Lack of survival advantage among re-resected elderly glioblastoma patients: a SEER-Medicare study

Abstract

Background: The survival benefit of re-resection for glioblastoma (GBM) remains controversial, owing to the immortal time bias inadequately considered in many studies where re-resection was treated as a fixed, rather than a time-dependent factor. Using the Surveillance, Epidemiology, and End Results-Medicare (SEER-Medicare) database, we assessed treatment patterns for older adults and evaluated the association between re-resection and overall survival (OS), accounting for the timing of re-resection.

Methods: This retrospective cohort study included elderly patients (age ≥66) in the SEER-Medicare linked database diagnosed with GBM between 2006 and 2015 who underwent initial resection. Time-dependent Cox regression was used to assess the association between re-resection and OS, controlling for age, gender, race, poverty level, geographic region, marital status, comorbidities, receipt of radiation + temozolomide, and surgical complications.

Results: Our analysis included 3604 patients with median age 74 (range: 66-96); 54% were men and 94% were white. After initial resection, 44% received radiation + temozolomide and these patients had a lower hazard of death (hazard ratio [HR]: 0.28, 95% confidence interval [CI]: 0.26-0.31, P < .001). In total, 9.5% (n = 343) underwent re-resection. In multivariable analyses, no survival benefit was seen for patients who underwent re-resection (HR: 1.12, 95% CI: 0.99-1.27, P = .07).

Conclusions: Re-resection rates were low among elderly GBM patients, and no survival advantage was observed for patients who underwent re-resection. However, patients who received standard of care at initial diagnosis had a lower risk of death. Older adults benefit from receiving radiation + temozolomide after initial resection, and future studies should assess the relationship between re-resection and OS taking the time of re-resection into account.

Keywords: SEER-Medicare; elderly patients; glioblastoma; repeat resection; time-dependent analysis.

Figure 1.

Flow chart of patient selection. Our final sample included N = 3604 from N = 13 915 GBM patients from SEER-Medicare. The majority of patient exclusions were the result of insufficient Medicare coverage for claims identification (N = 3770) or patients younger than 66 years (N = 4120). **In accordance with SEER-Medicare data use agreement, cells with N < 11 were masked to prevent identification.

Figure 2.

Landmarked Kaplan–Meier plot. Survival curves were estimated from 7.7 months after initial resection (landmark time), which was the median time between initial and re-resection (ie, the time at which 50% of patients had received re-resection). “Yes,” shown in orange, indicates patients who underwent re-resection by the landmark time and “No,” shown in blue, indicates patients who did not have a re-resection by the landmark time. Patients who died prior to the landmark time were excluded from the curves. Patients who underwent re-resection by 7.7 months had a median OS of 6.7 months (95% CI: 5.3–9.1) compared to a median of 7.9 months (95% CI: 7.3–8.4) in those who did not. No censoring marks or number at risk could be provided under the SEER-Medicare data use agreement.

Figure 3.

Forest plot of interaction effects. Hazard ratios are displayed from the interaction models between demographics and re-resection for the association with overall survival. The dashed line represents a hazard ratio of 1. Hazard ratios to the right (left) of the line indicate subgroups that had a higher (lower) hazard of death in patients who underwent re-resection compared to those who did not undergo re-resection. For the continuous factors, age, and CCI, the significance tests were derived from the interaction between the continuous variable and re-resection, but hazard ratios of discrete levels were presented for easier visualization.