Abstract
BackgroundMelanoma brain metastases (MBM) often cause morbidity and mortality for stage IV melanoma patients. An ongoing randomised phase III trial (NCT01503827 – WBRT-Mel) evaluates the role of adjuvant whole brain radiotherapy (WBRT) following local treatment of MBM. Hippocampal avoidance during WBRT (HA-WBRT) has shown memory and neurocognitive function (NCF) preservation in the RTOG-0933 phase II study. This study assessed the quality assurance of HA-WBRT within the WBRT-Mel trial according to RTOG-0933 study criteria.MethodsHippocampal avoidance was allowed in approved centres with intensity-modulated radiotherapy capability. Patients treated by HA-WBRT were not randomized within the WBRT arm. The RTOG 0933 contouring Atlas was used to contour hippocampi. In the trial co-ordinating centre, patients were treated with volumetric modulated arc therapy using complementary arcs; similar techniques were used at other sites. Dosimetric data were extracted retrospectively and analysed in accordance with RTOG 0933 study constraints criteria.ResultsAmong the 215 patients accrued to the WBRT-Mel study between April 2009 and September 2017, 107 were randomized to the WBRT arm, 22 were treated by HA-WBRT in 4 centers. Eighteen patients were treated in the same centre. The median age was 65 years. The commonest (91%) HA-WBRT schema was 30 Gy in 10 fractions. Prior to HA-WBRT, 10 patients had been treated by surgery alone, six by radiosurgery alone, four by surgery and radiosurgery and two exclusively by simultaneous integrated boost concurrent to HA-WBRT. Twenty patients were treated with intention to spare both hippocampi and two patients had MBM close to one hippocampus and were treated with intention to spare the contralateral hippocampus. According to RTOG-0933 study criteria, 18 patients (82%) were treated within constraints and four patients (18%) had unacceptable deviation in just one hippocampus.ConclusionsThis dosimetric quality assurance study shows good compliance (82%) according to RTOG-0933 study dosimetric constraints. Indeed, all patients respected RTOG hippocampal avoidance constraints on at least one hippocampus. In the futureanalysis of the WBRT-Mel trial, the NCF of patients on the observation arm, WBRT arm and with HA-WBRT arm will be compared.
Highlights
Melanoma brain metastases (MBM) often cause morbidity and mortality for stage IV melanoma patients
It was found that the hippocampus in oligometastatic disease was relatively spared from metastasis [16,17,18] and the intensity-modulated radiotherapy (IMRT) technique has been developed to spare the hippocampus during whole brain radiotherapy (WBRT) to preserve the neurocognitive function (NCF) [19,20,21]
An Radiation therapy oncology group (RTOG) phase II trial showed that hippocampal avoidance during WBRT (HA-WBRT) could minimise the neurocognitive decline at six months compared to historical controls [13]
Summary
Melanoma brain metastases (MBM) often cause morbidity and mortality for stage IV melanoma patients. The long-term effects of radiotherapy treatment on and neurocognitive function and quality of life have become even more important [12, 13] Prior to this changing landscape, a phase III randomized trial (RCT) was started in 2009 to compare whole brain radiotherapy (WBRT) with observation following local treatment (surgery or radiosurgery) of 1–3 MBM An RTOG phase II trial showed that hippocampal avoidance during WBRT (HA-WBRT) could minimise the neurocognitive decline at six months compared to historical controls [13] With these new data, the WBRT-Mel protocol was modified in 2013 to allow HA-WBRT for those randomized to the WBRT arm. The plan is to analyse the NCF endpoints in the three treatment cohorts: observation, HA-WBRT and non HA-WBRT
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