Exploring Barriers to Combined-Modality Therapy for LS-SCLC

By Anna Farago, MD, PhD

Small cell lung cancer (SCLC) accounts for approximately 15% of all new lung cancer diagnoses in the United States. Approximately 30% of patients with newly diagnosed SCLC have limited-stage (LS) disease based on the Veterans’ Administration Lung Study Group staging system; this means that the radiographically evident disease is localized within the hemithorax in a distribution treatable within a radiation field. For these patients, the optimal treatment is concurrent chemotherapy and radiation. This strategy is supported by several studies, including a meta-analysis published by Pignon and colleagues,1 which demonstrated that concurrent chemotherapy and radiation improves local control and improves 3-year overall survival by approximately 5% compared to chemotherapy alone. Furthermore, multiple studies have shown that the optimal timing of radiation is to start within the first two cycles of chemotherapy.

In a recent brief report in JAMA Oncology, Pezzi et al.2 explored barriers to combined-modality therapy for LS-SCLC. Using the National Cancer Database (NCDB), the authors analyzed initial management of all LS-SCLC cases between 2004 and 2013, with the goal of estimating utilization rates and factors associated with chemotherapy and radiation therapy delivery for LS-SCLC. The authors reviewed more than 70,200 cases with a median follow up of 62.3 months. They found that 55% of patients received chemotherapy and radiation as their initial treatment, 20.5% received chemotherapy alone, 3.5% received radiation alone, and 20% received neither. Notably, the NCDB did not provide information about whether chemotherapy and radiation were delivered concurrently or sequentially. Overall, outcomes were better for those patients who received combined modality therapy versus those who received chemotherapy alone, radiation therapy alone, or no therapy (median survival 18.2, 10.5, 8.3, and 3.7 months, respectively).

Differences in Outcomes Explained
Although one might speculate that the different outcomes among the four groups could reflect both selection bias (with more fit patients receiving combined modality therapy) and the superior anticancer activity of combined modality therapy, the authors sought to identify specific factors that were associated with differences in outcomes.

Access to health insurance and type of health insurance emerged as factors associated with overall survival. On multivariable analysis, the authors found that being uninsured was associated with a lower likelihood of patients receiving either chemotherapy or radiation therapy. Interestingly, Medicare/Medicaid insurance had no effect on chemotherapy use but did result in a decreased likelihood of radiation therapy delivery. Lack of health insurance, Medicaid, and Medicare coverage were all independently and significantly associated with a shorter overall survival on adjusted analysis (HR 1.19, 1.27, and 1.12, respectively), whereas chemotherapy and radiation therapy were associated with a survival benefit (HR 0.55 and 0.62, respectively).

The authors also found that the type of facility was associated with differences in outcomes. Patients who received care at an academic/research program had superior outcomes compared to those who received care at a community cancer center, comprehensive community cancer program, or integrated network cancer program (HR 1.19, 1.08, and 1.07, respectively; compared to a reference HR of 1 for the academic/ research program). The authors noted that similar trends have been observed for outcomes of patients with NSCLC. They speculated that possible explanations could include patient selection, coordination of care, and access to subspecialists.

Implications for Clinical Practice
This study represents an important step toward better understanding of barriers to care for patients with LS-SCLC. In practice, concurrent chemotherapy and radiation for LS-SCLC poses several challenges for patients. Among these are time and cost associated with transportation for appointments, as well as scheduling challenges, particularly with twice-daily radiation. Supporting patients through these obstacles is a crucial element to providing optimal care. The Pezzi et al. study now further directs our attention to how insurance coverage may influence barriers to care.

Based on this study, it is important to consider whether expanding the financial assistance for radiation therapy delivery may enable more patients to receive this important element of their care.

The reasons for a lower likelihood of radiation therapy for patients with Medicare or Medicaid are not well understood at this point, but further research is certainly indicated to help determine whether the barriers for these patients are financial, logistic, or other. Reimbursement from insurance carriers may be a relevant factor. There are programs such as 340B and the Medicaid Drug Rebate Program that allow hospitals to deliver chemotherapy with competitive reimbursement. However, these programs do not provide financial assistance for radiation therapy delivery. The authors speculate that this may partially explain why patients with government insurance were less likely to receive radiation therapy in this cohort. Based on this study, it is important to consider whether expanding the financial assistance for radiation therapy delivery may enable more patients to receive this important element of their care.

By better understanding barriers to care for patients with LS-SCLC and working to overcome them, we hope ultimately to provide optimal evidence-based care for all medically eligible patients. ✦

About the Author: Dr. Farago is an instructor of medicine at Harvard Medical School and an assistant of medicine at Massachusetts General Hospital.

Related Article: Dr. Howard ‘Skip’ Burris III Shares His Views on Clinical Trial Eligibility Criteria, Payer Involvement


1. Pignon JP, Arriagada R, Ihde DC, et al. A Meta-Analysis of Thoracic Radiotherapy for Small-Cell Lung Cancer. N Engl J Med. 1992;327:1618-1624.
2. Pezzi TA, Schwartz DL, Mohamed ASR, et al. Barriers to Combined-Modality Therapy for Limited-Stage Small-Cell Lung Cancer. JAMA Oncol. 2018 Jan 4. [Epub ahead of print].