Nuestros investigadores

Rafael Martínez Monge

Publicaciones científicas más recientes (desde 2010)

Autores: Tagliaferri, L.; Pagliara, M. M.; Fionda, B., (Autor de correspondencia); et al.
Revista: JOURNAL OF CONTEMPORARY BRACHYTHERAPY
ISSN 1689-832X  Vol. 11  Nº 1  2019  págs. 54 - 60
Purpose: To report the results of a patient's tailored therapeutic approach using a second course of interventional radiotherapy (brachytherapy) in patients with locally recurrent uveal melanoma. Material and methods: Patients who had already undergone ocular brachytherapy treated at our IOC (Interventional Oncology Center) were considered. Five patients who has received a second course of treatment with a plaque after local recurrences were included in our study. Re-irradiation was performed with Ruthenium-106 (prescribed dose to the apex 100 Gy) or with Iodine-125 plaques (prescribed dose to the apex 85 Gy). Moreover, a systematic literature search was conducted through three electronic databases, including Medline/PubMed, Scopus, and Embase. Results: All patients were initially treated with Ruthenium-106 plaque; the re-irradiation was performed with Ruthenium-106 plaque in three cases and with Iodine in two cases. Mean time between the first and the second plaque was 56.8 months (range, 25-93 months). Local tumor control rate was 100%, no patient underwent secondary enucleation owing to re-treatment failure. Distant metastasis occurred in 1 patient after 6 months from re-treatment. After a median follow-up of 44.2 months (range, 26-65 months) from re-treatment, all patients experienced worsening of the visual acuity (median visual acuity was 0.42 at time of recurrence and decline to 0.24 at the most recent follow-up); cataract occurred in two cases, no patient developed scleral necrosis. We considered 2 papers for a systematic review. Conclusions: In selected cases, especially in presence of marginal local recurrence, a personalized re-treatment strategy with a plaque may offer high probability of tumor control and organ preservation but worsening of visual acuity.
Autores: San-Julian M; Cambeiro, Felix Mauricio; et al.
Revista: RADIOTHERAPY AND ONCOLOGY
ISSN 0167-8140  Vol. 135  2019  págs. 91 - 99
Background: To analyze toxicity, patterns of failure, and survival in 106 adult patients with soft tissue sarcomas of the extremity and the superficial trunk treated in a prospective controlled trial of combined Perioperative High Dose Rate Brachytherapy (PHDRB) and external beam radiotherapy (EBRT). Methods: Patients were treated with surgical resection and 16 Gy or 24 Gy of PHDRB for negative or close/positive margins, respectively. EBRT (45 Gy) was added postoperatively. Adjuvant chemotherapy was given to selected patients with high-grade tumors. Results: The median follow-up was 7.1 years (range, 0.6-16.0). Grade >= 3 adverse events were observed in 22 patients (20.8%), and grade >= 4 events in 14 patients (13.2%). No grade 5 events were noted. Multivariate analysis (p = 0.003) found that Grade >= 3 toxic events increased with increasing implant volume (TV100). Local control, locoregional control, and distant control rates at 5 and 10 years were 89% and 87%, 82% and 80% and 75% and 69%, respectively. Multivariate analysis (p = 0.024) found that positive margins correlated with decreased local control. Disease-free survival and overall survival rates at 5 and 10 years were 64% and 59% and 73% and 62%, respectively. In multivariate analysis, disease-free survival rates decreased with increasing tumor size (p = 0.0001) and inadequate margins (p = 0.024), and overall survival decreased with increasing tumor size (p = 0.001) and male gender (p = 0.039). Conclusions: The combination of conservative surgery, high-dose PHDRB, and EBRT produces adequate function and local control in the majority of patients with soft tissue sarcomas of the extremities and the superficial trunk, including a substantial percentage of cases with positive margins. Patients with larger tumors are at a higher risk of complications, treatment failure, and cancer-related death and require an individualized treatment approach. (C) 2019 Elsevier B.V. All rights reserved.
Autores: Martínez-Monge, Rafael, (Autor de correspondencia); Cambeiro, Felix Mauricio; et al.
Revista: BRACHYTHERAPY
ISSN 1538-4721  Vol. 17  Nº 6  2018  págs. 1045
Autores: Tagliaferri, L.; Budrukkar, A.; Lenkowicz, J., (Autor de correspondencia); et al.
Revista: JOURNAL OF CONTEMPORARY BRACHYTHERAPY
ISSN 1689-832X  Vol. 10  Nº 3  2018  págs. 260 - 266
Purpose: Clinical data collecting is expensive in terms of time and human resources. Data can be collected in different ways; therefore, performing multicentric research based on previously stored data is often difficult. The primary objective of the ENT COBRA (COnsortium for BRachytherapy data Analysis) ontology is to define a specific terminological system to standardized data collection for head and neck (H&N) cancer patients treated with interventional radiotherapy. Material and methods: ENT-COBRA is a consortium for standardized data collection for H&N patients treated with interventional radiotherapy. It is linked to H&N and Skin GEC-ESTRO Working Group and includes 11 centers from 6 countries. Its ontology was firstly defined by a multicentric working group, then evaluated by the consortium followed by a multi-professional technical commission involving a mathematician, an engineer, a physician with experience in data storage, a programmer, and a software expert. Results: Two hundred and forty variables were defined on 13 input forms. There are 3 levels, each offering a specific type of analysis: 1. Registry level (epidemiology analysis); 2. Procedures level (standard oncology analysis); 3. Research level (radiomics analysis). The ontology was approved by the consortium and technical commission; an ad-hoc software architecture ("broker") remaps the data present in already existing storage systems of the various centers according to the shared terminology system. The first data sharing was successfully performed using COBRA software and the ENT COBRA Ontology, automatically collecting data directly from 3 different hospital databases (Lubeck, Navarra, and Rome) in November 2017. Conclusions: The COBRA Ontology is a good response to the multi-dimensional criticalities of data collection, retrieval, and usability. It allows to create a software for large multicentric databases with implementation of specific remapping functions wherever necessary. This approach is well-received by all involved parties, primarily because it does not change a single center's storing technologies, procedures, and habits.
Autores: Walle, T.; Martínez-Monge, Rafael; Cerwenka, A.; et al.
Revista: THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY
ISSN 1758-8340  Vol. 10  2018 
Radiotherapy (RT) is currently used in more than 50% of cancer patients during the course of their disease in the curative, adjuvant or palliative setting. RT achieves good local control of tumor growth, conferring DNA damage and impacting tumor vasculature and the immune system. Formerly regarded as a merely immunosuppressive treatment, pre- and clinical observations indicate that the therapeutic effect of RT is partially immune mediated. In some instances, RT synergizes with immunotherapy (IT), through different mechanisms promoting an effective antitumor immune response. Cell death induced by RT is thought to be immunogenic and results in modulation of lymphocyte effector function in the tumor microenvironment promoting local control. Moreover, a systemic immune response can be elicited or modulated to exert effects outside the irradiation field (so called abscopal effects). In this review, we discuss the body of evidence related to RT and its immunogenic potential for the future design of novel combination therapies.
Autores: Martínez-Monge, Rafael, (Autor de correspondencia); Cambeiro, Felix Mauricio; et al.
Revista: BRACHYTHERAPY
ISSN 1538-4721  Vol. 17  Nº 5  2018  págs. 734 - 741
PURPOSE: To determine the long-term results of a Phase II trial of perioperative high-dose-rate brachytherapy (PHDRB) in primary advanced or recurrent gynecological cancer. METHODS AND MATERIALS: Fifty patients with locally advanced and recurrent gynecological cancer suitable for salvage surgery were included. Unirradiated patients (n = 25) received preoperative chemoradiation followed by surgery and PHDRB (16-24 Gy). Previously irradiated patients (n = 25) received surgery and PHDRB alone (32-40 Gy). RESULTS: Median followup was 11.5 years. Eight unirradiated patients (32%) developed Grade >= 3 toxic events including two fatal events. Local and locoregional control rates at 16 years were 87.3% and 78.9%, respectively. Sixteen-year disease-free and overall survival rates were 42.9% and 46.4%, respectively. Ten previously irradiated patients (40.0%) developed Grade >= 3 adverse events, including four fatal events. Local and locoregional control rates at 14 years were 59.6% and 42.6%, respectively. Fourteen-year disease-free and overall survival rates were 16.0% and 19.2%, respectively. CONCLUSIONS: PHDRB allows effective salvage of a subset of unfavorable gynecological tumors with high-risk surgical margins. Toxicity was unacceptable at the initial dose levels but deescalation resulted in the absence of severe toxicity without a negative impact on locoregional control. A substantial percentage of patients remain alive and controlled at >10 years including a few previously irradiated cases with positive margins. (C) 2018 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.
Autores: Cambeiro, Felix Mauricio; Díez Caballero, Fernando José; et al.
Revista: RADIOTHERAPY AND ONCOLOGY
ISSN 0167-8140  Vol. 127  Nº Supl. 1  2018  págs. S129 - S129
Autores: Kovacs, G.; Martínez-Monge, Rafael; Budrukkar, A.; et al.
Revista: RADIOTHERAPY AND ONCOLOGY
ISSN 0167-8140  Vol. 122  Nº 2  2017  págs. 248 - 254
The Head and Neck Working Group of the GEC-ESTRO (Groupe Européen de Curiethérapie - European Society for Therapeutic Radiology and Oncology) published in 2009 the consensus recommendations for low-dose rate, pulsed-dose rate and high-dose rate brachytherapy in head & neck cancers. The use of brachytherapy in combination with external beam radiotherapy and/or surgery was also covered as well as the use of brachytherapy in previously irradiated patients. Given the developments in the field, these recommendations needed to be updated to reflect up-to-date knowledge. The present update does not repeat basic knowledge which was published in the first recommendation but covers in a general part developments in (1) dose and fractionation, (2) aspects of treatment selection for brachytherapy alone versus combined BT+EBRT and (3) quality assurance issues. Detailed expert committee opinion intends to help the clinical practice in lip-, oral cavity-, oropharynx-, nasopharynx-, and superficial cancers. Different aspects of adjuvant treatment techniques and their results are discussed, as well the possibilities of salvage brachytherapy applications.
Autores: Alcalde, Juan Manuel; Cambeiro, Felix Mauricio; et al.
Revista: RADIOTHERAPY AND ONCOLOGY
ISSN 0167-8140  Vol. 122  Nº 2  2017  págs. 255 - 259
Surgical resection and PHDRB is a successful treatment strategy in selected patients with previously irradiated head and neck cancer. Long-term locoregional control can be achieved in a substantial number of cases despite a high rate of inadequate surgical resections although at the expense of substantial toxicity.
Autores: Takacsi-Nagy, Z.; Martínez-Monge, Rafael; Mazeron, J. J.; et al.
Revista: BRACHYTHERAPY
ISSN 1538-4721  Vol. 16  Nº 1  2017  págs. 44 - 58
Irradiation plays an important role in the treatment of cancers of the head and neck providing a high locoregional tumor control and preservation of organ functions. External beam irradiation (EBI) results in unnecessary radiation exposure of the surrounding normal tissues increasing the incidence of side effects (xerostomy, osteoradionecrosis, and so forth). Brachytherapy (BT) seems to be the best choice for dose escalation over a short treatment period and for minimizing radiation-related normal tissue damage due to the rapid dose falloff around the source. Low-dose-rate BT is being increasingly replaced by pulsed-dose-rate and high-dose-rate BT because the stepping source technology offers the advantage of optimizing dose distribution by varying dwell times. Pulsed-dose and high-dose rates appear to yield local control and complication rates equivalent to those of low-dose rate. BT may be applied alone; but in case of high risk of nodal metastases, it is used together with EBI. This review presents the results and the indications of combined BT and EBI in carcinoma of the base of tongue and other sites of the head and neck region, as well as the role BT plays among other normal tissue protecting modern radiotherapy modalities (intensity modulated radiotherapy, stereotactic radiotherapy) applied in these localizations. (C) 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.
Autores: Cambeiro, Felix Mauricio; Martínez, Fernando; Rodríguez-Spiteri, Natalia; et al.
Revista: BRACHYTHERAPY
ISSN 1538-4721  Vol. 15  Nº 4  2016  págs. 485 - 494
Purpose: To assess the safety, feasibility, and efficacy of free-hand intraoperative multicatheter breast implant (FHIOMBI) and perioperative high-dose-rate brachytherapy (PHDRBT) in early breast cancer. Methods and Materials: Patients with early breast cancer candidates for breast conservative surgery (BCS) were prospectively enrolled. Patients suitable for accelerated partial breast irradiation (APBI) (low or intermediate risk according GEC-ESTRO criteria) received PHDRBT (3.4 Gy BID × 10 in 5 days). Patients not suitable for APBI (high risk patients according GEC-ESTRO criteria) received PHDRBT boost (3.4 Gy BID × 4 in 2 days) followed by whole breast irradiation. Results: From June 2007 to November 2014, 119 patients were treated and 122 FHIOMBI procedures were performed. Median duration of FHIOMBI was 25 minutes. A median of eight catheters (range, 4-14) were used. No severe intraoperative complications were observed. Severe early postoperative complications (bleeding) were documented in 2 patients (1.6%), wound healing complications in 3 (2.4%), and infection (mastitis or abscess) in 2 (1.6%). PHDRBT was delivered as APBI in 88 cases (72.1%) and as a boost in 34 (27.8%). The median clinical target volume T was 40.8 cc (range, 12.3-160.5); median D90 was 3.32 Gy (range, 3.11-3.85); median dose homogeneity index was 0.72 (range, 0.48-0.82). With a median followup of 38.4 months (range, 8.7-98.7) no local, elsewhere, or regional relapses were observed; there was only one distant failure in PHDRBT boost. No major (acute or late) RTOG grade 3 or higher were documented in any of the 119 patients treated with PHDRBT. Cosmetic outcome in APBI patients was excellent or good in (87.0%) and fair or poor in (11.9%) while in boost patients was excellent or good in (76.4%) and fair in (23.5%). Conclusion: The FHIOMBI-PHDRBT program does not add complications to conservative surgery. It allows precise selection of APBI patients and offers excellent results in disease control and cosmetics. It also offers logistic advantages because it dramatically shortens the time of local treatment and avoids further invasive procedures.
Autores: Sole, Claudio V.; Calvo, Felipe Ángel; Alvarez, Eduardo; et al.
Revista: RADIOTHERAPY AND ONCOLOGY
ISSN 1879-0887  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 R1 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.
Autores: Isabel Martinez-Fernandez, Maria; Legaspi Folgueira, Jairo; Valtuena Peydro, German; et al.
Revista: INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER
ISSN 1525-1438  Vol. 26  Nº 6  2016  págs. 1162-1168
Autores: Cambeiro, Felix Mauricio; Moreno, Marta; et al.
Revista: BRACHYTHERAPY
ISSN 1873-1449  Vol. 15  Nº 2  2016  págs. 127 - 135
Purpose: To compare rectal toxicity, urinary toxicity, and nadir+2 PSA relapse-free survival (bRFS) in two consecutive Phase II protocols of high-dose-rate (HDR) brachytherapy used at the authors institution from 2001 to 2012. Methods and Materials: Patients with National Comprehensive Cancer Network high risk and very high risk prostate cancer enrolled in studies HDR4 (2001-2007, n = 183) and HDR2 (2007-2012, n = 56) were analyzed. Patients received minipelvis external beam radiation therapy/intensity-modulated external radiotherapy to 54 Gy and 2 years of androgen blockade along with HDR brachytherapy. HDR4 protocol consisted of four 4.75 Gy fractions delivered in 48 hours; the HDR2 protocol delivered two 9.5 Gy fractions in 24 hours. Average 2-Gy equivalent dose (¿/ß = 1.2) prostate D90 doses for the HDR4 and HDR2 groups were 89.8 Gy and 110.5 Gy, respectively (p = 0.0001). Both groups were well balanced regarding risk factors. Prior transurethral resection of the prostate was more frequent in the HDR2 group (p = 0.001). Results: After a median followup of 7.4 years (range, 2-11.2), there was no difference in adverse grade ¿ 2 rectal events (HDR4 = 10.4% vs. HDR2 = 12.5%; p = ns) or grade ¿3 (HDR4 = 2.2% vs. HDR2 = 3.6%; p = ns). No differences in urinary grade ¿2 adverse events (HDR4 = 23% vs. HDR2 = 26.8%; p = ns) or grade ¿3 (HDR4 = 7.7% vs. HDR2 = 8.9%; p = ns) were detected. The 7-year bRFS for HDR4 and HDR2 protocols was 88.7% and 87.8%, respectively (p = ns). Conclusions: HDR4 and HDR2 protocols produce similar results in terms of toxicity and bRFS at the intermediate time point of 7 years.
Autores: Martínez-Monge, Rafael; Santisteban, Marta; et al.
Revista: BRACHYTHERAPY
ISSN 1538-4721  Vol. 14  Nº 4  2015  págs. 565 - 570
To determine whether the time to loading (TTL) affects locoregional control. METHODS AND MATERIALS: Locoregional control status was determined in 301 patients enrolled in several perioperative high-dose-rate brachytherapy (PHDRB) prospective studies conducted at the University of Navarre. The impact of the time elapsed from catheter implantation to the first PHDRB treatment (TTL) was analyzed. Patients treated with PHDRB alone (n = 113), mainly because of prior irradiation, received 32 Gy in eight twice-a-day treatments or 40 Gy in 10 twice-a-day treatments for negative or close/positive margins, respectively. Patients treated with PHDRB + external beam radiation therapy (EBRT) (n = 188) received 16 Gy in four twice-a-day treatments or 24 Gy in six twice-a-day treatments for negative or close/positive margins followed by 45 Gy of EBRT in 25 treatments. RESULTS: After a median followup of 6.5 years (range, 2-13.6+), 113 patients have failed (37.5%), 65 in the PHDRB-alone group (57.5%) and 48 in the combined PHDRB + EBRT group (25.5%). Patients who started PHDRB before Postoperative Day 5 had a 10-year locoregional control rate of 66.7% and patients who started PHDRB on Postoperative Day 5 or longer had a 10-year locoregional control rate of 51.8% (p = 0.009). Subgroup analysis detected that this difference was only observed in the recurrent cases treated with PHDRB alone (Subset 2; n = 99; p = 0.004). No correlation could be detected between locoregional control rate and TTL in the other patient subsets although a trend toward a decreased locoregional control rate after a longer TTL was observed when they were grouped together (p = 0.089). CONCLUSIONS: Patients should start PHDRB as soon as possible to maximize locoregional control especially in those recurrent cases treated with PHDRB alone. The time effect in other disease scenarios is less clear.
Autores: Cambeiro, Felix Mauricio, (Autor de correspondencia); Aristu, José Javier; Moreno, Marta; et al.
Revista: BRACHYTHERAPY
ISSN 1873-1449  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 3.7years (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. ¿4cm (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.
Autores: Martínez-Monge, Rafael, (Autor de correspondencia); Cambeiro, Felix Mauricio; et al.
Revista: BRACHYTHERAPY
ISSN 1538-4721  Vol. 13  Nº 4  2014  págs. 400 - 404
PURPOSE: To develop a simple clinical model predictive of locoregional failure after complete surgical resection followed by perioperative high-dose-rate brachytherapy (PHDRB) and external beam irradiation (EBRT). PATIENT AND METHODS: Patients (n=166) enrolled in several PHDRB prospective studies conducted at the University of Navarre were analyzed. PHDRB was given to total doses of 16 Gy/4 b.i.d. or 24 Gy/6 b.i.d. treatments for negative or close/positive margins along with 45Gy of EBRT. RESULTS: After a median followup of 7.4 years (range, 3-12+), 50 patients have failed and 116 remain controlled at last followup. Tumor size, with a cutoff point set at 3cm (p=0.041) and margin status (positive and <1mm vs. negative ¿1mm, p=0.0001) were independent predictors of locoregional control. These two parameters were used to develop a four-tiered, hierarchical scoring system that stratified patients into low-risk (negative ¿1mm margins and size ¿3cm), intermediate-risk (negative ¿1mm margins, and size >3cm), high-risk (positive and <1mm margins and size ¿3cm), and very high-risk categories (positive and <1mm margins and size >3cm). This classification yields 5-year locoregional control rates of 92.3%, 78.0%, 65.5%, and 48.0% for low-, intermediate-, high-, and very high-risk categories, respectively. The predictive ability of the model is highly significant (p=0.0001) with an area under the curve of 0.72 (0.64-0.81). CONCLUSIONS: The risk of locoregional failure after combined surgical resection, PHDRB, and EBRT is mainly determined by the number of residual clonogens, which is inversely proportional to the status of the surgical margins and directly related to the size of the resected tumor. These two parameters generate a four-tiered predictive model that seems to be valid for a number of different common tumors and clinical settings.
Autores: Martínez-Monge, Rafael; Cambeiro, Felix Mauricio; et al.
Revista: BRACHYTHERAPY
ISSN 1538-4721  Vol. 13  Nº 6  2014  págs. 591 - 596
PURPOSE: To determine whether perioperative high-dose-rate brachytherapy (PHDRB) implants with larger high-dose regions produce increased locoregional control. METHODS AND MATERIALS: Patients (n=166) enrolled in several PHDRB prospective studies conducted at the University of Navarre were analyzed. The PHDRB was given to total doses of 16Gy/4 b.i.d. or 24Gy/6 b.i.d. treatments for negative or close/positive margins along with 45Gy/25 Rx of external beam radiation therapy. The histogram-based generalized equivalent uniform dose (EUD) formulism was used to quantify and standardize the dose-volume histogram into 2-Gy equivalents. The region of interest analyzed included: tissue volume encompassed by the prescription isodose of 4Gy (TV100). Routine dose reporting parameters such as physical dose and single-point 2-Gy equivalent dose were used for reference. RESULTS: After a median followup of 7.4 years (range, 3-12+), 50 patients have failed, and 116 remain controlled at last followup. Overall, EUD was not different in the patients who failed compared with controls (89.1Gy vs. 86.5Gy; p=not significant). When patients were stratified by risk using the University of Navarre Predictive Model, very high-risk patients (i.e., tumors ¿3cm resected with close <1mm/positive margins) had an improved locoregional control with higher EUD values (p=0.028). This effect was not observed in low-, intermediate-, and high-risk University of Navarre Predictive Model categories. CONCLUSIONS: In very high-risk patients, enlarged high-dose regions can produce a dose-response effect. Routine dose reporting methods such as physical dose and single-point 2-Gy equivalent dose may not show this effect, but it can be revealed by histogram-based EUD assessment.
Autores: Cambeiro, Felix Mauricio; et al.
Revista: HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK
ISSN 1043-3074  Vol. 34  Nº 8  2012  págs. 1081-1088
Background This study aimed to test the safety of using perioperative high-dose-rate brachytherapy (PHDRB) in resected head and neck cancer. Methods From 2000 to 2008, 97 patients received PHDRB after complete macroscopic resection. Group 1 (previously irradiated patients) received 32 to 40 Gray (Gy) of PHDRB in 8 to 10 twice-daily (bid) treatments (R0R1 resections). Group 2 (unirradiated patients) received 16 to 24 Gy of PHDRB in 4 to 6 bid treatments (R0R1 resections) followed by external beam irradiation (EBRT) of 45 Gy/25 daily fractions +/- concomitant chemotherapy. Results The median follow-up was 4.3 years. The cumulative hazard of 2-year grade = 3 complications in group 1 was 45.9%, and the rate of grade = 3 complications in group 2 was 24.6%. Actuarial locoregional control at 2 and 5 years for group 1 was 60.9% and for group 2, 84.1% and 79.4%. Conclusions Complications and locoregional failure rates were similar to those reported in the reference standards despite a much smaller treatment volume. (c) 2012 Wiley Periodicals, Inc. Head Neck, 2012
Autores: Arbea, Leire; Martínez-Monge, Rafael; Diaz-Gonzalez, JA; et al.
Revista: INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
ISSN 0360-3016  Vol. 83  Nº 2  2012  págs. 587-593
PURPOSE: To validate tolerance and pathological complete response rate (pCR) of a 4-week preoperative course of intensity-modulated radiation therapy (IMRT) with concurrent capecitabine and oxaliplatin (CAPOX) in patients with locally advanced rectal cancer. METHODS AND MATERIALS: Patients with T3 to T4 and/or N+ rectal cancer received preoperative IMRT (47.5 Gy in 19 fractions) with concurrent capecitabine (825 mg/m(2) b.i.d., Monday to Friday) and oxaliplatin (60 mg/m(2) on Days 1, 8, and 15). Surgery was scheduled 4 to 6 weeks after the completion of chemoradiation. Primary end points were toxicity and pathological response rate. Local control (LC), disease-free survival (DFS), and overall survival (OS) were also analyzed. RESULTS: A total of 100 patients were evaluated. Grade 1 to 2 proctitis was observed in 73 patients (73%). Grade 3 diarrhea occurred in 9% of the patients. Grade 3 proctitis in 18% of the first 50 patients led to reduction of the dose per fraction to 47.5 Gy in 20 treatments. The rate of Grade 3 proctitis decreased to 4% thereafter (odds ratio, 0.27). A total of 99 patients underwent surgery. A pCR was observed in 13% of the patients, major response (96-100% of histological response) in 48%, and pN downstaging in 78%. An R0 resection was performed in 97% of the patients. After a median follow-up of 55 months, the LC, DFS, and OS rates were 100%, 84%, and 87%, respectively. CONCLUSIONS: Preoperative CAPOX-IMRT therapy (47.5 Gy in 20 fractions) is feasible
Autores: Diaz-Gonzalez, JA; Rodríguez, Javier; Hernández, José Luis; et al.
Revista: INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
ISSN 0360-3016  Vol. 80  Nº 3  2011  págs. 698-704
PURPOSE: To analyze the rate of pathologic response in patients with locally advanced gastric cancer treated with preoperative chemotherapy with and without chemoradiation at our institution. METHODS AND MATERIALS: From 2000 to 2007 patients were retrospectively identified who received preoperative treatment for gastric cancer (cT3-4/ N+) with induction chemotherapy (Ch) or with Ch followed by concurrent chemoradiotherapy (45 Gy in 5 weeks) (ChRT). Surgery was planned 4-6 weeks after the completion of neoadjuvant treatment. Pathologic assessment was used to investigate the patterns of pathologic response after neoadjuvant treatment. RESULTS: Sixty-one patients were analyzed. Of 61 patients, 58 (95%) underwent surgery. The R0 resection rate was 87%. Pathologic complete response was achieved in 12% of the patients. A major pathologic response (<10% of residual tumor) was observed in 53% of patients, and T downstaging was observed in 75%. Median follow-up was 38.7 months. Median disease-free survival (DFS) was 36.5 months. The only patient-, tumor-, and treatment-related factor associated with pathologic response was the use of preoperative ChRT. Patients achieving major pathologic response had a 3-year actuarial DFS rate of 63%. CONCLUSIONS: The patterns of pathologic response after preoperative ChRT suggest encouraging intervals of DFS. Such a strategy may be of interest to be explored in gastric cancer.
Autores: Martínez-Monge, Rafael; Cambeiro, Felix Mauricio; Moreno, Marta; et al.
Revista: INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
ISSN 0360-3016  Vol. 79  Nº 4  2011  págs. 1158 - 1163
Purpose To determine patient, tumor, and treatment factors predictive of local control (LC) in a series of patients treated with either perioperative high-dose-rate brachytherapy (PHDRB) alone (Group 1) or with PHDRB combined with external-beam radiotherapy (EBRT) (Group 2). Patient and Methods Patients (n = 312) enrolled in several PHDRB prospective Phase I¿II studies conducted at the Clínica Universidad de Navarra were analyzed. Treatment with PHDRB alone, mainly because of prior irradiation, was used in 126 patients to total doses of 32 Gy/8 b.i.d. or 40 Gy/10 b.i.d. treatments after R0 or R1 resections. Treatment with PHDRB plus EBRT was used in 186 patients to total doses of 16 Gy/4 b.i.d. or 24 Gy/6 b.i.d. treatments after R0 or R1 resections along with 45 Gy of EBRT with or without concomitant chemotherapy. Results No dose-margin interaction was observed in Group 1 patients. In Group 2 patients there was a significant interaction between margin status and 2-Gy equivalent (Eq2Gy) dose (p = 0.002): (1) patients with negative margins had 9-year LC of 95.7% at Eq2Gy = 62.9Gy; (2) patients with close margins of >1 mm had 9-year LC of 92.4% at Eq2Gy = 72.2Gy, and (3) patients with positive/close <1-mm margins had 9-year LC of 68.0% at Eq2Gy = 72.2Gy. Conclusions Two-gray equivalent doses ¿70 Gy may compensate the effect of close margins ¿1 mm but do not counterbalance the detrimental effect of unfavorable (positive/close <1 mm) resection margins. No dose¿margin interaction is observed in patients treated at lower Eq2Gy doses ¿50 Gy with PHDRB alone.
Autores: Arbea, Leire; Diaz-Gonzalez, JA; Subtil, José Carlos; et al.
Revista: INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
ISSN 0360-3016  Vol. 81  Nº 2  2011  págs. 439 - 444
Purpose: The main goals of preoperative chemoradiotherapy (CHRT) in rectal cancer are to achieve pathological response and to ensure tumor control with functional surgery when possible. Assessment of the concordance between clinical and pathological responses is necessary to make decisions regarding alternative conservative procedures. The present study evaluates the patterns of response after a preoperative CHRT regimen, and the value of endoscopic ultrasound (EUS) in assessing response. Methods and Materials: A total of 51 EUS-staged T3 to T4 and/or N0 to N+ rectal cancer patients received preoperative CHRT (intensity-modulated radiation therapy and capecitabine/oxaliplatin (XELOX) followed by radical resection. Clinical response was assesed by EUS. Rates of pathological tumor regression grade (TRG) and lymph node (LN) involvement were determined in the surgical specimen. Clinical and pathological responses were compared, and the accuracy of EUS in assessing response was calculated. Results: Twenty-four patients (45%) achieved a major pathological response (complete or >95% pathological response (TRG 3+/4)). Sensitivity, specificity, negative predictive value, and positive predictive value of EUS in predicting pathological T response after preoperative CHRT were 77.8%, 37.5%, 60%, and 58%, respectively. The EUS sensitivity, specificity, negative predictive value, and positive predictive value for nodal staging were 44%, 88%, 88%, and 44%, respectively. Furthermore, EUS after CHRT accurately predicted the absence of LN involvement in 7 of 7 patients (100%) with major pathological response of the primary tumor. Conclusion: Preoperative IMRT with concomitant XELOX induces favorable rates of major pathological response. EUS has a limited ability to predict primary tumor response after preoperative CHRT, but it is useful for accurately determining LN status. EUS may have a potential value in identifying patients with a very low risk of LN involvement in association with a good pathological response as potential candidates for conservative local surgical protocols. (C) 2011 Elsevier Inc.
Autores: San-Julian M; Cambeiro, Felix Mauricio; et al.
Revista: INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
ISSN 0360-3016  Vol. 81  Nº 4  2011  págs. e523 - e539
Purpose: The present study was undertaken to determine factors predictive of toxicity, patterns of failure, and survival in 60 adult patients with soft tissue sarcomas of the extremity and superficial trunk treated with combined perioperative high-dose-rate brachytherapy and external beam radiotherapy. Methods and Materials: The patients were treated with surgical resection and perioperative high-dose-rate brachytherapy (16 or 24 Gy) for negative and close/microscopically positive resection margins, respectively. External beam radiotherapy (45 Gy) was added postoperatively to reach a 2-Gy equivalent dose of 62.9 and 72.3 Gy, respectively. Adjuvant chemotherapy with ifosfamide and doxorubicin was given to patients with advanced high-grade tumors. Results: Grade 3 toxic events were observed in 18 patients (30%) and Grade 4 events in 6 patients (10%). No Grade 5 events were observed. A location in the lower limb was significant for Grade 3 or greater toxic events on multivariate analysis (p =.013), and the tissue volume encompassed by the 150% isodose line showed a trend toward statistical significance (p =.086). The local control, locoregional control, and distant control rate at 9 years was 77.4%, 69.5%, and 63.8%, respectively. On multivariate analysis, microscopically involved margins correlated with local control (p =.036) and locoregional control (p =.007) and tumor size correlated with distant metastases (p =.004). The 9-year disease-free survival and overall survival rate was 47.0% and 61.5%, respectively. Multivariate analysis showed poorer disease-free survival rates for patients with tumors >6 cm (p =.005) and microscopically involved margins (p =.043), and overall survival rates decreased with increasing tumor size (p =.011). Conclusions: Grade 3 or greater wound complications can probably be decreased using meticulous treatment planning to decrease the tissue volume encompassed by the 150% isodose line, especially in lower limb locations. Microscopically involved margins remain a predictor of local and locoregional failure, despite radiation doses >70 Gy. Patients with tumors ¿6 cm and microscopically involved margins are at high risk of treatment failure and death from the development of distant metastases.
Autores: Aramendía, José Manuel; Espinos, Jaime; et al.
Revista: CANCER CHEMOTHERAPY AND PHARMACOLOGY
ISSN 0344-5704  Vol. 65  Nº 3  2010  págs. 457 - 465
Purpose Capecitabine is effective against metastatic breast cancer (MBC). We hypothesized that sequential treatment with dose-dense epirubicin/cyclophosphamide (EC) and docetaxel/capecitabine would be active and tolerable in the adjuvant/neoadjuvant setting. Methods In this prospective phase II clinical trial patients with HER2-negative and node-positive or locally advanced tumors were eligible to receive four cycles of EC (100/600 mg/m2) every 2 weeks with G-CSF on days 3¿10, followed by four cycles of docetaxel/capecitabine (75/1,000 mg/m2 b.i.d., days 1¿14) every 3 weeks. Results Fifty-five patients were enrolled with median age of 49, and 80% had hormone receptor-positive disease. The median tumor size was 2.5 cm, with a median of two axillary nodes involved. Seventy-five percent of the first 20 patients had grade 2/3 hand-foot syndrome (HFS). Dose reduction of capecitabine to 800 mg/m2 reduced the grade 2/3 HFS incidence to 31% in the remaining patients. No grade 4/5 toxicities were observed. All 20 patients treated preoperatively responded, with 5 (25%) pathologic complete responses and 3 additional pT0N1 tumors. At a median follow-up of 48 (range 28¿60) months, the event-free and overall survival rates are 91 and 98%, respectively. Conclusions Sequential treatment with dose-dense EC followed by docetaxel/capecitabine, using a lower capecitabine dose than that approved for MBC, has an acceptable toxicity profile and encouraging activity when used as neoadjuvant or adjuvant treatment of breast cancer.
Autores: Jurado, Matías; Alcázar, Juan Luis; Martínez-Monge, Rafael;
Revista: GYNECOLOGIC ONCOLOGY
ISSN 0090-8258  Vol. 116  Nº 1  2010  págs. 38 - 43
Objective (1) To determine the accuracy of a standard clinical and radiological assessment of resectability in patients with previously irradiated recurrent cervical cancer (PIRCC), and (2) to report the outcome and prognostic factors in this high-risk population treated with an exenterative procedure. Methods Forty-eight patients with centrally located (n=20, 41.7%) or lateralized (n=28, 58.3%) PIRCC treated with exenterative procedures were analyzed. All patients underwent standard assessment of resectability with pelvic exam and radiological studies. Patients with centrally located tumors were considered as resectable and lateralized tumors were deemed unresectable. Results Complete surgical resection with negative margins (R0) was achieved in 28.6% of the patients with lateral recurrences and in 65.0% of the patients with central recurrences (p<0.019). After a median follow-up of 114.6 months (3.0¿244.9 months), the 10-year local control rate for the whole group was 36.3%, 43.1% in the central PIRCC group and 31.5% in the lateral PIRCC group, respectively (p=0.290). Multivariate analysis showed that improved local control was significantly associated with the presence of negative margins (p=0.004). The 10-year distant failure rate was 69%, 56.6% in the central PIRCC group and 83.2% in the lateral PIRCC group (p=0.178), respectively. Multivariate analysis showed that the development of distant metastases was significantly correlated with the absence of local control (p=0.01). The 10-year disease-specific survival (DSS) for central and lateral PIRCC was 27.2% and 14.9%, respectively (p=0.239). Multivariate analysis showed that negative margins (p=0.001), local control (p=0.001) and distant control (p=0.006) were all significantly associated with improved DSS. Location of PIRCC (central vs. lateral) was irrelevant for DSS in completely resected (R0) patients. Overall morbidity rate was 65.0% and 73.3% for central and lateral PIRCC patients, respectively (p=0.528). Conclusion About one-third of the patients with lateral PIRCC classified as unresectable with non-surgical means may ultimately undergo complete (R0) resections and about one-third of the patients with centrally located PIRCC and judged as resectable will undergo non-curative (R1) resections. A curative (R0) resection significantly impacts local control rates, distant metastases-free rates and DSS.
Autores: Martínez-Monge, Rafael; Aramendía, José Manuel; et al.
Revista: INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER
ISSN 1048-891X  Vol. 20  Nº 1  2010  págs. 133 - 140
Objectives: This study was undertaken to determine the tolerability of a 7-week schedule of external beam radiation therapy, high-dose-rate brachytherapy, and weekly cisplatin and paclitaxel in patients with locally advanced carcinoma of the cervix. Methods: Twenty-nine patients with International Federation of Gynecology and Obstetrics stages IB2 to IVa cervical cancer were treated with 40 mg/m2 per week of intravenous (i.v.) cisplatin and 50 mg/m2 per week of i.v. paclitaxel combined with 45 Gy of pelvic external beam radiation therapy and 30 Gy of high-dose-rate brachytherapy. Results: Eleven patients (37.9%) were able to complete the 6 scheduled cycles of chemotherapy. The median number of weekly chemotherapy cycles administered was 5 (range, 2-7). Thirty-five (20.1%) of 174 cycles of chemotherapy were not given because of toxicity. The median dose intensity of cisplatin was 31 mg/m2 per week (95% confidence interval [CI], 25.2-36.8); that of paclitaxel was 44 mg/m2 per week (95% CI, 39.9-48.3). Twenty-two patients (78.6%) were able to complete the planned radiation course in less than 7 weeks. Median radiation treatment length was 45 days (95% CI, 43.4-46.6). After a median follow-up of 48 months, 7 patients (24.1%) experienced severe (Radiation Therapy Oncology Group grade 3 or higher) late toxicity. No fatal events were observed. Seven patients have failed, 1 locally and 6 at distant sites. The 8-year local/pelvic control rate was 95.7%, and the 8-year freedom from systemic failure rate was 76.1%. Eight-year actuarial disease-free survival and overall survival were 63.1% and 75.9%, respectively. Conclusions: This study demonstrated unacceptable toxicity of combining the stated doses of concurrent cisplatin and paclitaxel chemotherapy with definitive radiotherapy for patients with advanced cervical cancer. Additional phase I/II trials are recommended to clearly establish the recommended phase II dose for these drugs.