Longitudinal trajectory of quality of life for patients with melanoma brain metastases: A secondary analysis from a whole brain radiotherapy randomized clinical trial

Purpose: Brain metastases are common in patients with advanced melanoma. This study describes 12-month quality of life (QoL) trajectories following local management of 1–3 melanoma brain metastases. Methods: This study assessed QoL data collected during a multi-center, prospective, open-label, phase III randomized controlled trial comparing the efficacy of adjuvant whole brain radiotherapy (WBRT) with observation after local treatment of 1–3 melanoma brain metastases. Patients completed the European Organization for Research and Treatment of Cancer Quality of Life Core (QLQ-C30) and Brain Tumour (BN-20) questionnaires at baseline and every 2 months, for 12 months.Using growth mixture modelling, QoL trajectories were identified for global health status, QLQ-C30 and BN-20 subscales for patients with baseline and at least one follow-up assessment. Multivariable logistic regression was used to examine associations between trajectories, demographic, and clinical factors. Results: After combining QoL data from observation and WBRT arms, QLQ-C30 and BN-20 trajectories were calculated for 139 and 137 patients respectively. Depending on the QoL domain, 9–54 % of patients reported a deterioration in QoL. Older age (≥65 years) was significantly associated with deterioration in global health status (OR = 2.88, 95 %CI = 1.27–6.54), physical (OR = 3.49, 95 %CI = 1.29–9.41), role (OR = 4.15, 95 %CI = 1.77–9.71), social (OR = 4.42, 95 % CI = 1.57–12.46), cognitive (OR = 6.70, 95 % CI = 1.93–23.29) and motor functioning (OR = 4.95, 95 %CI = 1.95–12.61) and increased future uncertainty (OR = 0.20, 95 %CI = 0.07–0.53). Female sex (OR = 0.10, 95 %CI = 0.02–0.41), not having neurosurgery at baseline (OR = 0.09, 95 %CI = 0.02–0.52), 2–3 brain metastases (OR = 5.75, 95 %CI = 1.76–18.85) or receiving adjuvant WBRT (OR = 6.77, 95 %CI = 2.00–22.99) were associated with poorer physical, emotional, cognitive and social outcomes respectively. Conclusions: Poorer QoL outcomes in the first 12 months after diagnosis of melanoma brain metastases were observed in patients aged ≥ 65 years, females, having 2–3 brain metastases, non-surgical treatment of metastases or adjuvant WBRT.Clinical Trial Registration Number:Whole Brain Radiotherapy Trial (WBRTMel) was registered with the Australian Clinical Trials Registry (ACTRN12607000512426) and ClinicalTrials.gov (NCT01503827).Study Support:This project was funded by Cancer Australia PdCCRS (Grants No. 512358, 1009485, and 1084046) and the National Helath and Medical Research Coucil of Australia (NHMRC; Grant No. 1135285).ADT was supported by a Cancer Australia Priority-driven Collaborative Cancer Research Scheme. Project #1046923. RLM was supported by an NHMRC Fellowship #1194703 and a University of Sydney, Robinson Fellowship. JFT was supported by an NHMRC Program Grant #1093017

Brain metastases with poor vascular function are susceptible to pseudoprogression after stereotactic radiation surgery

Purpose: This study aimed to investigate the hemodynamic status of cerebral metastases prior to and after stereotactic radiation surgery (SRS) and to identify the vascular characteristics that are associated with the development of pseudoprogression from radiation-induced damage with and without a radionecrotic component. Methods and materials: Twenty-four patients with 29 metastases from non-small cell lung cancer or malignant melanoma received SRS with dose of 15 Gy to 25 Gy. Magnetic resonance imaging (MRI) scans were acquired prior to SRS, every 3 months during the first year after SRS, and every 6 months thereafter. On the basis of the follow-up MRI scans or histology after SRS, metastases were classified as having response, tumor progression, or pseudoprogression. Advanced perfusion MRI enabled the estimation of vascular status in tumor regions including fractions of abnormal vessel architecture, underperfused tissue, and vessel pruning. Results: Prior to SRS, metastases that later developed pseudoprogression had a distinct poor vascular function in the peritumoral zone compared with responding metastases (P < .05; number of metastases = 15). In addition, differences were found between the peritumoral zone of pseudoprogressing metastases and normal-appearing brain tissue (P < .05). In contrast, for responding metastases, no differences in vascular status between peritumoral and normal-appearing brain tissue were observed. The dysfunctional peritumoral vasculature persisted in pseudoprogressing metastases after SRS. Conclusions: Our results suggest that the vascular status of peritumoral tissue prior to SRS plays a defining role in the development of pseudoprogression and that advanced perfusion MRI may provide new insights into patients' susceptibility to radiation-induced effects