Prophylactic cranial irradiation (PCI) is an important treatment modality of patients with limited stage small cell lung cancer (LD-SCLC). However, PCI is also associated with several side effects, such as decline in memory and other cognitive functions. This provides the rationale to explore the clinical feasibility of hippocampal avoidance during WBRT. Previous studies have demonstrated the dosimetric capabilities of IMRT to conformally avoid the hippocampus without detriment to the radiation dose the remaining brain receives. The aims of this study is to evaluate the therapy efficacy and the safety profile of hippocampal-sparing whole-brain radiation therapy (HS-WBRT) for PCI in patients with LD-SCLC.

Chemotherapy plus thoracic radiation followed by prophylactic cranial irradiation (PCI) is the standard of care in management of limited stage small cell lung cancer patients. However, whole brain radiation therapy (WBRT) is also associated with many side effects including consolidation of new memory, poor attention span/concentration, visual spatial difficulties, difficulty with executive planning, and poor fine motor control. There exists significant preclinical and clinical evidence that radiation induced injury to the hippocampus correlates with neurocognitive decline of patients who received WBRT. Reducing radiation dose to the hippocampus during WBRT has been postulated as an approach to mitigate neurocognitive impairment. The present study hypothesize that hippocampal sparing PCI will allow improved performance on tests of short term memory and executive function compared to a historical control receiving the same dose of conventional PCI. The primary objective of this study is to evaluate performance on the Hopkins Verbal Learning Test-Revised for delayed recall at 6 months following hippocampal-sparing PCI relative to the historical control. Secondary objectives are to estimate: composite cognitive function following hippocampal-sparing PCI relative to the historical control and the rate of metastases in the hippocampus at 2 years following hippocampal-sparing PCI.

Inclusion Criteria:

• Patient must have newly diagnosed and confirmed small-cell lung cancer (SCLC)
• Patient must have a performance status of 1 or higher
• Patients must not have received previous irradiation to the brain
• Patients must have limited stage disease with CR (complete response) to chemotherapy and consolidative chest radiotherapy that was documented at least on standard chest x-rays within one month of study entry
• Negative MRI or CT scan of the brain at least one month before protocol entry
• Women of child-bearing potential must have a negative pregnancy test and also agree to use adequate contraceptives while on protocol
• Patient must be able to understand and sign the informed consent document
• Patient must be informed of the investigational aspect to this trial prior to singing the informed consent document

Exclusion Criteria:

• Patients receiving prior external beam irradiation to the head or neck, including any form of stereotactic irradiation
• Radiographic evidence of brain metastases and/or ipsilateral lung metastases/malignant pleural effusion
• Planned concurrent chemotherapy or antitumoral agent during PCI
• Concomitant malignancy or malignancy within the past five years other than nonmelanomatous skin cancer or carcinoma in situ of the cervix
• Patients with minimal pleural effusion evident on CXR (chest X-ray); minimal pleural effusion visible on chest CT is allowed.
• Patients with epilepsy requiring permanent oral medication _ Patients must not have a serious medical or psychiatric illness that would, in the opinion of the investigator, prevent informed consent or completion of protocol treatment, and/or follow-up visits.