Patients with small cell lung cancer have ‘real choice’ in radiotherapy regimen
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Key takeaways:
- Survival outcomes appeared comparable between patients assigned higher-dose once-daily regimen and a lower-dose twice daily regimen.
- Serious adverse events also appeared comparable between groups.
Patients with limited-stage small cell lung cancer who received higher-dose, once-daily radiotherapy achieved outcomes comparable to those who received the standard lower-dose, once-daily regimen, according to phase 3 study results.
The findings suggest physicians now have two equal options to discuss with their patients, researchers concluded.
“It allows patients a real choice, understanding that there may be some differences in [adverse] effects or their ability to complete the longer therapy, but now they know both regimens can be associated with good outcomes,” Jeffrey Bogart, MD, radiation oncologist with Upstate Medical University, said in a press release. “We still offer the twice-a-day for small cell [lung cancer] but now we are more comfortable with the high dose once a day because of the results from this trial. That’s been a big change, and I think [it] gives providers more comfort.”
Background and methods
Level-one evidence supports twice-daily radiotherapy dosed at 45 Gy as standard treatment for patients with limited-stage small cell lung cancer. However, in clinical practice, the majority of patients receive higher-dose once-daily regimens, according to study background.
It remained unclear whether increasing radiotherapy dose improved outcomes.
Bogart and colleagues accrued patients for the CALGB 30610/RTOG 0538 trial between March 15, 2008, and Dec. 1, 2019.
Investigators conducted the trial in two stages.
In the initial stage, researchers randomly assigned patients with limited-stage disease to one of three radiotherapy regimens — 45 Gy twice daily, 70 Gy once daily or 61.2 Gy concomitant-boost — starting with the first or second of four chemotherapy cycles.
In the second stage, after a planned interim toxicity analysis, investigators discontinued the 61.2-Gy concomitant-boost regimen. The trial continued with the two other treatment groups.
OS in the intention-to-treat population served as the primary endpoint.
Results
The current analysis included 638 patients randomly assigned to radiotherapy dosed at 45 Gy twice daily (n = 313) or 70 Gy once daily (n = 325).
After median follow-up of 4.7 years, results showed no statistically significant difference in OS (median, 30.1 months for once daily vs. 28.5 months for twice-daily; HR = 0.94; 95% CI, 0.76-1.17).
Researchers reported comparable 5-year OS between the twice-daily and once-daily groups (29% vs. 32%).
They also reported similar rates of severe adverse events — including pulmonary and esophageal toxicity — between groups.
Implications and next steps
Although the 45-Gy, twice-daily radiotherapy remains the standard of care, this study provides “the most robust information available” to guide decision-making for this patient population, Bogart and colleagues concluded.
Additional study is necessary to evaluate the benefit of each treatment protocol based on factors such as age or sex, Bogart said.
“The goal over time is to get away from the one-size-fits-all approach to now offer better, more personalized therapy,” Bogart said in the release. “The findings of this study move us in that direction. Our findings need to be confirmed in subsequent trials, but it can provide a lot of information to help design future trials, as well.”
References:
- Bogart J, et al. J Clin Oncol. 2023;doi:10.1200/JCO.22.01359.
- Findings of large clinical trial has major implications for the treatment of small-cell lung cancer (press release). Available at: https://www.newswise.com/articles/findings-of-large-clinical-trial-has-major-implications-for-the-treatment-of-small-cell-lung-cancer. Posted Jan. 31, 2023. Accessed March 24, 2023.
Perspective
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Kevin Stephans, MD
The ideal radiation regimen for limited-stage small cell lung cancer has not been absolutely established.The publication of CALGB 30610/RTOG 0538 in conjunction with the previously published CONVERT trial suggest similar survival outcomes for 45 Gy given twice daily compared with 66 Gy to 70 Gy given once daily, and both of these can be considered standard-of-care regimens for concurrent chemoradiation.
Patients who received the 70-Gy daily regimen did have more difficulty completing radiation (79% completed), had higher rates of leukopenia and lymphopenia, and had numerically greater rates of grade 5 toxicity (11 events, compared with 4 in the 45 Gy twice-daily group).
There currently is no role for dose-escalation beyond 60 Gy in non-small cell lung cancer, with RTOG 0617 suggesting a potential detriment to increasing radiation dose to 74 Gy, and the preliminary results of RTOG 1106 showing feasibility but no improvement in loco-regional failure with higher dose-adaptive radiation.
CALGB 30610 and CONVERT do not appear to support dose escalation for small cell lung cancer. The THORA trial — comparing 45 Gy twice daily with 60 Gy twice daily — remains preliminary, with a small number of patients and relatively short follow-up.
Small cell lung cancer also appears to have a unique biology, typically considered more radiosensitive than NSCLC. Although once-daily radiation to 45 Gy in 25 fractions is inferior to twice-daily radiation in the landmark Intergroup 0096 trial, the potential role for altered-fractionation daily radiation regimens remains quite intriguing in small cell lung cancer. Given the potential for accelerated repopulation, it is possible that acceleration of the treatment regimen may have a significant effect on outcomes, and the interaction of radiation dose and radiation biology in small cell lung cancer remains incompletely understood.
Notably, accelerated but lower dose once-daily radiation regimens — such as the NCIC 40 Gy in 15 fractions — achieved similar outcomes to its contemporary trials, such as INT 0096, offering patients a very convenient once-daily alternative. Unfortunately, this regimen has not been tested in a randomized fashion compared with the current standard regimens of 45 Gy twice daily or 66 Gy to 70 Gy daily. We do feel comfortable offering this regimen in practice; however, its precise position compared with other alternatives remains untested. Given the combination of convenience and low toxicity, our patients with limited-stage small cell lung cancer are offered 45 Gy twice daily vs. 40 Gy once-daily regimens, both completed in 3 weeks.
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