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Frequency and Dosage of Radiotherapy in Chemoradiotherapy for Limited-Stage SCLC


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As reported in the Journal of Clinical Oncology by Jeffrey Bogart, MD, and colleagues, the phase III CALGB 30610/RTOG 0538 trial has shown no significant difference in overall survival with 70-Gy once-daily vs 45-Gy twice-daily radiotherapy in a chemoradiotherapy regimen for limited-stage small cell lung cancer (SCLC).

As stated by the investigators, “Although level 1 evidence supports 45-Gy twice-daily radiotherapy as standard for limited-stage SCLC, most patients receive higher-dose once-daily regimens in clinical practice. Whether increasing radiotherapy dose improves outcomes remains to be prospectively demonstrated.”

Jeffrey Bogart, MD

Jeffrey Bogart, MD

Study Details

In the two-stage U.S. multicenter trial, patients were randomly assigned between March 2008 and December 2019 to receive radiotherapy at 45 Gy in 1.5-Gy twice-daily fractions over 3 weeks, 70 Gy in 35-Gy once-daily fractions over 7 weeks, or 61.2-Gy concomitant-boost over 5 weeks, starting with the first or second of four cycles of cisplatin plus etoposide. In the second stage, allocation to the 61.2-Gy group was discontinued following planned interim toxicity analysis, and the study continued with the 45-Gy twice-daily group (n = 313) and the 75-Gy once-daily group (n = 325). The primary endpoint was overall survival in the intention-to-treat population in the two groups.

Overall Survival

Median follow-up was 4.7 years (interquartile range = 3.1–7.1 years). Median overall survival was 30.1 months (95% confidence interval [CI] = 24.4–37.2 months) in the 70-Gy group vs 28.5 months (95% CI = 25.4–34.5 months) in the 45-Gy group (hazard ratio [HR] = 0.94, 95% CI = 0.76–1.17, P = .594). Overall survival rates at 2 and 5 years were 57% vs 58% and 33% vs 29%, respectively. In an analysis restricted to the 291 vs 287 patients who initiated radiotherapy per protocol, median overall survival was 33.1 months (95% CI = 25.4–39.6 months) vs 29.4 months (95% CI = 26.5–36.8 months).

On investigator assessment, median progression-free survival was 14.2 months (95% CI = 11.9–17.5 months) in the 70-Gy group vs 13.5 months (95% CI = 11.7–15.8 months) in the 45-Gy group (HR = 0.97, 95% CI = 0.8–1.19, P = .785).

Adverse Events

For radiation-related adverse events, grade ≥ 3 esophageal toxicity occurred in 17.5% of the 70-Gy once-daily group vs 16% of the 45-Gy twice-daily group. Grade 3 dyspnea occurred in 7% vs 4%, with one case of grade 4 dyspnea in the 70-Gy group. Patients in the 70-Gy group had higher rates of grade ≥ 3 leukopenia (59% vs 50%, P = .03) and lymphopenia (16% vs 9%, P = .01) and a trend toward increased anemia (26% vs 20%, P = .08). Adverse events led to death in 11 patients in the 70-Gy group and 4 patients in the 45-Gy group.  Death in five patients in the 70-Gy group was considered at least possibly related to treatment, with causes consisting of sudden death in two patients, and adult respiratory distress syndrome, cardiac arrest, and infection in one patient each. Death was considered at least possibly related to treatment in two patients in the 45-Gy group, with causes consisting of infection and multiorgan failure.

Conclusions

The investigators stated, “To our knowledge, CALGB 30610 is the largest study conducted to date for limited-stage SCLC. We hypothesized that raising the nominal radiotherapy dose by more than 50%, from 45-Gy twice-daily to 70-Gy once-daily, would improve tumor control and overall survival for patients treated with concurrent chemoradiotherapy. Although overall survival was not better with high-dose radiotherapy, outcomes on both arms of the current trial are reasonably favorable, with median survival in the range of 28 to 30 months and approximately 30% of patients surviving at least 5 years…. Both regimens also appeared tolerable, likely due in part to modern radiotherapy planning and integrated quality assurance, with similar overall rates of severe adverse events.”

They concluded, “Although 45-Gy twice-daily radiotherapy remains the standard of care, this study provides the most robust information available to help guide the choice of thoracic radiotherapy regimen for patients with limited-stage SCLC.”

Dr. Bogart, of the Department of Radiation Oncology, State University of New York, Upstate Medical University, Syracuse, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by the National Cancer Institute. For full disclosures of the study authors, visit ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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