International Journal of

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Clinical Investigation

Risk of Hippocampal Metastases in Small Cell Lung Cancer Patients at Presentation and After Cranial Irradiation: A Safety Profile Study for Hippocampal Sparing During Prophylactic or Therapeutic Cranial Irradiation Vijayananda Kundapur, MD, DMRT, FRCR,* Tasha Ellchuk, FRCPC,z Shahid Ahmed, FRCPC,* and Vinai Gondi, MDx *Saskatoon Cancer Center, College of Medicine, and zDepartment of Radiology, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada; and xCadence Health Brain Tumor Center and Cadence Health Proton Center, Chicago, Illinois Received Jul 24, 2014, and in revised form Dec 5, 2014. Accepted for publication Dec 10, 2014.

Summary A recently completed intergroup study showed that minimizing dose to hippocampus would prevent memory loss during whole brain radiation treatment (WBRT). However, this study excluded small cell lung cancer (SCLC) patients on the assumption that these patients would have more diffuse deposits in brain, thus an increased risk of hippocampal deposits compared with other malignancies. Our study shows that assumption is not correct. SCLC patients would benefit the most with

Purpose: Neurocognitive impairment (NI) in patients with small cell lung cancer (SCLC) after whole brain radiation treatment (WBRT) is a significant cause of morbidity. Hippocampal avoidance (HA) during WBRT may mitigate or prevent NI in such patients. However, this has not been tested in SCLC patients. The estimated risk of metastases in the HA region (HM) in patients with SCLC at diagnosis or after WBRT is unknown. Our study aimed to determine the risk of HM in patients with SCLC and to assess correlated clinical factors. Methods and Materials: Patients with SCLC who experienced brain metastases (BM) at presentation (de novo) or after WBRT treated at the Saskatoon Cancer Centre between 2005 and 2012 were studied. Relevant neuroimaging was independently reviewed by a neuroradiologist. HM was defined as metastases within 5 mm of the hippocampus. Logistic regression analysis was performed to assess correlation between various clinical variables and HM. Results: Seventy eligible patients were identified. Of 59 patients presenting with de novo BM, 3 patients (5%, 95% confidence interval [CI]: 0%-10.7%) had HM. Collectively there were 359 (range, 1-33) de novo BM with 3 (0.8%, 95% CI: 0%-1.7%) HM deposits. Twenty patients experienced progression of metastatic disease in the brain after WBRT. Of the 20 patients, only 1 patient (5%, 95% CI: 0%-14.5%) experienced HM. On logistic regression, no factors significantly correlated with HM.

Reprint requests to: Dr Vijayananda Kundapur, MD, DMRT, FRCR, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, S7N 4H4, Canada. Tel: (306) 655-2740; E-mail: Vijayananda. [email protected] Int J Radiation Oncol Biol Phys, Vol. 91, No. 4, pp. 781e786, 2015 0360-3016/$ - see front matter Ó 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ijrobp.2014.12.026

Presented in part in abstract form at the annual meeting of the American Society of Clinical Oncology, May 31 to June 4, 2013, Chicago, Illinois. Conflict of interest: none.

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International Journal of Radiation Oncology  Biology  Physics

Kundapur et al.

this technique because most of these patients receive WBRT.

Conclusion: The overall incidence of HM before or after WBRT in SCLC patients is low, providing preliminary support for the safety of HA during planned clinical trials of HA-WBRT for SCLC. Ó 2015 Elsevier Inc. All rights reserved.

Introduction Nearly 10% to 18% of patients with small cell lung cancer (SCLC) present with metastatic deposits in the brain, and the number of patients experiencing metastatic deposits in the brain proportionally increases with time (1-6). Among patients with extensive-stage SCLC, the incidence of metastatic disease in the brain can be as high as 80% (7). A meta-analysis by Auperin et al (8) has shown significant improvement in central nervous system (CNS) disease control and overall survival in patients with SCLC with the use of prophylactic whole brain radiation therapy (PWBRT). Even for extensive-stage SCLC patients, the European Organization for Research and Treatment of Cancer (EORTC) study has demonstrated that PWBRT could improve both CNS progression-free survival and overall survival (9). As a result of these landmark research works, PWBRT has become an important treatment component for most patients with diagnoses of SCLC with no proven metastatic disease in the brain (8, 9). Nevertheless, the quality of life data after PWBRT in patients with SCLC has shown significant impairment in short-term memory, intellectual deficit, and communication deficit (10, 11). Grosshans et al (12) demonstrated that although a large proportion of SCLC patients have a baseline neurocognitive deficit, these patients experience further deterioration in areas of attention span, visual spatial construction, and executive functions after PWBRT. Furthermore, a prospective phase III intergroup study reported similar neurocognitive decline in patients treated with therapeutic whole brain radiation therapy (TWBRT) for known metastatic deposits in the brain (13). Preclinical and clinical data support the memory specificity and radiosensitivity of a neural stem cells compartment located in the hippocampal dentate gyrus (14, 15). Reducing radiation dose to the hippocampus (HC) during whole brain radiation treatment (WBRT) has been postulated as an approach to mitigate or prevent neurocognitive impairment (NI). However, conformal HC avoidance (HA) during WBRT raises the risk of relapse within this region, which is defined as the HC plus

Risk of hippocampal metastases in small cell lung cancer patients at presentation and after cranial irradiation: a safety profile study for hippocampal sparing during prophylactic or therapeutic cranial irradiation.

Neurocognitive impairment (NI) in patients with small cell lung cancer (SCLC) after whole brain radiation treatment (WBRT) is a significant cause of m...
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