By Samir P. Kanani, MD
Associate Clinical Professor of Neurosurgery and Radiation Oncology, George Washington University, Radiation Oncology, Inova Fairfax Hospital, Falls Church, VA
Dr. Kanani reports no financial relationships relevant to this field of study.
Synopsis: Using the SEER database, this report examined 1926 patients aged ≥ 70 years who were diagnosed with limited-stage small cell lung cancer between 1988 and 1997. Overall survival (OS) for patients who received prophylactic cranial irradiation (PCI) vs those who did not was estimated using the Kaplan-Meier method and compared with the log-rank test. A Cox proportional hazards model was fitted to estimate the effect of PCI on OS after adjusting for age, race, sex, and tumor. A total of 138 patients (7.2 %) received PCI. The 2-year and 5-year OS rates were 33.3% and 11.6%, respectively, among patients who received PCI vs 23.1% and 8.6%, respectively, among patients who did not receive PCI (P = 0.028). On multivariable analysis, PCI was found to be an independent predictor of OS (hazard ratio, 0.72; 95% confidence interval, 0.54-0.97; P = 0.032]). On subgroup analysis, PCI remained an independent predictor of OS among patients aged ≥ 75 years, but not among patients aged ≥ 80 years.
Source: Eaton BR, et al. Effect of prophylactic cranial irradiation on survival in elderly patients with limited-stage small cell lung cancer. Cancer 2013;119:3753-3760.
Multiple prospective trials have demonstrated a significant benefit in brain metastases-free survival and a pivotal meta-analysis1 demonstrated a significant benefit in overall survival (OS) with the use of prophylactic cranial irradiation (PCI) in patients with limited-stage small cell lung cancer (SCLC) who have a complete response to chemotherapy and radiotherapy (RT). Elderly patients represented a small minority of patients included in trials evaluating the efficacy of PCI and thus the benefit of PCI in this population has been questioned. The authors note that the incidence of SCLC is rising in the elderly population, making this type of statistical analysis of the Surveillance, Epidemiology, and End Results (SEER) database vital. The authors from Emory University queried the SEER public use database, which represents more than 28% of the U.S. population. They looked at cases between 1988 and 1997. They found nearly 3400 cases of non-metastatic SCLC. They excluded patients with < 6 months OS and those with no information about PCI. This left 1926 patients for analysis. Patient-related and treatment-related characteristics including age at diagnosis, sex, race, tumor size, extent of lymph node involvement, AJCC stage of disease, receipt of brain RT (PCI), receipt of thoracic RT, and receipt of surgery were collected. Patients who received PCI and those who did not were well balanced with regard to race, sex, lymph node status, and tumor size. Patients who received PCI were younger at the time of diagnosis, were more often diagnosed with stage III vs stage I or II disease, and were more often treated with thoracic RT. The median OS for the entire population was 1.2 years. The 2-year Kaplan-Meier estimate of OS for patients who received PCI was significantly higher than for patients who did not receive PCI: 33.3% vs 23.1%. The 5-year Kaplan-Meier estimate of OS for patients who received PCI was also significantly higher than for patients who did not receive PCI: 11.6% vs 8.6%. The 2-year and 5-year Kaplan-Meier estimates of cause-specific survival (CSS) were also significantly higher for patients who received PCI compared with those who did not: 37.5% and 19.3%, respectively, vs 27% and 12.5%, respectively. In a separate analysis of patients ≥ 75 years of age, the OS advantage remained significant. The 2-year Kaplan-Meier estimate of OS for patients ≥ 75 years who received PCI was significantly higher than those for patients who did not receive PCI: 36.8% vs 10.5%. The 5-year Kaplan-Meier estimate of OS for patients ≥75 years who received PCI was also significantly higher than for patients who did not receive PCI: 10.5% vs 7.9%. The CSS in patients ≥ 75 years was improved with PCI, although the results did not reach statistical significance as the P value was 0.059. On multivariable analysis, receipt of PCI was found to be an independent significant predictor of both improved OS and CSS. In the last subgroup analysis of patients ≥ 80 years, the OS and CSS were also higher in patients who received PCI, but the results were not statistically significant, likely given the small numbers.
COMMENTARY
The study summarized above provides a rationale to not withhold potentially beneficial treatment to patients solely based on age. In the landmark meta-analysis by Auperin et al,1 the relative risk of death with the use of PCI was only slightly changed after controlling for age (relative risk, 0.84 vs 0.83). The meta-analysis demonstrated a 5.4% absolute benefit in survival at 3 years from 15.3% in patients not receiving PCI and 20.7% in patients who did receive PCI. In this SEER analysis, the absolute benefit was closer to 10% at 2 years. The randomized trials contributing to the meta-analysis had limited patients > 70 years of age. The interesting part of this study was that it looked at patients > 80 years of age. In this population, there was still a benefit to adding PCI (not a detriment), although the differences were not found to be statistically significant, likely because of small sample size and insignificant power. While this study could be used to justify the use of PCI in the elderly population, clinicians should weigh the potential benefits of PCI against the potential neurocognitive effects. A number of studies have indicated declining physical function, motor function, and memory in patients who receive PCI. This can be worse with advanced age.2 Decisions regarding the benefit of PCI should be individualized to the patient; advanced age and comorbidities should be included in the decision-making process. This SEER analysis provides justification for the use of PCI in patients ≥ 70 years and even those ≥ 80 years.
References
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Aupérin A, et al. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. N Engl J Med 1999;341:476-484.
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Le Péchoux C, et al. Clinical neurological outcome and quality of life among patients with limited small cell cancer treated with two different doses of prophylactic cranial irradiation in the intergroup phase III trial (PCI99-01, EORTC 22003-08004, RTOG 0212 and IFCT 99-01). Ann Oncol 2011;22:1154-1163.
