Randomized prospective trial of fractionated stereotactic radiosurgery with chemotherapy versus chemotherapy alone for bevacizumab-resistant high-grade glioma

Bergman, David; Modh, Ankit; Schultz, Lonni; Snyder, James M.; Mikkelsen, Tom; Shah, Mira; Ryu, Samuel; Siddiqui, M. Salim; Walbert, Tobias

doi:10.1007/s11060-020-03526-4

Cited by 21 publications

(27 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[21] Another randomized trial was recently conducted by Henry Ford Hospital comparing bevacizumab alone to bevacizumab with fractionated radiosurgery to 32 Gy/4 fractions with similar clinical and toxicity outcomes. [22] These studies appear to con rm the safety pro le and potential to delay disease progression for modestly-dosed hypofractionated reirradiation regimens. This strategy may be particularly useful for high-grade recurrences.…”

Section: Discussionmentioning

confidence: 74%

Outcomes After Proton Therapy Reirradiation for Malignant Glioma: Prospective Analysis of Over 100 Patients from the Proton Collaborative Group

Press¹,

Hasan²,

Choi³

et al. 2021

Preprint

View full text Add to dashboard Cite

Purpose: The optimal salvage treatment for malignant glioma after prior radiotherapy (RT) is not well established. Proton therapy (PT) is an attractive treatment modality for reirradiation (ReRT) of recurrent disease; however, data are limited.Methods: The prospective, multi-institutional Proton Collaborative Group (PCG) registry was queried for patients with malignant glioma who previously received RT and underwent PT-ReRT between 7/2011-10/2018. Overall survival (OS) and progression-free survival (PFS) were assessed using the Kaplan-Meier method and Cox proportional hazards regression analysis. Results: 109 consecutive patients were identified. Median follow-up was 11.2 months and median time interval (TI) from prior RT (median 59.3 Gy) to PT-ReRT (median 49.6 Gy) was 45.7 months. Primary histology was glioblastoma (n=62), oligodendroglioma (n=26), and astrocytoma (n=20). Median PFS and OS was 6.1 and 11.1 months, respectively. On UVA, improved PFS was associated with oligodendroglioma (HR 0.39) and astrocytoma (HR 0.55) histologies, WHO Grade III (HR 0.36), TI (HR 0.989), surgical resection (HR 0.39), and PT-ReRT dose ≥50 Gy (HR 0.59) (all p<0.03), while improved OS was associated with oligodendroglioma histology (HR 0.35), WHO grade III (HR 0.33), ECOG 0 (HR 0.47), TI (HR 0.985), and PT-ReRT dose ≥50 Gy (HR 0.58) (all p<0.04). Late Grade 3 toxicities occurred in 5.6% of patients with no attributable acute or late Grade 4-5 events.Conclusion: In the largest series of glioma PT-ReRT reported to date, retreatment appears well tolerated with acceptable outcomes and favorable toxicities compared to photon historical controls. Dose escalation achievable with PT may improve outcomes for well-selected patients.

show abstract

Section: Discussionmentioning

confidence: 74%

Outcomes After Proton Therapy Reirradiation for Malignant Glioma: Prospective Analysis of Over 100 Patients from the Proton Collaborative Group

Press¹,

Hasan²,

Choi³

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…These results suggest that ReRT/Bev prolongs PFS but does not have survival bene ts compared to Bev alone for Bev-naïve patients with recurrence [15]. Bergman et al reported that ReRT/Bev-based chemotherapy also increased PFS, and that it tended to prolong OS compared to Bev-based chemotherapy alone for patients with progression after Bev [16]. Although the optimal timing of reirradiation before and after Bev remains unclear, based on our results and those of Bergman, differing reirradiation after Bev might be a preferred option to minimise the potential risk of radiation necrosis.…”

Section: Discussionmentioning

confidence: 92%

“…A few studies have investigated the outcomes of ReRT/Bev for patients with high-grade gliomas that progressed after Bev (Table 4) [6,7,11,[16][17][18][19]. The median survival times after ReRT/Bev ranged from 3.3 to 14.7 months, and the median PFS times ranged from 2.6 to 6. and an increased trend in OS (7.3 vs 4.8 months; p = 0.11); therefore, they concluded that FSRT with Bevbased chemotherapy might be a valuable option for extending PFS and improving local control [16]. Our results indicating that the median OS and PFS were 6.1 and 3.8 months, respectively, are comparable to those of previous studies.…”

Section: Discussionmentioning

confidence: 99%

“…The optimal timing of reirradiation is controversial [14][15][16]. Palmer et al retrospectively analysed 114 patients who received sequential reirradiation and Bev for disease recurrence or progression and reported that the median survival times from recurrence were 13.9 months for patients administered reirradiation rst and 13.3 months for those administered Bev rst (p = 0.75), indicating that the sequence of reirradiation and Bev does not matter [14].…”

Section: Discussionmentioning

confidence: 99%

“…We hypothesised that ReRT/Bev for patients with highgrade gliomas that progressed after Bev may result in improved patient outcomes. There have been few reports regarding ReRT/Bev for patients with high-grade gliomas that progressed after Bev [6,7,11,[16][17][18][19]; therefore, we evaluated the potential e cacy and safety of our therapeutic approach.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Outcomes of Salvage Fractionated Reirradiation Combined With Bevacizumab for Recurrent High-grade Gliomas That Progressed After Treatment With Bevacizumab

Yonezawa

Ohno

Igaki

et al. 2021

Preprint

View full text Add to dashboard Cite

Background: This study evaluated the outcomes of reirradiation combined with bevacizumab (Bev) for patients with recurrent high-grade gliomas that progressed after treatment with Bev.Methods: Between January 2015 and September 2019, 14 patients who experienced progression after Bev treatment were treated with reirradiation consisting of 25 Gy in five fractions combined with Bev (ReRT/Bev). The isocitrate dehydrogenase (IDH) 1/2 mutation status was analysed by pyrosequencing. Results: The diagnoses of 14 patients at the time of reirradiation included six cases of glioblastoma (GBM) with IDH-wildtype, four cases of GBM with IDH-mutant, one case of anaplastic astrocytoma (AA) with IDH-wildtype, one case of AA with IDH-mutant, and one case of GBM not otherwise specified (NOS), and one case of radiologically diagnosed brainstem glioma. The median overall survival (OS) and progression-free survival (PFS) times with ReRT/Bev were 6.1 months and 3.8 months, respectively. The 6-month OS and PFS rates were 54.5% and 15.7%, respectively. The median OS and PFS did not differ significantly between patients with IDH-wildtype (N=7) and IDH-mutant (N=5) (OS: 7.3 [wildtype] vs 6.0 [mutant] months, p = 0.64; PFS: 3.8 [wildtype] vs 3.7 [mutant] months, p = 0.56). The median OS and PFS did not differ significantly between patients with a diagnosis of GBM (N=6) and those with a diagnosis of non-GBM (N=7) (OS: 9.3 [GBM] vs 6.0 [non-GBM] months, p = 0.19; PFS: 4.0 [GBM] vs 3.8 [non-GBM] months, p = 0.31). Four patients (28.6%) achieved a complete or partial radiological response and three patients (21.4%) experienced improvement after ReRT/Bev. Tumor recurrences were observed in 12 patients, including 3 (21.4%) in-field recurrence; 5 (35.7%) marginal recurrence, 3 (21.4%) out-field recurrence, and 1 (7.1%) had in-field and out-field recurrence. Grade 3/4 toxicities included leukopenia in four patients (28.6%), hypertension in three (21.4%), proteinuria in one (7.1%), and gastrointestinal haemorrhage in one (7.1%) with ReRT/Bev. Conclusions: ReRT/Bev for patients with high-grade glioma who experienced progression after Bev was effective and involved acceptable toxicities.

show abstract

Prospective randomized clinical studies involving reirradiation: update of a systematic review

Nieder¹,

Willmann²,

Andratschke³

2023

Strahlenther Onkol

View full text Add to dashboard Cite

Background Reirradiation is a potentially useful option for many patients with recurrent cancer, aiming at cure or symptom palliation, depending on disease/recurrence type and stage. The purpose of this follow-up study to a previous review from 2016 was to summarize all recently published randomized trials. Points of interest again included identifcation of methodological strengths and weaknesses, practice-changing results, and open questions. Material and methods Systematic review of trials published between 2015 and February 2023. Results We reviewed 7 additional trials, most of which addressed reirradiation of head and neck or brain tumours. The median number of patients was 60. Mirroring the previous review, trial design, primary endpoints and statistical hypotheses varied widely. The updated results only impact on decision making for reirradiation of nasopharynx cancer and glioma. Patients with one of these diseases, as well as other head and neck cancers, may benefit from reirradiation-induced local control, e.g. in terms of progression-free survival. For the first time, hyperfractionated radiotherapy emerged as preferred option for recurrent, inoperable nasopharynx cancer. Despite better therapeutic ratio with hyperfractionation, serious toxicity remains a concern after high cumulative total doses. Randomized trials are still lacking for prostate cancer and other sites. Conclusion Multicentric randomized trials on reirradiation are feasible and continue to refine the current standard of care for recurrent disease after previous radiotherapy. Ongoing prospective studies such as the European Society for Radiotherapy and Oncology and European Organisation for Research and Treatment of Cancer (ESTRO-EORTC) observational cohort ReCare (NCT: NCT03818503) will further shape the clinical practice of reirradiation.

show abstract

Randomized prospective trial of fractionated stereotactic radiosurgery with chemotherapy versus chemotherapy alone for bevacizumab-resistant high-grade glioma

Cited by 21 publications

References 27 publications

Outcomes After Proton Therapy Reirradiation for Malignant Glioma: Prospective Analysis of Over 100 Patients from the Proton Collaborative Group

Outcomes After Proton Therapy Reirradiation for Malignant Glioma: Prospective Analysis of Over 100 Patients from the Proton Collaborative Group

Outcomes of Salvage Fractionated Reirradiation Combined With Bevacizumab for Recurrent High-grade Gliomas That Progressed After Treatment With Bevacizumab

Prospective randomized clinical studies involving reirradiation: update of a systematic review

Contact Info

Product

Resources

About