Quality assurance analysis of hippocampal avoidance in a melanoma whole brain radiotherapy randomized trial shows good compliance

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.

Melanoma Brain Metastases: A Systematic Review of Opportunities for Earlier Detection, Diagnosis, and Treatment

“…Hippocampal avoidant radiotherapy was shown using probabilistic sensitivity analysis as the preferred method in 77% of simulations. Other studies have confirmed the data quality from observational methods such as whole brain radiotherapy and the preferred hippocampal avoidant radiotherapy [ 35 , 36 ]. Aside from the cost considerations, additional research addressing improvable features of utilized observational methods could lead to better patient outcomes and conserve clinical resources.…”

“…Manipulating WBRT dosage also showed no difference in effect on brain tumor size change or overall survivability, again indicating that WBRT is most likely not a favorable treatment approach [ 34 ]. Though most reporting on and the analysis of WBRT efficacy in MBM cases align with the aforementioned negative findings, a select few studies have seen WBRT improve palliation by prolonging both intracerebral and intracranial control [ 35 , 36 ]. Additionally, Janavicius and colleagues promoted WBRT as a means of preserving memory and neurocognitive function in MBM patients, which is in direct contention with earlier findings.…”

Gastric cancer with brain metastasis: from molecular characteristics and treatment

“…In a large phase III trial, Brown et al ( 101) reported that hippocampal avoidance-WBRT (HA-WBRT) can better protect cognitive function than traditional WBRT. Similarly, avoiding the hippocampus during WBRT has been shown to be closely related to improved neurocognitive function, avoidance of personality changes, and improved quality of life, as mentioned by V. Pareek (102). In addition, the results of phase III trial (NCT02360215) showed that the combined use of memantine after HA-WBRT resulted in a 23.3% deterioration of executive function after 4 months, with declines of 11.5% and 16.4% in learning and memory after 6 months (103).…”

Volumetric modulated arc therapy (VMAT) for extensive skin field cancerisation (ESFC) – exploring the limits of treatment volumes with a case series of backs

“…This further refinement of the VMAT technique is known as the addition of a simultaneous integrated boost (SIB). 13 Extensive skin field cancerisation (ESFC) has been defined as that which has a clinically detectable surface area of over 50cm 2 . 14 In some anatomical sites (e.g.…”