Changes in hospital variation in the probability of receiving treatment with curative intent for esophageal and gastric cancer

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 (O

Effect of neoadjuvant chemoradiotherapy on health-Related quality of life in esophageal or junctional cancer: Results from the randomized CROSS trial

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: 20.93, P, .001; 0.47, P, .001; 20.84, 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: 21.00, 0.33, 20.47, 20.34, 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 20.53, 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

Nationwide comprehensive gastro-intestinal cancer cohorts: the 3P initiative

Background: The increasing sub-classification of cancer patients due to more detailed molecular classification of tumors, and limitations of current trial designs, require innovative research designs. We present the design, governance and current standing of three comprehensive nationwide cohorts including pancreatic, esophageal/gastric, and colorectal cancer patients (NCT02070146). Multidisciplinary collection of clinical data, tumor tissue, blood samples, and patient-reported outcome (PRO) measures with a nationwide coverage, provides the infrastructure for future and novel trial designs and facilitates research to improve outcomes of gastrointestinal cancer patients. Material and methods: All patients aged ≥18 years with pancreatic, esophageal/gastric or colorectal cancer are eligible. Patients provide informed consent for: (1) reuse of clinical data; (2) biobanking of primary tumor tissue; (3) collection of blood samples; (4) to be informed about relevant newly identified genomic aberrations; (5) collection of longitudinal PROs; and (6) to receive information on new interventional studies and possible participation in cohort multiple randomized controlled trials (cmRCT) in the future. Results: In 2015, clinical data of 21,758 newly diagnosed patients were collected in the Netherlands Cancer Registry. Additional clinical data on the surgical procedures were registered in surgical audits for 13,845 patients. Within the first two years, tumor tissue and blood samples were obtained from 1507 patients; during this period, 1180 patients were included in the PRO registry. Response rate for PROs was 90%. The consent rate to receive information on new interventional studies and possible participation in cmRCTs in the future was >85%. The number of hospitals participating in the cohorts is steadily increasing. Conclusion: A comprehensive nationwide multidisciplinary gastrointestinal cancer cohort is feasible and surpasses the limitations of classical study designs. With this initiative, novel and innovative studies can be performed in an efficient, safe, and comprehensive setting

Neoadjuvant chemoradiotherapy plus surgery versus active surveillance for oesophageal cancer: A stepped-wedge cluster randomised trial

Background: Neoadjuvant chemoradiotherapy (nCRT) plus surgery is a standard treatment for locally advanced oesophageal cancer. With this treatment, 29% of patients have a pathologically complete response in the resection specimen. This provides the rationale for investigating an active surveillance approach. The aim of this study is to assess the (cost-)effectiveness of active surveillance vs. standard oesophagectomy after nCRT for oesophageal cancer. Methods: This is a phase-III multi-centre, stepped-wedge cluster randomised controlled trial. A total of 300 patients with clinically complete response (cCR, i.e. no local or disseminated disease proven by histology) after nCRT will be randomised to show non-inferiority of active surveillance to standard oesophagectomy (non-inferiority margin 15%, intra-correlation coefficient 0.02, power 80%, 2-sided α 0.05, 12% drop-out). Patients will undergo a first clinical response evaluation (CRE-I) 4-6 weeks after nCRT, consisting of endoscopy with bite-on-bite biopsies of the primary tumour site and other suspected lesions. Clinically complete responders will undergo a second CRE (CRE-II), 6-8 weeks after CRE-I. CRE-II will include 18F-FDG-PET-CT, followed by endoscopy with bite-on-bite biopsies and ultra-endosonography plus fine needle aspiration of suspected lymph nodes and/or PET- positive lesions. Patients with cCR at CRE-II will be assigned to oesophagectomy (first phase) or active surveillance (second phase of the study). The duration of the first phase is determined randomly over the 12 centres, i.e., stepped-wedge cluster design. Patients in the active surveillance arm will undergo diagnostic evaluations similar to CRE-II at 6/9/12/16/20/24/30/36/48 and 60 months after nCRT. In this arm, oesophagectomy will be offered only to patients in whom locoregional regrowth is highly suspected or proven, without distant dissemination. The main study parameter is overall survival; secondary endpoints include percentage of patients who do not undergo surgery, quality of life, clinical irresectability (cT4b) rate, radical resection rate, postoperative complications, progression-free survival, distant dissemination rate, and cost-effectiveness. We hypothesise that active surveillance leads to non-inferior survival, improved quality of life and a reduction in costs, compared to standard oesophagectomy. Discussion: If active surveillance and surgery as needed after nCRT leads to non-inferior survival compared to standard oesophagectomy, this organ-sparing approach can be implemented as a standard of care

Nationwide comprehensive gastro-intestinal cancer cohorts: the 3P initiative

Background: The increasing sub-classification of cancer patients due to more detailed molecular classification of tumors, and limitations of current trial designs, require innovative research designs. We present the design, governance and current standing of three comprehensive nationwide cohorts including pancreatic, esophageal/gastric, and colorectal cancer patients (NCT02070146). Multidisciplinary collection of clinical data, tumor tissue, blood samples, and patient-reported outcome (PRO) measures with a nationwide coverage, provides the infrastructure for future and novel trial designs and facilitates research to improve outcomes of gastrointestinal cancer patients. Material and methods: All patients aged ≥18 years with pancreatic, esophageal/gastric or colorectal cancer are eligible. Patients provide informed consent for: (1) reuse of clinical data; (2) biobanking of primary tumor tissue; (3) collection of blood samples; (4) to be informed about relevant newly identified genomic aberrations; (5) collection of longitudinal PROs; and (6) to receive information on new interventional studies and possible participation in cohort multiple randomized controlled trials (cmRCT) in the future. Results: In 2015, clinical data of 21,758 newly diagnosed patients were collected in the Netherlands Cancer Registry. Additional clinical data on the surgical procedures were registered in surgical audits for 13,845 patients. Within the first two years, tumor tissue and blood samples were obtained from 1507 patients; during this period, 1180 patients were included in the PRO registry. Response rate for PROs was 90%. The consent rate to receive information on new interventional studies and possible participation in cmRCTs in the future was >85%. The number of hospitals participating in the cohorts is steadily increasing. Conclusion: A comprehensive nationwide multidisciplinary gastrointestinal cancer cohort is feasible and surpasses the limitations of classical study designs. With this initiative, novel and innovative studies can be performed in an efficient, safe, and comprehensive setting

Pre-treatment visualization of predicted radiation-induced acute alopecia in brain tumour patients

Background and purpose: Temporary alopecia is a common side-effect in brain tumour patients receiving cranial radiotherapy with a significant psychological burden for the affected patient. The purpose of this study was to generate a method in our treatment planning system (TPS) to visualize the expected radiation-induced alopecia 4 weeks after treatment, in order to inform the patients thereupon before the start of radiotherapy. Material and methods: A pilot study was conducted in ten patients receiving hypo- (HF) or conventionally fractionated (CF) photon beam Volumetric Modulated Arc Therapy (VMAT) for an intracranial lesion. Dose calculations were correlated to visible alopecia four weeks after the end of treatment to create a structure predictive of alopecia in our TPS. These alopecia structures for both fractionation schedules were validated in two cohorts of 69 HF and 78 CF patients undergoing radiotherapy between 2016 and 2019. Results: In the pilot cohort, a total physical dose of 4 Gy for HF and 12.6 Gy for CF radiotherapy were found to be predictive of alopecia 4 weeks after treatment. Applying these doses to our validation cohort, we found an accurate prediction of alopecia in 59/69 (86%) HF and 73/78 (96%) CF patients. For the total patient group of 147 patients, the predicted amount of alopecia was accurate in 90% of the cases. All inaccurate predictions overestimated the expected extent of alopecia. Conclusion: The presented straightforward method to visualize predicted alopecia 4 weeks after treatment has proven to predict the extent alopecia highly accurate in the vast majority of patients. Sharing these results with the patients pre-treatment may result in stress reduction before cranial irradiation

Pre-treatment visualization of predicted radiation-induced acute alopecia in brain tumour patients

BACKGROUND AND PURPOSE: Temporary alopecia is a common side-effect in brain tumour patients receiving cranial radiotherapy with a significant psychological burden for the affected patient. The purpose of this study was to generate a method in our treatment planning system (TPS) to visualize the expected radiation-induced alopecia 4 weeks after treatment, in order to inform the patients thereupon before the start of radiotherapy. MATERIAL AND METHODS: A pilot study was conducted in ten patients receiving hypo- (HF) or conventionally fractionated (CF) photon beam Volumetric Modulated Arc Therapy (VMAT) for an intracranial lesion. Dose calculations were correlated to visible alopecia four weeks after the end of treatment to create a structure predictive of alopecia in our TPS. These alopecia structures for both fractionation schedules were validated in two cohorts of 69 HF and 78 CF patients undergoing radiotherapy between 2016 and 2019. RESULTS: In the pilot cohort, a total physical dose of 4 Gy for HF and 12.6 Gy for CF radiotherapy were found to be predictive of alopecia 4 weeks after treatment. Applying these doses to our validation cohort, we found an accurate prediction of alopecia in 59/69 (86%) HF and 73/78 (96%) CF patients. For the total patient group of 147 patients, the predicted amount of alopecia was accurate in 90% of the cases. All inaccurate predictions overestimated the expected extent of alopecia. CONCLUSION: The presented straightforward method to visualize predicted alopecia 4 weeks after treatment has proven to predict the extent alopecia highly accurate in the vast majority of patients. Sharing these results with the patients pre-treatment may result in stress reduction before cranial irradiation

Deciphering the glioblastoma phenotype by computed tomography radiomics

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/)

Deciphering the glioblastoma phenotype by computed tomography radiomics

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/)

Patient- and physician-reported radiation-induced toxicity of short-course radiotherapy with a prolonged interval to surgery for rectal cancer

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