The standard of care for elderly glioblastoma patients is 40 Gy in 15 fraction radiotherapy with temozolomide (TMZ). However, this regimen has a lower biologic equivalent dose (BED) compared to the Stupp regimen of 60 Gy in 30 fractions. We hypothesize that accelerated hypofractionated radiation of 52.5 Gy in 15 fractions (BED equivalent to Stupp) will have superior survival compared to 40 Gy in 15 fractions. Elderly patients (≥ 65 years old) who received hypofractionated radiation with TMZ from 2010 to 2020 were included in this analysis. Overall survival (OS) and progression free survival were defined as the time elapsed between surgery/biopsy and death from any cause or progression. Baseline characteristics were compared between patients who received 40 and 52.5 Gy. Univariable and multivariable analyses were performed. Sixty-six newly diagnosed patients were eligible for analysis. Thirty-nine patients were treated with 40 Gy in 15 fractions while twenty-seven were treated with 52.5 Gy in 15 fractions. Patients had no significant differences in age, sex, methylation status, or performance status. OS was superior in the 52.5 Gy group (14.1 months) when compared to the 40 Gy group (7.9 months, p = 0.011). Isoeffective dosing to 52.5 Gy was shown to be an independent prognostic factor for improved OS on multivariable analysis. Isoeffective dosing to 52.5 Gy in 15 fractions was associated with superior OS compared to standard of care 40 Gy in 15 fractions. These hypothesis generating data support accelerated hypofractionation in future prospective trials.

Abstract PURPOSE Radiation treatment planning for meningiomas conventionally involves MRI contrast enhanced images to define residual tumor. However, the gross tumor volume may be difficult to delineate for patients with a meningioma in the skull base, sagittal sinus, or post resection. Advanced PET imaging using 68(GA)DOTATATE PET, which has been shown to be more sensitive and specific than MRI imaging, can be used for target volume delineation in these circumstances. We hypothesize that 68(GA)DOTATATE PET scan-based treatment planning will lead to smaller radiation volumes and will detect additional areas of disease compared to standard MRI alone. METHODS Our data evaluated retrospective, deidentified, and blinded gross tumor volume (GTV) contour delineation with 7 CNS specialists (3 neuroradiologists, 4 CNS radiation oncologists) for 26 patients diagnosed with a meningioma who received both a 68(GA)DOTATATE PET and an MRI for radiation treatment planning. Both the MRI and the PET were non-sequentially contoured by each physician for each patient. RESULTS The mean MRI volume for each physician ranged from 24.14-35.52 ccs. The mean PET volume for each physician ranged from 10.59-20.54 ccs. The PET volumes were significantly smaller for 6 out of the 7 physicians. In addition, 7/26 (27%) patients had new non-adjacent areas contoured on PET by at least 6 of the 7 physicians that were not contoured by these physicians on the corresponding MRI. These new areas would not have been in the traditional MRI based volumes. CONCLUSION Our study supports that 68(GA)DOTATATE PET imaging can help radiation oncologist create smaller and more precise radiation treatment volumes. Utilization of 68(GA)DOTATATE PET may find undetected areas of disease which in turn can improve local control and progression free survival. 68(GA)DOTATATE PET guided treatment planning should be studied prospectively.

Background: The standard of care for elderly glioblastoma (GBM) patients is 40 Gy in 15 fraction radiotherapy with temozolomide (TMZ). However, this regimen has a lower biologic equivalent dose (BED) compared to the Stupp regimen of 60 Gy in 30 fractions. We hypothesize that accelerated hypofractionated radiation of 52.5 Gy in 15 fractions (BED equivalent to Stupp) will have superior survival compared to 40 Gy in 15 fractions. Methods: Elderly patients (≥ 65 years old) who received hypofractionated radiation with TMZ from 2010-2020 were included in this analysis. Overall survival (OS) and progression free survival (PFS) were defined as the time elapsed between surgery/biopsy and death from any cause or progression. Baseline characteristics were compared between patients who received 40 Gy and 52.5 Gy. Univariable and multivariable analyses were performed. Results: Sixty-six newly diagnosed patients were eligible for analysis. Thirty-nine patients were treated with 40 Gy in 15 fractions while twenty-seven were treated with 52.5 Gy in 15 fractions. Patients had no significant differences in age, sex, methylation status, or performance status. Overall survival (OS) was superior in the 52.5 Gy group (14.1 months) when compared to the 40 Gy group (7.9 months, p = 0.011). Isoeffective dosing to 52.5 Gy was shown to be an independent prognostic factor for improved OS on multivariable analysis. Conclusions: Isoeffective dosing to 52.5 Gy in 15 fractions was associated with superior OS compared to standard of care 40 Gy in 15 fractions. These hypothesis generating data support accelerated hypofractionation in future prospective trials.

Abstract PURPOSE The standard of care (SOC) for elderly or frail glioblastoma (GBM) patients is 40 Gy in 15 fraction radiotherapy. However, this regimen has a lower BED compared to the Stupp regimen, 60 Gy in 30 fractions. We hypothesize that isoeffective hypofractionated radiation of 52.5 Gy in 15 fractions (BED equivalent to Stupp) will have superior survival compared to standard of care. METHODS Elderly GBM patients treated with 52.5 Gy in 15 fractions were pooled from 2 phase II studies, 1 phase 1 and a prospective observation study. Overall survival (OS) and progression free survival (PFS) were defined as the time elapsed between surgery/biopsy and death from any cause or progression. Univariate and multivariate analyses were performed. RESULTS 62 newly-diagnosed patients were eligible for this analysis. Median follow-up was 10 months. The median OS and PFS was 10.3 and 6.9 mos, respectively. Patients with KPS ≥ 70 and < 70 had a median OS of 15.3 and 9.5 mos. No survival difference was seen between unmethylated and methylated patients with a median OS of 10.2 and 10.3 months, respectively. Multivariable analysis demonstrated that concurrent chemotherapy was an independent prognostic factor for improved PFS and OS. Grade 3 neurologic toxicity was seen in 2 patients (3.2%). CONCLUSION This is the first pooled, prospective analysis of elderly/frail GBM patients treated with dose-escalated hypofractionated radiation. Treatment was well tolerated and demonstrated excellent OS and PFS, exceeding that from prior elderly trials (Roa; 6.5 mo [poor KPS]/Perry; 9.3mo [good KPS]). This treatment regimen gives the elderly population an alternative to Stupp that is not de-escalating therapy. Future prospective trials are needed to validate these results.