Concurrent chemo-radiotherapy should be a treatment option for elderly patients with LS-SCLC
Elderly patients with limited-stage small cell lung cancer (LS-SCLC) showed similar survival and toxicity compared to their younger counterparts when treated with concurrent chemo-radiotherapy. Concurrent chemo-radiotherapy should be a treatment option for fit patients aged 70 years or older.
Lung cancer is the most common cancer and the leading cause of cancer-related deaths worldwide. SCLC constitutes between 10-15% of lung cancer diagnoses and of those 30% are characterized as limited-stage disease or stage I-III according to the TNM classification. The elderly makes up a large population of patients diagnosed with LS-SCLC but are often underrepresented in clinical trials and have limited treatment options. Consequently, the optimal treatment for elderly patients with LS-SCLC is not established and warrants further investigation.
A group of international investigators compared the outcomes of patients aged 70 years or greater to their younger counterparts within the Concurrent ONce-daily VErsus twice-daily RadioTherapy (CONVERT) trial, an international, multicenter, phase III randomized controlled trial. There was no upper age limit in the CONVERT trial and patients were followed for five years following treatment. Patients were randomized to receive radiotherapy at 45 gray (Gy)/30 twice-daily fractions for 3 weeks or 66 Gy/33 once-daily fractions for 6.5 weeks concurrently with platinum-based chemotherapy. Overall survival and progression free survival were evaluated using Kaplan-Meier methodology and Cox proportional hazards regression.
The results of the study were published in the Journal of Thoracic Oncology, the official journal of the International Association for the Study of Lung Cancer (IASLC). Between April 2008 and November 2013, 547 patients were randomized to the CONVERT trial. Of those 490 patients included in this analysis, 67 patients were aged ? 70 years with a median age of 73 years (range 70-82), 21 patients were aged ? 75 years, and 4 patients aged ? 80 years. The median age of the younger group was 60 years (range 29-70). Amongst the patients ? 70 years, 20 (43%) were randomized to twice-daily and 38 (57%) to once-daily radiotherapy arms. Fewer older patients received the optimal number of radiotherapy fractions (73% vs. 85%; P=0.03); however, chemotherapy compliance was similar in both groups (p=0.24). Neutropenia grade 3-4 occurred more frequently in the elderly compared to the younger group (84% vs. 70%; p=0.02), but rates of neutropenic sepsis (4% vs. 7%; p=0.07) and death (3% vs. 1.4%; p=0.67) were similar in both groups. Median survival in the elderly vs. younger groups was 29 (95% confidence interval (CI) 21-39) vs. 30 months (95% CI 26-35). Median time to progression in the elderly vs. younger groups was 18 (95% CI 13-31) vs. 16 months (95% CI 14-19).
The authors comment that, "This analysis is the largest chemo-radiotherapy randomized trial reported in elderly LS-SCLC patients and we demonstrated comparable survival and toxicity between older and younger patients. Certainly, up to age of 80, chronological age as a sole factor should not be a barrier to this type of treatment. In CONVERT, hematological toxicity was higher in the elderly but there was no increased risk of neutropenic sepsis or hospitalization, and fatal toxicity was similar in the two age groups. However, the small group of patients aged ? 80 years experienced severe toxicity including one treatment-related death reported as dementia from percutaneous coronary intervention. Overall, our results are particularly relevant as robust evidence to guide treatment decisions in elderly LS-SCLC patients is lacking."