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Gastric cancer; Metastasectomy; Oligometastasis Cáncer gástrico; Metastasectomía; Oligometástasis Càncer gàstric; Metastasectomia; Oligometàstasi Background Local treatment improves the outcomes for oligometastatic disease (OMD, i.e. an intermediate state between locoregional and widespread disseminated disease). However, consensus about the definition, diagnosis and treatment of oligometastatic oesophagogastric cancer is lacking. The aim of this study was to develop a multidisciplinary European consensus statement on the definition, diagnosis and treatment of oligometastatic oesophagogastric cancer. Methods In total, 65 specialists in the multidisciplinary treatment for oesophagogastric cancer from 49 expert centres across 16 European countries were requested to participate in this Delphi study. The consensus finding process consisted of a starting meeting, 2 online Delphi questionnaire rounds and an online consensus meeting. Input for Delphi questionnaires consisted of (1) a systematic review on definitions of oligometastatic oesophagogastric cancer and (2) a discussion of real-life clinical cases by multidisciplinary teams. Experts were asked to score each statement on a 5-point Likert scale. The agreement was scored to be either absent/poor (2 years, either upfront local treatment or systemic treatment followed by restaging was considered as treatment (fair agreement). Conclusion The OMEC project has resulted in a multidisciplinary European consensus statement for the definition, diagnosis and treatment of oligometastatic oesophagogastric adenocarcinoma and squamous cell cancer. This can be used to standardise inclusion criteria for future clinical trials.

Contains fulltext : 293876.pdf (Publisher’s version ) (Open Access) INTRODUCTION: Patients with early-stage and locally advanced rectal cancer are often treated with neoadjuvant therapy followed by surgery or watch and wait. This study evaluated the role of circulating tumor DNA (ctDNA) to measure disease after neoadjuvant treatment and surgery to optimize treatment choices. MATERIALS AND METHODS: Patients with rectal cancer treated with both chemotherapy and radiotherapy were included and diagnostic biopsies were analyzed for tumor-specific mutations. Presence of ctDNA was measured in plasma by tracing the tumor-informed mutations using a next-generation sequencing panel. The association between ctDNA detection and clinicopathological characteristics and progression-free survival was measured. RESULTS: Before treatment ctDNA was detected in 69% (35/51) of patients. After neoadjuvant therapy ctDNA was detected in only 15% (5/34) of patients. In none of the patients with a complete clinical response who were selected for a watch and wait strategy (0/10) or patients with ypN0 disease (0/8) ctDNA was detected, whereas it was detected in 31% (5/16) of patients with ypN + disease. After surgery ctDNA was detected in 16% (3/19) of patients, of which all (3/3) developed recurrent disease compared to only 13% (2/16) in patients with undetected ctDNA after surgery. In an exploratory survival analysis, both ctDNA detection after neoadjuvant therapy and after surgery was associated with worse progression-free survival (p = 0.01 and p = 0.007, respectively, Cox-regression). CONCLUSION: These data show that in patients with early-stage and locally advanced rectal cancer tumor-informed ctDNA detection in plasma using ultradeep sequencing may have clinical value to complement response prediction after neoadjuvant therapy and surgery. 01 juli 2023

PURPOSE To analyze the effect of radiation dose escalation to the primary tumor on local tumor control in definitive chemoradiation (dCRT) for patients with esophageal cancer. PATIENTS AND METHODS Patients with medically inoperable and/or irresectable esophageal carcinoma, referred for dCRT, were randomly assigned between a standard dose (SD) of 50.4 Gy/1.8 Gy for 5.5 weeks to the tumor and regional lymph nodes and a high dose (HD) up to a total dose of 61.6 Gy to the primary tumor. Chemotherapy consisted of courses of concurrent carboplatin (area under the curve 2) and paclitaxel (50 mg/m2) in both arms once a week for 6 weeks. The primary end point was local progression-free survival. RESULTS Between September 2012 and June 2018, 260 patients were included. Squamous cell carcinoma (SCC) was present in 61% of patients, and 39% had adenocarcinoma (AC). Radiation treatment was completed by 94%, and 85% had at least five courses of chemotherapy. The median follow-up time for all patients was 50 months. The 3-year local progression-free survival (LPFS) was 70% in the SD arm versus 73% in the HD arm (not significant). The LPFS for SCC and AC was 75% versus 79% and 61% versus 61% for SD and HD, respectively (not significant). The 3-year locoregional progression-free survival was 52% and 59% for the SD and HD arms, respectively ( P = .08). Overall, grade 4 and 5 common toxicity criteria were 12% and 5% in the SD arm versus 14% and 10% in the HD arm, respectively ( P = .15). CONCLUSION In dCRT for esophageal cancer, radiation dose escalation up to 61.6 Gy to the primary tumor did not result in a significant increase in local control over 50.4 Gy. The absence of a dose effect was observed in both AC and SCC.

Introduction: The aim of this retrospective study was to determine the patterns of recurrence and overall survival (OS) in patients achieving clinical complete response after treatment with definitive chemoradiation (CRT) for proximal esophageal cancer.Materials and methods: Patients with proximal esophageal cancer treated with CRT between 2004 and 2014 in 11 centers in the Netherlands were included. OS and progression-free survival (PFS) were calculated using the Kaplan-Meier method. Cumulative incidence of first recurrence (locoregional or distant) and locoregional recurrence (LRR) were assessed using competing risk analyses.Results: In 197 of the 200 identified patients, response was evaluated, 133 (68%) showed a complete response. In complete responders, median OS, three-year OS, and PFS were 45.0 months (95% CI 34.8-61.5 months), 58% (95% CI 48-66), and 49% (95% CI 40-57), respectively. Three- and five-year risk of recurrence were respectively 40% (95% CI 31-48), and 45% (95% CI 36-54). Three- and five-year risk of LRR were 26% (95% CI 19-33), and 30% (95% CI 22-38). Eight of 32 patients with an isolated LRR underwent salvage surgery, with a median OS of 32.0 months (95% CI 6.8-not reached).Conclusion: In patients with a complete response after definitive CRT for proximal esophageal cancer, most recurrences were locoregional and developed within the first three years after CRT. These findings suggest to shorten locoregional follow-up from five to three years. (C) 2021 The Authors. Published by Elsevier Ltd.

Aim A prolonged interval (>4 weeks) between short-course radiotherapy (25 Gy in five fractions) (SCRT-delay) and total mesorectal excision for rectal cancer has been associated with a decreased postoperative complication rate and offers the possibility of organ preservation in the case of a complete tumour response. This prospective cohort study systematically evaluated patient-reported bowel dysfunction and physician-reported radiation-induced toxicity for 8 weeks following SCRT-delay. Method Patients who were referred for SCRT-delay for intermediate risk, oligometastatic or locally advanced rectal cancer were included. Repeated measurements were done for patient-reported bowel dysfunction (measured by the low anterior resection syndrome [LARS] questionnaire and categorized as no, minor or major LARS) and physician-reported radiation-induced toxicity (according to Common Terminology Criteria for Adverse Events version 4.0) before start of treatment (baseline), at completion of SCRT and 1, 2, 3, 4, 6 and 8 weeks thereafter. Results Fifty-one patients were included; 31 (61%) were men and the median age was 67 years (range 44-91). Patient-reported bowel dysfunction and physician-reported radiation-induced toxicity peaked at weeks 1-2 after completion of SCRT and gradually declined thereafter. Major LARS was reported by 44 patients (92%) at some time during SCRT-delay. Grade 3 radiation-induced toxicity was reported in 17 patients (33%) and concerned predominantly diarrhoea. No Grade 4-5 radiation-induced toxicity occurred. Conclusion During SCRT-delay, almost every patient experiences temporary mild-moderate radiation-induced toxicity and major LARS, but life-threatening toxicity is rare. SCRT-delay is a safe alternative to SCRT-direct surgery that should be proposed when counselling rectal cancer patients on neoadjuvant strategies.

Contains fulltext : 229287.pdf (Publisher’s version ) (Open Access) BACKGROUND AND PURPOSE: A matched comparison of external beam radiotherapy (EBRT) versus brachytherapy recently demonstrated that EBRT appears at least as effective for palliating dysphagia in patients with incurable esophageal cancer. The aim of this analysis was to compare patient-reported outcomes (PROs) after EBRT versus brachytherapy. MATERIALS AND METHODS: In a multicenter prospective cohort study, patients with incurable esophageal cancer requiring palliation of dysphagia were included to undergo EBRT (20 Gy in 5 fractions). This EBRT cohort was compared to the single-dose 12 Gy brachytherapy cohort of the previously reported SIREC-trial. Propensity score matching was applied to adjust for baseline imbalances. The primary endpoint of dysphagia improvement was reported previously. PROs were secondary outcomes and assessed at baseline and 3 months after treatment using EORTC QLQ-C30 and QLQ-OES18 questionnaires. RESULTS: A total of 115 enrolled EBRT patients and 93 brachytherapy patients were eligible. After matching, 69 well-balanced pairs remained. At follow-up, significant deteriorations in functioning (i.e. physical, role, social), pain, appetite loss, and trouble with taste were observed after brachytherapy. In the EBRT group, such deterioration was observed only for role functioning, while significant improvements in trouble with eating and pain were found. Between-group comparison showed mostly comparable PRO changes, but significantly favored EBRT with regard to nausea, vomiting, pain, and appetite loss. CONCLUSION: Short course EBRT results in similar or better PROs at 3 months after treatment compared to single-dose brachytherapy for the palliation of malignant dysphagia. These findings further support its use and inclusion in clinical practice guidelines.

Introduction: Glioblastoma (GBM) is the most common malignant primary brain tumour which has, despite extensive treatment, a median overall survival of 15 months. Radiomics is the high-throughput extraction of large amounts of image features from radiographic images, which allows capturing the tumour phenotype in 3D and in a non-invasive way. In this study we assess the prognostic value of CT radiomics for overall survival in patients with a GBM. Materials and methods: Clinical data and pre-treatment CT images were obtained from 218 patients diagnosed with a GBM via biopsy who underwent radiotherapy +/- temozolomide between 2004 and 2015 treated at three independent institutes (n = 93, 62 and 63). A clinical prognostic score (CPS), a simple radiomics model consisting of volume based score (VPS), a complex radiomics prognostic score (RPS) and a combined clinical and radiomics (C + R)PS model were developed. The population was divided into three risk groups for each prognostic score and respective Kaplan-Meier curves were generated. Results: Patient characteristics were broadly comparable. Clinically significant differences were observed with regards to radiation dose, tumour volume and performance status between datasets. Image acquisition parameters differed between institutes. The cross-validated c-indices were moderately discriminative and for the CPS ranged from 0.63 to 0.65; the VPS c-indices ranged between 0.52 and 0.61; the RPS cindices ranged from 0.57 to 0.64 and the combined clinical and radiomics model resulted in c-indices of 0.59-0.71. Conclusion: In this study clinical and CT radiomics features were used to predict OS in GBM. Discrimination between low-, middle- and high-risk patients based on the combined clinical and radiomics model was comparable to previous MRI-based models. (c) 2021 The Author(s). Published by Elsevier B.V. Radiotherapy and Oncology 160 (2021) 132-139 This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Background and purpose: Patients with advanced cancer may develop painful bone metastases, potentially resulting in pathological fractures. Adequate fracture risk assessment is of key importance to prevent fracturing and maintain mobility. This study aims to validate the clinical reliability of axial cortical involvement with a 30 mm threshold on conventional radiographs to assess fracture risk in femoral bone metastases.Materials and methods: All patients with bone metastases who received radiotherapy for pain included in two multicentre prospective studies were selected. Conventional radiographs obtained at a maximum of two months prior to radiotherapy were collected. Three experts independently measured lesions and scored radiographic characteristics. Sensitivity, specificity, positive (PPV) and negative predictive value (NPV) were calculated.Results: Hundred patients were included with a median follow-up of 23.0 months (95%CI: 10.6-35.5). Two fractures occurred in lesions with axial cortical involvement = 30 mm. Sensitivity, specificity, PPV and NPV of axial cortical involvement for predicting femoral fractures were 86%, 50%, 20% and 96%, respectively. Patients with lesions >= 30 mm had a 5.3 times higher fracture risk than patients with smaller lesions.Conclusion: Our validation study confirmed the use of 30 mm axial cortical involvement to assess fracture risk in femoral bone metastases. Until a more accurate and practically feasible method has been developed, this clinical parameter remains an easy method to assess femoral fracture risk to aid patients and clinicians to choose the optimal individual treatment modality. (C) 2019 Elsevier B.V. All rights reserved.

Background The STAR-TReC trial is an international multi-center, randomized, phase II study assessing the feasibility of short-course radiotherapy or long-course chemoradiotherapy as an alternative to total mesorectal excision surgery. A new target volume is used for both (chemo)radiotherapy arms which includes only the mesorectum. The treatment planning QA revealed substantial variation in dose to organs at risk (OAR) between centers. Therefore, the aim of this study was to determine the treatment plan variability in terms of dose to OAR and assess the effect of a national study group meeting on the quality and variability of treatment plans for mesorectum-only planning for rectal cancer. Methods Eight centers produced 25 × 2 Gy treatment plans for five cases. The OAR were the bowel cavity, bladder and femoral heads. A study group meeting for the participating centers was organized to discuss the planning results. At the meeting, the values of the treatment plan DVH parameters were distributed among centers so that results could be compared. Subsequently, the centers were invited to perform replanning if they considered this to be necessary. Results All treatment plans, both initial planning and replanning, fulfilled the target constraints. Dose to OAR varied considerably for the initial planning, especially for dose levels below 20 Gy, indicating that there was room for trade-offs between the defined OAR. Five centers performed replanning for all cases. One center did not perform replanning at all and two centers performed replanning on two and three cases, respectively. On average, replanning reduced the bowel cavity V20Gy by 12.6%, bowel cavity V10Gy by 22.0%, bladder V35Gy by 14.7% and bladder V10Gy by 10.8%. In 26/30 replanned cases the V10Gy of both the bowel cavity and bladder was lower, indicating an overall lower dose to these OAR instead of a different trade-off. In addition, the bowel cavity V10Gy and V20Gy showed more similarity between centers. Conclusions Dose to OAR varied considerably between centers, especially for dose levels below 20 Gy. The study group meeting and the distribution of the initial planning results among centers resulted in lower dose to the defined OAR and reduced variability between centers after replanning. Trial registration The STAR-TReC trial, ClinicalTrials.gov Identifier: NCT02945566. Registered 26 October 2016, https://clinicaltrials.gov/ct2/show/NCT02945566).

323 Background: Definitive chemoradiotherapy (dCRT) can achieve durable local control and even curation in patients with locally advanced irresectable esophageal carcinoma. However, due to side-effects of this treatment, survival benefit may come at the cost of quality of life (QoL). This study aims to report prospectively collected patient-reported outcome measures (PROMs) after dCRT. Methods: Patients with squamous cell carcinoma or adenocarcinoma of the esophagus receiving dCRT and participating in the Prospective Observational Cohort Study of Oesophageal-gastric cancer Patients (POCOP) were eligible. dCRT was defined as radiotherapy consisting of at least 50.4Gy/28F with concomitant weekly carboplatin and paclitaxel. PROMs were extracted from the POCOP database, which uses validated questionnaires EORTC QLQ-C30 and OG25. Questionnaires were collected at baseline, at three months (3M), at six months (6M) and every three months thereafter for a total follow-up of 2 years. Clinical data were derived from the nationwide Netherlands Cancer Registry (NCR). PROMs were compared to baseline values using mixed effect models. Results: In total, 153 patients were included. The median age was 70 years and patients were predominantly male (73.2%). 51% of patients had esophageal adenocarcinoma and the majority had a performance status score 0 (39.9%) or 1 (46.4%). The number of returned questionnaires ranged from 96 at baseline to 106 at 3M and 36 at 2 years. Global Health Status at baseline was 69.9 (SD 17.6) and declined at 3M, although not significantly. At later time points, scores showed a trend towards improvement compared to baseline. Patients reported significantly lower physical (71.5, SD 19.4), role (67.8, SD 31.0) and social functioning (72.4, SD 29.1) at 3M compared to baseline (82.7, 79.7 and 81.5 respectively, all p

BACKGROUNDThe management of proximal esophageal cancer differs from that of tumors located in the mid and lower part of the esophagus due to the close vicinity of vital structures. Non-surgical treatment options like radiotherapy and definitive chemoradiation (CRT) have been implemented. The trends in (non-)surgical treatment and its impact on overall survival (OS) in patients with proximal esophageal cancer are unclear, related to its rare disease status. To optimize treatment strategies and counseling of patients with proximal esophageal cancer, it is therefore essential to gain more insight through real-life studies.AIMTo establish trends in treatment and OS in patients with proximal esophageal cancer.METHODSIn this population-based study, patients with proximal esophageal cancer diagnosed between 1989 and 2014 were identified in the Netherlands Cancer Registry. The proximal esophagus consists of the cervical esophagus and the upper thoracic section, extending to 24 cm from the incisors. Trends in radiotherapy, chemotherapy, and surgery, and OS were assessed. Analyses were stratified by presence of distant metastasis. Multivariable Cox proportional hazards regression analyses was performed to assess the effect of period of diagnosis on OS, adjusted for patient, tumor, and treatment characteristics.RESULTSIn total, 2783 patients were included. Over the study period, the use of radiotherapy, resection, and CRT in non-metastatic disease changed from 53%, 23%, and 1% in 1989-1994 to 21%, 9%, and 49% in 2010-2014, respectively. In metastatic disease, the use of chemotherapy and radiotherapy increased over time. Median OS of the total population increased from 7.3 mo [95% confidence interval (CI): 6.4-8.1] in 1989-1994 to 9.5 mo (95%CI: 8.1-10.8) in 2010-2014 (logrank P CONCLUSIONOS significantly improved in non-metastatic proximal esophageal cancer, likely to be associated with an increased use of CRT. Patterns in metastatic disease did not change significantly over time.

To reduce the risk of local recurrence after rectal cancer surgery, neoadjuvant radiotherapy (RT) can be applied. However, as this causes morbidity and increases mortality, new Dutch guidelines withhold RT in low-risk patients. The aim of this study is to investigate if early local recurrence and one-year mortality in rectal cancer patients has changed since this more restricting indication for neoadjuvant RT was introduced in 2014.This retrospective study included all consecutive patients treated with a mesorectal excision for primary rectal cancer in the Amphia Hospital, the Netherlands, between January 2011 and July 2016. Data were extracted from the electronic patient records. Survival data were collected from the Municipal Personal Records Database.Between 2011 and July 2016, 407 resections of primary rectal cancer without synchronic metastases were performed, 225 under the old guidelines and 182 under the new guidelines. Significantly fewer patients received neoadjuvant treatment under the new guidelines (89% vs 41%, p 0.001). Both clinical tumour stage (p = 0.001) and clinical lymph node stage (p 0.001) were lower in the new group, but no difference in pathologic TN-stage was found. There was no difference in one-year local recurrence (2.2% in both groups, p = 0.987), nor in one-year mortality (5.3% vs 3.8%, p = 0.479).Introducing a new guideline and thereby restricting the indication for neoadjuvant RT in rectal cancer patients did not increase the early local recurrence rate or decreased one-year mortality in our hospital.

Background and purpose:Two plausible mechanisms to explain the appearance of visual phosphenes are: direct activation of the photochemicals in the retina and the generation of Cherenkov radiation in the vitreous humour. In this clinical trial we investigated the occurrence of visual phosphenes in external photon beam radiation therapy.Material and methods: Logistic regression analysis is used to examine whether seeing light flashes and seeing steady light depended on the ambient light intensity and the dose.Results: In total, 465 treatments of 25 patients were analysed. The odds of seeing light flashes multiply by 0,926 as the ambient light intensity increases by 10 lux. Similarly, the odds multiply by 1,604 as the dose to the retina increases by 10 cGy. The odds of seeing steady light multiply by 1,540 as the dose to the vitreous humour increases by 10 cGy.Conclusions: We postulate that one should reduce the dose rate, instruct patients to keep the eyes open and increase the illuminance in the treatment room to reduce the probability of experiencing visual phosphenes. We hypothesize that melanopsin is involved in the visual phosphenes and that fatigue of patients might be correlated with the observation of visual phosphenes.

PURPOSE Preoperative chemoradiotherapy according to the chemoradiotherapy for esophageal cancer followed by surgery study (CROSS) has become a standard of care for patients with locally advanced resectable esophageal or junctional cancer. We aimed to assess long-term outcome of this regimen. METHODS From 2004 through 2008, we randomly assigned 366 patients to either five weekly cycles of carboplatin and paclitaxel with concurrent radiotherapy (41.4 Gy in 23 fractions, 5 days per week) followed by surgery, or surgery alone. Follow-up data were collected through 2018. Cox regression analyses were performed to compare overall survival, cause-specific survival, and risks of locoregional and distant relapse. The effect of neoadjuvant chemoradiotherapy beyond 5 years of follow-up was tested with time-dependent Cox regression and landmark analyses. RESULTS The median follow-up was 147 months (interquartile range, 134-157). Patients receiving neoadjuvant chemoradiotherapy had better overall survival (hazard ratio [HR], 0.70; 95% CI, 0.55 to 0.89). The effect of neoadjuvant chemoradiotherapy on overall survival was not time-dependent ( P value for interaction, P = .73), and landmark analyses suggested a stable effect on overall survival up to 10 years of follow-up. The absolute 10-year overall survival benefit was 13% (38% v 25%). Neoadjuvant chemoradiotherapy reduced risk of death from esophageal cancer (HR, 0.60; 95% CI, 0.46 to 0.80). Death from other causes was similar between study arms (HR, 1.17; 95% CI, 0.68 to 1.99). Although a clear effect on isolated locoregional (HR, 0.40; 95% CI, 0.21 to 0.72) and synchronous locoregional plus distant relapse (HR, 0.43; 95% CI, 0.26 to 0.72) persisted, isolated distant relapse was comparable (HR, 0.76; 95% CI, 0.52 to 1.13). CONCLUSION The overall survival benefit of patients with locally advanced resectable esophageal or junctional cancer who receive preoperative chemoradiotherapy according to CROSS persists for at least 10 years.

Background: Previous studies describe a large variation in the proportion of patients undergoing treatment with curative intent for esophageal (EC) and gastric cancer (GC). Since centralization of surgical care was initiated and more awareness regarding hospital practice variation was potentially present, we hypothesized that hospital practice variation for potentially curable EC and GC patients changed over time. Methods: Patients with potentially curable EC (n = 10,115) or GC (n = 3988) diagnosed between 2012–2017 were selected from the Netherlands Cancer Registry. Multilevel multivariable logistic regression was used to analyze the differences in the probability of treatment with curative intent between hospitals of diagnosis over time, comparing 2012−2014 with 2015−2017. Relative survival (RS) between hospitals with different probabilities of treatment with curative intent were compared. Results: The range of proportions of patients undergoing treatment with curative intent per hospital of diagnosis for EC was 45–95 % in 2012−2014 and 54–89 % in 2015−2017, and for GC 52–100 % and 45–100 %. The adjusted variation declined for EC with Odds Ratios ranging from 0.50 to 1.72 between centers in the first period to 0.70–1.44 in the second period (p < 0.001) and did not change for GC (Odds Ratios ranging from 0.78 to 1.23 to 0.82–1.23, (p = 1.00)). A higher probability of treatment with curative intent was associated with a better survival for both malignancies. Conclusion: Although substantial variation between hospitals of diagnosis in the probability in receiving treatment with curative intent still exists for both malignancies, it has decreased for EC. A low probability of receiving curative treatment remained associated with worse survival.

Geographical variation in cancer care has been observed between and within countries. Variation in treatment may occur at any point along the cancer care continuum attributing to potentially avoidable disparities in patient outcomes such as survival. Other studies have shown a large variation in the proportion of patients undergoing treatment with curative intent for esophageal(EC) and gastric cancer(GC). Due to these studies and thus an increased awareness, we hypothesize that variation has decreased over time. Methods Patients with potentially curable EC (n = 10,115) or GC (n = 3,983) diagnosed between 2012-2017 were selected from the Netherlands Cancer Registry. Multilevel multivariable logistic regression was used to examine the differences in the probability of treatment with curative intent between hospitals of diagnosis, comparing 2012-2014 with 2015-2017. We compared relative survival (RS) and relative excess risk of death (RER) between hospitals with different probabilities of treatment with curative intent. Results The range of proportions of patients undergoing treatment with curative intent per hospital of diagnosis was 45-95% in 2012-2014 and 54-89% in 2015-2017 for EC, and 52-100% and 45-100% for GC. The adjusted variation declined for EC with Odds Ratios (ORs) ranging from 0.50 to 1.72 between hospitals in the first period to 0.70–1.44 in the second period (p Conclusion Although substantial variation between hospitals of diagnosis in the probability in receiving treatment with curative intent still exists for both malignancies, it has decreased for EC, but did not change for GC. A low probability of receiving curative treatment was associated with a worse survival. Further research is needed to elucidate the factors associated with the observed variability.

Purpose To determine whether patient-specific finite element (FE) computer models are better at assessing fracture risk for femoral bone metastases compared to clinical assessments based on axial cortical involvement on conventional radiographs, as described in current clinical guidelines. Methods Forty-five patients with 50 femoral bone metastases, who were treated with palliative radiotherapy for pain, were included (64% single fraction (8 Gy), 36% multiple fractions (5 or 6 x 4 Gy)) and were followed for six months to determine whether they developed a pathological femoral fracture. All plain radiographs available within a two month period prior to radiotherapy were obtained. Patient-specific FE models were constructed based on the geometry and bone density obtained from the baseline quantitative CT scans used for radiotherapy planning. Femoral failure loads normalized for body weight (BW) were calculated. Patients with a failure load of 7.5 x BW or lower were identified as having high fracture risk, whereas patients with a failure load higher than 7.5 x BW were classified as low fracture risk. Experienced assessors measured axial cortical involvement on conventional radiographs. Following clinical guidelines, patients with lesions larger than 30 mm were identified as having a high fracture risk. FE predictions were compared to clinical assessments by means of diagnostic accuracy values (sensitivity, specificity and positive (PPV) and negative predictive values (NPV)). Results Seven femurs (14%) fractured during follow-up. Median time to fracture was 8 weeks. FE models were better at assessing fracture risk in comparison to axial cortical involvement (sensitivity 100% vs. 86%, specificity 74% vs. 42%, PPV 39% vs. 19%, and NPV 100% vs. 95%, for the FE computer model vs. axial cortical involvement, respectively). Conclusions Patient-specific FE computer models improve fracture risk assessments of femoral bone metastases in advanced cancer patients compared to clinical assessments based on axial cortical involvement, which is currently used in clinical guidelines.

Purpose To compare pre-agreed health-related quality of life (HRQOL) domains in patients with esophageal or junctional cancer who received neoadjuvant chemoradiotherapy (nCRT) followed by surgery or surgery alone. Secondary aims were to examine the effect of nCRT on HRQOL before surgery and the effect of surgery on HRQOL. Patients and Methods Patients were randomly assigned to nCRT (carboplatin plus paclitaxel with concurrent 41.4-Gy radiotherapy) followed by surgery or surgery alone. HRQOL was measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Core 30 (QLQ-C30) and –Oesophageal Cancer Module (QLQ-OES24) questionnaires pretreatment and at 3, 6, 9, and 12 months postoperatively. The nCRT group also received preoperative questionnaires. Physical functioning (PF; QLQ-C30) and eating problems (EA; QLQ-OES24) were chosen as predefined primary end points. Predefined secondary end points were global QOL (GQOL; QLQ-C30), fatigue (FA; QLQ-C30), and emotional problems (EM; QLQ-OES24). Results A total of 363 patients were analyzed. No statistically significant differences in postoperative HRQOL were found between treatment groups. In the nCRT group, PF, EA, GQOL, FA, and EM scores deteriorated 1 week after nCRT (Cohen’s d: −0.93, P < .001; 0.47, P < .001; −0.84, P < .001; 1.45, P < .001; and 0.32, P = .001, respectively). In both treatment groups, all end points declined 3 months postoperatively compared with baseline (Cohen’s d: −1.00, 0.33, −0.47, −0.34, and 0.33, respectively; all P < .001), followed by a continuous gradual improvement. EA, GQOL, and EM were restored to baseline levels during follow-up, whereas PF and FA remained impaired 1 year postoperatively (Cohen’s d: 0.52 and −0.53, respectively; both P < .001). Conclusion Although HRQOL declined during nCRT, no effect of nCRT was apparent on postoperative HRQOL compared with surgery alone. In addition to the improvement in survival, these findings support the view that nCRT according to the Chemoradiotherapy for Esophageal Cancer Followed by Surgery Study–regimen can be regarded as a standard of care.

Highlights • Surface scanning is used for positioning and for intra-fractional motion monitoring. • Patients are able to lie still below a threshold of 3 mm. • A limited number of repositioning procedures per fraction was needed. • Two lateral fields with a CTV-PTV margin of 5 mm were used for WBRT without a mask., The aim of the study was to investigate the clinical feasibility of whole-brain radiation therapy without a thermoplastic mask. Positioning and intra-fractional motion monitoring were performed using optical surface scanning. The motion threshold was 3 mm/3 degrees. The group mean vector deviation was 1.1 mm. The roll was larger compared to pitch and rotation. Two patients out of 30 were not able to lie still. All other patients completed their treatment successfully without a mask. With a probability of success of 93%, we concluded that irradiation without a mask is a clinically feasible method.

Background: Whole brain radiotherapy (WBRT) is considered standard of care for patients with multiple brain metastases or unfit for radical treatment modalities. Recent studies raised discussion about the expected survival after WBRT. Therefore, we analysed survival after WBRT for brain metastases ‘in daily practice’ in a large nationwide multicentre retrospective cohort. Methods: Between 2000 and 2014, 6325 patients had WBRT (20 Gy in 4 Gy fractions) for brain metastases from non-small cell lung cancer (NSCLC; 4363 patients) or breast cancer (BC; 1962 patients); patients were treated in 15 out of 21 Dutch radiotherapy centres. Survival was calculated by the Kaplan–Meier method from the first day of WBRT until death as recorded in local hospital data registration or the Dutch Municipal Personal Records Database. Findings: The median survival was 2.7 months for NSCLC and 3.7 months for BC patients (p 70 years, survival was 4.0, 3.0, 2.8 and 2.1 months, respectively (p 70 years being 1.05, 1.19 and 1.34, respectively. Primary BC (HR: 0.83) and female sex (HR: 0.85) were related to better survival (p

Purpose: To investigate whether the Geriatric 8 (G8) and the Timed Get Up and Go Test (TGUGT) and clinical and demographic patient characteristics were associated with acute toxicity of radiation therapy and noncompliance in elderly cancer patients being irradiated with curative intent.Methods and Materials: Patients were eligible if aged >= 65 years and diagnosed with breast, non-small cell lung, prostate, head and neck, rectal, or esophageal cancer, and were referred for curative radiation therapy. We recorded acute toxicity and noncompliance and identified potential predictors, including the G8 and TGUGT.Results: We investigated 402 patients with a median age of 72 years (range, 65-96 years). According to the G8, 44.4% of the patients were frail. Toxicity grade >= 3 was observed in 22% of patients who were frail according to the G8 and 9.1% of patients who were not frail. The difference was 13% (confidence interval 5.2%-20%; P=.0006). According to the TGUGT 18.8% of the patients were frail; 21% of the frail according to the TGUGT developed toxicity grade > 3, compared with 13% who were not frail. The difference was 7.3% (confidence interval -2.7% to 17%; P=.11). Overall compliance was 95%. Toxicity was most strongly associated with type of primary tumor, chemotherapy, age, and World Health Organization performance status. Compliance was associated with type of primary tumor and age.Conclusions: The usefulness of the TGUGT and G8 score in daily practice seems to be limited. Type of primary tumor, chemoradiotherapy, age, and World Health Organization performance status were more strongly associated with acute toxicity. Only chemoradiotherapy and age were associated with noncompliance. Overall the compliance was very high. To allow better-informed treatment decisions, a more accurate prediction of toxicity is desirable. (C) 2017 Published by Elsevier Inc.

Aim To report the long term results of the CROSS trial with a minimum follow-up of 10 years. Background Neoadjuvant chemoradiotherapy according to the Dutch randomised controlled ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) has become standard of care for patients with cancer of the oesophagus or oesophagogastric junction. Methods Patients with locally advanced resectable squamous cell carcinoma or adenocarcinoma of the oesophagus or oesophagogastric junction were randomised between neoadjuvant chemoradiotherapy (five weekly cycles of intravenous carboplatin [AUC 2 mg/mL per min] and intravenous paclitaxel [50 mg/m² of body-surface area]) with concurrent 41.4 Gy radiotherapy given in 23 fractions of 1.8 Gy, 5 days per week) plus surgery versus surgery alone. Primary endpoint was overall survival, defined from date of randomisation to date of all-cause death or to last day of follow-up. Analysis was by intention-to-treat. Results Between March 2004 and 2008, eight centres enrolled 368 patients. Some 178 were analysed in the chemoradiotherapy plus surgery group and 188 in the surgery alone group. After a median follow-up for surviving patients of 146.6 months (IQR 133.5-156.6), median overall survival was 49.0 months (95%CI 34.7-76.6) in the neoadjuvant chemoradiotherapy plus surgery group compared to 25.1 months (95%CI 19.1-39.4) in the surgery alone group, which was significantly different (HR 0.71 [95%CI 0.55-0.90]; log-rank p=0·005). Ten-year overall survival was 38% (95%CI 31%-45%) in the neoadjuvant chemoradiotherapy followed by surgery group compared to 26% (95%CI 20%-33%) in the surgery alone group (HR 0.69 [95%CI 0.54-0.89]). For patients with squamous cell carcinoma ten-year overall survival was 46% (95%CI 33%-64%) in the neoadjuvant chemoradiotherapy plus surgery group compared to 23% (95%CI 13%-40%) in the surgery alone group. For patients with adenocarcinoma ten-year overall survival was 36% (95%CI 29%-45%) in the neoadjuvant chemoradiotherapy plus surgery group compared to 26% (95%CI 20%-35%) in the surgery alone group. Conclusion Survival benefit of patients with locally advanced resectable squamous cell carcinoma or adenocarcinoma of the oesophagus or oesophagogastric junction receiving neoadjuvant chemoradiotherapy persists for at least 10 years compared to patients undergoing surgery alone.

Objectives According to new Dutch guidelines for rectal cancer, MRI-defined tumour stage determines whether preoperative radiotherapy is indicated. Therefore, we sought to evaluate if preoperative MRI accurately predicts the indication for neoadjuvant treatment in rectal cancer cases in daily practice according to the new Dutch guidelines. Methods Data for all rectal cancer patients who underwent mesorectal excision in our hospital, between January 2011 and January 2018 were collected retrospectively. We compared histopathologic outcome with tumour staging on preoperative MRI for patients who received no radiotherapy prior to resection or short-course radiotherapy directly followed by resection. Results Of 223 patients treated according to the old guidelines, 94% received neoadjuvant therapy. Of 301 patients treated according to the new guidelines, only 49% did. Under the old guidelines, MRI predicted lymph node metastases with a sensitivity of 74.2% and a specificity of 52.6%. With the new guidelines, sensitivity was 47.5% and specificity was 77.3%. The new guidelines resulted in 45% more patients not being exposed to disadvantages of radiotherapy, but 13% of all patients were undertreated. Conclusions Concordance between clinical lymph node staging on preoperative MRI and histopathologic staging is limited, resulting in many rectal cancer patients not receiving adequate neoadjuvant therapy.

Background: We assessed the use of external beam radiotherapy, brachytherapy chemoradiotherapy and chemotherapy in patients with metastatic esophageal cancer and evaluated the effect on overall survival.Methods: We included all patients diagnosed with synchronous metastatic esophageal cancer in the south of the Netherlands between 1 January 1994 and 31 December 2013. Proportions of patients treated with external beam radiotherapy, brachytherapy, chemoradiotherapy and chemotherapy were described with respect to the period of diagnosis, patient and tumor characteristics. Independent risk factors for death were discriminated.Results: A total of 1020 patients were included, 61.5% of these patients received palliative treatment with external beam radiotherapy, chemoradiotherapy, brachytherapy and/or chemotherapy. The use of external beam radiotherapy decreased from 44.5% in 1994 to 22.2% in 2013 (p = 0.0001), whereas the use of chemoradiotherapy increased from 2.9% in 1994 to 19.1% in 2013 (p Conclusion: The median overall survival of patients diagnosed with metastatic esophageal cancer improved from 18 weeks in 1994–1998 to 25 weeks in 2009–2013. Although this increase could be attributed to stage migration, our population-based study suggests that major changes in treatment strategies and appropriate patient selection might have played a role as well.

Background: Personalized prediction of treatment outcomes can aid patients with cancer when deciding on treatment options. Existing prediction models for esophageal and gastric cancer, however, have mostly been developed for survival prediction after surgery (ie, when treatment has already been completed). Furthermore, prediction models for patients with metastatic cancer are scarce. The aim of this study was to develop prediction models of overall survival at diagnosis for patients with potentially curable and metastatic esophageal and gastric cancer (the SOURCE study). Methods: Data from 13,080 patients with esophageal or gastric cancer diagnosed in 2015 through 2018 were retrieved from the prospective Netherlands Cancer Registry. Four Cox proportional hazards regression models were created for patients with potentially curable and metastatic esophageal or gastric cancer. Predictors, including treatment type, were selected using the Akaike information criterion. The models were validated with temporal cross-validation on their C-index and calibration. Results: The validated model’s C-index was 0.78 for potentially curable gastric cancer and 0.80 for potentially curable esophageal cancer. For the metastatic models, the c-indices were 0.72 and 0.73 for esophageal and gastric cancer, respectively. The 95% confidence interval of the calibration intercepts and slopes contain the values 0 and 1, respectively. Conclusions: The SOURCE prediction models show fair to good c-indices and an overall good calibration. The models are the first in esophageal and gastric cancer to predict survival at diagnosis for a variety of treatments. Future research is needed to demonstrate their value for shared decision-making in clinical practice.

281 Background: To analyze the effect of radiation dose escalation to the primary tumor on local control, locoregional control, survival and toxicity in definitive chemoradiation for esophageal cancer. Methods: Patients with clinical stage T2-4, N0-3, M0 carcinoma of the esophagus were randomized between a standard dose of 50.4 Gy/1.8 Gy/5,5 weeks to the tumor and regional lymph nodes (SD) versus the same dose combined with an integrated boost of 0,4 Gy per fraction (total 61,6 Gy) to the primary tumor (HD). Chemotherapy consisted of 6 weekly concurrent carboplatin (AUC 2) and paclitaxel (50 mg/m2) in both arms. The primary endpoint was local progression free survival (LPFS) and 260 patients were needed to detect a difference of 15% (power: 80%). Secondary endpoints were locoregional progression free survival (LRPFS), overall survival (OS) and toxicity. Patients were stratified for histological subtype. Results: Between September 2012 and June 2018, 260 patients were included. Reasons for inoperability were proximal localization and patient preference (44%), comorbidity (30%), unresectable lymph nodes (11%), T4 (5%), local recurrence 2% and combinations (7%). 61% of the patients had a squamous cell carcinoma (SCC) and 39% had an adenocarcinoma (AC). 94% completed radiation treatment and 85% had at least 5 courses chemotherapy. Median follow up time was 45 months. 3-year LPFS was 70% in the SD arm versus 76% in the HD arm (ns). LPFS for SCC and AC was 74% versus 81% and 62% versus 65% for SD and HD, resp. (ns). 3-year LRPFS was 53% and 63% for the SD and HD arm resp. (p = 0.08). 1 year any progression free survival was 60% for SCC and 50% for AC, without a significant difference between SD and HD (p = 0,5). 3-year OS was 41% versus 40% for SD and HD resp. Overall grade 4 and 5 CTC toxicity was 12% and 4% in the SD arm versus 14% and 10% in the HD arm, resp. Conclusions: In definitive chemoradiation for esophageal cancer, radiation dose escalation up to 61,6 Gy to the primary tumor did not result in a significant increase in local control over 50,4 Gy. Numerical improvement of locoregional control after HD was observed with an increase in toxicity and without improving OS. Clinical trial information: NL38343.018.11.

Introduction: The HERBERT study evaluated a high-dose-rate endorectal brachytherapy boost (HDREBT) after EBRT in medically inoperable/elderly patients with rectal cancer. The response-rates are promising but not without risk of toxicity. The current analysis provides a comprehensive overview of patient reported, physician reported and endoscopically observed toxicity. Material and methods: A brachytherapy dose finding study was performed in 38 inoperable/elderly patients with T2-T4N0-1 rectal cancer. Patients received EBRT (13 x 3 Gy) followed by three weekly HDREBT applications (5-8 Gy). Toxicity was assessed via three methods: patient and physician (CTCAEv3) reported rectal symptoms and endoscopically. Wilcoxon's signed rank test, paired t-test and Spearman's correlation were used. Results: Patient reported bowel symptoms showed a marked increase at the end of EBRT and two weeks after HDREBT. Acute grade 2 and 3 proctitis occurred in 68.4% and 13.2% respectively while late grade 2 and >= 3 proctitis occurred in 48% and 40%. Endoscopic evaluation mainly showed erythema and telangiectasia. In three patients frank haemorrhage or ulceration occurred. Most severe toxicity was observed 12-18 months after treatment. Conclusion: For elderly patients with rectal cancer, definitive radiotherapy can provide good tumour response but has a substantial risk of toxicity. The potential benefit and risks of a HDREBT boost above EBRT alone must be further evaluated. (C) 2018 Elsevier B.V. All rights reserved.

Item does not contain fulltext BACKGROUND: Both perioperative chemotherapy and postoperative chemoradiotherapy improve survival in patients with resectable gastric cancer from Europe and North America. To our knowledge, these treatment strategies have not been investigated in a head to head comparison. We aimed to compare perioperative chemotherapy with preoperative chemotherapy and postoperative chemoradiotherapy in patients with resectable gastric adenocarcinoma. METHODS: In this investigator-initiated, open-label, randomised phase 3 trial, we enrolled patients aged 18 years or older who had stage IB- IVA resectable gastric or gastro-oesophageal adenocarcinoma (as defined by the American Joint Committee on Cancer, sixth edition), with a WHO performance status of 0 or 1, and adequate cardiac, bone marrow, liver, and kidney function. Patients were enrolled from 56 hospitals in the Netherlands, Sweden, and Denmark, and were randomly assigned (1:1) with a computerised minimisation programme with a random element to either perioperative chemotherapy (chemotherapy group) or preoperative chemotherapy with postoperative chemoradiotherapy (chemoradiotherapy group). Randomisation was done before patients were given any preoperative chemotherapy treatment and was stratified by histological subtype, tumour localisation, and hospital. Patients and investigators were not masked to treatment allocation. Surgery consisted of a radical resection of the primary tumour and at least a D1+ lymph node dissection. Postoperative treatment started within 4-12 weeks after surgery. Chemotherapy consisted of three preoperative 21-day cycles and three postoperative cycles of intravenous epirubicin (50 mg/m(2) on day 1), cisplatin (60 mg/m(2) on day 1) or oxaliplatin (130 mg/m(2) on day 1), and capecitabine (1000 mg/m(2) orally as tablets twice daily for 14 days in combination with epirubicin and cisplatin, or 625 mg/m(2) orally as tablets twice daily for 21 days in combination with epirubicin and oxaliplatin), received once every three weeks. Chemoradiotherapy consisted of 45 Gy in 25 fractions of 1.8 Gy, for 5 weeks, five daily fractions per week, combined with capecitabine (575 mg/m(2) orally twice daily on radiotherapy days) and cisplatin (20 mg/m(2) intravenously on day 1 of each 5 weeks of radiation treatment). The primary endpoint was overall survival, analysed by intention-to-treat. The CRITICS trial is registered at ClinicalTrials.gov, number NCT00407186; EudraCT, number 2006-004130-32; and CKTO, 2006-02. FINDINGS: Between Jan 11, 2007, and April 17, 2015, 788 patients were enrolled and randomly assigned to chemotherapy (n=393) or chemoradiotherapy (n=395). After preoperative chemotherapy, 372 (95%) of 393 patients in the chemotherapy group and 369 (93%) of 395 patients in the chemoradiotherapy group proceeded to surgery, with a potentially curative resection done in 310 (79%) of 393 patients in the chemotherapy group and 326 (83%) of 395 in the chemoradiotherapy group. Postoperatively, 233 (59%) of 393 patients started chemotherapy and 245 (62%) of 395 started chemoradiotherapy. At a median follow-up of 61.4 months (IQR 43.3-82.8), median overall survival was 43 months (95% CI 31-57) in the chemotherapy group and 37 months (30-48) in the chemoradiotherapy group (hazard ratio from stratified analysis 1.01 (95% CI 0.84-1.22; p=0.90). After preoperative chemotherapy, in the total safety population of 781 patients (assessed together), there were 368 (47%) grade 3 adverse events; 130 (17%) grade 4 adverse events, and 13 (2%) deaths. Causes of death during preoperative treatment were diarrhoea (n=2), dihydropyrimidine deficiency (n=1), sudden death (n=1), cardiovascular events (n=8), and functional bowel obstruction (n=1). During postoperative treatment, grade 3 and 4 adverse events occurred in 113 (48%) and 22 (9%) of 233 patients in the chemotherapy group, respectively, and in 101 (41%) and ten (4%) of 245 patients in the chemoradiotherapy group, respectively. Non-febrile neutropenia occurred more frequently during postoperative chemotherapy (79 [34%] of 233) than during postoperative chemoradiotherapy (11 [4%] of 245). No deaths were observed during postoperative treatment. INTERPRETATION: Postoperative chemoradiotherapy did not improve overall survival compared with postoperative chemotherapy in patients with resectable gastric cancer treated with adequate preoperative chemotherapy and surgery. In view of the poor postoperative patient compliance in both treatment groups, future studies should focus on optimising preoperative treatment strategies. FUNDING: Dutch Cancer Society, Dutch Colorectal Cancer Group, and Hoffmann-La Roche.

Item does not contain fulltext BACKGROUND: Initial results of the ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) comparing neoadjuvant chemoradiotherapy plus surgery versus surgery alone in patients with squamous cell carcinoma and adenocarcinoma of the oesophagus or oesophagogastric junction showed a significant increase in 5-year overall survival in favour of the neoadjuvant chemoradiotherapy plus surgery group after a median of 45 months' follow-up. In this Article, we report the long-term results after a minimum follow-up of 5 years. METHODS: Patients with clinically resectable, locally advanced cancer of the oesophagus or oesophagogastric junction (clinical stage T1N1M0 or T2-3N0-1M0, according to the TNM cancer staging system, sixth edition) were randomly assigned in a 1:1 ratio with permuted blocks of four or six to receive either weekly administration of five cycles of neoadjuvant chemoradiotherapy (intravenous carboplatin [AUC 2 mg/mL per min] and intravenous paclitaxel [50 mg/m(2) of body-surface area] for 23 days) with concurrent radiotherapy (41.4 Gy, given in 23 fractions of 1.8 Gy on 5 days per week) followed by surgery, or surgery alone. The primary endpoint was overall survival, analysed by intention-to-treat. No adverse event data were collected beyond those noted in the initial report of the trial. This trial is registered with the Netherlands Trial Register, number NTR487, and has been completed. FINDINGS: Between March 30, 2004, and Dec 2, 2008, 368 patients from eight participating centres (five academic centres and three large non-academic teaching hospitals) in the Netherlands were enrolled into this study and randomly assigned to the two treatment groups: 180 to surgery plus neoadjuvant chemoradiotherapy and 188 to surgery alone. Two patients in the neoadjuvant chemoradiotherapy group withdrew consent, so a total of 366 patients were analysed (178 in the neoadjuvant chemoradiotherapy plus surgery group and 188 in the surgery alone group). Of 171 patients who received any neoadjuvant chemoradiotherapy in this group, 162 (95%) were able to complete the entire neoadjuvant chemoradiotherapy regimen. After a median follow-up for surviving patients of 84.1 months (range 61.1-116.8, IQR 70.7-96.6), median overall survival was 48.6 months (95% CI 32.1-65.1) in the neoadjuvant chemoradiotherapy plus surgery group and 24.0 months (14.2-33.7) in the surgery alone group (HR 0.68 [95% CI 0.53-0.88]; log-rank p=0.003). Median overall survival for patients with squamous cell carcinomas was 81.6 months (95% CI 47.2-116.0) in the neoadjuvant chemoradiotherapy plus surgery group and 21.1 months (15.4-26.7) in the surgery alone group (HR 0.48 [95% CI 0.28-0.83]; log-rank p=0.008); for patients with adenocarcinomas, it was 43.2 months (24.9-61.4) in the neoadjuvant chemoradiotherapy plus surgery group and 27.1 months (13.0-41.2) in the surgery alone group (HR 0.73 [95% CI 0.55-0.98]; log-rank p=0.038). INTERPRETATION: Long-term follow-up confirms the overall survival benefits for neoadjuvant chemoradiotherapy when added to surgery in patients with resectable oesophageal or oesophagogastric junctional cancer. This improvement is clinically relevant for both squamous cell carcinoma and adenocarcinoma subtypes. Therefore, neoadjuvant chemoradiotherapy according to the CROSS trial followed by surgical resection should be regarded as a standard of care for patients with resectable locally advanced oesophageal or oesophagogastric junctional cancer. FUNDING: Dutch Cancer Foundation (KWF Kankerbestrijding).

Purpose To evaluate the toxicity and efficacy of the combination of external beam radiation therapy (EBRT) followed by high-dose-rate endorectal brachytherapy (HDREBT) boost in elderly and medically inoperable patients with rectal cancer. Methods and Materials A phase 1 dose-escalation study was performed. Treatment consisted of EBRT (13 × 3 Gy) followed by 3 weekly brachytherapy applications 6 weeks later. The HDREBT dose started at 5 Gy per fraction, increasing with 1 Gy per fraction if dose-limiting toxicity (DLT, defined as grade ≥3 proctitis

Objectives: We aimed to examine the association between total number of resected nodes and survival in patients after esophagectomy with and without nCRT.Background: Most studies concerning the potentially positive effect of extended lymphadenectomy on survival have been performed in patients who underwent surgery alone. As nCRT is known to frequently "sterilize" regional nodes, it is unclear whether extended lymphadenectomy after nCRT is still useful. Methods: Patients from the randomized CROSS-trial who completed the entire protocol (ie, surgery alone or chemoradiotherapy + surgery) were included. With Cox regression models, we compared the impact of number of resected nodes as well as resected positive nodes on survival in both groups.Results:One hundred sixty-one patients underwent surgery alone, and 159 patients received multimodality treatment. The median (interquartile range) number of resected nodes was 18 (12-27) and 14 (9-21), with 2 (1-6) and 0 (0-1) resected positive nodes, respectively. Persistent lymph node positivity after nCRT had a greater negative prognostic impact on survival as compared with lymph node positivity after surgery alone. The total number of resected nodes was significantly associated with survival for patients in the surgeryalone arm (hazard ratio per 10 additionally resected nodes, 0.76; P = 0.007), but not in the multimodality arm (hazard ratio 1.00; P = 0.98). Conclusions: The number of resected nodes had a prognostic impact on survival in patients after surgery alone, but its therapeutic value is still controversial. After nCRT, the number of resected nodes was not associated with survival. These data question the indication for maximization of lymphadenectomy after nCRT.

Background Proximal oesophageal cancer is commonly treated with definitive chemoradiation (CRT). The radiation dose and type of chemotherapy backbone in CRT are still under debate. The objective of this study is to compare the treatment benefit of four contemporary CRT regimens. Methods In this retrospective observational cohort study, we included patients with locally advanced squamous cell cancer of the proximal oesophagus, from 11 centers in the Netherlands, treated with definitive CRT between 2004-2014. Each center had a preferential CRT regimen, based on cisplatin (Cis) or carboplatin/paclitaxel (CP) combined with low (≤50.4 Gy) or high (>50.4 Gy) dose radiotherapy (RT). Differences in overall survival (OS) between CRT regimens were assessed using a fully adjusted Cox proportional hazards and propensity score (PS) model. Safety profiles were compared using the Chi-square test. Results Two-hundred patients were included. Fifty-four, 39, 95, and 12 patients were treated with Cis-low-dose RT, Cis-high-dose RT, CP-low-dose RT, and CP-high-dose RT, respectively. Median follow-up was 62.6 months (95% CI 47.9-77.2 months). Median OS (21.9 months; 95% CI 16.9-27.0 months) was comparable between treatment groups (logrank P = 0.88), confirmed in the fully adjusted and PS weighted model (P > 0.05). Grade 3-5 acute adverse events were less frequent in patients treated with CP-low-dose RT (P = 0.01). Conclusions Our study results suggest that carboplatin and paclitaxel combined with RT at a dose of 50.4 Gy is the preferred CRT regimen in patients with locally advanced proximal oesophageal squamous cell cancer, showing comparable OS and a significantly more favourable safety profile when compared with cisplatin-based or higher RT dose regimens. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure J. de Vos-Geelen: Travel / Accommodation / Expenses: BTG; Research grant / Funding (institution), Travel / Accommodation / Expenses: Servier; Advisory / Consultancy: Shire. B.T.A. de Greef: Research grant / Funding (institution): Prinses Beatrix Spierfonds (W.OR12-01). H.W.M. van Laarhoven: Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy, Research grant / Funding (institution): Celgene; Advisory / Consultancy, Research grant / Funding (institution): Lilly; Advisory / Consultancy, Research grant / Funding (institution): Nordic; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Merck Serono; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Philips; Research grant / Funding (institution): Roche. V.E.P.P. Lemmens: Research grant / Funding (institution): Roche. V.C.G. Tjan-Heijnen: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Lilly; Honoraria (self), Travel / Accommodation / Expenses: Accord Healthcare; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Eisai. All other authors have declared no conflicts of interest.

The incidence of esophageal cancer has grown over the recent decades and 30% of esophageal cancer patients are now 75 years or older at the time of diagnosis. The aim of this study was to evaluate trends in management and survival of patients aged 75 years or older with esophageal cancer.In the Netherlands cancer registry, we identified all patients aged 75 years or older who were diagnosed with esophageal cancer between 1989 and 2008. Trends in management and survival were analyzed by time period (1989-2001 vs. 2002-2008), TNM stage, and age (75-79, 80-84, and 85+ years). χ2 testing was used to analyze time trends in treatment, Kaplan-Meier analysis and log-rank testing to estimate survival, and Cox regression model to calculate hazard ratios for death.Some 7,253 patients were included in the study. The surgical resection rate increased over the 1989-2008 period from 8.9 to 12.6% (p=0.028), especially among patients aged 75-79 years (44.6 vs. 55.4%, p0.001) and patients with TNM stage I disease (12.7 vs. 22.0%, p0.001). The use of definitive chemoradiotherapy (CRT) also increased (0.19 vs. 2.20%, p0.001). Whereas the use of chemotherapy as a single-modality treatment more than doubled (0.64 vs. 1.54%, p=0.004), that of radiotherapy alone decreased (38.1 vs. 31.6%, p0.001). Although median survival time was marginally higher in the 2002-2008 period than in 1989-2001, overall 5 year survival rates remained low at 6 and 5%, respectively (p0.001). Five-year survival rate after surgery increased from 16 to 30% (p0.001).In patients of 75 years or older, surgical treatment and use of definitive CRT have increased between 1989 and 2008. Also, an increase in the use of chemotherapy as a single modality was noted. Overall 5 year survival for all cancer patients was stable but remained poor, while survival of patients who underwent esophagectomy improved significantly in the Netherlands since 1989.

Background: The shared decision making (SDM) model states that patients' values and preferences should be clarified to choose a strategy that best fits the patient. This study aimed to assess whether values and preferences of rectal cancer patients are voiced and considered in deciding about preoperative radiotherapy (PRT), and whether this makes patients feel more involved in treatment decision making. Methods: Pre-treatment consultations of radiation oncologists and patients eligible for PRT were audio taped (N= 90). Tapes were transcribed and coded to identify patients' values and treatment preferences. Patients filled in a post-consultation questionnaire on their perceived involvement in decision making (N= 60). Results: Patients' values were voiced for 62/611 of benefits harms addressed (10%), in 38/90 consultations (42%; maximum 4 values per consultation), and most often related to major long-term treatment outcomes. Patients' treatment preferences were discussed in 20/90 consultations (22%). In 16/90 consultations (18%), the oncologists explicitly indicated to consider patients' values or preferences. Patients perceived a significantly more active role in decision making if their values or preferences had been voiced or considered. Conclusions: Patients' values and treatment preferences are voiced or considered in a minority of consultations. If they are, this increases patients' perceived involvement in the decision making process. (C) 2015 Elsevier Ireland Ltd. All rights reserved

To investigate the information provision concerning possible benefits and harms of short-course preoperative radiotherapy (PRT) at pre-treatment consultations between radiation oncologists and rectal cancer patients.Observational study.We audiotaped the consultations between 17 radiation oncologists and 81 patients with primary rectal cancer who were eligible for PRT. The recordings were transcribed and analysed descriptively.A median of seven benefits/harms of PRT were addressed at each consultation (range, 2-13). This number differed both in and between individual oncologists and was not consistently associated with the patient's characteristics. A total of 30 different treatment outcomes was addressed. The effect of PRT on local control was addressed in all consultations, and the effect on survival in 16%. The most important adverse effects according to the literature are bowel dysfunction and sexual dysfunction. These were addressed in 82% and 85% of consultations, respectively; sexual problems were discussed significantly more often with male than female patients. Four out of five patients did not initiate discussion on potential benefits/harms.There was a considerable variation in the number and nature of benefits and harms of PRT that were discussed prior to treatment. This variation indicates a lack of clarity concerning which benefits/harms of radiotherapy should be discussed with newly-diagnosed patients. This suboptimal provision of information to patients hampers the process of shared decision making, in which the decision is based on each individual patient's weighing of benefits and harms. We do not believe our findings to be specific for PRT, but expect to find similar variation in provision of information with regard to other treatment decisions.

Background:For shared decision making to be successful, patients should receive sufficient information on possible benefits and harms of treatment options. The aim of this study was to evaluate what information radiation oncologists provide during the decision consultation about preoperative radiotherapy with rectal cancer patients.Methods:Decision consultations of 17 radiation oncologists with 81 consecutive primary rectal cancer patients, eligible for short-course radiotherapy followed by a low-anterior resection, were audio taped. Tapes were transcribed and analysed using the ACEPP (Assessing Communication about Evidence and Patient Preferences) coding scheme.Results:A median of seven benefits/harms were addressed per consultation (range, 2-13). This number ranged within and between oncologists and was not clearly associated with the patient's characteristics. A total of 30 different treatment outcomes were addressed. The effect of radiotherapy on local control was addressed in all consultations, the effect on survival in 16%. The most important adverse effects are bowel and sexual dysfunction. These were addressed in 82% and 85% of consultations, respectively; the latter significantly less often in female than in male patients. Four out of five patients did not initiate discussion on any benefits/harms.Conclusions:Our results showed considerable inconsistency between and within oncologists in information provision, which could not be explained by patient characteristics. This variation indicates a lack of clarity on which benefits/harms of radiotherapy should be discussed with newly-diagnosed patients. This suboptimal patient information hampers the process of shared decision making, in which the decision is based on each individual patients' weighing of benefits and harms.British Journal of Cancer advance online publication, 21 October 2014; doi:10.1038/bjc.2014.546 www.bjcancer.com.

Purpose: The aim of this study was to measure and improve the quality of target volume delineation by means of national consensus on target volume definition in early-stage rectal cancer.Methods and materials: The CTV's for eight patients were delineated by 11 radiation oncologists in 10 institutes according to local guidelines (phase 1). After observer variation analysis a workshop was organized to establish delineation guidelines and a digital atlas, with which the same observers re-delineated the dataset (phase 2). Variation in volume, most caudal and cranial slice and local surface distance variation were analyzed.Results: The average delineated CTV volume decreased from 620 to 460 cc (p Conclusions: The large variation in target volume delineation could significantly be reduced by use of consensus guidelines and a digital delineation atlas. Despite the significant reduction there is still a need for further improvement. (C) 2011 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 102 (2012) 14-21