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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.

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.

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.

Highlights • Radiation dose-escalation with intraoperative electron beam radiation therapy to the posterior resection margin and/or to residual disease is feasible with limited toxicity. • Preoperative therapy prolongs the interval to surgery and IOERT, allowing an improved selection of patients who are candidates for local treatment intensification. • Primary systemic therapy combined with chemoradiation allows to boost with IOERT in over 70% of patients with R0 surgical tumour beds. • Median survival time ranges from 19 to 35 months in electron boosted patients. • Overall survival at 5 years of over 30% is reported by contemporary expert IOERT institutions., Radiation therapy (RT) is a valuable component of multimodal treatment for localized pancreatic cancer. Intraoperative radiation therapy (IORT) is a very precise RT modality to intensify the irradiation effect for cancer involving upper abdominal structures and organs, generally delivered with electrons (IOERT). Unresectable, borderline and resectable disease categories benefit from dose-escalated chemoradiation strategies in the context of active systemic therapy and potential radical surgery. Prolonged preoperative treatment may act as a filter for selecting patients with occult resistant metastatic disease. Encouraging survival rates have been documented in patients treated with preoperative chemoradiation followed by radical surgery and IOERT (>20 months median survival, >35% survival at 3 years). Intensive preoperative treatment, including induction chemotherapy followed by chemoradiation and an IOERT boost, appears to prolong long-term survival within the subset of patients who remain relapse-free for>2 years (>30 months median survival; >40% survival at 3 years). Improvement of local control through higher RT doses has an impact on the survival of patients with a lower tendency towards disease spread. IOERT is a well-accepted approach in the clinical scenario (maturity and reproducibility of results), and extremely accurate in terms of dose-deposition characteristics and normal tissue sparing. The technique can be adapted to systemic therapy and surgical progress. International guidelines (National Comprehensive Cancer Network or NCCN guidelines) currently recommend use of IOERT in cases of close surgical margins and residual disease. We hereby report the ESTRO/ACROP recommendations for performing IOERT in borderline-resectable pancreatic cancer.

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

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

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).

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).

We report a pooled analysis evaluating the combination of gross complete limb-sparing surgery, intraoperative electron radiation therapy (IOERT), and external beam radiation therapy (EBRT) in patients with extremity soft tissue sarcoma (STS). Individual data of 259 patients (median follow-up 63 months) with extremity STS from three European expert centers were pooled. Median age was 55 years and median tumor size was 8 cm. Eighty percent of patients presented with primary disease, mainly located in the lower limb (81%). Union for International Cancer Control 7th edition stage at presentation was as follows: stage I: 9%; stage II: 47%; stage III: 39%; stage IV: 5%. Most patients showed high-grade lesions (91%), predominantly liposarcoma (31%). Median IOERT dose was 12 Gy, preceeded (17%) or followed (83%) by EBRT, with a median dose of 45 Gy. Surgery resulted in R0 resections in 71% of patients and R1 resections in 29% of patients. The 5-year local control (LC) rate was 86%, and significant factors in univariate analysis were disease status and resection margin. Only margin remained significant in multivariate analysis. The 5-year distant control rate was 69%, and significant factors in univariate analysis were histology, grading, resection margin, and metastases prior to/at IOERT. Only grading and metastases remained significant in multivariate analysis. Actuarial 5-year rates of freedom from treatment failure and OS were 61% and 78%, respectively. Significant factors for OS were grading and metastases prior to/at IOERT (univariate, multivariate). Limb preservation and good functional outcome were achieved in 95% and 81% of patients. Our pooled analysis confirmed prior reports of encouraging LC and survival, with excellent rates of preserved limb function with this treatment approach. Resection margin remained the most important factor for LC, while grading and metastases prior to/at IOERT mainly predicted survival.

High-grade gliomas (HGG) are the most frequent primary central nervous system tumors; treatment of HCGs includes surgery and post-operative conformal radiotherapy associated with temozolomide (TMZ or procarbazine/lomustine/vincristine [PCV], specifically in patients with anaplastic oligodendrogliomas or anaplastic oligoastrocytomas). However, recurrence is common. Re-irradiation has been utilized in this setting for years and remains a feasible option, although there is always a concern regarding toxicity. Modern high-precision conformal techniques, including stereotactic radiosurgery (SRS), could improve the therapeutic ratio by delivering high biologically equivalent doses while reducing high-dose radiotherapy (RT) to normal brain tissue. In this paper, we present the results obtained after prolonged follow-up in patients who underwent SRS as a treatment for recurrent high-grade gliomas at San Francisco Hospital in Madrid, Spain.

Purpose/Objective(s) The optimal duration of androgen deprivation (AD) combined with high-dose radiotherapy (HDRT) in prostate cancer remains a matter of controversy. We did a phase 3 trial designed to determine whether long-term AD (LTAD) is superior to short-term AD (STAD) when combined with HDRT. In this report, we present the 10-year survival results. The hypothesis is that long-term AD (LTAD) compared to short-term AD (STAD) improves overall survival among high-risk patients receiving HDRT. Materials/Methods This open-label, phase 3 randomized controlled trial, recruited patients from ten university hospitals throughout Spain. Eligibility included patients with cT1c-T3aN0M0 adenocarcinoma of prostate with intermediate and high-risk factors according to NCCN criteria and PSA less than 100 ng/ml. All patients received 4 months of neoadjuvant and concomitant AD (STAD) + HDRT (median radiation dose 78 Gy) before randomization to adjuvant goserelin for two years (LTAD). Stratification was performed according to risk group (intermediate risk [IR] versus high risk [HR]). Study endpoints included overall survival (OS), metastasis free survival (MFS), disease free survival (DFS) and biochemical-disease free survival (bDFS). Survival analyses were done with Kaplan-Meier (KM) curves. Fine & Gray (FG FG FG F&G P = 0.057, HR, 1.12, 95% CI, 0.46 to 2.73). Only 11 patients died from PCa, all of them in the high-risk subgroup. Conclusion Long term results failed to show a significant benefit with LTAD compared to STAD in patients treated with HDRT. The subgroup of patients with high-risk PCa treated with LTAD had a non-significant improvement in bDFS, MFS and OS compared with STAD. The relatively small simple size, a low number of events and an effective salvage treatment could be responsible for the lack of a statistical significance. The trial is registered at ClinicalTrials.gov, number NCT 02175212.

Introduction/Background This study aims to understand what was the impact of the LACC trial (Laparoscopy in cervical cancer) among the members of ESGO. We have explored members’ understanding of the results and changes in the clinical practice. Methodology Methods A questionnaire addressing multiple issues related to the LACC trial and surgical management of early cervical cancer was designed and sent to ESGO members before and after the publication of the LACC trial in the NEJM. The survey was entirely confidentially and could be completed in a short period of time. Responses from 394 and 326 members from 33 European countries were obtained. The respondents were divided into two groups depending on whether or not they belong to European countries. Results Characteristics and perceptions of the responders are shown in tables 1 and 2. 97% of responders knew the results of the trial and 92% had read the manuscript. 83% did not expect the results. 56% of members confirmed that have changed their practice after the publication of the trial. Before the trial, only 29% operated cervical cancer by laparotomy and after the publication 63% does. figure 1 and 2. In cervical cancer patients who have undergone conization with clear margins 73% would offer MIS to the patient while only 49% would if the specimen margins was positive. Members consider that uterine manipulator an incorrect tumor handling occasioned the poorer result of MIS. 9 out 10 of members are willing to discuss the LACC trial with their patients and 80% consider unethical avoiding this discussion. 85% think that ESGO should promote a new randomized clinical trial and meanwhile 65% would be interested to participate in a observational study. Conclusion Among ESGO members, the publication of LACC trial has objectively modified the surgical approach in early cervical cancer. Disclosure Nothing to disclose.

Introduction/Background To develop an ultrasound-based score for predicting debulking surgery outcome in advanced stage ovarian cancer. Methodology Retrospective analysis of data from a prospective cohort study comprising 65 women (mean age: 59 y.o.) with surgically confirmed stage IIB–IV epithelial ovarian cancer and ECOG status performance 0–2. All women had undergone transabdominal and transvaginal ultrasound evaluation for assessing disease spread prior to surgery. 12 anatomical areas were evaluated for the presence/absence of disease (recto-sigma involvement, carcinomatosis of pelvic peritoneum, major omentum, carcinomatosis of upper abdomen peritoneum, root of mesentery, pelvic lymph nodes, aorto-cava lymph nodes, lesser omentum, liver, spleen, hepatic hilum and ascites). All women included underwent surgery at our institution (diagnostic laparoscopy followed by upfront surgery if patient deemed adequate for optimal (R Parameter Score CA-125 >500 1. Bowel 1. Mesogastrium 1. Major omentum 1. Pelvic lymph nodes 1. Root mesentery 2. Liver parenchyma 2. Spleen parenchyma 2. Para-aortic lymph nodes 2. Hepatic hilium 2. Results Cytoreduction was complete or optimal in 51 patients (78.5%), suboptimal in 3 (4.6%) and upfront surgery was discarded in 11 women (16.9%). A score >3 predicted correctly 44 out 51 patients (86%) with complete/optimal cytoreduction in and 8 out of 14 (57%) of those with suboptimal or non-cytoreduction surgery. AUC was 0.76, with correct prediction in 80% of all cases. Conclusion Albeit the series is small, the developed ultrasound-based score has a good performance for predicting surgical results in IIB–IV stage epithelial ovarian cancer. Disclosure Nothing to disclose.

Background: To evaluate the impact of radiation dose on overall survival (OS) in patients treated with adjuvant chemoradiation (CRT) for pancreatic ductal adenocarcinoma (PDAC). Methods: A multicenter retrospective analysis on 514 patients with PDAC (T1-4; N0-1; M0) treated with surgical resection with macroscopically negative margins (R0-1) followed by adjuvant CRT was performed. Patients were stratified into 4 groups based on radiotherapy doses (group 1: < 45 Gy, group 2: ≥ 45 and < 50 Gy, group 3: ≥ 50 and < 55 Gy, group 4: ≥ 55 Gy). Adjuvant chemotherapy was prescribed to 141 patients. Survival functions were plotted using the Kaplan-Meier method and compared through the log-rank test. Results: Median follow-up was 35 months (range: 3-120 months). At univariate analysis, a worse OS was recorded in patients with higher preoperative Ca 19.9 levels (≥ 90 U/ml; p < 0.001), higher tumor grade (G3-4, p = 0.004), R1 resection (p = 0.004), higher pT stage (pT3-4, p = 0.002) and positive nodes (p < 0.001). Furthermore, patients receiving increasing doses of CRT showed a significantly improved OS. In groups 1, 2, 3, and 4, median OS was 13.0 months, 21.0 months, 22.0 months, and 28.0 months, respectively (p = 0.004). The significant impact of higher dose was confirmed by multivariate analysis. Conclusions: Increasing doses of CRT seems to favorably impact on OS in adjuvant setting. The conflicting results of randomized trials on adjuvant CRT in PDAC could be due to < 45 Gy dose generally used.

BACKGROUND: Presurgical carbohydrate antigen 19-9 (CA19-9) level predicts overall survival (OS) in resected pancreatic adenocarcinoma (PaC). The aim of this pooled analysis was to evaluate if presurgical CA19-9 level can also predict local control (LC) and distant metastasis-free survival (DMFS). METHODS: Seven hundred patients with PaC from eight institutions who underwent surgical resection ± adjuvant treatment between 2000 and 2014 were analyzed. Patients were divided based on four presurgical CA19-9 level cutoffs (5, 37, 100, 353 U/ml). Weibull regression model to identify independent predictors of OS on 404 patients with complete information was fitted. RESULTS: Median follow-up was 17 months (range: 2-225 months). Univariate analysis showed a better prognosis in pT1-2, pN0, diameter 353.1: 10.9%, 50.2%, and 23.4%, respectively. At multivariate analysis, CA19-9 >100 and 30 mm (P50.0 Gy showed improved OS (P

Background: To evaluate, in a context of innovative multidisciplinary clinical practice, the efficacy of oxaliplatin in adjuvant administration (chemotherapy, CT) in relation to the total administered dose, in terms of prognosis with other clinical and therapeutic factors, in the heterogeneous model of locally advanced rectal cancer (LARC), which is characterized by a risk pattern of dominant systemic progression. Methods: Observational-analytical, retrospective, unicentric, non-randomized study of two cohorts of patients receiving FOLFOX-4 induction CT in neoadjuvancy, radiochemotherapy and surgery, differing in that one cohort did not receive any adjuvant post-surgical treatment and the other one received adjuvant CT with FOLFOX-4 cycles. A total of 212 patients from the Radiotherapy Oncology Service at the University Hospital Gregorio Maranon were studied: the neoadjuvant CT treatment group with oxaliplatin consisted of 110 patients and adjuvant CT treatment group with oxaliplatin consisted of 102 patients. The median follow-up time for the whole study population was 72 months (6 years). Results: The sociodemographic, clinical and diagnostic characteristics were very similar in both cohorts of patients, but with a pattern of therapeutic selection towards elements of adversity in pathological post-neoadjuvant staging. The dose of oxaliplatin in adjuvance (postoperative) superior to 6 cycles was positively associated with the locoregional control (LRC) at 5 years (P=0.012) and with the overall survival (OS) (P=0.048) at 5 years. In the responders to neoadjuvance with oxaliplatin [patients with tumor regression grade (TRG 3–4)], the dose of oxaliplatin greater than 5 cycles in adjuvance (postoperative) was positively associated with OS (P=0.06). And the dose of oxaliplatin in the range of 4–5 cycles in adjuvance (postoperative) was positively associated with distant metastasis-free survival (DMFS) and disease-free survival (DFS) in the cohort of responding patients (P=0.015 and 0.004, respectively). Conclusions: The contribution of adjuvant oxaliplatin in the oncological evolution shows a favorable effect of LRC, DMFS, DFS and OS in the subgroups of patients that exhibit elements of response to neoadjuvant oxaliplatin (categories TRG 3–4, and pN0, downstaging T, downstaging N). Therefore, this neoadjuvant response profile with oxaliplatin, measured with highly reliable methodology (validated microscopic pathological response scales), defines a population of oxaliplatin-sensitive patients who benefits significantly from the administration of adjuvant oxaliplatin in sufficient cumulative doses (more of 5 cycles).

Purpose To assess long-term outcomes and toxicity of intraoperative electron-beam radiation therapy (IOERT) in the management of pediatric patients with Ewing sarcomas (EWS) and rhabdomyosarcomas (RMS). Methods and Materials Seventy-one sarcoma (EWS n=37, 52%; RMS n=34, 48%) patients underwent IOERT for primary (n=46, 65%) or locally recurrent sarcomas (n=25, 35%) from May 1983 to November 2012. Local control (LC), overall survival (OS), and disease-free survival were estimated using Kaplan-Meier methods. For survival outcomes, potential associations were assessed in univariate and multivariate analyses using the Cox proportional hazards model. Results After a median follow-up of 72 months (range, 4-310 months), 10-year LC, disease-free survival, and OS was 74%, 57%, and 68%, respectively. In multivariate analysis after adjustment for other covariates, disease status ( P =.04 and P =.05) and R1 margin status ( P P =.04) remained significantly associated with LC and OS. Nine patients (13%) reported severe chronic toxicity events (all grade 3). Conclusions A multimodal IOERT-containing approach is a well-tolerated component of treatment for pediatric EWS and RMS patients, allowing reduction or substitution of external beam radiation exposure while maintaining high local control rates.

Purpose To evaluate the influence of equivalent dose (EQD2) in clinical outcomes of patients with isolated locally recurrent tumors (ILRT), treated with salvage surgery and intra-operative electron beam radiation therapy (IOERT). Methods and materials We retrospectively reviewed 128 patients with non-metastatic ILRT of different tissues (soft tissue sarcomas, head and neck, uterine, and colorectal). Patients had received salvage surgery (R0/R1/R2) and IOERT. Previously not irradiated patients had received additional external beam radiation therapy (EBRT). Results IOERT was delivered at a median dose of 15Gy (range, 5–25Gy). Seventy-five patients (60.9%) received additional EBRT of 46Gy. Median EQD2 of salvage program was 62Gy and median EQD2 of exclusive IORT was 31.2Gy. Median follow-up was 19.2months (range: 1.3–220). Thirty-one patients (24.2%) developed severe (grade 3–5) complications. New locoregional recurrence was documented in 86 (67.2%) of the 123 cases. Five-year rates were 31% for locoregional control, 57% for distant metastasis-free and 31% for overall survival. On multivariate analysis, R0–1 vs. R2 resection (HR 2.2, 95 CI: 1.2–4.1) was statistically significant for locoregional recurrence and EQD2 ⩾62Gy for survival (HR 2.2, 95 CI: 1.1–4.1). Conclusions Surgical radicality (gross macroscopic resection) and radiation dose (EQD2 ⩾62Gy in radiation salvage program) are the dominant prognostic factors beside ILRT histology. Modest rates of long-term disease control are expected when both factors are fulfilled.

To analyze long-term outcomes and prognostic factors in patients with paraaortic lymph-node oligometastases (LNO) from gynecological malignancies treated in a multimodal protocol. Patients with a histological diagnosis of LNO gynecological cancer [uterine cervix (n = 14, 40 %), endometrial (n = 18, 51 %), ovarian (n = 3, 9 %)] who underwent surgery with radical intent and intraoperative radiotherapy (IORT), median dose 12.5 Gy) were considered eligible for participation in this study. Additionally, 51 % received external-beam radiotherapy (EBRT). From 1997 to 2012, a total of 35 patients from a single institution were analyzed. With a median follow-up time of 55 months (range 2–148), 5-year loco-regional control (LRC), disease-free survival (DFS) and overall survival (OS) were 79, 44 and 49 %, respectively. On multivariate analysis, no EBRT treatment to the LNO (p = 0.03), and time interval from primary tumor diagnosis to LNO

The aim of this study was to analyze long-term outcomes and prognostic factors associated with survival in patients with locoregional oligo-recurrent (LROR) pelvic malignancies treated in a multimodal protocol. Patients with an histologic diagnosis of LROR pelvic cancer (rectal 50 %, gynecological 50 %) with absence of distant metastases, undergoing surgery with radical intent and intraoperative radiotherapy (median dose 12.5 Gy) were considered eligible for participation in this study. Additionally, 48 % received external beam radiotherapy (EBRT) (median dose 50 Gy). From 1995 to 2012, a total of 143 patients from a single institution were analyzed. With a median follow-up time of 48 months (range 2–189), 5-year locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) were 53, 44, and 46 %, respectively. On multivariate analysis, no EBRT treatment to the locoregional (p ≤ 0.001), R1 margin status (p = 0.03), time interval from primary tumor diagnosis to LROR

Recent literature suggests that the benefit of adjuvant chemotherapy (aCT) for rectal cancer patients might depend on the response to neoadjuvant chemoradiation (CRT). Aim was to evaluate whether the effect of aCT in rectal cancer is modified by response to CRT and to identify which patients benefit from aCT after CRT, by means of a pooled analysis of individual patient data from 13 datasets. Patients were categorized into three groups: pCR (ypT0N0), ypT1-2 tumour and ypT3-4 tumour. Hazard ratios (HR) for the effect of aCT were derived from multivariable Cox regression analyses. Primary outcome measure was recurrence-free survival (RFS). One thousand seven hundred and twenty three (1723) (52%) of 3,313 included patients received aCT. Eight hundred and ninety eight (898) patients had a pCR, 966 had a ypT1-2 tumour and 1,302 had a ypT3-4 tumour. For 122 patients response, category was missing and 25 patients had ypT0N+. Median follow-up for all patients was 51 (0-219) months. HR for RFS with 95% CI for patients treated with aCT were 1.25(0.68-2.29), 0.58(0.37-0.89) and 0.83(0.66-1.10) for patients with pCR, ypT1-2 and ypT3-4 tumours, respectively. The effect of aCT in rectal cancer patients treated with CRT differs between subgroups. Patients with a pCR after CRT may not benefit from aCT, whereas patients with residual tumour had superior outcomes when aCT was administered. The test for interaction did not reach statistical significance, but the results support further investigation of a more individualized approach to administer aCT after CRT and surgery based on pathologic staging.

Intraoperative irradiation was implemented 4 decades ago, pioneering the efforts to improve precision in local cancer therapy by combining real-time surgical exploration/resection with high single dose radiotherapy (Gunderson et al., Intraoperative irradiation: techniques and results, 2011). Clinical and technical developments have led to very precise radiation dose deposit. The ability to deliver a very precise dose of radiation is an essential element of contemporary multidisciplinary individualized oncology. This issue of Radiation Oncology contains a collection of expert review articles and updates with relevant data regarding intraoperative radiotherapy. Technology, physics, biology of single dose and clinical results in a variety of cancer sites and histologies are described and analyzed. The state of the art for advanced cancer care through medical innovation opens a significant opportunity for individualize cancer management across a broad spectrum of clinical practice. The advantage for tailoring diagnostic and treatment decisions in an individualized fashion will translate into precise medical treatment.

Intraoperative electron radiation therapy (IOERT) involves irradiation of an unresected tumour or a post-resection tumour bed. The dose distribution is calculated from a preoperative computed tomography (CT) study acquired using a CT simulator. However, differences between the actual IOERT field and that calculated from the preoperative study arise as a result of patient position, surgical access, tumour resection and the IOERT set-up. Intraoperative CT imaging may then enable a more accurate estimation of dose distribution. In this study, we evaluated three kilovoltage (kV) CT scanners with the ability to acquire intraoperative images. Our findings indicate that current IOERT plans may be improved using data based on actual anatomical conditions during radiation. The systems studied were two portable systems (“O-arm”, a cone-beam CT [CBCT] system, and “BodyTom”, a multislice CT [MSCT] system) and one CBCT integrated in a conventional linear accelerator (LINAC) (“TrueBeam”). TrueBeam and BodyTom showed good results, as the gamma pass rates of their dose distributions compared to the gold standard (dose distributions calculated from images acquired with a CT simulator) were above 97% in most cases. The O-arm yielded a lower percentage of voxels fulfilling gamma criteria owing to its reduced field of view (which left it prone to truncation artefacts). Our results show that the images acquired using a portable CT or even a LINAC with on-board kV CBCT could be used to estimate the dose of IOERT and improve the possibility to evaluate and register the treatment administered to the patient. Dosisverteilung wird aus einer präoperativen Computertomographie (CT)-Studie berechnet, für die ein CT-Simulator verwendet wurde. Resultierend aus der Patientenposition, dem chirurgischen Zugang, der Tumorresektion und dem IOERT-Aufbau tritt jedoch eine Abweichung zwischen dem tatsächlichen IOERT-Feld und dem aus der präoperativen Aufnahme berechneten Feld auf. Die Intraoperative CT-Bildgebung kann unter diesen Umständen eine genauere Einschätzung der Dosisverteilung ermöglichen. In dieser Studie haben wir drei Kilovolt (kV)-Computertomographgeräte bewertet, die intraoperative Bilder erstellen können. Unsere Ergebnisse weisen darauf hin, dass aktuelle IOERT-Behandlungspläne mittels Daten verbessert werden können, die auf tatsächlichen anatomischen Gegebenheiten während der Bestrahlung basieren. Es wurden zwei tragbare Systeme („O-Arm“, ein cone-beam-CT [CBCT]-System und „BodyTom“, ein Mehrschicht-CT [MSCT]-System) und ein in einen konventionellen Linearbeschleuniger integriertes CBCT-System (LINAC) namens „TrueBeam“ untersucht. TrueBeam und BodyTom zeigten gute Ergebnisse, da die Gamma-Akzeptanzrate der Dosisverteilungen im Vergleich zum Goldstandard (Berechnung der Dosisverteilungen anhand von mit einem CT-Simulator aufgenommenen Bildern) in den meisten Fällen über 97% lag. Der O-Arm ergab einen niedrigeren Prozentsatz an Voxel, die die Gamma-Kriterien erfüllen. Dies liegt an seinem verminderten Sichtfeld, das seine Anfälligkeit für Truncation-Artefakte erhöht. Unsere Ergebnisse belegen die Verwendbarkeit von Bildern zur Einschätzung der IOERT-Dosis, die mit Hilfe eines tragbaren CT oder sogar eines LINAC mit On-Board-kV-CBCT erstellt wurden. Hierdurch können die Behandlungsdosen der Patienten besser bewertet und erfasst werden. This study was supported by projects IPT-2012-0401-300000, TEC2013-48251-C2-1-R, DTS14/00192, PI-15/02121 (Ministerio de Economía y Competitividad, ISCIII), TOPUS-CM S2013/MIT-3024 (Comunidad de Madrid) and FEDER funds. We would like to acknowledge the support of the Madrid-MIT M+Vision Consortium in facilitating this study. KG Vosburgh received support from the National Center for Image Guided Therapy under NIH P41 EB015898. The authors also extend their gratitude to Medtronic, NeuroLogica Corporation, Department of Radiation Oncology at Clínica La Luz, Hospital Universitario La Paz, radiotherapy technicians at Hospital General Universitario Gregorio Marañón and Iván Balsa for their support with data acquisition. We are also grateful to the Department of Radiation Oncology at Hospital Universitario Ramón y Cajal for providing the electron density phantom, CIRS company for supplying the chemical composition of the phantom, Cristina González and Ramón Polo for providing image quality performance of the CT simulator, and Claudia de Molina and Alejandro Sisniega for technical assistance with CT artefacts. We would also like to express our sincere gratitude to the late Professor Juan Antonio Santos-Miranda for his practical and insightful suggestions regarding the task of improving IOERT procedures. Publicado

To perform a joint analysis of data from 3 contributing centers within the intraoperative electron-beam radiation therapy (IOERT)-Spanish program, to determine the potential of IOERT as an anticipated boost before external beam radiation therapy in the multidisciplinary treatment of pediatric extremity soft-tissue sarcomas.From June 1993 to May 2013, 62 patients (aged21 years) with a histologic diagnosis of primary extremity soft-tissue sarcoma with absence of distant metastases, undergoing limb-sparing grossly resected surgery, external beam radiation therapy (median dose 40 Gy) and IOERT (median dose 10 Gy) were considered eligible for this analysis.After a median follow-up of 66 months (range, 4-235 months), 10-year local control, disease-free survival, and overall survival was 85%, 76%, and 81%, respectively. In multivariate analysis after adjustment for other covariates, tumor size5 cm (P=.04) and R1 margin status (P=.04) remained significantly associated with local relapse. In regard to overall survival only margin status (P=.04) retained association on multivariate analysis. Ten patients (16%) reported severe chronic toxicity events (all grade 3).An anticipated IOERT boost allowed for external beam radiation therapy dose reduction, with high local control and acceptably low toxicity rates. The combined radiosurgical approach needs to be tested in a prospective trial to confirm these results.

Aim The purpose of this report is to store the information of the pre-planning and compare this data with the actual data of the procedure. Background Currently, intraoperative electron beam radiotherapy clinical practice lacks a treatment planning system. Materials and methods The RADIANCE concept approaches treatment planning by providing the user with a navigation platform based on a three-dimensional imaging system in which the radiation oncologist can target the tumor and risk areas in different sections (axial, coronal, sagittal), while a volume rendering engine displays a 3D image that is automatically updated as we make any changes of the space. Finally, the user may select the parameters of the applicator, energy and dose of treatment to optimize the procedure. Six cases are clinically described and illustrated. Results RADIANCE is a useful tool in planning IOERT. Tumor segmentation and risk areas with minimal guide in the selection of parameters for the applicator. Complex locations are challenging, where the experience and skill of the radiation oncologist is necessary to optimize the process. New developments include imaging innovated uses. Intraoperative imaging will approach reality and allow real time, dosimetry estimations, stereotactic recognition of patient and tumor bed position, will guide automatization of radiation beam recognition and pre-robotic arrangements with linear accelerator movements. Conclusions RADIANCE offers a new imaging expansion for IOERT, in the context of a multidisciplinary approach to optimize and define the treatment parameters to approximate the actual treatment radiotherapy procedure.

BackgroundIntraoperative radiotherapy (IORT) refers to the delivery of a high dose of radiation at the time of surgery.AimTo analyze clinical and research-oriented innovative activities developed in a 17-year period using intraoperative electron-radiation therapy (IOeRT) as a component of treatment in a multidisciplinary approach for cancer management.Materials and methodsFrom 01/1995 to 03/2012 IOeRT procedures were registered in a specific Hospital-based database. Research and developments in imaging and recording for treatment planning implementation are active since 2006.Results1004 patients were treated and 1036 IORT procedures completed. Median age of patients was 61 (range 5 months to 94 years). Gender distribution was male in 54% of cases and female in 46%. Disease status at the time of IORT was 796 (77%) primary and 240 (23%) recurrent. Cancer type distribution included: 62% gastrointestinal, 18% sarcoma, 5% pancreas, 2% paediatric, 3% breast, 77 7% oligotopic recurrences, 2% other. IORT technical characteristics were: Applicator size 5cm 22%, 6cm 21%, 7cm 21%, 8cm 15%, 9cm 6%, 10cm 7% 12cm 5% 15cm 3%. Electron energies: 6MeV 19%, 8MeV 15%, 10MeV 15%, 12MeV 23%, 15MeV 19%, 18MeV 6%, other 3%. Multiple fields: 108 (11%). Dose: 7.5Gy 3%, 10Gy 35%, 12Gy 3%, 12.5Gy 49%, 15Gy 5%, other 5%.ConclusionAn IORT programme developed in an Academic Hospital based on practice-oriented medical decisions is an attractive interdisciplinary oncology initiative proven to be able to generate an intensive clinical activity for cancer patient quality care and a competitive source of scientific patient-oriented research, development and innovation.

The optimal waiting period between neoadjuvant treatment completion and surgery in locally advanced rectal cancer (LARC) is controversial. The specific purpose of this study was to evaluate the effect of prolonging this interval on the pathologic response, postoperative morbidity, and long-term oncologic outcomes. Retrospective data analysis is reported from LARC patients who had been treated with chemoradiation followed by surgery and intra-operative radiotherapy, between February 1995 and December 2012. In total, two groups were studied, according to the time elapsed between neoadjuvant treatment and surgery: conventional interval (CI

A joint analysis of data from three contributing centres within the intraoperative electron-beam radiation therapy (IOERT) Spanish program was performed to investigate the main contributions of IORT to the multidisciplinary treatment of high-risk extremity soft tissue sarcoma (STS). Patients with an histologic diagnosis of primary extremity STS, with absence of distant metastases, undergoing limb-sparing surgery with radical intent, external beam radiotherapy (median dose 45 Gy) and IOERT (median dose 12.5 Gy) were considered eligible for participation in this study. From 1986–2012, a total of 159 patients were analysed in the study from three Spanish institutions. With a median follow-up time of 53 months (range 4–316 years), 5-year local control (LC) was 82 %. The 5-year IOERT in-field control, disease-free survival (DFS) and overall survival (OS) were 86, 62 and 72 %, respectively. On multivariate analysis, only microscopically involved margin (R1) resection status retained significance in relation to LC (HR 5.20, p

Age is an important feature at the time of early breast cancer diagnosis. Radiotherapy is a mandatory component of treatment for breast-conserving strategies in early disease stages. Breast radiotherapy has rapidly evolved in the last 20 years. A tendency to less treatment volume (partial-breast irradiation) and less treatment time (hypofractionation) is consolidated in modern radiation oncology practice. Age and risk for local recurrence guide the decision-making process to electro-optimal treatment. Radiotherapy technological versatility offers multiple options for individualized (risk-age adapted) recommendations.

This study aimed to analyze outcomes in a multi-institutional cohort of patients with advanced or recurrent renal cell carcinoma (RCC) who were treated with intraoperative radiation therapy (IORT).Between 1985 and 2010, 98 patients received IORT for advanced or locally recurrent RCC at 9 institutions. The median follow-up time for surviving patients was 3.5 years. Overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) were estimated with the Kaplan-Meier method. Chained imputation accounted for missing data, and multivariate Cox hazards regression tested significance.IORT was delivered during nephrectomy for advanced disease (28%) or during resection of locally recurrent RCC in the renal fossa (72%). Sixty-nine percent of the patients were male, and the median age was 58 years. At the time of primary resection, the T stages were as follows: 17% T1, 12% T2, 55% T3, and 16% T4. Eighty-seven percent of the patients had a visibly complete resection of tumor. Preoperative or postoperative external beam radiation therapy was administered to 27% and 35% of patients, respectively. The 5-year OS was 37% for advanced disease and 55% for locally recurrent disease. The respective 5-year DSS was 41% and 60%. The respective 5-year DFS was 39% and 52%. Initial nodal involvement (hazard ratio [HR] 2.9-3.6, P.01), presence of sarcomatoid features (HR 3.7-6.9, P.05), and higher IORT dose (HR 1.3, P.001) were statistically significantly associated with decreased survival. Adjuvant systemic therapy was associated with decreased DSS (HR 2.4, P=.03). For locally recurrent tumors, positive margin status (HR 2.6, P=.01) was associated with decreased OS.We report the largest known cohort of patients with RCC managed by IORT and have identified several factors associated with survival. The outcomes for patients receiving IORT in the setting of local recurrence compare favorably to similar cohorts treated by local resection alone suggesting the potential for improved DFS with IORT.

The goal of the present study was to analyze prognostic factors in patients treated with external-beam radiation therapy (EBRT), surgical resection and intraoperative electron-beam radiotherapy (IOERT) for oligorecurrent gynecological cancer (ORGC).From January 1995 to December 2012, 61 patients with ORGC [uterine cervix (52 %), endometrial (30 %), ovarian (15 %), vagina (3 %)] underwent IOERT (12.5 Gy, range 10-15 Gy), and surgical resection to the pelvic (57 %) and paraaortic (43 %) recurrence tumor bed. In addition, 29 patients (48 %) also received EBRT (range 30.6-50.4 Gy). Survival outcomes were estimated using the Kaplan-Meier method, and risk factors were identified by univariate and multivariate analyses.Median follow-up time for the entire cohort of patients was 42 months (range 2-169 months). The 10-year rates for overall survival (OS) and locoregional control (LRC) were 17 and 65 %, respectively. On multivariate analysis, no tumor fragmentation (HR 0.22; p = 0.03), time interval from primary tumor diagnosis to locoregional recurrence (LRR) 24 months (HR 4.02; p = 0.02) and no EBRT at the time of pelvic recurrence (HR 3.95; p = 0.02) retained significance with regard to LRR. Time interval from primary tumor to LRR 24 months (HR 2.32; p = 0.02) and no EBRT at the time of pelvic recurrence (HR 3.77; p = 0.04) showed a significant association with OS after adjustment for other covariates.External-beam radiation therapy at the time of pelvic recurrence, time interval for relapse ≥ 24 months and not multi-involved fragmented resection specimens are associated with improved LRC in patients with ORGC. As suggested from the present analysis a significant group of ORGC patients could potentially benefit from multimodality rescue treatment.

Background/objectives To analyze prognostic factors associated with long-term outcomes in patients with pancreatic cancer treated with chemoradiation therapy (CRT) and surgery with or without intraoperative electron beam radiotherapy (IOERT). Patients and methods From January 1995 to December 2012, 60 patients with adenocarcinoma of the pancreas and locoregional disease (clinical stage IB [ n = 13; 22%], IIA [ n = 16; 27%], IIB [ n = 22; 36%], IIIC [ n = 9; 15%]) were treated with CRT (45–50.4 Gy before surgery [ n = 19; 32%] and after surgery [ n = 41; 68%]) and curative resection (R0 [ n = 34; 57%], R1 [ n = 26, 43%]). Twenty-nine patients (48%) also received a pre-anastomosis IOERT boost (applicator diameter size, 7–10 cm; dose, 10–15 Gy; beam energy, 9–18 MeV). Results With a median follow-up of 15.9 months (range, 1–182), 5-year overall survival (OS), disease-free survival (DFS), and locoregional control were 20%, 13%, and 58%, respectively. Univariate analyses showed that R1 margin resection status (HR, 3.17; p = 0.04), not receiving IOERT (HR, 7.33; p = 0.01), and postoperative CRT (HR, 5.12; p = 0.04) were associated with a higher risk of locoregional recurrence. In the multivariate analysis, only margin resection status (HR, 3.0; p = 0.05) and not receiving IOERT (HR, 6.75; p = 0.01) retained significance with regard to locoregional recurrence. Postoperative mortality and perioperative complications were 3% ( n = 2) and 43% ( n = 26). Conclusions Although local control is good in the radiation-boosted area, OS remains modest owing to high risk of distant metastases. Intensified locoregional treatment needs to be tested in the context of more efficient systemic therapy.

The optimal schedule and regimen of chemotherapy (CT) in association with chemoradiation has not been established in stage III non-small-cell lung cancer (NSCLC). We have compared three schedules of non-platinum-based CT plus either radiotherapy or chemoradiation. From May 2001 to June 2006, 158 patients with unresectable stage III NSCLC were enrolled in a randomized phase II trial with overall response rate (ORR) as the primary endpoint. The initial design included three arms: sequential CT followed by thoracic radiation (TRT); concurrent CT/TRT followed by consolidation CT; and induction CT followed by concurrent CT/TRT. However, based on the preliminary results of the RTOG 9410 trial, the sequential arm was closed when 19 patients had been enrolled. All patients received two cycles of docetaxel 40 mg/m(2) days 1 and 8 plus gemcitabine 1200 mg/m(2) days 1 and 8, as either induction or consolidation therapy. Concurrent CT/TRT consisted of docetaxel 20 mg/m(2) and carboplatin AUC 2 weekly plus 60 Gy TRT. No differences were found in ORR between the two arms (56% and 57%). Hematological toxicity was mild but significantly superior with consolidation CT; the esophagitis rate was similar in both arms (16% and 15%). With a median follow-up of 57 months, no differences were found in median survival (13.07 and 13.8 months) or 5-year survival (16.4% and 22%). This regimen cannot be recommended as an alternative to platinum-based CT/TRT although it has an acceptable toxicity profile and encouraging long-term survival data (ClinicalTrials.gov NCT01652820).

To report feasibility, tolerance, anatomical topography of locoregional recurrence (LRR), and long-term outcome for esophageal and esophagogastric (EG) cancer patients treated with preoperative chemoradiation (CRT) and surgery with or without a radiation boost of intraoperative electron beam radiotherapy (IOERT). From January 1995 to December 2010, 53 patients with primary esophageal (n = 26; 44 %) or EG carcinoma (n = 30; 56 %), and disease confined to locoregional area [clinical stage: IIb (n = 30; 57 %), IIIa (n = 14; 26 %), IIIb (n = 6; 11 %), IIIc (n = 3; 6 %)], were treated with preoperative CRT, curative (R0) resection with an extended (two-field) lymph node dissection in all cases. Thirty-seven patients also received a preanastomotic reconstruction IOERT boost (applicator diameter size 6–9 cm, dose 10–15 Gy, beam energy 6–15 MeV) over the tumor bed in the mediastinum and upper abdominal lymph node area. With a median follow-up time of 27.9 months (range, 0.2–148), LRR rate was 15 % (n = 8). Five-year overall survival (OS) and disease-free survival was 48 and 36 %, respectively. Univariate log-rank analyses showed that receiving IOERT was associated with lower risk of LRR (p = 0.004). On multivariate analysis, only the IOERT group retained significance in relation to LRR (odds ratio, 0.08; 95 % confidence interval, 0.01–0.48; p = 0.01). Postoperative mortality and perioperative complications were 11 % (n = 6) and 30 % (n = 16). Local control is high in the radiation-boosted area, but OS remains modest, given the high risk of distant metastases. Intensified locoregional treatment needs to be tested in the context of more efficient concurrent, neo-, and adjuvant systemic therapy.

Borderline resectable pancreatic head carcinoma is a challenging disease that requires multidisciplinary approach to obtain maximal benefits from current therapeutical possibilities. We review current knowledge and therapeutic options for the patients from the surgical, medical oncology and radiotherapy views and emphasize the need for a coordinated multidisciplinary approach to obtain optimal results.

To investigate the outcomes and risk factors of patients treated with stereotactic ablative radiotherapy (SABR) delivered by image-guided helical tomotherapy (HT) for extracranial oligometastases.From August 2006 through July 2011, 42 consecutive patients (median age 69 years [range 16-87]) with oligometastases (≤3) received HT to all known cancer sites (lung, n = 28; liver, n = 12; adrenal, n = 2). Prognostic factors were assessed by Cox's proportional hazards regression analysis.A total of 60 lesions were treated with hypofractionated HT (median dose 39 Gy [range 36-72.5]; median dose per fraction 12 Gy [range 5-20]). Complete or partial response was observed in 40 (54 %) patients. With a median follow-up period of 15 months, 1- and 2-year overall survival (OS) was 84 and 63 %, respectively; and 1- and 2-year local control (LC) was 92 and 86 %, respectively. Four patients had pneumonitis Grade ≥2 and two patients had lower gastrointestinal toxicity Grade ≥2. Only the lack of complete/partial response was associated with higher risk of mortality on univariate (HR = 3.8, P = 0.04) and multivariate (HR = 6.6, P = 0.01) analyses.SABR delivered by image-guided HT is well tolerated and offers adequate LC with low acute morbidity in patients with extracranial oligometastatic disease. We found that the response to HT was the only predictor for OS.

To report feasibility, tolerance, anatomical sites of upper abdominal locoregional recurrence and long-term outcome of gastric cancer patients treated with surgery and a component of intraoperative electron beam radiotherapy (IORT). From January 1995 to December 2010, 32 patients with primary gastric adenocarcinoma treated with curative resection (R0) [total gastrectomy (n = 9; 28 %), subtotal (n = 23; 72 %) and D2 lymphadenectomy in all patients] and apparent disease confined to locoregional area [Stage: II (n = 15; 47 %), III (n = 17; 53 %)] were treated with a component of IORT (IORT applicator size 5–9 cm in diameter, dose 10–15 Gy, beam energy 6–5 MeV) over the celiac axis and peripancreatic nodal areas. Sixteen (50 %) patients also received adjuvant treatment (external beam radiotherapy n = 6, chemoradiation n = 9, chemotherapy alone n = 1). With a median follow-up time of 40 months (range, 2–60), locoregional recurrence was observed in five (16 %) patients (4 nodal in hepatic hilum and 1 anastomotic). Only pN1 patients developed locoregional relapse. No recurrence was observed in the IORT-treated target volume (celiac trunk and peripancreatic nodes). Overall survival at 5 years was 54.6 % (95 % CI: 48.57–60.58). Postoperative mortality was 6 % (n = 2) and postoperative complications 19 % (n = 6). It is feasible to integrate IORT as a component of radiotherapy in combined modality therapy of gastric cancer. Local control is high in the radiation boosted area, but marginal regional extension (in particular, involving the hepatic hilum) might be considered as part of the anatomic IORT target volume at risk in pN+ patients.

Little is known of practice patterns on advanced prostate cancer (PC) in Spain. The study objectives were to investigate practice patterns in the management of PC and to determine the adherence to the 2007 Spanish guidelines for the management of PC. An epidemiological, cross-sectional study was undertaken. Study-specific questionnaires were distributed to all centers with radiation oncology (RO) facilities delivering megavoltage radiation therapy (RT) in Spain (n = 108). A questionnaire evaluated diagnostic and treatment approaches to PC in low-risk and high-risk cases. And a 12-item questionnaire was used to assess guidelines adherence. Responses were obtained from 102 centers (94.0 % response rate). In the high-risk scenario, the majority of clinicians (99.0 %) chose combined modality treatment with RT and androgen deprivation (AD) and 93.0 % recommended long-term AD. External-beam RT (EBRT) doses ranging 72–76 Gy were used in 59.5 % of centers and >76 Gy was employed in 40.5 %. In the low-risk scenario, EBRT was chosen by 59.6 %, brachytherapy by 39.4 %, and active surveillance by 1 %. The consensus was high (score 5 + 4 ≥ 90 %) on 8/12 questions assessing adherence to guidelines, being high specifically on items related to RT technique, RT dose, combination of HT and RT in intermediate/high-risk patients, and prognostic factors. This is the largest survey to date of Spanish RO departments dealing with PC. The study results therefore likely provide a highly reliable picture of clinical practice in Spain in this century and show how this practice is influenced by clinical evidence from randomized trials and consensus conferences.

Background Standard treatment of advanced squamous cell carcinoma of the head and neck (SCCHN) is concurrent chemoradiation. Erlotinib is an oral tyrosine kinase inhibitor of epidermal growth factor receptor, which has shown activity in SCCHN. Phase I study aims to determine the maximum tolerated dose and dose-limiting toxicity (DLT) of adding erlotinib to chemoradiation therapy in patients with surgically resected locally advanced SCCHN. Patients and methods Inclusion criteria—SCCHN patients with T3 or T4 primary lesion (except T3N0 with negative resection margins); pathologic N2–N3 disease; poor prognostic findings; age 18–70 years; Eastern Cooperative Oncology Group performance status of zero to one; no evidence of metastasis; adequate organic function and written informed consent. Study design—dose-escalating phase I study with three cohorts of three to six patients each that received increasing doses of erlotinib (100–150 mg/day p.o.) and cisplatin (30–40 mg/m2 i.v., day 1) for 7 weeks. Radiotherapy—standard regimen of 1.8 Gy daily (5 fractions/week) to a maximum total dose of 63 Gy in 7 weeks. Results Thirteen male (median age: 57 years) were enrolled. Overall, the regimen was well tolerated. Two of three patients treated at dose level III (erlotinib: 150 mg/day; cisplatin: 40 mg/m2) developed DLT consisting of grade 3 infection and grade 3 mucositis. Other toxic effects included diarrhea, asthenia, and rash. Recommended dose for additional studies: erlotinib 150 mg/day p.o.; cisplatin 30 mg/m2/week i.v. Conclusion Erlotinib can be safely combined with chemoradiation without requiring dose reduction of chemo- or radiotherapy in this postsurgical population.

Introduction: Identification of patients at risk of hereditary cancer is an essential component of oncology practice, since it enables clinicians to offer early detection and prevention programs. However, the large number of hereditary syndromes makes it difficult to take them all into account in daily practice. Consequently, the National Cancer Institute (NCI) has suggested a series of criteria to guide initial suspicion. Objective: It was the aim of this study to assess the perception of the risk of hereditary cancer according to the NCI criteria in our medical oncology service. Methods: We retrospectively analyzed the recordings of the family history in new cancer patients seen in our medical oncology service from January to November 2009, only 1 year before the implementation of our multidisciplinary hereditary cancer program. Results: The family history was recorded in only 175/621 (28%) patients. A total of 119 (19%) patients met 1 or more NCI criteria (1 criterion, n = 91; 2 criteria, n = 23; 3 criteria, n = 4; and 4 criteria, n = 1), and only 14 (11.4%) patients were referred to genetic counseling. Conclusion: This study shows that few clinicians record the family history. The perception of the risk of hereditary cancer is low according to the NCI criteria in our medical oncology service. These findings can be explained by the lack of a multidisciplinary hereditary cancer program when the study was performed