MD Conference Express - ELCC 2015 - (Page 23)

SELECTED UPDATES Strategies for Optimizing Radiation Therapy for Small Cell Lung Cancer Written by Mary Mosley Small cell lung cancer (SCLC) is characterized by rapid tumor growth, initially high response rates to chemotherapy and radiation therapy (RT) followed by rapid treatment resistance, and about a 10% survival rate at 5 years. Different treatment approaches may be needed for different tumors, because experimental data have demonstrated a high level of cell heterogeneity, phenotypic variability, and a differential expression of epithelial-mesenchymal transition among different cell lines of SCLC, stated Rebecca Bütof, MD, University Hospital, TU Dresden, Dresden, Germany. The optimal time to initiate RT appears to be early (within 30 days) after the start of chemotherapy. In part, this may be due to the accelerated repopulation of tumor cells that typically occurs after any cytotoxic therapy, noted Prof Bütof. Two meta-analyses showed a survival benefit with early vs late initiation of RT [Pijls-Johannesma M et al. Cancer Treat Rev. 2007; Fried DB et al. J Clin Oncol. 2004]. Regarding the optimal dose of RT, the total gross tumor volume was shown to be an independent prognostic factor for overall survival (OS) [Reymen B et al. Int J Radiat Oncol Biol Phys. 2013], thus volume-based dosing may be needed. Turrisi and colleagues showed in 1999 that twice-daily RT delivered over a shorter period of time (3 weeks, vs 5 weeks for once-daily RT) resulted in better median survival (23 months vs 19 months) and 5-year survival (26% vs 16%). Delivering RT in more (15) fractions was shown to improve 3-year OS vs conventional fractionation (39.4% vs 19.1%; P = .004) [Socha J et al. J BUON. 2015]. However, the results of the CALGB 30610 [NCT00632853] and CONVERT [NCT00433563] trials are awaited to provide definitive answers for the optimal timing, dosing, and fractionation for RT in SCLC. Research is also underway to develop RT techniques that will spare normal tissue to ultimately reduce side effects related to RT. PROPHYLACTIC CRANIAL IRRADIATION IN SCLC Prophylactic cranial irradiation (PCI) became the standard of care to reduce the incidence of brain metastases (BMs) in patients with SCLC based on a meta-analysis showing that PCI prevented, rather than delayed, BMs [Aupérin A et al. N Engl J Med. 1999]. These findings were supported by the EORTC trial in patients with extensive-stage (ES) SCLC [Slotman B et al. N Engl J Med. 2007]. However, new data from a Japanese study in patients with ES-SCLC raise new questions about the use of PCI, because this study showed a higher incidence of BMs and no improvement in OS [Seto T et al. J Clin Oncol. 2014 (abstr 7503)]. Notably, the Japanese study used magnetic resonance imaging to define BMs, rather than symptomatic BMs as used previously. Yet, this trial was terminated early and the publication of the complete final results is needed to determine whether recommendations for the use of PCI should change, stated Cecile Le Péchoux, MD, Institut Gustave Roussy, Villejuif, France. Further, differences in patient selection and the use of more second-line treatment in the Japanese study may contribute to differences in results between the studies. Neurocognitive toxicity is a concern with PCI, with reports of a higher risk of decline in self-reported cognitive functions at 6 and 12 months (P < .0001) and declines in recall on the Hopkins Verbal Learning Test (HVLT) at 6 and 12 months (P = .002) [Gondi V et al. Int J Radiat Oncol Biol Phys. 2013]. A significant decline in memory at 1 year was also reported [Sun A et al. J Clin Oncol. 2011]. Hippocampal avoidance (HA) when delivering whole brain RT was shown to preserve memory and quality of life in a study of this approach performed in 42 patients with lung or breast cancer who were compared with historical controls [Gondi V et al. J Clin Oncol. 2014]. The prospective, phase 3 HA-PCI trial [NCT01780675] is investigating the impact of this approach on Peer-Reviewed Highlights From the European Society for Medical Oncology 2015 European Lung Cancer Conference April 15-18, 2015 Geneva, Switzerland Peer-Reviewed Highlights From the European Society for Medical Oncology 2015 European Lung Cancer Conference 23

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MD Conference Express - ELCC 2015