Dose Escalated Radiation Therapy for Glioblastoma Multiforme: An International Systematic Review and Meta-Analysis of 22 Prospective Trials

Singh, Raj; Lehrer, Eric J.; Wang, Ming; Perlow, Haley K.; Zaorsky, Nicholas G.; Trifiletti, Daniel M.; Bovi, Joseph; Navarria, Pierina; Scoccianti, Silvia; Gondi, Vinai; Brown, Paul D.; Palmer, Joshua D.

doi:10.1016/j.ijrobp.2021.05.001

Cited by 30 publications

(29 citation statements)

References 49 publications

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“…The optimal treatment paradigm for patients with GBM requires a multidisciplinary approach that typically involves maximal surgical resection followed by radiation therapy (RT) with concurrent and adjuvant TMZ chemotherapy and, finally, tumor-treating fields (TTF) [ 5 , 6 , 7 , 8 , 9 ]. However, treatment decision making is often complex and multiple factors must be considered, such as patient age and performance status, as certain populations are more likely to benefit from either intensified or de-intensified therapies [ 4 , 57 , 58 , 59 , 60 ]. This section provides an overview of current treatment strategies for GBM and describes how the available data influences the decision-making process.…”

Section: Treatment Overviewmentioning

confidence: 99%

“…Dose escalation beyond 60 Gy remains a controversial topic in the management of GBM [ 4 ]. The only prospective evidence comparing standard of care chemoradiotherapy to dose-escalated radiotherapy is NRG BN-001.…”

Section: Treatment Overviewmentioning

confidence: 99%

“…GBM are highly aggressive tumors with a grim prognosis that are markedly resistant to treatment [ 4 , 5 ]. In the setting of optimal treatment, the median overall survival (OS) for patients with GBM ranges from 15–21 months with a 5-year OS rate of <5% [ 6 , 7 , 8 , 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

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Preoperative Stereotactic Radiosurgery for Glioblastoma

Lehrer

Ruiz‐Garcia

Nehlsen

et al. 2022

Biology

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Glioblastoma is a devastating primary brain tumor with a median overall survival of approximately 15 months despite the use of optimal modern therapy. While GBM has been studied for decades, modern therapies have allowed for a reduction in treatment-related toxicities, while the prognosis has largely been unchanged. Adjuvant stereotactic radiosurgery (SRS) was previously studied in GBM; however, the results were disappointing. SRS is a highly conformal radiation technique that permits the delivery of high doses of ionizing radiation in 1–5 sessions while largely sparing surrounding healthy tissues. Furthermore, studies have shown that the delivery of ablative doses of ionizing radiation within the central nervous system is associated with enhanced anti-tumor immunity. While SRS is commonly used in the definitive and adjuvant settings for other CNS malignancies, its role in the preoperative setting has become a topic of great interest due to the potential for reduced treatment volumes due to the treatment of an intact tumor, and a lower risk of nodular leptomeningeal disease and radiation necrosis. While early reports of SRS in the adjuvant setting for glioblastoma were disappointing, its role in the preoperative setting and its impact on the anti-tumor adaptive immune response is largely unknown. In this review, we provide an overview of GBM, discuss the potential role of preoperative SRS, and discuss the possible immunogenic effects of this therapy.

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Section: Treatment Overviewmentioning

confidence: 99%

Section: Treatment Overviewmentioning

confidence: 99%

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Preoperative Stereotactic Radiosurgery for Glioblastoma

Lehrer

Ruiz‐Garcia

Nehlsen

et al. 2022

Biology

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“…To date, brachytherapy, hypofractionation, accelerated hyperfractionation, and stereotactic radiotherapy boost have failed to significantly improve overall survival in GBM compared to CFRT of 60 Gy in a phase 3 prospective randomized trial. Although a recent meta-analysis revealed that dose-escalated RT demonstrated a survival benefit compared with standard RT of 60 Gy, the difference in survival diminished in patients treated with RT plus TMZ [ 57 ]. Furthermore, the multicenter phase 3 SPECTRO-GLIO trial comparing standard CFRT of 60 Gy (30 fractions) and simultaneous integrated boost of up to 72 Gy (30 fractions) for regions of high choline to N-acetyl aspartate ratios identified by magnetic resonance spectroscopy in GBM treated with RT/TMZ→TMZ was recently presented at the European Society Radiation Oncology 2021 Meeting [ 58 59 ].…”

Section: Radiation Oncologist’s Perspective and Conclusionmentioning

confidence: 99%

Radiotherapy for Newly Diagnosed Glioblastoma in the Elderly: What Is the Standard?

Wee

2022

Brain Tumor Res Treat

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Nearly half of the patients with newly diagnosed glioblastomas are aged ≥65 years. Unfortunately, these elderly patients with glioblastoma (GBM-e) demonstrate detrimental survival. However, the optimal treatment for GBM-e after surgery remains controversial. Conventionally fractionated radiotherapy (CFRT) of 60 Gy, hypofractionated radiotherapy (HFRT), temozolomide (TMZ), or a combination of these treatments with or without tumor treating fields can be considered. Although evidence has indicated a non-inferiority of HFRT compared to CFRT in GBM-e treated with radiotherapy (RT) alone throughout the past, the optimal RT scheme (CFRT vs. HFRT), when combined with TMZ, has never been investigated in a prospective randomized fashion for GBM-e patients suitable for radiochemotherapy. Several other issues make the treatment of GBM-e even more challenging. In this review, current evidence regarding RT in GBM-e, as well as issues that need to be addressed, is discussed.

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“…More recently, a systematic review and meta-analysis of 22 prospective trials demonstrated progression-free and overall survival benefits to dose-escalated radiotherapy (defined as equivalent dose in 2-Gy fractions) >60 Gy versus 60 Gy standard-dose radiotherapy without chemotherapy (19). In analysis comparing 108 patients across 4 studies treated with dose-escalated radiotherapy without chemotherapy versus 1,001 patients across 6 studies treated with standard-dose radiotherapy without chemotherapy, 1-year OS was significantly higher (46.3% vs. 23.4%, P=0.02).…”

Section: Radiotherapy Intensification Without Chemotherapymentioning

confidence: 99%

Dose Escalated Radiation Therapy for Glioblastoma Multiforme: An International Systematic Review and Meta-Analysis of 22 Prospective Trials

Cited by 30 publications

References 49 publications

Preoperative Stereotactic Radiosurgery for Glioblastoma

Preoperative Stereotactic Radiosurgery for Glioblastoma

Radiotherapy for Newly Diagnosed Glioblastoma in the Elderly: What Is the Standard?

Radiotherapy intensification for glioblastoma: enhancing the backbone of treatment

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