Grupos Investigadores

Líneas de Investigación

  • Patterns of Tumor Bed Homing in Circulating Tumor Cells.
  • Interaction of Tumor Bed Microenvironment on Radiation Resistance.
  • Identification of Tumor Bed Radiation Sensitive Time Zones.
  • Development of Tissue Microarrays in Adjuvant Radiation-Resistant Patients.
  • Development of Murine Models of Surgery and Adjuvant Irradiation.
  • Analysis of Gene Signatures of Resistance to Adjuvant Irradiation.

Palabras Clave

  • Tumor Bed
  • Surgery
  • Resistance
  • Radiation
  • Oncology
  • Brachytherapy
  • Adjuvant

Publicaciones Científicas desde 2018

  • Autores: Kishan, A. U. (Autor de correspondencia); Steigler, A.; Denham, J. W.; et al.
    Revista: JAMA ONCOLOGY
    ISSN 2374-2437 Vol.8 N° 3 2022 págs. e216871
    Y IMPORTANCE Radiotherapy combined with androgen deprivation therapy (ADT) is a standard of care for high-risk prostate cancer. However, the interplay between radiotherapy dose and the required minimum duration of ADT is uncertain. OBJECTIVE To determine the specific ADT duration threshold that provides a distant metastasis-free survival (DMFS) benefit in patients with high-risk prostate cancer receiving external beam radiotherapy (EBRT) or EBRT with a brachytherapy boost (EBRT+BT). DESIGN, SETTINGS, AND PARTICIPANTS This was a cohort study of 3 cohorts assembled from a multicenter retrospective study (2000-2013); a post hoc analysis of the Randomized Androgen Deprivation and Radiotherapy 03/04 (RADAR; 2003-2007) randomized clinical trial (RCT); and a cross-trial comparison of the RADAR vs the Deprivacion Androgenica y Radio Terapia (Androgen Deprivation and Radiation Therapy; DART) 01/05 RCT (2005-2010). In all, the study analyzed 1827 patients treated with EBRT and 1108 patients treated with EBRT+BT from the retrospective cohort; 181 treated with EBRT and 203 with EBRT+BT from RADAR; and 91 patients treated with EBRT from DART. The study was conducted from October 15, 2020, to July 1, 2021, and the data analyses, from January 5 to June 15, 2021. EXPOSURES High-dose EBRT or EBRT+BT for an ADT duration determined by patient-physician choice (retrospective) or by randomization (RCTs). MAIN OUTCOMES AND MEASURES The primary outcomewas DMFS; secondary outcomewas overall survival (OS). Natural cubic spline analysis identified minimum thresholds (months). RESULTS This cohort study of 3 studies totaling 3410 men (mean age [SD], 68 [62-74] years; race and ethnicity not collected) with high-risk prostate cancer found a significant interaction between the treatment type (EBRT vs EBRT+BT) and ADT duration (binned to <6, 6 to <18, and >= 18 months). Natural cubic spline analysis identified minimum duration thresholds of 26.3 months (95% CI, 25.4-36.0 months) for EBRT and 12 months (95% CI, 4.9-36.0 months) for EBRT+BT for optimal effect on DMFS. In RADAR, the prolongation of ADT for patients receiving only EBRT was not associated with significant improvements in DMFS (hazard ratio [HR], 1.01; 95% CI, 0.65-1.57); however, for patients receiving EBRT+BT, a longer duration was associated with improved DMFS (DMFS HR, 0.56; 95% CI, 0.36-0.87; P=.01). For patients receiving EBRT alone (DART), 28 months of ADT was associated with improved DMFS compared with 18 months (RADAR HR, 0.37; 95% CI, 0.17-0.80; P=.01). CONCLUSIONS AND RELEVANCE These cohort study findings suggest that the optimal minimum ADT duration for treatment with high-dose EBRT alone is more than 18 months; and for EBRT+BT, it is 18 months or possibly less. Additional studies are needed to determine more precise minimum durations.
  • Autores: Baptista Jardín, Peter Michael; Diaz Zufiaurre, Natalia; Garaycochea Mendoza del Solar, Octavio; et al.
    ISSN 2077-0383 Vol.11 N° 4 2022 págs. 990
    Transoral robotic surgery (TORS) for Obstructive Sleep Apnea (OSA) is a relatively young technique principally devised for managing apneas in the tongue base area. This study summarizes and presents our personal experience with TORS for OSA treatment, with the aim to provide information regarding its safety, efficacy, and postoperative complications. A retrospective study was conducted on patients undergoing TORS with lingual tonsillectomy through the Da Vinci robot. The effectiveness of the surgical procedure was assessed employing the Epworth Sleepiness Scale (ESS) and overnight polysomnography with the Apnea-Hypopnea Index (AHI). A total of 57 patients were included. Eighteen patients (31.6%) had undergone previous surgery. The mean time of TORS procedure was 30 min. Base of tongue (BOT) management was associated with other procedures in all patients: pharyngoplasty (94%), tonsillectomy (66%), and septoplasty (58%). At 6 months follow-up visit, there was a significant improvement in AHI values (from 38.62 +/- 20.36 to 24.33 +/- 19.68) and ESS values (from 14.25 +/- 3.97 to 8.25 +/- 3.3). The surgical success rate was achieved in 35.5% of patients. The most frequent major complication was bleeding, with the need for operative intervention in three cases (5.3%). The most common minor complications were mild dehydration and pain. TORS for OSA treatment appears to be an effective and safe procedure for adequately selected patients looking for an alternative therapy to CPAP.
  • Autores: Ruiz Fernández de Córdoba, Francisco de Borja; Moreno, H.; Valencia Leoz, Karmele; et al.
    ISSN 2159-8274 Vol.12 N° 5 2022 págs. 1356 - 1377
    Locoregional failure (LRF) in breast cancer patients post-surgery and post-irradiation (IR) is linked to a dismal prognosis. In a refined new model, we identified Enpp1 (Ectonucleotide pyrophosphatase /phosphodiesterase 1/CD203a) to be closely associated with LRF. Enpp1high circulating tumor cells (CTC) contribute to relapse by a self-seeding mechanism. This process requires the infiltration of PMN-MDSC and neutrophil extracellular traps (NET) formation. Genetic and pharmacological Enpp1 inhibition or NET blockade extend relapse-free survival. Furthermore, in combination with fractionated irradiation (FD), Enpp1 abrogation obliterates LRF. Mechanistically, Enpp1-generated adenosinergic metabolites enhance Haptoglobin (Hp) expression. This inflammatory mediator elicits myeloid invasiveness and promotes NET formation. Accordingly, a significant increase in ENPP1 and NET formation is detected in relapsed human breast cancer tumors. Moreover, high ENPP1 or HP levels are associated with poor prognosis. These findings unveil the ENPP1/HP axis as an unanticipated mechanism exploited by tumor cells linking inflammation to immune remodeling favoring local relapse.
  • Autores: Baptista Jardín, Peter Michael (Autor de correspondencia); Prieto Matos, Carlos (Autor de correspondencia); Alegre Esteban, Manuel; et al.
    ISSN 2231-3796 Vol.74 N° 2 2022 págs. 158 - 165
    Obstructive sleep apnea (OSA) is the most common respiratory disease in the developed world and is commonly treated with positive airway pressure therapy (PAP). Recently, hypoglossal nerve (HNS) has been introduced as alternative treatment for OSA patients with PAP intolerance. We report the initial results with HNS treatment from Spain. Patients with OSA and PAP intolerance were screened for HNS treatment with the Inspire (TM) system. After implantation and activation, efficacy was evaluated with polysomnography and indication-specific questionnaires. Adherence data was recorded from the stimulation system. 18 patients (51.83 +/- 11.64 years, 94% male, mean Body Mass Index 27.94 +/- 3.20) received an Inspire (TM) UAS system and were included for analysis. Mean procedure time was 202.83 +/- 64.87 min. and average hospital stay 26.67 +/- 7.54 h. Mean Apnea-Hypopnea-Index was reduced by 63.44% (p <= 0.0001), while daytime sleepiness improved to a mean ESS score of 6.60 +/- 1.25 (p <= 0.0001 Therapy response (AHI reduction > 50% and final AHI < 20), was reached in 64.70 and normalization of daytime sleepiness (final ESS score < 10) in 100% of patients. Therapy adherence was 6.32 +/- 1.71 h per night. HNS is a safe and leads to effective OSA control and symptom normalization in selected OSA patients with PAP intolerance. Stimulation therapy is well accepted, as demonstrated by high adherence. Implementation of HNS therapy into an OSA program in Spain is feasible with acceptable learning curve and moderate resource utilization.
  • Autores: Cruz-Morandé, S. (Autor de correspondencia); Dotor, J.; San Julián Aranguren, Miguel
    ISSN 1198-0052 Vol.29 N° 4 2022 págs. 2650 - 2661
    Radiation-induced fibrosis (RIF) is a severe side effect related with soft tissues sarcomas (STS) radiotherapy. RIF is a multicellular process initiated primarily by TGF-beta 1 that is increased in irradiated tissue, whose signaling leads to intracellular Smad2/3 phosphorylation and further induction of profibrotic target genes. P144 (Disetertide(C)) is a peptide inhibitor of TGF-beta 1 and is proposed as a candidate compound for reducing RIF associated wound healing problems and muscle fibrosis in STS. Methods: A treatment and control group of WNZ rabbits were employed to implement a brachytherapy animal model, through catheter implantation at the lower limb. Two days after implantation, animals received 20 Gy isodosis, intended to induce a high RIF grade. The treatment group received intravenous P144 administration following a brachytherapy session, repeated at 24-72 h post-radiation, while the control group received placebo. Four weeks later, affected muscular tissues underwent histological processing for collagen quantification and P-Smad2/3 immunohistochemistry through image analysis. Results: High isodosis Brachytherapy produced remarkable fibrosis in this experimental model. Results showed retained macro and microscopical morphology of muscle in the P144 treated group, with reduced extracellular matrix fibrosis, with a lower area of collagen deposition measured through Masson's trichrome staining. Intravenous P144 also induced a significant reduction in Smad2/3 phosphorylation levels compared with the placebo group. Conclusions: P144 administration clearly reduces RIF and opens a new potential co-treatment approach to reduce complications in soft tissue sarcoma (STS) radiotherapy. Further studies are required to establish whether the dosage and timing optimization of P144 administration, in different RIF phases, might entirely avoid fibrosis associated with STS brachytherapy.
  • Autores: Kovacs, G. (Autor de correspondencia); Martínez Monge, Rafael; Budrukkar, A.; et al.
    ISSN 0167-8140 Vol.155 2021 págs. e3 - e4
  • Autores: Philipson, R. G.; Romero, T.; Wong, J. K.; et al.
    ISSN 0302-2838 Vol.80 N° 2 2021 págs. 142 - 146
    The natural history of radiorecurrent high-risk prostate cancer (HRPCa) is not well-described. To better understand its clinical course, we evaluated rates of distant metastases (DM) and prostate cancer-specific mortality (PCSM) in a cohort of 978 men with radiorecurrent HRPCa who previously received either external beam radiation therapy (EBRT, n = 654, 67%) or EBRT + brachytherapy (EBRT + BT, n = 324, 33%) across 15 institutions from 1997 to 2015. In men who did not die, median follow-up after treatment was 8.9 yr and median follow-up after biochemical recurrence (BCR) was 3.7 yr. Local and systemic therapy salvage, respectively, were delivered to 21 and 390 men after EBRT, and eight and 103 men after EBRT + BT. Overall, 435 men developed DM, and 248 were detected within 1 yr of BCR. Measured from time of recurrence, 5-yr DM rates were 50% and 34% after EBRT and EBRT + BT, respectively. Measured from BCR, 5-yr PCSM rates were 27% and 29%, respectively. Interval to BCR was independently associated with DM (p < 0.001) and PCSM (p < 0.001). These data suggest that radiorecurrent HRPCa has an aggressive natural history and that DM is clinically evident early after BCR. These findings underscore the importance of further investigations into upfront risk assessment and prompt systemic evaluation upon recurrence in HRPCa. PATIENT SUMMARY: High-risk prostate cancer that recurs after radiation therapy is an aggressive disease entity and spreads to other parts of the body (metastases). Some 60% of metastases occur within 1 yr. Approximately 30% of these patients die from their prostate cancer.
  • Autores: Xiang, M. (Autor de correspondencia); Ma, T. M.; Savjani, R.; et al.
    ISSN 2574-3805 Vol.4 N° 12 2021
    IMPORTANCE Prostate-specific membrane antigen (PSMA) positron emission tomography/ computed tomography (PET/CT) can detect low-volume, nonlocalized (ie, regional or metastatic) prostate cancer that was occult on conventional imaging. However, the long-term clinical implications of PSMA PET/CT upstaging remain unclear. OBJECTIVES To evaluate the prognostic significance of a nomogram that models an individual's risk of nonlocalized upstaging on PSMA PET/CT and to compare its performance with existing riskstratification tools. DESIGN, SETTING, AND PARTICIPANTS This cohort study included patients diagnosed with highrisk or very high-risk prostate cancer (ie, prostate-specific antigen [PSA] level >20 ng/mL, Gleason score 8-10, and/or clinical stage T3-T4, without evidence of nodal or metastatic disease by conventional workup) from April 1995 to August 2018. This multinational study was conducted at 15 centers. Data were analyzed from December 2020 to March 2021. EXPOSURES Curative-intent radical prostatectomy (RP), external beam radiotherapy (EBRT), or EBRT plus brachytherapy (BT), with or without androgen deprivation therapy. MAIN OUTCOMES AND MEASURES PSMA upstage probability was calculated from a nomogram using the biopsy Gleason score, percentage positive systematic biopsy cores, clinical T category, and PSA level. Biochemical recurrence (BCR), distant metastasis (DM), prostate cancer-specific mortality (PCSM), and overall survival (OS) were analyzed using Fine-Gray and Cox regressions. Model performance was quantified with the concordance (C) index. RESULTS Of 5275 patients, the median (IQR) age was 66 (60-72) years; 2883 (55%) were treated with RP, 1669 (32%) with EBRT, and 723 (14%) with EBRT plus BT; median (IQR) PSA level was 10.5 (5.9-23.2) ng/mL; 3987 (76%) had Gleason grade 8 to 10 disease; and 750 (14%) had stage T3 to T4 disease. Median (IQR) follow-up was 5.1 (3.1-7.9) years; 1221 (23%) were followed up for at least 8 years. Overall, 1895 (36%) had BCR, 851 (16%) developed DM, and 242 (5%) died of prostate cancer. PSMA upstage probabilitywas significantly prognostic of all clinical end points, with 8-year C indices of 0.63 (95% CI, 0.61-0.65) for BCR, 0.69 (95% CI, 0.66-0.71) for DM, 0.71 (95% CI, 0.67-0.75) for PCSM, and 0.60 (95% CI, 0.57-0.62) for PCSM (P <.001). The PSMA nomogram outperformed existing risk-stratification tools, except for similar performance to Staging Collaboration for Cancer of the Prostate (STAR-CAP) for PCSM(eg, DM: PSMA, 0.69 [95% CI, 0.66-0.71] vs STAR-CAP, 0.65 [95% CI, 0.62-0.68]; P <.001; Memorial Sloan Kettering Cancer Center nomogram, 0.57 [95% CI, 0.54-0.60]; P <.001; Cancer of the Prostate Risk Assessment groups, 0.53 [95% CI, 0.51-0.56]; P <.001). Results were validated in secondary cohorts from the Surveillance, Epidemiology, and End Results database and the National Cancer Database. CONCLUSIONS AND RELEVANCE These findings suggest that PSMA upstage probability is associated with long-term, clinically meaningful end points. Furthermore, PSMA upstaging had superior risk discrimination compared with existing tools. Formerly occult, PSMA PET/CT-detectable nonlocalized disease may be the main driver of outcomes in high-risk patients.
  • Autores: Ramos García, Luis Isaac; Pérez-Azorín, J. F.; Anguiano, M.; et al.
    ISSN 0031-9155 Vol.66 N° 4 2021 págs. 045011
    Collection efficiency is an important quantity in dosimetry with ionization chambers. It can be calculated by solving a hyperbolic system of partial differential equations. This system can be solved only in few, simple, idealized geometries, but for more realistic designs an analytical resolution is no longer possible. In the present work a Monte Carlo scheme that could permit to calculate the collection efficiency for any ionization chamber geometry is proposed. This scheme has been tested against Boag's approach for three chambers with plane-parallel, cylindrical and spherical geometries, operated in the recombination regime. The results obtained in the full Monte Carlo simulation closely agree with the Boag's ones for the three ideal geometries considered. The largest relative difference, similar to 0.3%, has been found for the plane-parallel chamber in case of 50 V, the lowest potential difference investigated in this study. Results appear to be stable against changes in the chamber volume, the ion mobility and the recombination constant. The method proposed could be a useful tool to calculate collection efficiencies of ionization chambers, provided the electric field inside them is known.
  • Autores: Jablonska, Paola Anna; Cambeiro Vázquez, Felix Mauricio; Gimeno Morales, Marta; et al.
    ISSN 1699-048X Vol.23 N° 9 2021 págs. 1934-1941
    Background Pelvic recurrences from previously irradiated gynecological cancer lack solid evidence for recommendation on salvage. Methods A total of 58 patients were included in this clinical analysis. Salvage surgery was performed for locoregional relapse within previously irradiated pelvic area after initial surgery and adjuvant radiotherapy or radical external beam radiotherapy. The primary tumor diagnosis included cervical cancer (n = 47, 81%), uterine cancer (n = 4, 7%), and other types (n = 7, 12%). Thirty-three patients received adjuvant IOERT (1984-2000) at a median dose of 15 Gy (range 10-20 Gy) and 25 patients received adjuvant PHDRB (2001-2016) at a median dose of 32 Gy (range 24-40 Gy) in 6, 8, or 10 b.i.d. fractions. Results The median follow-up was 5.6 years (range 0.5-14.2 years). Twenty-nine (50.0%) patients had positive surgical margins. Grade >= 3 toxic events were recorded in 34 (58.6%) patients. The local control rate at 2 years was 51% and remained stable up to 14 years. Disease-free survival rates at 2, 5, and 10 years were 17.2, 15.5, and 15.5%, respectively. Overall survival rates at 2, 5, and 10 years were 58.1, 17.8, and 17.8%, respectively. Conclusions IOERT and PHDRB account for an effective salvage in oligorecurrent gynecological tumors. Patients with previous pelvic radiation suitable for salvage surgery and at risk of inadequate margins could benefit from adjuvant reirradiation in form of IOERT or PHDRB. However, the rate of severe grade >= 3 toxicity associated with the entire treatment program is relevant and needs to be closely counterbalanced against the expected therapeutic gain.
  • Autores: Payo Ollero, Jesús; Moreno-Figaredo, V.; Llombart Blanco, Rafael; et al.
    ISSN 1268-7731 Vol.27 N° 2 2021 págs. 143 - 149
    Background: The literature published about osteoid osteoma (OO) in the ankle-foot consists mainly on case reports. Methods: We performed a retrospective study in which we analyzed demographic parameters, pain characteristics, treatment options and functional outcomes measured using the AOFAS and the SEFAS scales. Results: We treated 17 patients with OO around the ankle-foot. Eighty-eight percent of patients had night pain that was relieved with NSAIDs. The bones most often affected were the talus and calcaneus. OO was diagnosed 21 months after the onset of symptoms. Mean follow-up was 17.3 years. The surgical techniques most used were curettage and curettage and bone grafting. There was a significant increase in AOFAS and SEFAS scores after surgery. Conclusions: Suspicion is the base of a prompt and a correct diagnosis of OO. The OO should be especially suspected in patients who present night pain that can be relieved with NSAIDs.
  • Autores: García-Consuegra, A.; Gimeno-Morales, M.; Cambeiro, M.; et al.
    ISSN 0167-8140 Vol.154 2021 págs. 128 - 134
    Background: The Head and Neck and Skin (HNS) Working group of the GEC-ESTRO acknowledges the lack of widely accepted Dose Volume Histogram (DVH) constraints in adjuvant head and neck brachytherapy and issues recommendations to minimize mandibular Osteoradionecrosis (ORN) and Soft Tissue Necrosis (STN). Methods: A total of 227 patients with the diagnosis of head and neck cancer treated with surgery and adjuvant HDR brachytherapy alone or combined with other treatment modalities during the period 2000-2018 were analyzed. Results: STN was observed in 28 out of 227 cases (12.3%) with an average time to appearance of 4.0 months. In previously unirradiated cases, there was a positive correlation between CTV size and STN (p = 0.017) and a trend towards significance between Total EQD2-DVH TV100 dose and STN (p = 0.06). The risk of STN in the absence of both factors (i.e, CTV < 15 cm3 and Total EQD2-DVH TV100 dose < 87 Gy) was 2%, with one factor present 15.7% and with both factors 66.7% (p = 0.001). ORN was observed in 13 out of 227 cases (5.7%) with an average time to appearance of 26.2 months. In unirradiated cases, ORN correlated with Total Physical Dose to Mandible2cm3 (p = 0.027). Patients receiving Total Physical Doses greater than 61 Gy had a 20-fold increased risk of ORN. Conclusions: In Unirradiated patients the panel recommends to avoid implantation of postoperative CTVs exceeding 15 cm3 at Total EQD2-DVH TV100 doses in excess of 87 Gy as well as to limit the irradiation of the Mandible2cm3 to 61 Gy. In previously irradiated patients the panel cannot make a recommendation based on the available results.
  • Autores: Lamo-Espinosa, J. (Autor de correspondencia); Gómez Alvarez, Jorge; Gatica, J.; et al.
    Revista: GERIATRICS
    ISSN 2308-3417 Vol.6 N° 1 2021 págs. 23
    Several studies have shown that double mobility (DM) cups reduce postoperative dislocations. Does the cemented dual mobility cup reduce dislocations in a specific cohort of elder patients with a high dislocation risk? Our hypothesis is that this implant is optimal for elder patients because it reduces early dislocation. We have retrospectively reviewed elder patients who underwent total hip arthroplasty (THA) with cemented double mobility cup between March 2009 and January 2018. The inclusion criteria were patients (>75 years) who were operated on for primary THA (osteoarthritis or necrosis) with a cemented dual mobility cup and a high-risk instability (at least two patient-dependent risk factors for instability). The exclusion criteria were revision surgeries or hip fracture. In all the cases, the same surgical approach was performed with a Watson Jones modified approach in supine position. We have collected demographic data, instability risk factors. Patients were classified using the Devane's score, Merle d'Aubigne score and the patient's likelihood of falling with the Morse Fall Scale. Surgical and follow-up complications were collected from their medical history. Sixty-eight arthroplasties (68 patients) were included in the study. The median age was 81.7 years (SD 6.4), and the American Society of Anesthesiologists (ASA) score showed a distribution: II 27.94%, III 63.24% and IV 8.82%. Devane's score was less than five in all of the cases. At least two patient-dependent risk factors for instability (87% had three or more) were present in each case. The median follow-up time was 49.04 months (SD 22.6). Complications observed were two cases of infection and one case of aseptic loosening at 15 months which required revision surgery. We did not observe any prosthetic dislocation. The cemented dual mobility cup is an excellent surgical option on primary total hip arthroplasties for elder patients with high-risk instability.
  • Autores: Kishan, A. U.; Wong, J. K.; Merrick, G. S.; et al.
    ISSN 0360-3016 Vol.111 N° 3 2021 págs. S76 - S77
  • Autores: Valle, L.; Xiang, M.; Kishan, A.; et al.
    ISSN 0277-3732 Vol.44 N° 10 2021 págs. S8 - S9
  • Autores: Ma, T. M.; Xiang, M.; Tilki, D.; et al.
    ISSN 0360-3016 Vol.111 N° 3 2021 págs. S51 - S52
  • Autores: Martínez Monge, Rafael
    ISSN 0167-8140 Vol.158 N° Supl. 1 2021 págs. S60 - S61
  • Autores: Schutgens, E. M. (Autor de correspondencia); Picci, P.; Baumhoer, D.; et al.
    ISSN 0021-9355 Vol.102 N° 19 2020 págs. 1703 - 1713
    Background: Osteofibrous dysplasia-like adamantinoma (OFD-AD) and classic adamantinoma (AD) are rare, neoplastic diseases with only limited data supporting current treatment protocols. We believe that our retrospective multicenter cohort study is the largest analysis of patients with adamantinoma to date. The primary purpose of this study was to describe the disease characteristics and evaluate the oncological outcomes. The secondary purpose was to identify risk factors for local recurrence after surgical treatment and propose treatment guidelines. Methods: Three hundred and eighteen confirmed cases of OFD-AD and AD for which primary treatment was carried out between 1985 and 2015 were submitted by 22 tertiary bone tumor centers. Proposed clinical risk factors for local recurrence such as size, type, and margins were analyzed using univariable and multivariate Cox regression analysis. Results: Of the 318 cases, 128 were OFD-AD and 190 were AD. The mean age at diagnosis was 17 years (median, 14.5 years) for OFD-AD and 32 years (median, 28 years) for AD; 53% of the patients were female. The mean tumor size in the OFD-AD and AD groups combined was 7.8 cm, measured histologically. Sixteen percent of the patients sustained a pathological fracture prior to treatment. Local recurrence was recorded in 22% of the OFD-AD cases and 24% of the AD cases. None of the recurrences in the OFD-AD group progressed to AD. Metastatic disease was found in 18% of the AD cases and fatal disease, in 11% of the AD cases. No metastatic or fatal disease was reported in the OFD-AD group. Multivariate Cox regression analysis demonstrated that uncontaminated resection margins (hazard ratio [HR] = 0.164, 95% confidence interval [CI] = 0.092 to 0.290, p < 0.001), pathological fracture (HR = 1.968, 95% CI = 1.076 to 3.600, p = 0.028), and sex (female versus male: HR = 0.535, 95% CI = 0.300 to 0.952, p = 0.033) impacted the risk of local recurrence. Conclusions: OFD-AD and AD are parts of a disease spectrum but should be regarded as different entities. Our results support reclassification of OFD-AD into the intermediate locally aggressive category, based on the local recurrence rate of 22% and absence of metastases. In our study, metastatic disease was restricted to the AD group (an 18% rate). We advocate wide resection with uncontaminated margins including bone and involved periosteum for both OFD-AD and AD.
  • Autores: Apinaniz, E. A.; Zafon, C. ; Rey, I. R.; et al.
    Revista: ENDOCRINE
    ISSN 1355-008X Vol.70 N° 3 2020 págs. 538 - 543
    Purpose The adequate extent of surgery for 1-4 cm low-risk papillary thyroid carcinoma (PTC) is unclear. Our objective was to analyze the applicability of the 2015 ATA Guidelines recommendation 35B (R35) for the management low-risk PTC. Methods This multicentre study included patients with low-risk PTC who had undergone total thyroidectomy (TT). Retrospectively we selected those who met the R35 criteria for the performance of a thyroid lobectomy (TL). The aim was to identify the proportion of low-risk PTC patients treated using TT who would have required reintervention had they had a TL in accordance with R35. Results We identified 497 patients (400 female; 80.5%). Median tumor size (mm): 21.2 (11-40). A tumor size >= 2 cm was found in 252 (50.7%). Most of them, 320 (64.4%), were in Stage I (AJCC 7th Edition). Following R35, 286 (57.5%) would have needed TT. Thus, they would have required a second surgery had they undergone TL. The indications for reintervention would have included lymph node involvement (35%), extrathyroidal extension (22.9%), aggressive subtype (8%), or vascular invasion (22.5%). No presurgical clinical data predict TT. Conclusions The appropriate management of low-risk PTC is unclear. Adherence to ATA R35 could lead to a huge increase in reinterventions when a TL is performed, though the need for them would be questionable. In our sample, more than half of patients (57.5%) who may undergo a TL for a seemingly low-risk PTC would have required a second operation to satisfy international guidelines, until better preoperative diagnostic tools become available.
  • Autores: Fernández González, Secundino; Garaycochea Mendoza del Solar, Octavio; Prieto Matos, Carlos (Autor de correspondencia); et al.
    ISSN 2468-5488 Vol.17 2020 págs. 100227
    We present a case report of a 25-year-old male patient who was complaining about a sensation and noise described as a ''sponge crunching'' in the right preauricular region and right ear that was more noticeable when inflating the cheeks. Under the clinical suspicion of a pneumoparotid case, a CT scan was performed. The study revealed the presence of air in the ductal system and within the gland. The patient was diagnosed with pneumoparotid and was treated conservatively. Herein, we review the literature and discussion the management of this uncommon condition. © 2020
  • Autores: Garaycochea Mendoza del Solar, Octavio (Autor de correspondencia); Alcalde Navarrete, Juan Manuel; del Rio, B.; et al.
    ISSN 0892-1997 Vol.33 N° 5 2019 págs. 812.e15 - 812.e18
    Objectives. Muscle tension dysphonia (MTD) is generally diagnosed through clinical history and physical examination. Several diagnostic or classification systems exist, such as those of Van Lawrence, Morrison-Rammage, and Koufman, that delineate MTD and distinguish subtypes on the basis of laryngoscopic features. The aim of this study is to determine which of the clinical features included in these classifications are most related to the aerodynamic profile of MTD. Study design. This is an analytic retrospective study. Material and methods. This study evaluates a series of 30 consecutive patients, all over 18 years old, who attended the voice clinic consult of our department and were diagnosed with MTD. All subjects underwent fiberoptic nasal endoscopy, acoustic voice assessment, and aerodynamic voice assessment. The study only includes patients with a pathological aerodynamic profile. Presence or absence of each laryngoscopic feature in the full range of features in the Van Lawrence, Morrison-Rammage, and Koufman classification systems was evaluated independently by three experts. Cohen's kappa coefficient was calculated to indicate the degree of concordance between the experts. The chi-squared test was used to determine the degree of association between clinical features and mean value of the subglottic pressure peak (mmH(2)O). Results. Clinical parameters that were found to have a statistically significant association (P<0.05) with an alteration in mean subglottic pressure peak were those related to anteroposterior and lateral compression of the larynx in Van Lawrence, Morrison-Rammage, and Koufman classification systems. Conclusions. While several studies have sought to clarify the laryngoscopic features of MTD, the current study is the first to evaluate these features in subjects who have been objectively diagnosed by means of aerodynamic voice assessment. The laryngoscopic features most strongly related to an aerodynamic profile of MTD were anteroposterior compression of the larynx, lateral compression of the larynx, and vestibular fold contribution to phonation.
  • Autores: Tagliaferri, L.; Pagliara, M. M.; Fionda, B. (Autor de correspondencia); et al.
    ISSN 1689-832X Vol.11 N° 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: Baptista Jardín, Peter Michael; Garaycochea Mendoza del Solar, Octavio; Prieto Matos, Carlos; et al.
    ISSN 1809-9777 Vol.23 N° 4 2019 págs. E422 - E426
    Introduction Chronic rhinosinusitis (CRS) is a highly prevalent pathology in our society. Due to the prevalence of this condition and to the persisting symptoms despite an appropriate medical treatment, surgical techniques are often required. Lately, minimal invasive techniques have been described, such as lacrimal diversion devices (LDDs). This technique offers a fast and convenient choice for delivery of sinus irrigation and topical medication. Objective We aimed to describe our experience with LDDs and evaluate the safety and effectiveness of the procedure in patients with moderate to severe CRS without nasal polyposis (CRSsNP) and persistent symptomatology despite medical therapy. Methods A total of 7 patients underwent bilateral lacrimal stents placement in the operating room. A retrospective observational study was conducted. The Sino-Nasal Outcome Test-20 (SNOT-20) survey was performed and the score obtained was compared before and 1month after the procedure. Results The LDDs were used for an average of 80 days. During the follow-up, only three patients had a mild complication with the device (granuloma in the punctum, obstruction, and early extrusion). The mean baseline SNOT-20 score dropped significantly ( p =0.015) from 25.85 to 11.57 (mean: - 14.29) 1month after the procedure. Conclusion According to our experience and results, the use of LDD is a novel, feasible, and less invasive technique to treat refractory CRS. It reduces the risk of mucosal stripping, provides short-term outcomes, and the surgical procedure does not require advanced training in endoscopic sinus surgery. Moreover, it can be performed in-office under local anesthesia or sedation.
  • Autores: Sala Elarre, Pablo; Oyaga-Iriarte, E. ; Yu, K. H.; et al.
    Revista: CANCERS
    ISSN 2072-6694 Vol.11 N° 5 2019 págs. 606
    Background: Although surgical resection is the only potentially curative treatment for pancreatic cancer (PC), long-term outcomes of this treatment remain poor. The aim of this study is to describe the feasibility of a neoadjuvant treatment with induction polychemotherapy (IPCT) followed by chemoradiation (CRT) in resectable PC, and to develop a machine-learning algorithm to predict risk of relapse. Methods: Forty patients with resectable PC treated in our institution with IPCT (based on mFOLFOXIRI, GEMOX or GEMOXEL) followed by CRT (50 Gy and concurrent Capecitabine) were retrospectively analyzed. Additionally, clinical, pathological and analytical data were collected in order to perform a 2-year relapse-risk predictive population model using machine-learning techniques. Results: A RO resection was achieved in 90% of the patients. After a median follow-up of 33.5 months, median progression-free survival (PFS) was 18 months and median overall survival (OS) was 39 months. The 3 and 5-year actuarial PFS were 43.8% and 32.3%, respectively. The 3 and 5-year actuarial OS were 51.5% and 34.8%, respectively. Forty-percent of grade 3-4 IPCT toxicity, and 29.7% of grade 3 CRT toxicity were reported. Considering the use of granulocyte colony-stimulating factors, the number of resected lymph nodes, the presence of perineural invasion and the surgical margin status, a logistic regression algorithm predicted the individual 2-year relapse-risk with an accuracy of 0.71 (95% confidence interval [CI] 0.56-0.84, p = 0.005). The model-predicted outcome matched 64% of the observed outcomes in an external dataset. Conclusion: An intensified multimodal neoadjuvant approach (IPCT + CRT) in resectable PC is feasible, with an encouraging long-term outcome. Machine-learning algorithms might be a useful tool to predict individual risk of relapse. A small sample size and therapy heterogeneity remain as potential limitations.
  • Autores: Gimeno Morales, Marta; San Julián Aranguren, Miguel; Cambeiro Vázquez, Felix Mauricio; et al.
    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: Tagliaferri, L. ; Pagliara, M. M.; Fionda, B.; et al.
    ISSN 0167-8140 Vol.133 2019 págs. S581 - S581
  • Autores: Tagliaferri, L.; Budrukkar, A.; Lenkowicz, J. (Autor de correspondencia); et al.
    ISSN 1689-832X Vol.10 N° 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.

Proyectos desde 2018

    Código de expediente: 0011-1411-2022-000066
    Investigador principal: ANA PATIÑO GARCIA.
    Financiador: GOBIERNO DE NAVARRA
    Convocatoria: 2022 GN PROYECTOS ESTRATEGICOS DE I+D 2022-2025
    Fecha de inicio: 01-06-2022
    Fecha fin: 31-12-2024
    Importe concedido: 536.739,00 €
    Fondos FEDER: NO
  • Título: Disección de los mecanismos de las recidivas locales post-resección y post braquiterapia.
    Código de expediente: PI19/01884
    Investigador principal: RAFAEL MARTINEZ MONGE.
    Convocatoria: 2019 AES Proyectos de investigación
    Fecha de inicio: 01-01-2020
    Fecha fin: 31-12-2022
    Importe concedido: 93.170,00 €
    Fondos FEDER: SI
  • Título: IDP4SCLC Optimización de fármacos en nuevas dianas terapéuticas IDP (ASCL1) para el tratamiento de cáncer microcítico de pulmón
    Código de expediente: RTC-2017-6585-1
    Investigador principal: FERNANDO LECANDA CORDERO.
    Fecha de inicio: 01-01-2018
    Fecha fin: 31-12-2020
    Importe concedido: 134.923,52 €
    Fondos FEDER: SI
  • Título: Disección de los mecanismos de las recidivas locales post-resección y post-braquiterapia
    Código de expediente: Pi16/01847
    Investigador principal: RAFAEL MARTINEZ MONGE.
    Fecha de inicio: 01-01-2017
    Fecha fin: 30-06-2020
    Importe concedido: 80.465,00 €
    Fondos FEDER: SI
    Código de expediente: SAF2015-71606-R
    Investigador principal: FERNANDO LECANDA CORDERO.
    Convocatoria: 2015 - PROYECTOS DE I+D RETOS
    Fecha de inicio: 01-01-2016
    Fecha fin: 31-12-2018
    Importe concedido: 151.840,00 €
    Fondos FEDER: SI
  • Título: Rediseño del impacto de la radioterapia en el cáncer de mama con nuevos actores: Papel de las células tumorales circulantes (CTC) y nuevas vulnerabilidades de base mecanística.
    Investigador principal: RAFAEL MARTINEZ MONGE
    Convocatoria: 2021 AECC Proyectos Estratégicos
    Fecha de inicio: 01-10-2021
    Fecha fin: 30-09-2024
    Importe concedido: 150.000,00 €
  • Título: Combinatorial Immunotherapies in a novel GEMM platform for sarcomas: Identification of Therapeutic Efficacy and anticipating Adverse Events
    Investigador principal: FERNANDO LECANDA CORDERO
    Convocatoria: FIMA 2020 Estratégicos AECC
    Fecha de inicio: 01-11-2020
    Fecha fin: 31-10-2023
    Importe concedido: 300.000,00 €
  • Título: BermejoE-ElkinLG_PIUNA2020_ Inteligencia emociona
    Convocatoria: 2020 Convocatoria PIUNA, 2021 Convocatoria PIUNA
    Fecha de inicio: 01-09-2020
    Fecha fin: 31-08-2022
    Importe concedido: 19.755,00 €
  • Título: Potenciación antitumoral y antimetastásica mediante la modulación del sistema de complemento
    Investigador principal: RUBEN PIO OSES
    Convocatoria: Proyectos AECC 2017
    Fecha de inicio: 01-12-2017
    Fecha fin: 31-03-2021
    Importe concedido: 300.000,00 €