PracticeUpdate: Haematology & Oncology

ASTRO 2016

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Adding several additional fractions of radiation directed to the lumpectomy cavity after whole breast radiation for DCIS provides an incremental benefit in decreasing local relapse, similar inmagnitude to the benefit of 4% at 20 years of the boost for invasive cancers.

Onmultivariate analysis, we identified younger age (<40 years) and higher- grade diseasewere associatedwith higher risk of locoregional recurrence and death. These patients, therefore, may bemore likely to benefit from radiation therapy. >10

Our results confirm 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. >11

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Reduced radiation boost volume is recommended but craniospinal axis dose remains unchanged in average-risk paediatric medulloblastoma A Children’s Oncology Group trial has found that survival is not compromised from smaller radiation volume to the posterior fossa. The authors uphold standard doses for craniospinal irradiation, however.

This outcome was reported at the ASTRO 2016. J eff M. Michalski, MD, MBA, of Washington University, St. Louis, Missouri, explained that in this largest trial of average-risk paediatric medulloblastoma, survival rates fol- lowing reduced radiation therapy boost volumes were compara- ble to standard treatment volumes for the primary tumour site. Lower doses of craniospinal axis irradiation were associated with higher event rates and worse survival. Findings from this phase 3 randomised trial indicate that physicians can adopt smaller boost volumes for posterior fossa radiotherapy but should maintain the standard radiotherapy dose for craniospinal irradiation. The most common type of brain malignancy in children, medulloblastoma is an aggressive tumour that originates in the lower, rear area of the brain but tends to spread to the upper brain and spine. As a result, the standard of care following surgical resection for these children has included systemic chemotherapy and irradiation to both the posterior fossa (pri- mary site) and craniospinal axis. Complications of craniospinal irradiation, however, include considerable negative effects on neurocognition, endocrinologic function, and hearing. We were disappointed to find that a lower dose of irradiation was associated with an increased rate of failure in the younger children. Reducing the treatment by just three fractions from 23.4 to 18 Gy was associated with a higher rate of events and diminished overall survival.

reduced dose of involved-field radiotherapy (n = 227). The 226 patients age 3 to 7 years were also randomised to a standard irradiation dose of 23.4 Gy to the craniospinal axis (n = 110) or a reduced dose of 18 Gy (n = 116). Following maximum surgery and within 31 days following resection, patients began 6 weeks of radiotherapy. After a 1-month break, they began to receive alternating cycles of cisplatin- and cytoxan-based chemotherapy. Primary outcomes included the amount of time from study entry to disease progression, disease recurrence, death from any cause, or a second malignant neoplasm. Researchers compared rates of overall survival, event-free survival, local failure, and distant failure. After a median of >6.5 years, reduction in the volume of radiotherapy boost to the posterior fossa did not compromise overall or event-free or survival in this cohort of paediatric patients with average-risk medulloblastoma. Overall survival at 5 years was 84.1 ± 2.8% for patients who received the reduced volume with involved-field radiotherapy and 85.2 ± 2.6% for patients who received the standard volume of radiation to the posterior fossa. Event-free survival at 5 years was 82.2 ± 2.9% for involved-field radiotherapy and 80.8 ± 3.0% for radiation to the posterior fossa. Rates of local failure did not vary significantly between treatment arms. Local failure at 5 years was 1.9 ± 0.1% for involved-field radiation and 3.7 ± 1.3% for radiation to the posterior fossa. Dr Michalski commented, “This trial – the largest of its kind to date – indicates that it is safe to adopt a limited posterior fossa boost for patients receiving radiation therapy for average risk medulloblastoma. These children can experience similar positive outcomes with lower chances of the radiation affecting surrounding brain tissue.” He added, “Additional data are needed, however, to address the appropriate volume for patients with higher-risk disease or metastasis at the time of diagnosis.” While reduced radiation volume to the posterior fossa did not impact survival rates, a low dose of craniospinal irradiation was associated with lower rates of event-free and overall survival in the youngest patients. Overall survival at 5 years was 78.1 ± 4.4% for those age 3 to 7 years who received low-dose irradiation therapy to the craniospinal axis versus 85.9 ± 3.8% for the standard dose to this axis. Event-free survival at 5 years was 72.1 ± 4.8% for children who received a low dose to the craniospinal axis, versus 82.6 ± 4.2% for those who received a standard dose to the axis. Rates of distant failure did not differ between groups. Isolated distant failure at 5 years was 12.8 ± 3.2% for low-dose radiation to the craniospinal axis and 8.2 ± 2.8% for standard-dose radiation to the axis. Dr Michalski concluded, “Unfortunately, we were disap- pointed to find that a lower dose of irradiation was associated with an increased rate of failure in the younger children. Re- ducing the treatment by just three fractions from 23.4 to 18 Gy was associated with a higher rate of events and diminished overall survival. Patients with average risk medulloblastoma should continue to receive a standard dose of 23.4 Gy to the craniospinal axis unless enrolled in a clinical trial.”

Researchers from the National Cancer Institute-supported Chil- dren’s Oncology Group set out to assess outcomes from a reduced ra- diation boost volume to the posterior fossa among paediatric average-risk medulloblastoma patients and a lower craniospinal dose, specifically in younger children. While several single-institution trials have found limited posterior fossa boost to be comparable to whole posterior fossa boost, this was the first trial that was sufficiently pow- ered to state definitively that the two approaches confer similar results in terms of survival. The findings are based on data from 464 patients age 3 to 21 years with average-risk medulloblastoma. Eli- gible patients had complete or near- complete resection of their primary tumours and no evidence of anaplasia or spread of the cancer beyond the posterior fossa. Patients were randomised to a standard radiation boost volume to the posterior fossa (n = 237) or a

VOL. 1 • No. 4 • 2016