News Briefing New Developments in Pediatric & Adult CNS Malignancies

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2 News Briefing New Developments in Pediatric & Adult CNS Malignancies Tuesday, Sept. 24, :45 p.m. Daphne Haas-Kogan, MD University of California, San Francisco

3 Cost-effectiveness of Proton Therapy Compared to Photon Therapy in the Management of Pediatric Medulloblastoma Raymond Mailhot Vega, Jane Kim, Marc Bussière, Jona Hattangadi, Abby Hollander, Jeff Michalski, Nancy Tarbell, Torunn Yock, Shannon M. MacDonald Massachusetts General Hospital, Harvard School of Public Health, Washington School of Medicine in St. Louis

4 Background Proton therapy has the potential to spare healthy tissue, but it is unclear if benefit gained validates increased costs Radiation therapy, while providing cancer control, can lead to long-term side effects Despite higher capital and operational costs, proton therapy may prove to be cost-effective for pediatric medulloblastoma patients by decreasing late adverse events

5 Methodology No difference in tumor control was assumed. Therefore, cost-effectiveness was influenced by comparing the differences of developing eight adverse events, including hearing loss, four hormone deficiencies, coronary artery disease, heart failure, and secondary malignancy Costs captured in the model were upfront capital cost of investment as well as downstream effects of managing eight adverse events. All costs were actual. This study used both data from real patients and modeling studies to inform the risk of adverse events in the model.

6 Analysis The goal was to assess the cost-effectiveness of proton therapy versus photon therapy, with the emphasis on side effects Proton therapy was more cost-effective than photon therapy

7 Conclusions This study did not attempt to explain if proton therapy is cost-effective in other malignancies With best available data, the utilization of proton therapy for the management of pediatric medulloblastoma is cost-effective, and, in most simulations, cost-saving

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9 SRS vs. WBRT + SRS for 1 to 4 Brain Metastases Individual Patient Data (IPD) Meta-Analysis Arjun Sahgal Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada Hidefumi Aoyama M.D. Ph.D. Niigata University Graduate School of Medical and Dental Sciences, Nigita, Japan Martin Kocher M.D. University of Cologne, Cologne, Germany Binod Neupane Ph.D. McMaster University, Hamilton, Canada Sandra Collette Ph.D. European Organisation for Research and Treatment of Cancer - Headquarters (EORTC HQ), Belgium Masao Tago M.D. Teikyo University, Mizonokuchi Hospital, Kanagawa, Japan Prakesh Shah M.D. Mount Sinai Hospital, University of Toronto, Canada Joseph Beyene Ph.D. McMaster University, Hamilton, Canada Eric Chang M.D. University of Southern California, Los Angeles, California MD Anderson Cancer Center, Houston, Texas

10 Methods Individual Patient Data (IPD) meta-analysis of the 3 RCTs (Japanese, EORTC, MDACC) comparing stereotactic radiosurgery (SRS) alone to whole brain radiotherapy (WBRT) plus SRS for patients presenting with 1 to 4 brain metastases Aim was to determine the effect of treatment on overall survival, distant brain control, and local control Adjusted a priori for co-variates: Age RPA (Recursive Partioning Analysis Score) Number of brain metastases (1 vs 2) Restricted inclusion to those with RPA 1 or 2 and KPS 70 Final cohort: 364 patients Median follow-up and survival: 9.2 months

11 Hazard Ratios for SRS Alone Overall Survival Age HR (95% CI) (0.24, 0.90) (0.29, 0.92) (0.35, 0.95) (0.42, 0.99) (0.49, 1.05) (0.56, 1.14) (0.62, 1.29) (0.67, 1.49) (0.71, 1.76) (0.73, 2.11) Overall survival significantly increased with SRS alone in patients age relative to their age matched cohort treated with WBRT+ SRS

12 Hazard Ratios for SRS Alone Local Failure Age HR (95% CI) (0.76, 11.79) (0.93, 9.09) (1.12, 7.08) (1.32, 5.64) (1.49, 4.7) (1.54, 4.26) (1.42, 4.35) (1.19, 4.86) (0.95, 5.7) (0.75, 6.85) Local failure significantly increased with SRS alone for ages relative to their age matched cohort treated with WBRT+ SRS

13 Hazard Ratios for SRS Alone Distant Brain Failure Age HR (95% CI) (0.42, 1.94) (0.56, 1.98) (0.73, 2.05) (0.95, 2.15) (1.19, 2.35) (1.40, 2.71) (1.55, 3.33) (1.64, 4.27) (1.70, 5.61) (1.75, 7.44) Distant brain failure significantly greater with SRS alone for age 55 relative to their age matched cohort treated with WBRT+ SRS

14 Conclusions Outcome Overall survival Aggregate Metaanalysis* No survival benefit for WBRT + SRS IPD Meta-analysis SRS alone favored for age 50 Local control WBRT + SRS favored WBRT + SRS favored Distant brain control WBRT + SRS favored WBRT + SRS favored for age 55 Our overall survival results support treatment with SRS alone and not WBRT + SRS for patients age 50 Spare these patients the adverse effects of WBRT *Tsao, Xu, Sahgal. A meta-analysis evaluating stereotactic radiosurgery, whole brain radiotherapy, or both for patients presenting with a limited number of brain metastases. Cancer. 118(9), ,2011.

15 Conclusions Recent RCT s have confirmed the detrimental effects of WBRT on both neurocognition and quality of life (Chang et al., Sun et al, Soffietti et al.): OS favoring SRS alone in younger patients (age 50) may be explained by the lack of benefit of WBRT with respect to distant brain control while exposing them to the toxicities of worse memory function and harming QOL Chang et al. Lancet Oncology, Lancet Oncol Nov;10(11): Sun et al. J Clin Oncol Jan 20;29(3): Soffietti et al. J Clin Oncol Jan 1;31(1):65-72

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17 Proton Radiotherapy for Pediatric Central Nervous System Ependymoma: Clinical Outcomes for 70 Patients Roshan V. Sethi, Beverly Lavally, Beow Y. Yeap, Karen J. Marcus, Paul Caruso, Margaret Pulsifer, Mary Huang, David Ebb, Nancy J. Tarbell, Torunn I. Yock, Shannon M. MacDonald Massachusetts General Hospital Harvard Medical School

18 Background Proton RT is more conformal than most forms of photon external beam RT We report the tumor outcomes and toxicities of 70 patients with ependymoma treated with proton RT Proton RT IMRT

19 Findings Disease control and survival outcomes were similar to outcomes in patients treated with photon RT

20 Findings IQ and adaptive skills were relatively preserved in a sub-set of patients

21 Conclusions Outcomes for localized ependymoma compare favorably to modern photon series Low incidence of endocrinopathy, auditory toxicity and cognitive decline This study supports consideration of proton RT for patients with ependymoma

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