PracticeUpdate: Haematology & Oncology

ASTRO 2016

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Postoperative stereotactic radiosurgery has become a standard of care for patients with resected brainmetastases

P aul D. Brown, MD, of the Mayo Clinic, Rochester, Min- nesota, explained that surgical resection of large symptomatic brain metastases is often indicated to con- firm diagnosis, remove lesion(s), or reduce pressure in the brain. Tu- mour recurrence after surgery alone, however, is frequent. Though postoperative whole brain radiotherapy reduces tumour recur- rence in the brain significantly and is the standard of care for patients fol- lowing resection, the treatment can negatively impact cognitive function and quality of life. Stereotactic radiosurgery targets escalated doses of radiation with extreme precision and can eliminate malignant cells in a single or small number of sessions while limiting the impact on surrounding tissue. Dr Brown remarked, “Stereotactic radiosurgery to the surgical cavity is widely used despite a lack of clini- cal trials to substantiate its effec- tiveness. Our randomised trial was the first to clearly demonstrate the efficacy of stereotactic radiosurgery vs whole brain radiotherapy in a postoperative setting.” From 2011 to 2015, 194 patients, each with one to four brain metas- tases, were randomised to stereo- tactic radiosurgery or whole brain

A multi-institutional trial has found comparable survival, less cognitive decline, and better quality of life follow- ing stereotactic versus whole brain radiotherapy after re- section of brain metastases.

radiosurgery than whole brain radio- therapy (mean change in quality of life from baseline –1.5 vs –7.0, P = 0.03; mean change in wellbeing change from baseline –6.4 vs –20.2, P = 0.002). At 6 months, physical wellbeing (decline of –3.2 vs –15.1, P = 0.016) remained significantly better in patients who received ste- reotactic radiosurgery Dr Brown said, “Our results con- firm that radiosurgery to the surgical cavity is a viable treatment option to improve local control, with less impact on cognitive function and quality of life than whole brain radiotherapy in resected metastatic brain disease. No significant dif- ference in survival was observed between postoperative radiosurgery and whole brain radiotherapy.” He added, “Radiosurgery avoids the well-known toxicities of whole brain radiotherapy. Furthermore, due to a smaller time commitment and quicker recovery after stereotac- tic radiosurgery, patients can restart systemic therapies sooner. Radio- surgery to the surgical cavity after resection of brain metastases should be considered a standard of care and a less toxic alternative to the historic standard of care.”

6 months following treatment. At 6 months, cognitive deterioration had occurred in 85.7% of patients who received whole brain radio- therapy, versus 53.8% of those who underwent stereotactic radiosurgery (P = 0.0006). A higher percentage of patients who underwent whole brain radiotherapy experienced worse immediate recall, memory, and attention than those treated with stereotactic radiosurgery. Whole brain radiotherapy provided higher overall intracranial tumour control rates at 6 and 12 months were 90.0 and 78.6% with whole brain radiotherapy vs 74.0 and 54.7% with stereotactic radiosurgery (P < 0.0001). No clinically meaningful difference was observed in median surgical bed relapse-free survival between treatment arms, though long-term follow-up showed better control with whole brain radiotherapy (7.7 vs 7.5 months, P = 0.04). Patients treated with stereotactic radiosurgery experienced better quality of life than those who re- ceived whole brain radiotherapy. Three months following treat- ment, declines in quality of life and physical wellbeing were sig- nificantly smaller after stereotactic

radiotherapy after surgical resection of one lesion. Seventy-seven percent of patients had a single brain and lung tumours were the primary site in 59%. Average patient age was 61 years, and study arms were balanced in baseline patient and tumour characteristics. Primary outcomes included over- all survival and cognitive deteriora- tion – free survival, defined as a decline greater than one standard deviation from baseline on any of six cognitive tests. Secondary endpoints included local control of the surgical bed, time to intracranial failure, and quality of life. After a median of 15.6 months, no statistically significant difference in overall survival rates was observed between groups (median overall sur- vival 11.5 months following stereo- tactic radiosurgery and 11.8 months following whole brain radiotherapy). Moreover, patients who received stereotactic radiosurgery experi- enced significantly longer survival without cognitive decline (median cognitive deterioration – free sur- vival 3.2 months for stereotactic ra- diosurgery and 2.8 months for whole brain radiotherapy [hazard ratio 2.0; P < 0.0001]). The cognitive impact of whole brain radiotherapy persisted at

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REQUES T THE BRAF TEST FOR YOUR PATIENTS WITH MELAN OMA.

PATIENTS WHO TEST POSITIVE FOR THE BRAF MUTATION MAY BE ELIGIBLE FOR TARGETED MELANOMA THERAPIES 1,2 BRAF mutation tests are recommended for the following patients: 2 MANDATORY • Unresectable stage III or IV HIGHLY RECOMMENDED • High-risk resected stage IIc or stage IIIb–IIIc

~40% OF PATIENTS WITH MELANOMA HARBOUR THE BRAF MUTATION 3

CONFIRM BRAF MUTATION STATUS EARLY HELP EXPEDITE ACCESS TO TARGETED THERAPIES FOR ADVANCED MELANOMA

References: 1. Pharmaceutical Benefits Scheme. Available from www.pbs.gov.au, accessed July 2016. 2. Dummer R et al. Ann Oncol 2015; 26 (Suppl 5): 126–32. 3. Kakavand H et al. Pathology 2016;48(2):194–202. Novartis Pharmaceuticals Australia Pty Ltd, ABN 18 004 244 160, 54 Waterloo Road, Macquarie Park, NSW 2113. Phone (02) 9805 3555. Item No.: MEL0168. Date of preparation: September 2016.

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