Limited-stage small cell lung cancer: Outcomes associated with prophylactic cranial irradiation over a 20-year period at the Princess Margaret Cancer Centre

Abstract

Background & purpose: Prophylactic cranial irradiation (PCI) is recommended for limited-stage small-cell lung cancer (LS-SCLC) patients with good response to concurrent chemoradiation. We report our institution's 20-year experience with this patient population and associated clinical outcomes. Materials & methods: A retrospective cohort of consecutive LS-SCLC patients treated with curative intent chemoradiation at our institution was reviewed. Overall survival (OS) was calculated using the Kaplan-Meier method, and significant covariates determined by the Cox proportional hazards model. Covariates predictive of PCI were determined using Fisher's exact test and the Mann-Whitney test. Brain failure risk (BFR) was calculated using the cumulative incidence method treating death as a competing event. Treatment cohorts (historic vs. contemporary) were stratified by the median year of diagnosis (2005). Results: A total of 369 patients with LS-SCLC were identified, of which 278 patients were notionally PCI eligible. PCI was given to 196 patients (71%). Younger age was associated with PCI utilization (p < 0.001). PCI utilization rates did not change between the historic and contemporary treatment era (p = 0.11), whereas magnetic resonance imaging (MRI) use at baseline and follow-up became more prevalent in the contemporary era (p = <0.001). On multivariable analysis, PCI utilization was associated with improved OS (HR 1.88, 95% CI 1.32-2.69) and decreased BFR (HR 4.66,. Patients who had MRI follow-up had a higher incidence of BFR (HR 0.35, 95% CI 0.18-0.66) in multivariable analyses. Conclusions: For LS-SCLC patients at our institution, PCI is more frequently utilized in younger patients, and the utilization rate did not change significantly over the past 20 years. PCI was independently associated with improved OS and lower BFR. Omission of PCI in LS-SCLC patients should not be routinely practiced in the absence of further prospective data.

One Cycle of Concurrent Chemotherapy vs. Two Cycles of Concurrent Chemotherapy With Radiation Therapy in Patients With Limited-Stage Small Cell Lung Cancer

“…Though with some controversy after the publication of Takahashi’s study ( 10 – 15 ), PCI is still recommended in many guidelines ( 16 – 18 ). However, the application of PCI is not consistently accepted by doctors or patients.…”

“…However, the application of PCI is not consistently accepted by doctors or patients. Only about 70% of patients with LS-SCLC received PCI in M. D. Cancer center ( 13 ) and in the Princess Margaret Cancer Centre ( 10 ), and 57% of the patients with CR or PR response after chemoradiotherapy received PCI in Nakamura’s report form Japan ( 14 ). In the present study, only 52.4% of the patients received PCI.…”

Prophylactic cranial irradiation (PCI) versus active surveillance in patients with limited-stage small cell lung cancer: a retrospective, multicentre study

“…Michael Yan et al reported the outcomes of PCI for LS-SCLC over a 20-year period at the Princess Margaret Cancer Centre. The findings showed that PCI contributed to improved OS and lower BM risk (HR 1.88, 95% CI 1.32–2.69; HR 4.66, 95% CI 2.58–8.40, respectively) [ 21 ]. Conversely, in a recent analysis of 297 patients with LS-SCLC, PCI was not independently associated with substantial improvement in OS (HR 0.844, 95% CI 0.604–1.180, p = 0.32) [ 18 ].…”

Limited-Stage Small-Cell Lung Cancer: Current Progress and the Next Frontier

“…A retrospective study at the Princess Margaret Cancer Centre showed improvements in OS and brain failure free survival for those that received PCI, however they observed some patients declined PCI due to patient or physician concerns related to toxicity and also patients older than 65 years of age were significantly less likely to receive PCI [23]. An updated study from the same institution showed PCI maintained its association with OS, even in the MRI era [24]. Another study from Memorial Sloan Kettering Cancer Center showed that patient concerns regarding neurotoxicity was the most cited reason for the omission of PCI.…”

“…Given the associated side effects with PCI, its utility to manage LS-SCLC patients when MRI brain surveillance is available is being questioned. In addition to the retrospective studies highlighted above, some studies have shown no associated improvement in OS or PFS with PCI for LS-SCLC in the MRI era [19,26] while other studies do report an OS benefit with PCI [24,27]. Further prospective results from clinical trials that include LS-SCLC patients, such as the SWOG S1827 MAVERICK (SWOG S1827) trial comparing PCI to MR surveillance (NCT04155034), are awaited to provide modern prospective evidence.…”