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Introduction A rapid deploy of unexpected early impact of the COVID pandemic in Spain was described in 2020. Oncology practice was revised to facilitate decision-making regarding multimodal therapy for prevalent cancer types amenable to multidisciplinary treatment in which the radiotherapy component searched more efficient options in the setting of the COVID-19 pandemic, minimizing the risks to patients whilst aiming to guarantee cancer outcomes. Methods A novel Proton Beam Therapy (PBT), Unit activity was analyzed in the period of March 2020 to March 2021. Institutional urgent, strict and mandatory clinical care standards for early diagnosis and treatment of COVID-19 infection were stablished in the hospital following national health-authorities’ recommendations. The temporary trends of patients care and research projects proposals were registered. Results 3 out of 14 members of the professional staff involved in the PBR intra-hospital process had a positive test for COVID infection. Also, 4 out of 100 patients had positive tests before initiating PBT, and 7 out of 100 developed positive tests along the weekly mandatory special checkup performed during PBT to all patients. An update of clinical performance at the PBT Unit at CUN Madrid in the initial 500 patients treated with PBT in the period from March 2020 to November 2022 registers a distribution of 131 (26%) pediatric patients, 63 (12%) head and neck cancer and central nervous system neoplasms and 123 (24%) re-irradiation indications. In November 2022, the activity reached a plateau in terms of patients under treatment and the impact of COVID pandemic became sporadic and controlled by minor medical actions. At present, the clinical data are consistent with an academic practice prospectively (NCT05151952). Research projects and scientific production was adapted to the pandemic evolution and its influence upon professional time availability. Seven research projects based in public funding were activated in this period and preliminary data on molecular imaging guided proton therapy in brain tumors and post-irradiation patterns of blood biomarkers are reported. Conclusions Hospital-based PBT in European academic institutions was impacted by COVID-19 pandemic, although clinical and research activities were developed and sustained. In the post-pandemic era, the benefits of online learning will shape the future of proton therapy education.

Experimental treatments (A) and tumor size follow-up until sacrifice (B) of tumors used to prepare cell suspensions for figures 3, 5 and supplementary figure 4. (C) Shows individual tumor lesion weights used to calculate lymphocytes/gram densities.

FACS analyses on cell suspensions (n=4) derived from non-irradiated MC38-derived tumors

Myeloid cell content (density per gram) in cell suspension from non-irradiated tumors as those in figure 5. Macrophages are defined as CD45+ CD11b+ F4/80+; Dendritic cells (DC) as CD45+CD11b+CD11c+; myeloid-derived suppressor cells (MDSC) as CD45+CD11b+Ly6C+ or CD45+CD11b+Ly6G+ to estimate monocytic (M-MDSC) and granulocytic (G-MDSC) subtypes.

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 TGFβ expression or activation increases in irradiated tissues, we tested whether TGFβ blockade may further enhance abscopal effects in conjunction with the anti–PD-1 plus anti-CD137 mAb combination. Indeed, TGFβ blockade with 1D11, a TGFβ-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 TGFβ in the nonirradiated contralateral tumor that showed smad2/3 phosphorylation increases in infiltrating CD8 T cells. In conclusion, radiotherapy-induced TGFβ hampers abscopal efficacy even upon combination with a potent immunotherapy regimen. Therefore, TGFβ blockade in combination with radioimmunotherapy results in greater efficacy.

Assessment of spontaneous lung metastases of 4T1 tumors in the indicated treatment groups corresponding to mice treated as in figure 2A. Metastases were detected and quantitated -number of lesions in the surface of the lung counted upon inspection under a magnification lens (left) and by real time RT-PCR for tumor specific gp70 RNA (right)-.

The optimal duration of androgen deprivation combined with high-dose radiotherapy in prostate cancer remains controversial. The DART 01/05 trial was designed to determine whether long-term androgen deprivation is superior to short-term androgen deprivation when combined with high-dose radiotherapy. The 5-year results showed that 2 years of adjuvant androgen deprivation combined with high-dose radiotherapy significantly improved biochemical control, metastasis, and overall survival, especially in patients with high-risk disease. In this report, we present the 10-year final results of the trial.This open-label, phase 3, randomised, controlled trial was done in ten hospitals in Spain. The eligibility criteria included patients aged 18 years or older with histologically confirmed T1c to T3, N0, and M0 adenocarcinoma of the prostate, according to the 2002 classification of the American Joint Committee on Cancer, with intermediate-risk and high-risk factors, prostate-specific antigen (PSA) less than 100 ng/mL, and a Karnofsky performance score of at least 70%. Patients were randomly assigned (1:1) to receive 4 months of neoadjuvant and concomitant short-term androgen deprivation (STAD) plus high-dose radiotherapy (minimum dose 76 Gy; median dose 78 Gy) or to receive the same treatment followed by 24 months of adjuvant long-term androgen deprivation (LTAD), via a randomisation scheduled generated by Statistical Analysis Software programme (version 9.1) and an interactive web response system. Patients assigned to the STAD group received 4 months of neoadjuvant and concomitant androgen deprivation (oral flutamide 750 mg per day or oral bicalutamide 50 mg per day) with subcutaneous goserelin (2 months before and 2 months combined with high-dose radiotherapy). Anti-androgen therapy was added during the first 2 months of treatment. Patients assigned to LTAD continued with goserelin every 3 months for another 24 months. The primary endpoint was biochemical disease-free survival at 5 years. For this 10-year study we analysed overall survival, metastasis-free survival, biochemical disease-free survival, and cause-specific survival. Analysis was by intention to treat. This trial is closed and is registered at ClinicalTrials.gov (NCT02175212) and in the EU Clinical Trials Register (EudraCT 2005-000417-36).Between Nov 7, 2005, and Dec 20, 2010, 355 patients were enrolled. One patient in the STAD group withdrew from the trial, hence 354 participants were randomly assigned to STAD (n=177) or LTAD (n=177). The median follow-up was 119·4 months (IQR 100·6-124·3). The 10-year biochemical disease-free survival for LTAD was 70·2% (95% CI 63·1-77·3) and for STAD was 62·3% (54·9-69·7; hazard ratio [HR] 0·84; 95% CI 0·50-1·43; p=0·52). At 10 years, overall survival was 78·4% (72·1-84·8) for LTAD and 73·3% (66·6-80·0) for STAD (HR 0·84; 95% CI 0·55-1·27; p=0·40), and metastasis-free survival was 76·0% (69·4-82·7) for LTAD and 70·9% (64·0-77·8) for STAD (HR 0·90; 95% CI, 0·37-2·19; p=0·81). For the subgroup of high-risk patients, the 10-year biochemical disease-free survival was 67·2% (57·2-77·2) for LTAD and 53·7% (43·3-64·1) for STAD (HR 0·90; 95% CI 0·49-1·64; p=0·73), the 10-year overall survival was 78·5% (69·6-87·3) for LTAD and 67·0% (57·3-76·7) for STAD (HR 0·58; 95% CI 0·33-1·01; p=0·054), and the 10-year metastasis-free survival was 76·6% (95% CI 67·6-85·6) for LTAD and 65·0% (55·1-74·8) for STAD (HR 0·89; 95% CI 0·33-2·43; p=0·82). Only 11 (3%) of 354 patients died from prostate cancer, all of them in the high-risk subgroup (five in the LTAD group and six in the STAD group). 76 (21%) patients died from other causes (mainly second malignancies in 31 [9%] and cardiovascular disease in 21 [6%]). No treatment-related deaths were observed.After an extended 10-year follow-up, we were unable to support the significant benefit of LTAD reported at 5 years. However, the magnitude of the benefit was clinically relevant in high-risk patients. Intermediate-risk patients treated with high-dose radiotherapy do not benefit from LTAD. A biological characterisation with the inclusion of genomic testing is needed in the decision-making process.Grupo de Investigación en Oncología Radioterápica and Sociedad Española de Oncología Radioterápica, the National Health Investigation Fund, and AstraZeneca.

Background Local cancer therapy by combining real-time surgical exploration and resection with delivery of a single dose of high-energy electron irradiation entails a very precise and effective local therapeutic approach. Integrating the benefits from minimally invasive surgical techniques with the very precise delivery of intraoperative electron irradiation results in an efficient combined modality therapy. Methods Patients with locally advanced disease, who are candidates for laparoscopic and/or thoracoscopic surgery, received an integrated multimodal management. Preoperative treatment included induction chemotherapy and/or chemoradiation, followed by laparoscopic surgery and intraoperative electron radiation therapy. Results In a period of 5 consecutive years, 125 rectal cancer patients were treated, of which 35% underwent a laparoscopic approach. We found no differences in cancer outcomes and tolerance between the open and laparoscopic groups. Two esophageal cancer patients were treated with IOeRT during thoracoscopic resection, with the resection specimens showing intense downstaging effects. Two oligo-recurrent prostatic cancer patients (isolated nodal progression) had a robotic-assisted surgical resection and post-lymphadenectomy electron boost on the vascular and lateral pelvic wall. Conclusions Minimally invasive and robotic-assisted surgery is feasible to combine with intraoperative electron radiation therapy and offers a new model explored with electron-FLASH beams.

The optimal prognostic value of testosterone following androgen deprivation therapy (ADT) is controversial. We studied the effect of serum testosterone levels on clinical outcome in localized prostate cancer (PCa) treated with ADT and high-dose radiotherapy (HRT).The DART01/05 trial randomized 355 men with intermediate and high-risk PCa to 4 months of ADT plus HRT (STADT, N = 178) or the same treatment followed by 24 months of ADT (LTADT, N = 177). This study included patients treated with LTADT who had at least 3 determinations of testosterone during ADT (N = 154). Patients were stratified into 3 subgroups by testosterone level: minimum20 ng/dL; median 20-49 ng/dL; and maximum ≥50 ng/dL. Kaplan-Meyer and Cox regression analysis were used for overall survival (OS) and FineGray regression model for metastasis free survival (MFS), biochemical disease-free survival (bDFS) and time to TT recovery.There were no statistically significant differences in 10-year bDFS, MFS, or OS between the20 ng/mL and 20-49 ng/dL subgroups. Multivariate analysis showed that a median testosterone ≥50 ng/dL was significantly associated with a decrease in bDFS (HR: 6.58, 95%CI 1.28-33.76, p = 0.03). Time to testosterone recovery after ADT did not correlate with bDFS, MFS, or OS and was not significantly associated with any of the testosterone subgroups.Our results do not support the concept that additional serum testosterone suppression below 20 ng/dL is associated with better outcomes than 20-49 ng/dL. Time to testosterone recovery after ADT and HRT did not impact clinical failure.

Introduction: The clinical practice and outcome results of intraoperative electron radiation therapy (IOeRT) in cancer patients have been extensively reported over 4 decades. Electron beams can be delivered in the promising FLASH dose rate. Methods and Materials: Several cancer models were approached by two alternative radiobiological strategies to optimize local cancer control: boost versus exclusive IOeRT. Clinical outcomes are revisited via a bibliometric search performed for the elaboration of ESTRO/ACROP IORT guidelines. Results: In the period 1982 to 2020, a total of 19,148 patients were registered in 116 publications concerning soft tissue sarcomas (9% of patients), unresected and borderline-resected pancreatic cancer (22%), locally recurrent and locally advanced rectal cancer (22%), and breast cancer (45%). Clinical outcomes following IOeRT doses in the range of 10 to 25 Gy (with or without external beam fractionated radiation therapy) show a wide range of local control from 40 to 100% depending upon cancer site, histology, stage, and treatment intensity. Constraints for normal tissue tolerance are important to maintain tumor control combined with acceptable levels of side effects. Conclusions: IOeRT represents an evidence-based approach for several tumor types. A specific risk analysis for local recurrences supports the identification of cancer models that are candidates for FLASH studies. This research has been funded in part by grants from: Instituto de Salud Carlos III, Asociación Española Contra el Cáncer, ERAPERMED PerPlanRT, AC20/00103, AC20/00102, 2020-110-1). Ministry of Science, Innovation and Education PID 2019-104558RB-100, Grant PID2019-110369RB-I00 (RADHOR), funded by MCIN/AEI/10.13039/501100011033

Purpose To evaluate our institutional experience of minimally invasive tumor bed implantation (MITBI) during breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS) to deliver peri-operative high-dose-rate brachytherapy (PHDRBT) as accelerated minimal breast irradiation (AMBI) or anticipated boost (A-PHDRBT-boost). Material and methods Patients older than 40, with clinical and radiological unifocal DCIS < 3 cm were considered potential candidates for accelerated partial breast irradiation (APBI) and were implanted during BCS using MITBI-technique. Patients who in final pathology reports showed free margins and no other microscopic tumor foci, received AMBI with PHDRBT (3.4 Gy BID in 5 days). Patients with adverse features received A-PHDRBT-boost with post-operative external beam radiotherapy (EBRT). Results Forty-one patients were implanted, and 36 were treated and analyzed. According to final pathology, 24 (67%) patients were suitable for AMBI and 12 (33%) were qualified for A-PHDRBT-boost. Reoperation rate for those with clear margins was 16.6% (6/36); this rate increased to 33% (4/12) for G3 histology, and 66% (4/6) were rescued using AMBI. Early complications were documented in 5 patients (14%). With a median follow-up of 97 (range, 42-138) months, 5-year rates of local, elsewhere, locoregional, and distant control were all 97.2%. 5-year ipsilateral breast tumor recurrence rates (IBTR) were 5.6% (2/36), 8.3% (2/24) for AMBI, and 0% (0/12) for A-PHDRBT-boost patients. Both instances of IBTR were confirmed G3 tumors in pre-operative biopsies; no IBTR was documented in G1-2 tumors. Cosmetic outcomes were excellent/good in 96% of AMBI vs. 67% in A-PHDRBT-boost (p = 0.034). Conclusions The MITBI-PHDRBT program allows selection of patients with excellent prognoses (G1-2 DCIS with negative margins and no multifocality), for whom AMBI could be a good alternative with low recurrence rate, decrease of unnecessary radiation, treatment logistics improvement, and over-treatment reduction. Patients whose pre-operative biopsy showed G3 tumor, presents with inferior local control and more risk of reoperation due to positive margins.

Gracias a los grandes avances de la tecnología, los últimos diez años, la impresión en tres dimensiones (3D) se ha convertido en una herramienta accesible, útil e innovadora para distintas áreas de la medicina. Entre ellas; planificación quirúrgica, creación de implantes y prótesis, educación médica e incluso comunicación médico-paciente.Con respecto a planificación quirúrgica, la impresión 3D cobra especial relevancia en cirugías de alta complejidad. En el caso del trasplante hepático con donante vivo, donde es prioritario garantizar la máxima seguridad para el donante, al mismo tiempo que la mejor calidad del injerto para el receptor, la planificación quirúrgica es mandatoria. En este aspecto, la impresión 3D de un modelo de hígado, anatómicamente comparable al del donante, entrega al cirujano la posibilidad de obtener una imagen más clara, directa y tangible, desde cualquier ángulo del órgano, que una imagen virtual tradicional. De esta forma, el cirujano tiene a su alcance una herramienta adicional para plantear el mejor abordaje quirúrgico, anticipar variaciones anatómicas e incluso, cuando el material de impresión lo permite, practicar el procedimiento.En Clínica Las Condes, el centro de trasplante junto al Centro de Innovación, trabajaron en conjunto en la impresión 3D de dos modelos de hígado, utilizados para la planificación quirúrgica de los primeros dos trasplantes hepáticos con donante vivo adulto-adulto realizados en Latinoamérica, donde la hepatectomia del donante se realizó de manera totalmente laparoscópica. El objetivo de este trabajo es describir el proceso de impresión 3D y analizar las dificultades y beneficios del proceso y sus resultados. Palabras clave: Impresión 3D, planificación quirúrgica, donante vivo, trasplante de hígado.

Introducción: La segmentectomía lateral izquierda es el procedimiento más empleado para la cirugía del donante en trasplante hepático con donante vivo adulto-pediátrico (THDVA-P), y ha demostrado ser seguro y reproducible. Sin embargo, la información aún es escasa respecto al abordaje laparoscópico. El objetivo de este artículo es dar a conocer los resultados postoperatorios de la segmentectomía lateral izquierda laparoscópica (SLI-L) para THDVA-P. Materiales y método: Realizamos un estudio retrospectivo, observacional, de un solo centro, Hospital del Salvador; con vasta experiencia en trasplante hepático y en resecciones hepáticas laparoscópicas. Se ofreció realizar el procedimiento de SLI-L para la cirugía del donante vivo. Se describe la técnica quirúrgica y los resultados postoperatorios de los donantes. Resultados: Entre abril 2015 y enero 2021, 36 pacientes, 25 de ellos hombres, fueron sometidos a SLI-L. El 86% eran madre o padre del receptor, con una mediana de 30 años (19-45). Mediana de tiempo operatorio de 360 min (240-480). Hubo conversión en un caso debido a sangrado venoso de difícil manejo y en dos oportunidades se utilizó técnica mano asistida por la misma causa. Morbilidad Clavien-Dindo III en un paciente debido a fuga biliar precoz, manejada con colangiopancreatografía retrógrada endoscópica exitosamente. La mediana de hospitalización fue de 4 días (3-12) y no hubo mortalidad. Conclusión: La SLI-L ha evolucionado, desde un procedimiento innovador hasta convertirse en el actual procedimiento estándar para THDVA-P. Los buenos resultados en términos de morbimortalidad sugieren que podría ser una técnica segura y reproducible en contextos similares al del centro.

Purpose To describe guidelines for the use of intraoperative radiation therapy (IORT) in the treatment of soft-tissue sarcomas (STS). Methods A panel of experts in the field performed a systematic literature review, supplemented their clinical experience and developed recommendations for the use of IORT in the treatment of STS. Results Based on the evidence from the systematic literature review and the clinical experience of the panel members, recommendations regarding patient selection, incorporation into multimodal treatment concepts and the IORT procedure itself are made. The rationale for IORT in extremity and retroperitoneal STS is summarized and results of the major series in terms of patient and treatment characteristics, oncological outcome and toxicity are presented. We define surgical factors, volumes for irradiation, technical requirements, dose prescription, recording and reporting, treatment delivery and care during the course of IORT covering the main IORT techniques used for the treatment of STS. In extremity STS, evidence originates from a few small prospective and mainly from retrospective single centre studies. Based on those reports, IORT containing-approaches result in very high local control rates with low rates of acute and late toxicity. In retroperitoneal sarcomas, evidence is derived from one prospective randomized trial, a few prospective and a large number of retrospective studies. The randomized trial compared IORT combined with moderate doses of postoperative external-beam radiation therapy (EBRT) to high-dose postoperative EBRT alone after gross total resection, clearly favouring the IORT-containing approach. These results have been confirmed by the prospective and retrospective studies, which similarly showed high local control rates with acceptable toxicity, mainly favouring combinations of preoperative EBRT and IORT. Conclusions IORT-containing approaches result in high rates of local control with low to acceptable toxicity rates. Based on the available evidence, we made recommendations for the use of IORT in STS. Clinicians and researchers are encouraged to use these guidelines in clinical routine as well as in the design of future trials.

Highlights • Radiation dose escalation with intraoperative electron beam is feasible in the pelvic region. • IORT is an option to minimize radiation toxicity to ureters, bladder, prostate, vagina, uterus, small bowel. • Preoperative therapy, including a re-irradiation component, allows selection of patient candidates for local treatment intensification. • R0 status IOERT results supports individualized recommendation in expert clinical practice. • Survival contribution is described in oligo-recurrent patients amenable for radical rescue surgery without previous pelvic radiotherapy., Multimodal strategies have been implemented for locally recurrent rectal cancer scheduled for complete surgical resection. Irradiation and systemic therapy have been added to improve the oncological outcome, as surgery alone was associated with a poor prognosis. Intraoperative irradiation (IORT) is a component of irradiation intensification. Long-term cancer control and a higher survival rate were consistently reported in patients who had IORT as a component of their multidisciplinary treatment. The experience reported by expert IORT groups is reviewed and recommendations to guide clinical practice are explained in detail.

El trasplante hepático con donante vivo (THDV) es un procedimiento complejo y desafiante para el cirujano, ya que exige garantizar tanto la máxima seguridad para el donante, así como también, la mejor calidad del injerto para el receptor. Debido a lo anterior, la implementación de la cirugía mini-invasiva ha sido lenta en esta área. Sin embargo, los ultimos 10 años, gracias a los avances que ha experimentado la cirugía hepática laparoscópica, ha aumentado el interés de algunos grupos altamente especializados por incorporar la cirugía mini-invasiva a la cirugía del donante, principalmente en trasplante hepático donante vivo adulto-pediatrico (THDVA-P). Los favorables resultados obtenidos en esta área, incluso han llevado a los expertos en el tema, a categorizar el abordaje laparoscópico para la cirugía del donante como el procedimiento estandar en THDVA-P. Contrario a lo anterior, la implementación de la laparoscopía para trasplante hepático donante vivo adulto-adulto (THDVA-A), es más compleja y requiere en su mayoría, una hepatectomía de lóbulo derecho o izquierdo para cumplir con las necesidades volumétricas del receptor. Esta cirugía es de mayor dificultad y riesgo para el donante, por lo que su indicación por vía mini-invasiva está limitada a centros de alto volumen y preparación, tanto en laparoscopía, como en trasplante hepático. En este trabajo, se busca dar a conocer la técnica quirúrgica y nuestra experiencia inicial con la primera hepatectomía derecha totalmente laparoscópica (HDTL) para THDVA-A realizada en Chile. Palabras clave: Trasplante hepático; Donante vivo; Hepatectomía derecha; Laparoscopía

BACKGROUND AND PURPOSE: Major differences exist among proton therapy (PT) centres regarding PT delivery in adult cancer patient. To obtain insight into current practice in Europe, we performed a survey among European PT centres. MATERIALS AND METHODS: We designed electronic questionnaires for eight tumour sites, focusing on four main topics: 1) indications and patient selection methods; 2) reimbursement; 3) on-going or planned studies, 4) annual number of patients treated with PT. RESULTS: Of 22 centres, 19 (86%) responded. In total, 4233 adult patients are currently treated across Europe annually, of which 46% consists of patients with central nervous system tumours (CNS), 15% head and neck cancer (HNC), 15% prostate, 9% breast, 5% lung, 5% gastrointestinal, 4% lymphoma, 0.3% gynaecological cancers. CNS are treated in all participating centres (n = 19) using PT, HNC in 16 centres, lymphoma in 10 centres, gastrointestinal in 10 centres, breast in 7 centres, prostate in 6 centres, lung in 6 centres, and gynaecological cancers in 3 centres. Reimbursement is provided by national health care systems for the majority of commonly treated tumour sites. Approximately 74% of centres enrol patients for prospective data registration programs. Phase II-III trials are less frequent, due to reimbursement and funding problems. Reasons for not treating certain tumour types with PT are lack of evidence (30%), reimbursement issues (29%) and/or technical limitations (20%). CONCLUSION: Across European PT centres, CNS tumours and HNC are the most frequently treated tumour types. Most centres use indication protocols. Lack of evidence for PT and reimbursement issues are the most reported reasons for not treating specific tumour types with PT. ispartof: RADIOTHERAPY AND ONCOLOGY vol:167 pages:7-13 ispartof: location:Ireland status: published

Introduction/Background* The primary objective of this project was to identify the independent clinical-pathological variables associated with the death after relapse in patients with stage IB1 cervical cancer who underwent radical hysterectomy. The secondary objective was to analysis survival post-relapse in these patients. Methodology Based on the SUCCOR study’s database . Patients were eligible if they had a relapse (local, distant or both) after underwent a radical hysterectomy in a European Institution for stage IB1 cervical cancer (FIGO 2009), from January 1st, 2013 to December 31st, 2014. To identify variables independently associated with death in these patients, we calculated the odds ratio using simple logistic regression models and subsequently a multivariate backward stepwise procedure. For the secondary end point we calculated Kaplan-Meyer and Cox regression using the results of the univariate and multivariate analysis . Result(s)* A total of 126 patients were selected, women who died were more likely to have tumors >2cm on the clinical examination (OR, 3.50; 95% CI, 1.35- 9.08) and to have a stromal infiltration higher than 1/3 (OR, 6.30; 95% CI, 1.31- 30.00). In contrast, the histologic subtype of adenocarcinoma and treatment with Bevacizumab were found as protective factors against death (OR, 0.32; 95% CI, 0.11- 0.95) and (OR, 0.23; 95% CI, 0.05- 0.99) respectively. The mean time of relapse of our population was 22.94 months and the median of survival after relapse was 18.5 months. Patients with tumors > 2cm on the clinical examination had a 3.39-times higher hazard of death after relapse (HR, 3.39; 95% CI, 1.52- 7.53) and the distant/both location of relapse had 2.23- times higher hazard of death (HR, 2.23; 95% CI, 1.14- 4.36) The 2-years survival rates after relapse were 76% for tumors 2cm on the clinical examination, 76% for local relapse and 47% for distant/both location relapse. Conclusion* The tumor size on clinical examination, the location of relapse, the histologic subtype and the treatment with Bevacizumab, modify the risks of death after relapse on patients with cervical cancer IB1. Tumor >2cm on clinical examination and distant recurrences have a shorter survival time after relapse

Introduction/Background* The study attempts to understand the impact of the different retrospective studies conducted by the SUCCOR group on the daily surgical practice among ESGO members. We intend to propose a new observational prospective European study, the SUCCOP study. We aim to know if the implementation of protective maneuvers in minimally invasive surgery (MIS) improves the outcome of patients with early cervical cancer (ECC). In this scenario, supported by the ESGO council, we have conducted a multinational survey to assess our ESGO members’ perspectives from the ethical and investigational viewpoints on this new observational prospective study. Methodology A 32-item questionnaire addressing multiple issues related to the SUCCOR study and surgical management of ECC was designed and sent from the ESGO account through a newsletter on February 23rd to all ESGO members from 54 countries of the ESGO directory. The survey was completely confidentially and could be completed in less than 5 minutes. Responses from 353 members were obtained. Descriptive statistical analysis and frequency tables, as well as two-sided Fisher’s exact test, were used. Result(s)* 92.9% of responders were aware of the findings of the SUCCOR study. 73.4% expected the results obtained. 5 out of 10 of members confirmed that have changed their practice after the publication of the manuscript. Currently, 34.8% of responders admit that they usually perform MIS (laparoscopy/robotic) for cervical tumours smaller than 2 cm, while for tumours larger than 2 cm (FIGO IB2) 15.1% state that they continue to carry out MIS. Between 63 and 64.1% apply protective maneuvers during this procedure. In ECC who have undergone conization, 56.1% would performed MIS for tumours smaller than 2 cm while only 30% would offer it for tumours larger than 2 cm. Finally, 84.1% of ESGO members consider ethically acceptable the development of a new European prospective observational study (Image 1) to evaluate the surgical approach in ECC (IB1-IB2). Conclusion* According to the ESGO members’ perspectives regarding the approach to ECC, it seems that MIS still has an important role to play, which should be evaluated in a new prospective study that reflects the European reality (Image 2).

Background: The purpose of this study was to investigate the prevalence of ypN+ status according to ypT category in patients with locally advanced rectal cancer treated with chemoradiotherapy and total mesorectal excision, and to assess the impact of ypN+ on disease recurrence and survival by pooled analysis of individual-patient data.Methods: Individual-patient data from 10 studies of chemoradiotherapy for rectal cancer were included. Pooled rates of ypN+ disease were calculated with 95 per cent confidence interval for each ypT category. Kaplan-Meier and Cox regression analyses were undertaken to assess influence of ypN status on 5-year disease-free survival (DFS) and overall survival (OS).Results: Data on 1898 patients were included in the study. Median follow-up was 50 (range 0-219)months. The pooled rate of ypN+ disease was 7 per cent for ypT0, 12 per cent for ypT1, 17 per cent for ypT2, 40 per cent for ypT3, and 46 per cent for ypT4 tumours. Patients with ypN+ disease had lower 5-year DFS and OS (46.2 and 63.4 per cent respectively) than patients with ypN0 tumours (74.5 and 83.2 per cent) (P

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 TGFβ expression or activation increases in irradiated tissues, we tested whether TGFβ blockade may further enhance abscopal effects in conjunction with the anti–PD-1 plus anti-CD137 mAb combination. Indeed, TGFβ blockade with 1D11, a TGFβ-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 TGFβ in the nonirradiated contralateral tumor that showed smad2/3 phosphorylation increases in infiltrating CD8 T cells. In conclusion, radiotherapy-induced TGFβ hampers abscopal efficacy even upon combination with a potent immunotherapy regimen. Therefore, TGFβ blockade in combination with radioimmunotherapy results in greater efficacy.

Poster-Abstract

Proton therapy is an efficient high-precision radiotherapy technique. The number of installed proton units and the available medical evidence has grown exponentially over the last 10 years. As a technology driven cancer treatment modality, specific sub-analysis based on proton beam characteristics and proton beam generators is feasible and of academic interest. International synchrotron technology-based institutions have been particularly active in evidence generating actions including the design of prospective trials, data registration projects and retrospective analysis of early clinical results. Reported evidence after 2010 of proton therapy from synchrotron based clinical results are reviewed. Physics, molecular, cellular, animal investigation and other non-clinical topics were excluded from the present analysis. The actual literature search (up to January 2020) found 192 publications, including description of results in over 29.000 patients (10 cancer sites and histological subtypes), together with some editorials, reviews or expert updated recommendations. Institutions with synchrotron-based proton therapy technology have shown consistent and reproducible results along the past decade. Bibliometrics of reported clinical experiences from 2008 to early 2020 includes 58% of publications in first quartile (1q) scientific journals classification and 13% in 2q (7% 3q, 5% 4q and 17% not specified). The distribution of reports by cancer sites and histological subtypes shown as dominant areas of clinical research and publication: lung cancer (23%), pediatric (18%), head and neck (17%), central nervous system (7%), gastrointestinal (9%), prostate (8%) and a miscellanea of neplasms including hepatocarcinoma, sarcomas and breast cancer. Over 50% of lung, pediatric, head and neck and gastrointestinal publications were 1q.

ispartof: RADIOTHERAPY AND ONCOLOGY vol:148 pages:213-215 ispartof: location:Ireland status: published

This manuscript represents a collaboration from an international group of quality and safety expert radiation oncologists. It is a position/review paper with the specific aim of defining the role of the radiation oncologist in quality and safety management. This manuscript is unique in that we recommend specific quality assurance/control tasks and correlated quality and indicators and safety measures that are the responsibility of the radiation oncologist. The article addresses the role of the radiation oncologist in quality and safety from a strong perspective of multidisciplinarity and teamwork. Our manuscript is "cross-cutting" and applicable to radiation oncologist in any practice setting (i.e. low middle-income countries).

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. This study was supported by Ministerio de Ciencia, Innovacion y Universidades (http://www.ciencia.gob.es) [grant number TEC2013–48251-C2 to JP, VG-V and MJL-C], co-funded by European Regional Development Fund (ERDF), “A way of making Europe” (https://ec.europa.eu/regional_policy/en/funding/erdf); by Ministerio de Ciencia, Innovacion y Universidades (http://www.ciencia.gob.es), Instituto de Salud Carlos III (https://www.isciii.es) [grant numbers DTS14/00192 to JP, VG-V and FAC; PI15/02121 to FAC and JC-H; PI18/01625 to JP], co-funded by European Regional Development Fund (ERDF), “A way of making Europe” (https://ec.europa.eu/regional_policy/en/funding/erdf); and by Comunidad de Madrid (http://www.comunidad.madrid) [grant number TOPUS-CM S2013/ MIT3024 to JP], co-funded by European Structural and Investment Fund (https://ec.europa.eu/info/funding-tenders/funding-opportunities/fundingprogrammes/overview-funding-programmes_en). The CNIC is supported by the Ministerio de Ciencia, Innovacion y Universidades (http://www.ciencia.gob.es) and the Pro CNIC Foundation (https://www.fundacionprocnic.es) [to MD], and is a Severo Ochoa Center of Excellence (SEV-2015-0505). Sí

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.

International audience; PurposePostoperative radiation therapy (poRT) of intracranial/skull base chondrosarcomas (CHSs) is standard treatment. However, consensus is lacking for poRT in extracranial CHS (eCHS) owing to their easier resectability and intrinsic radioresistance. We assessed the practice and efficacy of poRT in eCHS.Methods and MaterialsThis multicentric retrospective study of the French Sarcoma Group/Rare Cancer Network included patients with eCHS who were operated on between 1985 and 2015. Inverse propensity score weighting (IPTW) was used to minimize poRT allocation biases.ResultsOf 182 patients, 60.4% had bone and 39.6% had soft-tissue eCHS. eCHS were of conventional (31.9%), myxoid (28.6%; 41 extraskeletal, 11 skeletal), mesenchymal (9.9%), or other subtypes. En-bloc surgery with complete resection was performed in 52.6% and poRT in 36.8% of patients (median dose, 54 Gy). Irradiated patients had unfavorable initial characteristics, with higher grade and incomplete resection. Median follow-up time was 61 months. Five-year incidence of local relapse was 10% with poRT versus 21.6% without (P = .050). Using the IPTW method, poRT reduced the local relapse risk (hazard ratio, 0.27; 95% confidence interval, 0.14-0.52; P < .001). Five-year disease-free survival (DFS) was 71.8% with poRT and 64.2% without (P = .680). Using the IPTW method, poRT improved DFS (hazard ratio, 0.51; 95% confidence interval, 0.30-0.85; P = .010). The benefit of poRT on local relapse and DFS was confirmed after exclusion of the extraskeletal subtype. There was no difference in overall survival. Prognostic factors of poorer DFS in multivariate analysis were deeper location, higher grade, incomplete resection, and no poRT.ConclusionspoRT should be offered in patients with eCHS and high-grade or incomplete resection, regardless of the histologic subtype.

Background and purposeFew tools are available to predict tumor response to treatment. This retrospective study assesses visual and automatic heterogeneity from 18F-FDG PET images as predictors of response in locally advanced rectal cancer.MethodsThis study included 37 LARC patients who underwent an 18F-FDG PET before their neoadjuvant therapy. One expert segmented the tumor from the PET images. Blinded to the patient¿s outcome, two experts established by consensus a visual score for tumor heterogeneity. Metabolic and texture parameters were extracted from the tumor area. Multivariate binary logistic regression with cross-validation was used to estimate the clinical relevance of these features. Area under the ROC Curve (AUC) of each model was evaluated. Histopathological tumor regression grade was the ground-truth.ResultsStandard metabolic parameters could discriminate 50.1% of responders (AUC = 0.685). Visual heterogeneity classification showed correct assessment of the response in 75.4% of the sample (AUC = 0.759). Automatic quantitative evaluation of heterogeneity achieved a similar predictive capacity (73.1%, AUC = 0.815).ConclusionA response prediction model in LARC based on tumor heterogeneity (assessed either visually or with automatic texture measurement) shows that texture features may complement the information provided by the metabolic parameters and increase prediction accuracy. This work was partially supported by the Spanish Ministry of Economy and Competitiveness (TEC2016–78052-R, PID2019-109820RB-I00) (to AMB) and TEC2013-48251-C2 (to JP), Instituto de Salud Carlos III and European Regional Development Fund (FEDER) Funds from the European Commission, “A way of making Europe” (PI15/02121) and a Leonardo grant to Researchers and Cultural Creators 2017, BBVA Foundation (to AMB). PMG is supported by ‘Beca de Colaboración’ of the Spanish Ministry of Education, Culture and Sports. The CNIC is supported by the Ministry of Economy, Industry and Competitiveness (MEIC) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505).