Evaluation of Prognostic Variables in Patients With Small Cell Lung Cancer: The Role of Volumetric Response to Initial Therapy in Determining the Benefit of Prophylactic Cranial Irradiation

Abstract

Prophylactic cranial irradiation (PCI) improves survival in patients with both extensive-stage (ES) and limited-stage small cell lung cancer (LS) who have a complete response to chemotherapy and radiation, yet data on prognostic variables are limited. The purpose of this study is to analyze prognostic variables in patients receiving PCI for small cell lung cancer. A retrospective study of 336 patients diagnosed from April 2003 to August 2013 were identified. Sixty-one patients who received PCI with at least 6 months of follow up were analyzed. Twenty-five patients were found to have ES-SCLC and 36 with LS-SCLC. Data was collected on patient characteristics, toxicity, and treatment parameters. Response to initial therapy of thoracic disease was analyzed based on Response Evaluation Criteria for Solid Tumors (RECIST v1.1). Pre- and post-treatment imaging studies were used to compute the volumetric reduction in the index tumors to further quantify tumor response. Cox proportional hazard models were used to detect influence factors of brain metastatic free survival (BMFS) and Overall survival (OS). ES patients had significantly shorter follow up than patients with LS (median 12.3 months vs 24.9 months, p = 0.0002). ES patients survived for shorter duration than patients with LS disease (Median 16.27 vs 57.63, p = 0.004). Both the median cumulative thoracic radiation dose (30 Gy versus 45 Gy, p = .001) and the total PCI dose (25 Gy versus 45 Gy, p = .028) were lower in ES patients. No patient or treatment factors evaluated had an effect on BMFS or OS in ES patients. In LS patients no evaluated patient or treatment factors correlated with OS, however, improvement in BMFS was based on the degree of response to primary thoracic radiation and chemotherapy. Patients with a complete response had lower rates of developing brain metastasis (HR .025, 95% CI .001 - .545). The 3 year BMFS for patients with a complete response, partial response and progression was 88%, 50% and 50%, respectively (p = .007). Patients with a partial response were further analyzed to compute the volumetric reduction after therapy. Those with >80% volumetric reduction in disease had a trend towards increased 3 yr BMFS (65% vs 20%, p = 0.07). Provider and patient reported neurotoxicity was further evaluated. ES patients who had a complete response after initial therapy (OR .056, 95% CI .005 - .570) and those who developed no brain metastasis (OR .095, 95% CI .014 - .660) had lower rates of neurologic dysfunction. No factors were found to effect neurotoxicity in LS patients. Response to initial therapy continues to be an important factor in determining which patients may benefit from PCI. Volumetric response may be a more relevant evaluation tool in determining the benefit from PCI in patients with less than a complete response with LS disease. Further prospective analysis is needed.