Prophylactic cranial irradiation fails to extend survival in limited-stage small cell lung cancer
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Prophylactic cranial irradiation did not extend OS among a cohort of patients with limited-stage small cell lung cancer, according to results of a propensity-matched analysis published in JAMA Network Open.
“Since brain radiation causes significant acute and chronic morbidity for patients — particularly on neurocognitive functioning in at least 50% of patients — the utility of prophylactic cranial irradiation [PCI] needs to be reevaluated in the modern era, and we may need to better select patients for PCI in the near future,” Steven H. Lin, MD, PhD, oncologist in the division of radiation oncology at The University of MD Anderson Cancer Center in Houston, told Healio.
PCI is the standard of care for patients with small cell lung cancer. However, the role of PCI in the current era of brain MRI had not been established, Lin added.
“This was exactly what Takahashi and colleagues set out to assess in their 2017 study, which showed PCI did not offer any improvement in OS compared with no upfront PCI in patients with extensive-stage small cell lung cancer who had no documented brain metastasis on brain MRI,” he told Healio. “Whether this principle in extensive-stage small cell lung cancer also applies for [patients with limited-stage small cell lung cancer] was not known.”
Lin and colleagues sought to examine whether PCI conferred a benefit among 297 patients (54.5% men) diagnosed with limited-stage small cell lung cancer. Most patients (87.8%) had an ECOG performance status of 0 or 1. All had baseline MRI, confirmation of no intracranial metastasis and surveillance brain MRI after local treatment.
Investigators compared 205 patients (median age, 62.2 years; range, 27-85) who received PCI with 92 patients (median age, 68.6 years; range, 40-86) who did not receive PCI.
The researchers calculated propensity scores for 295 patients based on clinical and tumor factors and conducted a propensity-matched analysis to account for selection bias between the two groups.
Both groups received a median thoracic radiation treatment dose of 45 Gy, and most patients received 25 Gy to 30 Gy in 10 to 15 total fractions for PCI. Mean primary tumor size was 4.35 cm in the PCI group vs. 4.15 cm in the no-PCI group.
OS and intracranial control served as the primary endpoints.
Median follow-up was 83.64 months in the PCI group and 83.97 months in the no-PCI group (overall range, 2.5-235).
Results showed no significant difference in 3-year cumulative incidence of brain metastases between the no-PCI group (20.4%; 95% CI, 12.45-29.67) and the PCI group (11.2%; 95% CI, 5.4-19.2). Researchers observed no association between use of PCI and decreased risk for developing new brain metastases (HR = 0.51; 95% CI, 0.23-1.09).
In addition, PCI did not appear associated with an OS benefit (HR = 0.84; 95% CI, 0.6-1.18), even after adjustment for other prognostic covariates (HR = 0.78; 95% CI, 0.55-1.11).
“Our data suggest that the results seen for extensive-stage small cell lung cancer in the Takahashi trial may also apply for an even lower-risk group of patients with limited-stage small cell lung cancer,” Lin told Healio. “Modern trials should be conducted to answer the question of the need for PCI again, which is currently being done in the global, phase 3, randomized SWOG S1827 trial in both limited and extensive small cell lung cancer. We hope we will finally answer the utility of PCI for [patients with small cell lung cancer], and perhaps we will also learn which subsets of patients may benefit from PCI.” – by Jennifer Southall
For more information:
Steven H. Lin, MD, PhD, can be reached at The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030; email: shlin@mdanderson.org.
Disclosures: Lin reports grants from Genentech and Hitachi Chemical Diagnostics; grants and personal fees from Beyond Spring Pharmaceuticals; and personal fees from AstraZeneca, Elekta and Varian Medical Systems outside the submitted work. Please see the study for all other authors’ relevant financial disclosures.
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