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

Ten-year outcome of neoadjuvant chemoradiotherapy plus surgery for esophageal cancer: the randomized controlled CROSS trial

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.Development and application of statistical models for medical scientific researchAnalysis and support of clinical decision makin

Effect of Neoadjuvant Chemoradiotherapy on Health-Related Quality of Life in Esophageal or Junctional Cancer: Results From the Randomized CROSS Trial

PurposeTo 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 MethodsPatients 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).ResultsA 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 P P P 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 P ConclusionAlthough 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.FSW – Publicaties zonder aanstelling Universiteit Leide

Changes in body weight during various types of chemotherapy in breast cancer patients

Background & aims: Weight gain is a common problem for breast cancer patients treated with chemotherapy. It increases the risk of several comorbidities and possibly cancer recurrence. We assessed whether weight gain depends on the type of chemotherapy. Methods: In a retrospective study among 739 breast cancer patients, we assessed whether change in body weight during chemotherapy differed between types of chemotherapy. Information about weight, clinical and personal factors was retrieved from medical records of breast cancer patients treated with chemotherapy between 2001 and 2010 in 4 different hospitals. Results: Body weight information was complete in n=483 patients (66%). There was substantial between-patients variability in weight change during chemotherapy: within the upper quintile of weight change, median weight gain was+6kg, while in the bottom quintile median weight loss was of-3kg. Adjusted multivariate regression analysis showed that change in weight differed between types of chemotherapy: women treated with anthracyclines+taxanes gained+0.9kg (95%CI 0.1, 1.7) more than women treated with anthracyclines only. This differential change in weight was no longer statistically significant after taking into account that regimens with anthracyclines+taxanes have a longer duration than regimens with anthracyclines only. Conclusion: There was more weight gain among patients treated with anthracyclines+taxanes than among patients treated with anthracyclines-only. This is partly explained by the longer duration of regimes with anthracyclines+taxanes. © 2013 European Society for Clinical Nutrition and Metabolism

Effect of Neoadjuvant Chemoradiotherapy on Health-Related Quality of Life in Esophageal or Junctional Cancer: Results From the Randomized CROSS Trial

PurposeTo 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 MethodsPatients 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).ResultsA 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 P P P 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 P ConclusionAlthough 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

Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): overall survival and updated results of a randomised, double-blind, phase 3 trial

Background: Ramucirumab—an IgG1 vascular endothelial growth factor receptor 2 antagonist—plus docetaxel was previously reported to improve progression-free survival in platinum-refractory, advanced urothelial carcinoma. Here, we report the secondary endpoint of overall survival results for the RANGE trial. Methods: We did a randomised, double-blind, phase 3 trial in patients with advanced or metastatic urothelial carcinoma who progressed during or after platinum-based chemotherapy. Patients were enrolled from 124 investigative sites (hospitals, clinics, and academic centres) in 23 countries. Previous treatment with one immune checkpoint inhibitor was permitted. Patients were randomly assigned (1:1) using an interactive web response system to receive intravenous ramucirumab 10 mg/kg or placebo 10 mg/kg volume equivalent followed by intravenous docetaxel 75 mg/m2 (60 mg/m2 in Korea, Taiwan, and Japan) on day 1 of a 21-day cycle. Treatment continued until disease progression, unacceptable toxicity, or other discontinuation criteria were met. Randomisation was stratified by geographical region, Eastern Cooperative Oncology Group performance status at baseline, and visceral metastasis. Progression-free survival (the primary endpoint) and overall survival (a key secondary endpoint) were assessed in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT02426125; patient enrolment is complete and the last patient on treatment is being followed up for safety issues. Findings: Between July 20, 2015, and April 4, 2017, 530 patients were randomly allocated to ramucirumab plus docetaxel (n=263) or placebo plus docetaxel (n=267) and comprised the intention-to-treat population. At database lock (March 21, 2018) for the final overall survival analysis, median follow-up was 7·4 months (IQR 3·5–13·9). In our sensitivity analysis of investigator-assessed progression-free survival at the overall survival database lock, median progression-free survival remained significantly improved with ramucirumab compared with placebo (4·1 months [95% CI 3·3–4·8] vs 2·8 months [2·6–2·9]; HR 0·696 [95% CI 0·573–0·845]; p=0·0002). Median overall survival was 9·4 months (95% CI 7·9–11·4) in the ramucirumab group versus 7·9 months (7·0–9·3) in the placebo group (stratified HR 0·887 [95% CI 0·724–1·086]; p=0·25). Grade 3 or worse treatment-related treatment-emergent adverse events in 5% or more of patients and with an incidence more than 2% higher with ramucirumab than with placebo were febrile neutropenia (24 [9%] of 258 patients in the ramucirumab group vs 16 [6%] of 265 patients in the placebo group) and neutropenia (17 [7%] of 258 vs six [2%] of 265). Serious adverse events were similar between groups (112 [43%] of 258 patients in the ramucirumab group vs 107 [40%] of 265 patients in the placebo group). Adverse events related to study treatment and leading to death occurred in eight (3%) patients in the ramucirumab group versus five (2%) patients in the placebo group. Interpretation: Additional follow-up supports that ramucirumab plus docetaxel significantly improves progression-free survival, without a significant improvement in overall survival, for patients with platinum-refractory advanced urothelial carcinoma. Clinically meaningful benefit might be restricted in an unselected population. Funding: Eli Lilly and Company. © 2020 Elsevier Lt