 0732-183X  Vol. 28  Nº 15  2010 
Autores: Santos, M.; Calvo Manuel, Felipe; Salcedo, J.; et al.
Revista: RADIOTHERAPY AND ONCOLOGY
ISSN 0167-8140  Vol. 96  2010  págs. S264 - S264
Autores: Gonzalez-Domingo, M.; Calvo Manuel, Felipe; Garcia-Sabrido, J. L.; et al.
Revista: RADIOTHERAPY AND ONCOLOGY
ISSN 0167-8140  Vol. 96  2010  págs. IX - X
Autores: Pascau, J.; Miranda, J. A. S.; Bouche, A. ; et al.
Revista: RADIOTHERAPY AND ONCOLOGY
ISSN 0167-8140  Vol. 96  2010  págs. S558 - S558
Autores: Gonzalez-Domingo, M.; Calvo Manuel, Felipe; Garcia-Sabrido, J. L.; et al.
Revista: RADIOTHERAPY AND ONCOLOGY
ISSN 0167-8140  Vol. 96  2010  págs. S285 - S285
Autores: Santos, M.; Calvo Manuel, Felipe; Bustos, J. C.; et al.
Revista: RADIOTHERAPY AND ONCOLOGY
ISSN 0167-8140  Vol. 96  2010  págs. IX - IX
Autores: De la Mata, M. ; Calvo Manuel, Felipe; Espi, M. G.; et al.
Revista: INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
ISSN 0360-3016  Vol. 78  Nº 3  2010  págs. S302 - S302
Autores: Zapatero, A. ; Guerrero, A. ; Maldonado, X. ; et al.
Revista: JOURNAL OF CLINICAL ONCOLOGY
ISSN 0732-183X  Vol. 28  Nº 15  2010