Health-related quality of life following neoadjuvant chemoradiotherapy versus perioperative chemotherapy and esophagectomy for esophageal cancer: a European multicenter study.

Curative treatment for locally advanced esophageal cancer consists of (neo)adjuvant treatment followed by esophagectomy. Both neoadjuvant chemoradiotherapy and perioperative chemotherapy improve the 5-year overall survival rate compared with surgery alone. However, it is unknown whether these treatment strategies are associated with differences in long-term health-related quality of life (HRQL). The aim of this study is to compare long-term HRQL in patients after esophagectomy treated with neoadjuvant chemoradiotherapy or perioperative chemotherapy. Disease-free cancer patients having undergone esophagectomy and (neo)adjuvant treatment in one of the participating lasting symptoms after esophageal resection (LASER) study centers between 2010 and 2016, were identified from the LASER study dataset. Included patients completed the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30), EORTC QLQ-OG25, and LASER questionnaires at least 1 year after the completion of treatment. Long-term HRQL was compared between patients treated with neoadjuvant chemoradiotherapy or perioperative chemotherapy, using univariable and multivariable regression and presented as differences in mean score. Among the 565 included patients, 349 (61.8%) received neoadjuvant chemoradiotherapy, and 216 (38.2%) perioperative chemotherapy. Patients treated with perioperative chemotherapy reported more symptomatology for diarrhea (difference in means 5.93), reflux (difference in means 7.40), and odynophagia (difference in means 4.66). The differences did not exceed the 10 points to be of clinical relevance. No significant differences for the LASER key symptoms were observed. The observed differences in long-term HRQL are in favor of patients treated with neoadjuvant chemoradiotherapy compared with patients treated with perioperative chemotherapy; however, the differences were small. Patients need to be informed about long-term HRQL when considering allocation of (neo)adjuvant treatment.

Influence of postoperative complications following esophagectomy for cancer on quality of life: A European multicenter study.

INTRODUCTION: Postoperative complications following major surgery have been shown to be associated with reduced health-related quality of life (HRQL), and severe complications may have profound negative effects. This study aimed to examine whether long-term HRQL differs with the occurrence and severity of complications in a European multicenter prospective dataset of patients following esophagectomy for cancer. METHODS: Disease-free patients following esophagectomy for cancer between 2010 and 2016 from the LASER study were included. Patients completed the LASER, EORTC QLQ-C30 and EORTC QLQ-OG25 questionnaires >1 year following treatment. Long-term HRQL was compared between patients with and without postoperative complications, subgroup analysis was performed for severity of complications (no, minor [Clavien-Dindo I-II], severe [Clavien-Dindo ≥ III]), using univariable and multivariable regression. RESULTS: 645 patients were included: 283 patients with no, 207 with minor and 155 with severe complications. Significantly more dyspnea (QLQ-C30) was reported by patients with compared to patients without complications (differenceinmeans6.3). In subgroup analysis, patients with severe complications reported more dyspnea (difference in means 8.3) than patients with no complications. None of the differences were clinically relevant (difference in means ≥ 10 points). LASER-based low mood (OR2.3) was statistically different for minor versus severe complications. CONCLUSION: Comparable HRQL was found in patients with and without postoperative complications following esophagectomy for cancer, after a mean follow-up of 4.4 years. Furthermore, patients with different levels of severity of complications had comparable HRQL. The level of HRQL in esophageal cancer patients are more likely explained by the impact of the complex procedure of the esophagectomy itself.

Prognostic value of patient-reported quality of life for survival in oesophagogastric cancer: analysis from the population-based POCOP study.

BACKGROUND: Accumulating evidence of trials demonstrates that patient-reported health-related quality of life (HRQoL) at diagnosis is prognostic for overall survival (OS) in oesophagogastric cancer. However, real-world data are lacking. Moreover, differences in disease stages and tumour-specific symptoms are usually not taken into consideration. The aim of this population-based study was to assess the prognostic value of HRQoL, including tumour-specific scales, on OS in patients with potentially curable and advanced oesophagogastric cancer. METHODS: Data were derived from the Netherlands Cancer Registry and the patient reported outcome registry (POCOP). Patients included in POCOP between 2016 and 2018 were stratified for potentially curable (cT1-4aNallM0) or advanced (cT4b or cM1) disease. HRQoL was measured with the EORTC QLQ-C30 and the tumour-specific OG25 module. Cox proportional hazards models assessed the impact of HRQoL, sociodemographic and clinical factors (including treatment) on OS. RESULTS: In total, 924 patients were included. Median OS was 38.9 months in potentially curable patients (n = 795) and 10.6 months in patients with advanced disease (n = 129). Global Health Status was independently associated with OS in potentially curable patients (HR 0.89, 99%CI 0.82-0.97), together with several other HRQoL items: appetite loss, dysphagia, eating restrictions, odynophagia, and body image. In advanced disease, the Summary Score was the strongest independent prognostic factor (HR 0.75, 99%CI 0.59-0.94), followed by fatigue, pain, insomnia and role functioning. CONCLUSION: In a real-world setting, HRQoL was prognostic for OS in patients with potentially curable and advanced oesophagogastric cancer. Several HRQoL domains, including the Summary Score and several OG25 items, could be used to develop or update prognostic models.

Postoperative Complications and Long-Term Quality of Life After Multimodality Treatment for Esophageal Cancer: An Analysis of the Prospective Observational Cohort Study of Esophageal-Gastric Cancer Patients (POCOP).

BACKGROUND: Esophagectomy has major effects on health-related quality of life (HR-QoL). Postoperative complications might contribute to a decreased HR-QOL. This population-based study aimed to investigate the difference in HR-QoL between patients with and without complications after esophagectomy for cancer. METHODS: A prospective comparative cohort study was performed with data from the Netherlands Cancer Registry (NCR) and Prospective Observational Cohort Study of Esophageal-Gastric Cancer Patients (POCOP). All patients with esophageal and gastroesophageal junction (GEJ) cancer after esophagectomy in the period 2015-2018 were enrolled. The study investigated HR-QoL at baseline, then 3, 6, 9, 12, 18, and 24 months postoperatively, comparing patients with and without complications as well as with and without anastomotic leakage. RESULTS: The 486 enrolled patients comprised 270 patients with complications and 216 patients without complications. Significantly more patients with complications had comorbidities (69.6% vs 57.3%; p = 0.001). No significant difference in HR-QoL was found over time between the patients with and without complications. In both groups, a significant decline in short-term HR-QoL was found in various HR-QoL domains, which were restored to the baseline level during the 12-month follow-up period. No significant difference was found in HR-QoL between the patients with and without anastomotic leakage. The patients with grades 2 and 3 anastomotic leakage reported significantly more "choking when swallowing" at 6 months (ß = 14.5; 95% confidence interval [CI], - 24.833 to - 4.202; p = 0.049), 9 months (ß = 22.4, 95% CI, - 34.259 to - 10.591; p = 0.007), and 24 months (ß = 24.6; 95% CI, - 39.494 to - 9.727; p = 0.007) than the patients with grade 1 or no anastomotic leakage. CONCLUSION: In general, postoperative complications were not associated with decreased short- or long-term HR-QoL for patients after esophagectomy for esophageal or GEJ cancer. The temporary decrease in HR-QoL likely is related to the nature of esophagectomy and reconstruction itself.

Re-evaluating randomized clinical trials of psychological interventions: Impact of response shift on the interpretation of trial results.

BACKGROUND: Effectiveness of psychological treatment is often assessed using patient-reported health evaluations. However, comparison of such scores over time can be hampered due to a change in the meaning of self-evaluations, called 'response shift'. Insight into the occurrence of response shift seems especially relevant in the context of psychological interventions, as they often purposefully intend to change patients' frames of reference. AIMS: The overall aim is to gain insight into the general relevance of response shift for psychological health intervention research. Specifically, the aim is to re-analyse data of published randomized controlled trials (RCTs) investigating the effectiveness of psychological interventions targeting different health aspects, to assess (1) the occurrence of response shift, (2) the impact of response shift on interpretation of treatment effectiveness, and (3) the predictive role of clinical and background variables for detected response shift. METHOD: We re-analysed data from RCTs on guided internet delivered cognitive behavioural treatment (CBT) for insomnia in the general population with and without elevated depressive symptoms, an RCT on meaning-centred group psychotherapy targeting personal meaning for cancer survivors, and an RCT on internet-based CBT treatment for persons with diabetes with elevated depressive symptoms. Structural equation modelling was used to test the three objectives. RESULTS: We found indications of response shift in the intervention groups of all analysed datasets. However, results were mixed, as response shift was also indicated in some of the control groups, albeit to a lesser extent or in opposite direction. Overall, the detected response shifts only marginally impacted trial results. Relations with selected clinical and background variables helped the interpretation of detected effects and their possible mechanisms. CONCLUSION: This study showed that response shift effects can occur as a result of psychological health interventions. Response shift did not influence the overall interpretation of trial results, but provide insight into differential treatment effectiveness for specific symptoms and/or domains that can be clinically meaningful.

Using structural equation modeling to investigate change and response shift in patient-reported outcomes: practical considerations and recommendations.

BACKGROUND: Patient-reported outcomes (PROs) are of increasing importance for health-care evaluations. However, the interpretation of change in PROs may be obfuscated due to changes in the meaning of the self-evaluation, i.e., response shift. Structural equation modeling (SEM) is the most widely used statistical approach for the investigation of response shift. Yet, non-technical descriptions of SEM for response shift investigation are lacking. Moreover, application of SEM is not straightforward and requires sequential decision-making practices that have not received much attention in the literature. AIMS: To stimulate appropriate applications and interpretations of SEM for the investigation of response shift, the current paper aims to (1) provide an accessible description of the SEM operationalizations of change that are relevant for response shift investigation; (2) discuss practical considerations in applying SEM; and (3) provide guidelines and recommendations for researchers who want to use SEM for the investigation and interpretation of change and response shift in PROs. CONCLUSION: Appropriate applications and interpretations of SEM for the detection of response shift will help to improve our understanding of response shift phenomena and thus change in PROs. Better understanding of patients' perceived health trajectories will ultimately help to adopt more effective treatments and thus enhance patients' wellbeing.

Long-Term Quality of Life Following Transthoracic and Transhiatal Esophagectomy for Esophageal Cancer.

BACKGROUND: The impact of transthoracic (TTE) and transhiatal esophagectomy (THE) on long-term health-related quality of life (HR-QoL) in patients with distal esophageal or gastro-esophageal junction (GEJ) cancer has been studied with variable results. This study investigates long-term HR-QoL in patients having undergone TTE or THE. METHODS: Disease-free patients after TTE or THE for distal esophageal or GEJ cancer with a follow-up > 2 years were included. Patients who visited the outpatient clinic of a tertiary referral center between 2014 and 2018 were asked to complete EORTC-QLQ-C30 and EORTC-QLQ-OG25 questionnaires. Uni- and multivariable linear regression analysis of HR-QoL was performed in all patients and in subgroups of minimally invasive esophagectomy and neoadjuvant therapy. RESULTS: A total of 132 patients after TTE and 56 after THE were included. When compared with the general population, all patients reported worse HR-QoL in 'role functioning' and 'social functioning' and in a range of disease- and/or treatment-specific symptoms. The only significant difference between TTE and THE was a better HR-QoL score for "hair loss" following TTE (ß = 29.4,95%CI = -49.108 - -9.671, p = 0.016). Subgroup analysis of minimally invasively operated patients showed better scores in "physical functioning" following TTE (ß = 13.8,95%CI = 2.755-24.933, p = 0.030). No significant differences in HR-QoL were found between TTE and THE after neoadjuvant therapy. CONCLUSION: Long-term HR-QoL is largely comparable in disease-free patients following TTE or THE for distal esophageal or GEJ cancer. If there were differences between the surgical groups, they were in favor of TTE. These findings may aid in preoperative counseling of patients with esophageal or GEJ cancer.

The effects of art therapy on anxiety, depression, and quality of life in adults with cancer: a systematic literature review.

PURPOSE: While there is increasing evidence for the effectiveness of psychosocial support programs for cancer patients, little attention has been paid to creativity or art as a way of addressing their psychological problems and improving quality of life. This review provides an overview of interventional studies that investigate the effects of art therapy interventions on anxiety, depression, and quality of life in adults with cancer. METHODS: We conducted a literature review with a systematic search. The databases PubMed/MEDLINE, PsycINFO, and EMBASE were searched for articles on art therapy among adult (18 years and above) cancer patients, published between September 2009 up to September 2019. Search terms were established for each database specifically. A total of 731 publications was assessed for relevance by title and abstract. The remaining 496 articles were examined using three inclusion criteria: interventions were guided by an artist or art therapist, participants were actively involved in the creative process, and anxiety, depression, and/or quality of life were included as outcome measures. Methodological quality of the included studies was appraised using specific checklists. RESULTS: Seven papers met the inclusion criteria. Data was extracted from three non-randomized intervention studies and four randomized controlled trials. All studies used a quantitative design with validated outcome measures. Four articles described positive effects of art therapy on anxiety, depression, or quality of life in adults with cancer. CONCLUSION: Art therapy could possibly help decrease symptoms of anxiety and depression, and improve quality of life in adult cancer patients. However, because of the heterogeneity of the interventions and limited methodological quality of the studies, further research using stringent methods is needed.

Minimally important differences for interpreting the EORTC QLQ-C30 in patients with advanced colorectal cancer treated with chemotherapy.

AIM: The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) assesses the health-related quality of life of patients in cancer trials. There are currently no minimally important difference (MID) guidelines for the EORTC QLQ-C30 for colorectal cancer (CRC). This study aims to estimate MIDs for the EORTC QLQ-C30 scales in patients with advanced CRC treated with chemotherapy and enrolled in clinical trials. METHOD: The data were obtained from three published EORTC trials that treated CRC patients using chemotherapy. Potential anchors were selected from clinical variables based on their correlation with EORTC QLQ-C30 scales. Anchor-based MIDs for within-group change and between-group change were estimated via the mean change method and linear regression, respectively, and summarized using weighted correlation. Distribution-based MIDs were also examined. RESULTS: Anchor-based MIDs were determined for deterioration in 8 of the 14 EORTC QLQ-C30 scales and in 9 scales for improvement, and varied by scale, direction of change and anchor. MIDs for improvement (deterioration) ranged from 6 to 18 (-11 to -5) points for within-group change and 5 to 15 (-10 to -4) for between-group change. Summarized MIDs (in absolute values) per scale mostly ranged from 5 to 10 points. CONCLUSIONS: These findings have clinical relevance for the interpretation of treatment efficacy and the design of clinical trials by informing sample size requirements.

Long-term health-related quality of life after McKeown and Ivor Lewis esophagectomy for esophageal carcinoma.

INTRODUCTION: Both cervical (McKeown) and intrathoracic (Ivor Lewis) anastomosis of transthoracic esophagectomy are surgical procedures that can be performed for distal esophageal or gastro-esophageal junction (GEJ) cancer. The purpose of this study was to investigate the long-term health-related quality of life (HR-QoL) after McKeown and Ivor Lewis esophagectomy in a tertiary referral center. METHODS: Disease-free patients >1 year following a McKeown or an Ivor Lewis esophagectomy with a two-field lymphadenectomy for a distal or GEJ carcinoma visiting the outpatient clinic between 2014 and 2018 were asked to complete the EORTC QLQ-C30 and EORTC QLQ-OG25 questionnaires. HR-QoL was investigated in both groups. RESULTS: A total of 89 patients were included after McKeown and 115 after Ivor Lewis esophagectomy. Median follow-up was 2.4 years (IQR 1.7-3.6). Patients after McKeown esophagectomy reported more problems with 'eating with others' compared to patients after Ivor Lewis esophagectomy (mean scores: 49.9 vs. 38.8). This difference was both clinically relevant and significant after correction for multiple testing (ß = 11.1, 95% CI 3.105-19.127, P = 0.042). Patients in both groups reported a poorer HR-QoL (≥10 points) than the general population with respect to nausea and vomiting, dyspnea, appetite loss, financial difficulties, problems with eating, reflux, eating with others, choked when swallowing, trouble with coughing, and weight loss. CONCLUSION: Long-term HR-QoL of disease-free patients following a McKeown or Ivor Lewis esophagectomy for a distal or GEJ carcinoma is largely comparable. Irrespective of the surgical technique, patients' HR-QoL following esophagectomy is compromised. When given the choice, patients should be informed that after a McKeown esophagectomy more problems while eating with others can occur.

External Validation of the Dutch SOURCE Survival Prediction Model in Belgian Metastatic Oesophageal and Gastric Cancer Patients.

The SOURCE prediction model predicts individualised survival conditional on various treatments for patients with metastatic oesophageal or gastric cancer. The aim of this study was to validate SOURCE in an external cohort from the Belgian Cancer Registry. Data of Belgian patients diagnosed with metastatic disease between 2004 and 2014 were extracted (n = 4097). Model calibration and discrimination (c-indices) were determined. A total of 2514 patients with oesophageal cancer and 1583 patients with gastric cancer with a median survival of 7.7 and 5.4 months, respectively, were included. The oesophageal cancer model showed poor calibration (intercept: 0.30, slope: 0.42) with an absolute mean prediction error of 14.6%. The mean difference between predicted and observed survival was -2.6%. The concordance index (c-index) of the oesophageal model was 0.64. The gastric cancer model showed good calibration (intercept: 0.02, slope: 0.91) with an absolute mean prediction error of 2.5%. The mean difference between predicted and observed survival was 2.0%. The c-index of the gastric cancer model was 0.66. The SOURCE gastric cancer model was well calibrated and had a similar performance in the Belgian cohort compared with the Dutch internal validation. However, the oesophageal cancer model had not. Our findings underscore the importance of evaluating the performance of prediction models in other populations.

Long-Term Quality of Life After Total Gastrectomy Versus Ivor Lewis Esophagectomy.

BACKGROUND: There is scarce evidence on whether a total gastrectomy or an Ivor Lewis esophagectomy is preferred for gastroesophageal junction (GEJ) cancers regarding effects on morbidity, pathology, survival and health-related quality of life (HR-QoL). The aim of this study was to investigate the difference in long-term HR-QoL in patients undergoing total gastrectomy versus Ivor Lewis esophagectomy in a tertiary referral center. METHODS: Patients with a follow-up of >1 year after a total gastrectomy or an Ivor Lewis esophagectomy for GEJ/cardia carcinoma completed the EORTC QLQ-C30 and EORTC QLQ-OG25 questionnaires. 'Problems with eating,' 'reflux,' and 'nausea and vomiting' were the primary HR-QoL endpoints. The secondary endpoints were the remaining HR-QoL domains, postoperative complications and pathology results. RESULTS: Thirty patients after gastrectomy and 71 after esophagectomy were included. Mean age was 63 years. Median follow-up was 2 years (range 12-84 months). Patients after gastrectomy reported less 'choking when swallowing' and 'coughing' (ß = - 5.952, 95% CI - 9.437 to - 2.466; ß = - 13.084, 95% CI - 18.525 to - 7.643). More lymph nodes were resected in esophagectomy group (p = 0.008). No difference was found in number of positive lymph nodes, R0 resection or postoperative complications. CONCLUSIONS: After a follow-up of >1 year 'choking when swallowing' and 'coughing' were less common after a total gastrectomy. No differences were found in postoperative complications or radicality of surgery. Based on this study, no general preference can be given to either of the procedures for GEJ cancer. These results support shared decision making when a choice between the two treatment options is possible.

Quality of Life During and After Completion of Neoadjuvant Chemoradiotherapy for Esophageal and Junctional Cancer.

BACKGROUND: The course of health-related quality of life (HRQOL) during and after completion of neoadjuvant chemoradiotherapy (nCRT) for esophageal or junctional carcinoma is unknown. METHODS: This study was a multicenter prospective cohort investigation. Patients with esophageal or cancer to be treated with nCRT plus esophagectomy were eligible for inclusion in the study. The HRQOL of the patients was measured with European Organization for Research and Treatment of Cancer QLQ-C30, QLQ-OG25, and QLQ-CIPN20 questionnaires before and during nCRT, then 2, 4, 6, 8, 10, 12, 14, and 16 weeks after nCRT and before surgery. Predefined end points were based on the hypothesized impact of nCRT. The primary end points were physical functioning, odynophagia, and sensory symptoms. The secondary end points were global quality of life, fatigue, weight loss, and motor symptoms. Mixed modeling analysis was used to evaluate changes over time. RESULTS: Of 106 eligible patients, 96 (91%) were included in the study. The rate of questionnaires returned ranged from 94% to 99% until week 12, then dropped to 78% in week 16 after nCRT. A negative impact of nCRT on all HRQOL end points was observed during the last cycle of nCRT (all p < 0.001) and 2 weeks after nCRT (all p < 0.001). Physical functioning, odynophagia, and sensory symptoms were restored to pretreatment levels respectively 8, 4, and 6 weeks after nCRT. The secondary end points were restored to baseline levels 4-6 weeks after nCRT. Odynophagia, fatigue, and weight loss improved after nCRT compared with baseline levels at respectively 6 (p < 0.001), 16 (p = 0.001), and 12 weeks (p < 0.001). CONCLUSION: After completion of nCRT for esophageal cancer, HRQOL decreases significantly, but all HRQOL end points are restored to baseline levels within 8 weeks. Odynophagia, fatigue, and weight loss improved 6-16 weeks after nCRT compared with baseline levels.

The course of sexual interest and enjoyment in head and neck cancer patients treated with primary (chemo)radiotherapy.

INTRODUCTION: The aim of this prospective study was to investigate the course of sexual interest and enjoyment in relation to sociodemographic and clinical factors, health-related quality of life (HRQOL), and symptoms of psychological distress in head and neck cancer (HNC) patients treated with primary (chemo)radiotherapy. METHODS: HNC patients (n = 354) completed patient-reported outcome measures (PROMs) on HRQOL (EORTC QLQ-C30 and QLQ-H&N35, including the sexuality subscale covering less sexual interest and enjoyment), and psychological distress (HADS) pretreatment, at 6-week follow-up and at 3-, 6-, 12-, 18-, and 24-month follow-up (i.e., after treatment). Linear mixed models were used to analyze the course of sexuality from pretreatment to 24-month follow-up, and to investigate its relation to sociodemographic and clinical factors, HRQOL, and psychological distress as measured at baseline, and to investigate the course of sexuality from 6- to 24-month follow-up in relation to these factors measured at 6-month follow-up. RESULTS: Before start of treatment, 37% of patients reported having less sexuality, which increased to 60% at 6-week follow-up, and returned to baseline level from 12-month follow-up onwards. Older age (p = 0.037) and trouble with social contact (p < 0.001), weight loss (p = 0.013), and constipation (p = 0.041) before treatment were associated with less sexuality over time. Female gender (p = 0.021) and poor social functioning (p < 0.001) at 6-month follow-up were associated with less sexuality from 6- to 24-month follow-up. DISCUSSION: Less sexuality is often reported in HNC patients treated with (chemo)radiotherapy. Using PROMs in clinical practice may help identify patients who might benefit from supportive care targeting sexuality.

Prediction models for patients with esophageal or gastric cancer: A systematic review and meta-analysis.

BACKGROUND: Clinical prediction models are increasingly used to predict outcomes such as survival in cancer patients. The aim of this study was threefold. First, to perform a systematic review to identify available clinical prediction models for patients with esophageal and/or gastric cancer. Second, to evaluate sources of bias in the included studies. Third, to investigate the predictive performance of the prediction models using meta-analysis. METHODS: MEDLINE, EMBASE, PsycINFO, CINAHL, and The Cochrane Library were searched for publications from the year 2000 onwards. Studies describing models predicting survival, adverse events and/or health-related quality of life (HRQoL) for esophageal or gastric cancer patients were included. Potential sources of bias were assessed and a meta-analysis, pooled per prediction model, was performed on the discriminative abilities (c-indices). RESULTS: A total of 61 studies were included (45 development and 16 validation studies), describing 47 prediction models. Most models predicted survival after a curative resection. Nearly 75% of the studies exhibited bias in at least 3 areas and model calibration was rarely reported. The meta-analysis showed that the averaged c-index of the models is fair (0.75) and ranges from 0.65 to 0.85. CONCLUSION: Most available prediction models only focus on survival after a curative resection, which is only relevant to a limited patient population. Few models predicted adverse events after resection, and none focused on patient's HRQoL, despite its relevance. Generally, the quality of reporting is poor and external model validation is limited. We conclude that there is a need for prediction models that better meet patients' information needs, and provide information on both the benefits and harms of the various treatment options in terms of survival, adverse events and HRQoL.

Development and feasibility of a web-based question prompt sheet to support information provision of health-related quality of life topics after oesophageal cancer surgery.

We developed a web-based question prompt sheet (QPS) to support information provision of health-related quality of life (HRQL) topics after oesophageal cancer surgery. The QPS was evaluated and updated in three consecutive studies. In Study 1, eight patients were guided in using the QPS. Feasibility was assessed by cognitive walkthrough, questionnaire and interview. We obtained 430 notes (217 negative, 213 positive) of patients' actions and or remarks, and 91 suggestions. With minor support, most patients were able to use the QPS. In Study 2, forty patients independently used and appraised a modified version of the QPS by questionnaire. All patients deemed the QPS to be usable and useful. In Study 3, 21 patients and three surgeons used the QPS in clinical practice. Clinical feasibility was assessed by the number of QPS sent to the researcher/surgeon. Patients and surgeons were surveyed and the follow-up consultation was audio-recorded. Surgeons were additionally interviewed. Twenty/fourteen patients sent their QPS to the researcher/surgeon. Five QPSs were read by the consultation surgeon. Patients considered the QPS usable and useful. Surgeons considered the QPS of added value and helpful in informing patients, but currently not clinically feasible due to increased consultation time.

Impact of neoadjuvant chemoradiotherapy on health-related quality of life in long-term survivors of esophageal or junctional cancer: results from the randomized CROSS trial.

Background: Neoadjuvant chemoradiotherapy (nCRT) plus surgery is a standard of care for patients with esophageal or junctional cancer, but the long-term impact of nCRT on health-related quality of life (HRQOL) is unknown. The purpose of this study is to compare very long-term HRQOL in long-term survivors of esophageal cancer who received nCRT plus surgery or surgery alone. Patients and methods: Patients were randomly assigned to receive nCRT (carboplatin/paclitaxel with 41.4-Gy radiotherapy) plus surgery or surgery alone. HRQOL was measured using EORTC-QLQ-C30, EORTC-QLQ-OES24 and K-BILD questionnaires after a minimum follow-up of 6 years. To allow for examination over time, EORTC-QLQ-C30 and QLQ-OES24 questionnaire scores were compared with pretreatment and 12 months postoperative questionnaire scores. Physical functioning (QLQ-C30), eating problems (QLQ-OES24) and respiratory problems (K-BILD) were predefined primary end points. Predefined secondary end points were global quality of life and fatigue (both QLQ-C30). Results: After a median follow-up of 105 months, 123/368 included patients (33%) were still alive (70 nCRT plus surgery, 53 surgery alone). No statistically significant or clinically relevant differential effects in HRQOL end points were found between both groups. Compared with 1-year postoperative levels, eating problems, physical functioning, global quality of life and fatigue remained at the same level in both groups. Compared with pretreatment levels, eating problems had improved (Cohen's d -0.37, P = 0.011) during long-term follow-up, whereas physical functioning and fatigue were not restored to pretreatment levels in both groups (Cohen's d -0.56 and 0.51, respectively, both P < 0.001). Conclusions: Although physical functioning and fatigue remain reduced after long-term follow-up, no adverse impact of nCRT is apparent on long-term HRQOL compared with patients who were treated with surgery alone. In addition to the earlier reported improvement in survival and the absence of impact on short-term HRQOL, these results support the view that nCRT according to CROSS can be considered as a standard of care. Trial registration number: Netherlands Trial Register NTR487.

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.

Does severe toxicity affect global quality of life in patients with metastatic colorectal cancer during palliative systemic treatment? A systematic review.

Background: New palliative systemic treatment regimens in patients with metastatic colorectal cancer (mCRC) have significantly improved overall survival and prognosis. These treatment regimens are often accompanied by increased toxicity, which may impair patients' quality of life (QOL). We systematically reviewed whether severe toxicity affects global QOL in patients with mCRC receiving palliative systemic treatment in recent published randomized controlled trials (RCTs). Materials and methods: Phase III RCTs evaluating palliative systemic treatments in patients with mCRC and published between 2004 and 2016 were considered. Studies were evaluated on the basis of global QOL scores, toxicity during treatment (assessed by scoring relevant adverse events) and primary outcomes (POs). Results: A total of 30 studies were identified in which 19863 patients were included. In 25 out of these 30 trials (83%), no difference in global QOL between treatment arms was observed. In contrast, 22 out of 30 trials (73%) showed increased toxicity during treatment in the experimental arm as compared with the control arm. In 19 out of 22 trials with higher toxicity (86%) global QOL outcomes remained unaffected or improved. In ten out of eleven studies with a better PO, no improvement in global QOL was seen. Conclusion: Global QOL of patients with mCRC included in phase III RCTs evaluating palliative systemic treatment did not differ across treatment arms despite consistently higher toxicity during treatment of the experimental compared with the standard treatment arms. Based on these findings we conclude that the use of global QOL for comparing treatment arms in RCTs for patients with mCRC does not provide information of clinical relevance. Further consideration of how to better assess the net effect of new agents on patients' QOL is urgently needed.