In this study, we assessed treatment and survival in a population-based sample of patients with newly diagnosed GBM in 2006. To our knowledge, this is one of the largest cohorts of adult patients with GBM with detailed information on current standard of care treatment with surgery, chemotherapy, and RT and survival. Because our study was conducted after completion and publication of the pivotal clinical trial in 2005 that showed the survival advantage of concomitant TMZ and RT compared with RT alone after surgical resection,8
we were able to assess the diffusion of TMZ and RT in a community setting. We found that approximately 65% of patients received partial or total resection of their tumors, and most received at least some chemotherapy and/or RT. Among the patients with resection, approximately 70% received TMZ and RT, suggesting that this standard of care for GBM diffused rapidly in the community setting.
A higher percentage of patients with GBM in our study were treated in hospitals with residency programs and a large number of beds, compared with patients with newly diagnosed cancer in other SEER POC studies.15,16
Other studies have shown that patients treated at larger hospitals with residency programs and those affiliated with academic institutions are more likely to receive adjuvant chemotherapy and radiation.12
Referral to larger hospitals may also be associated with rapid diffusion or early adoption of novel treatments. We also found that a slightly higher proportion of patients with newly diagnosed GBM participated in treatment protocols than patients with other cancers in the SEER POC studies15
and in other studies based in community settings.17
Clinical trial participation is critical for evaluating the efficacy of novel cancer therapies, particularly for cancer sites, such as GBM, where median survival remains relatively short, even with a new standard therapy. Efforts to improve trial participation, including use of electronic medical records to identify eligible patients,18
development of clinical trial referral infrastructure,19
physician education efforts,20
and patient education and outreach,20
will be important for improving the quality of care.
Median survival in the entire sample, which included patients who did not undergo cancer-directed surgery, was short (10 months). However, for the subset of patients who received partial or total surgical resection followed by TMZ and RT, median survival was 16 months, more similar to the 14.6 months observed for the patients enrolled in the pivotal clinical trial establishing TMZ and RT as a standard of care.8
Because clinical trials typically have performance status requirements and other entry criteria related to prior treatment, patients who participate in clinical trials are highly selected, compared with the general population of patients with cancer. Other studies, such as the Glioma Outcomes Project,12
recruited patients from neurosurgery or neuro-oncology clinics. Patients included in our SEER POC study were identified from cancer registries and included patients who did not undergo any surgery (approximately 25%) and may never have been evaluated in neurosurgery or neuro-oncology clinics. Thus, comparisons of our findings with other studies requires consideration of the methods for identifying patients with newly diagnosed cancer; patient, tumor, and health care system characteristics; and the surgical and adjuvant therapy received. Furthermore, because some patients with newly diagnosed GBM treated in community settings do not have histologic confirmation, they may automatically be ineligible for clinical trials of treatment.
We found that older patients and those who were unmarried were less likely to receive TMZ and RT or any adjuvant radiation or chemotherapy following maximal surgical resection, compared with younger and married patients. Unmarried patients were also less likely to undergo any surgery. Less use of standard therapy for GBM in older and unmarried patients is consistent with earlier studies13,21
and is presumably associated with greater frailty and need for caregiving support, both real and perceived, in these patients. Controlling for the effects of patient, tumor, and health system characteristics, we found that older age was associated with poorer survival, a finding that is also consistent with prior studies.22,23
Because brain tumor incidence is increasing, particularly in the older population,5,6
and the US population is aging and increasing, the absolute number of older patients who received a diagnosis of GBM will increase in the future. Increasingly, clinical studies are showing that the benefits from surgery, RT, and chemotherapy treatment can also be realized in older patients.24,25
In RT and moderate-dose regimens have been reported to be effective.26,27
These benefits have not been shown for patients with GBM, however. In addition to patient preferences for treatment, performance status, and need for social support, physician recommendations for treatment are key components of the complex treatment decision-making process. Understanding and optimizing the GBM treatment decision-making process is important for ensuring optimal care for this increasing population of older patients with GBM.
We also found that sociodemographic factors, such as insurance status and income, were associated with whether patients with GBM who underwent maximal surgical resection also received adjuvant treatment, but not with survival in models controlling for adjuvant treatment. Because survival following diagnosis of GBM is short, the influence of these sociodemographic factors on survival may occur mainly through receipt of treatment. Further evaluation of sociodemographic factors in relation to both treatment and survival will be important in future research.
Despite the strengths of a large population-based sample, our study had several limitations. Although we controlled for comorbid conditions, age, and tumor characteristics in our multivariable analyses, the data in this study were observational and it is possible that unmeasured patient characteristics influenced both treatment selection and survival following diagnosis. We restricted our multivariable analyses of treatment and survival to patients who underwent either partial or total resection. Thus, our subsample was eligible to undergo surgical resection and may be more homogeneous with respect to comorbidity and ability to tolerate subsequent chemotherapy and RT.
We did not have information on mode of diagnosis or initial imaging studies that might more fully inform our measurement of the extent of disease. Because the exact date of diagnosis is not recorded by SEER and, as a result, was not available for this study, we assumed that all patients received a diagnosis on the first day of each month. Although there is some misclassification, it is unlikely that misclassification varied systematically by treatment. Furthermore, differences in survival time by treatment type were >1 month, suggesting that the impact of missing data for exact date of diagnosis is minimal. We did not have information about performance status at diagnosis, patient preferences or physician recommendations for surgery, or chemotherapy and RT, which are important predictors of receipt of treatment28
and, ultimately, prognosis. Our restriction of the sample for multivariable analysis to patients receiving partial or complete surgical resection and control for age, comorbidity score, and marital status were attempts to address the absence of performance status to some extent. Others have shown that MGMT promoter methylation is associated with greater effectiveness of TMZ,29
although it was not available for treatment selection at the time of this study. Finally, we did not have detailed data describing the completion of chemotherapy or radiation schedules. Our analysis used an intent-to-treat approach, which is consistent with the approach used in clinical trials, however, all of these patient, physician, and clinical measures will be important for inclusion in future studies of GBM treatment and survival.
In summary, we observed rapid diffusion of a new standard of treatment, TMZ and RT after maximal surgical resection, following the publication of a pivotal clinical trial in a national population of adult patients with newly diagnosed GBM. Patients who received TMZ and RT following surgical resection had longer survival, compared with patients who did not receive any adjuvant therapy following surgery.