Phase 3 Randomized Trial of Prophylactic Cranial Irradiation With or Without Hippocampus Avoidance in SCLC (NCT01780675)

Introduction: To compare neurocognitive functioning in patients with SCLC who received prophylactic cranial irradiation (PCI) with or without hippocampus avoidance (HA). Methods: In a multicenter, randomized phase 3 trial (NCT01780675), patients with SCLC were randomized to standard PCI or HA-PCI of 25 Gy in 10 fractions. Neuropsychological tests were performed at baseline and 4, 8, 12, 18, and 24 months after PCI. The primary end point was total recall on the Hopkins Verbal Learning Test-Revised at 4 months; a decline of at least five points from baseline was considered a failure. Secondary end points included other cognitive outcomes, evaluation of the incidence, location of brain metastases, and overall survival. Results: From April 2013 to March 2018, a total of 168 patients were randomized. The median follow-up time was 26.6 months. In both treatment arms, 70% of the patients had limited disease and baseline characteristics were well balanced. Decline on the Hopkins Verbal Learning Test-Revised total recall score at 4 months was not significantly different between the arms: 29% of patients on PCI and 28% of patients on HA-PCI dropped greater than or equal to five points (p = 1.000). Performance on other cognitive tests measuring memory, executive function, attention, motor function, and processing speed did not change significantly different over time between the groups. The overall survival was not significantly different (p = 0.43). The cumulative incidence of brain metastases at 2 years was 20% (95% confidence interval: 12%-29%) for the PCI arm and 16% (95% confidence interval: 7%-24%) for the HA-PCI arm. Conclusions: This randomized phase 3 trial did not find a lower probability of cognitive decline in patients with SCLC receiving HA-PCI compared with conventional PCI. No increase in brain metastases at 2 years was observed in the HA-PCI arm. (C) 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved

Patients' and clinicians' preferences in adjuvant treatment for high-risk endometrial cancer:Implications for shared decision making

Background. Decision making regarding adjuvant therapy for high-risk endometrial cancer is complex. The aim of this study was to determine patients' and clinicians' minimally desired survival benefit to choose chemoradiotherapy over radiotherapy alone. Moreover, influencing factors and importance of positive and negative treatment effects (i.e. attribute) were investigated. Methods. Patients with high-risk endometrial cancer treated with adjuvant pelvic radiotherapy with or without chemotherapy and multidisciplinary gynaecologic oncology clinicians completed a trade-off questionnaire based on PORTEC-3 trial data. Results. In total, 171 patients and 63 clinicians completed the questionnaire. Median minimally desired benefit to make chemoradiotherapy worthwhile was significantly higher for patients versus clinicians (10% vs 5%, p = 0.02). Both patients and clinicians rated survival benefit most important during decision making, followed by long-term symptoms. Older patients (OR 0.92 [95%CI 0.87 & ndash;0.97]; p = 0.003) with comorbidity (OR 0.34 [95% CI 0.12 & ndash;0.89]; p = 0.035) had lower preference for chemoradiotherapy, while patients with better numeracy skills (OR 1.2 [95%CI 1.05 & ndash;1.36], p = 0.011) and chemoradiotherapy history (OR 25.0 [95%CI 8.8 & ndash;91.7]; p < 0.001) had higher preference for chemoradiotherapy. & nbsp;Conclusions. There is a considerable difference in minimally desired survival benefit of chemoradiotherapy in high-risk endometrial cancer among and between patients and clinicians. Overall, endometrial cancer patients needed higher benefits than clinicians before preferring chemoradiotherapy. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/)

Radiation therapy quality assurance (RTQA) of concurrent chemoradiation therapy for locally advanced non-small cell lung cancer in the PROCLAIM Phase 3 trial

PURPOSE: Chemoradiation therapy trials of different tumors, including lung cancer, have shown a correlation between protocol deviations and adverse outcomes. Radiation therapy quality assurance (RTQA) was mandated for all patients treated in the PROCLAIM trial evaluating 2 different chemoradiation therapy regimens. The RTQA results were evaluated from the PROCLAIM study, and the impact of irradiation deviations on efficacy outcomes was investigated. METHODS AND MATERIALS: The study was conducted from 2008 to 2014. Review of the irradiation plan was mandated for all patients. Real-time review was performed prior to irradiation start for the first enrolled patient at each site and randomly in 20% of additional patients, with non-real-time review in the remainder. The RTQA criteria evaluated included planning target volume coverage, dose homogeneity, volume of lung receiving ≥20 Gy, and maximum point dose to spinal cord. RESULTS: Major RTQA violations occurred in 40 of 554 patients, treated at 28 sites. Seven sites treated ≥2 patients with major violations. Stage IIIB disease and larger planning target volume were observed more frequently in patients with major violations. Major violations were more prevalent in sites treating either 15 patients. Patients treated at sites enrolling ≥2 patients with major violations (n = 86) had lower median overall survival (21.1 months vs 29.8 months; hazard ratio, 1.442) and progression-free survival (7.3 months vs 11.3 months; hazard ratio, 1.345) than patients treated at sites without major violations. These findings remained significant for overall survival on multivariate analysis. CONCLUSIONS: Major violations in treatment plans were uncommon in the PROCLAIM study, possibly reflecting mandatory RTQA. The RTQA violations were more frequent in patients requiring more complex chemoradiation therapy plans. Poorer observed outcomes at centers with multiple major violations are hypothesis generating

Phase 3 Randomized Trial of Prophylactic Cranial Irradiation With or Without Hippocampus Avoidance in SCLC (NCT01780675)

Introduction: To compare neurocognitive functioning in patients with SCLC who received prophylactic cranial irradiation (PCI) with or without hippocampus avoidance (HA). Methods: In a multicenter, randomized phase 3 trial (NCT01780675), patients with SCLC were randomized to standard PCI or HA-PCI of 25 Gy in 10 fractions. Neuropsychological tests were performed at baseline and 4, 8, 12, 18, and 24 months after PCI. The primary end point was total recall on the Hopkins Verbal Learning Test—Revised at 4 months; a decline of at least five points from baseline was considered a failure. Secondary end points included other cognitive outcomes, evaluation of the incidence, location of brain metastases, and overall survival. Results: From April 2013 to March 2018, a total of 168 patients were randomized. The median follow-up time was 26.6 months. In both treatment arms, 70% of the patients had limited disease and baseline characteristics were well balanced. Decline on the Hopkins Verbal Learning Test-Revised total recall score at 4 months was not significantly different between the arms: 29% of patients on PCI and 28% of patients on HA-PCI dropped greater than or equal to five points (p = 1.000). Performance on other cognitive tests measuring memory, executive function, attention, motor function, and processing speed did not change significantly different over time between the groups. The overall survival was not significantly different (p = 0.43). The cumulative incidence of brain metastases at 2 years was 20% (95% confidence interval: 12%–29%) for the PCI arm and 16% (95% confidence interval: 7%–24%) for the HA-PCI arm. Conclusions: This randomized phase 3 trial did not find a lower probability of cognitive decline in patients with SCLC receiving HA-PCI compared with conventional PCI. No increase in brain metastases at 2 years was observed in the HA-PCI arm