Moving Second Courses of Radiotherapy Forward

Combs, Stephanie E.; Kessel, Kerstin A.; Hesse, Josefine; Straube, Christoph; Zimmer, Claus; Schmidt‐Graf, Friederike; Schlegel, Jürgen; Gempt, Jens

doi:10.1093/neuros/nyx629

Cited by 14 publications

(9 citation statements)

References 31 publications

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“…These prognostic factors are consistent with those suggested by Combs et al. 24 , 25 , 26 Interestingly, the reirradiation volume was not associated with differences in survival such that larger volume might not be an appropriate exclusion factor for patients who may otherwise be appropriately treated with this approach.…”

Section: Discussionsupporting

confidence: 88%

Re-irradiation for malignant glioma: Toward patient selection and defining treatment parameters for salvage

Shen

Kummerlowe

Redmond

et al. 2018

Advances in Radiation Oncology

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PurposeReirradiation for recurrent glioma remains controversial without knowledge of optimal patient selection, dose, fractionation, and normal tissue tolerances. We retrospectively evaluated outcomes and toxicity after conventionally fractionated reirradiation for recurrent high-grade glioma, along with the impact of concurrent chemotherapy.Methods and materialsWe conducted a retrospective review of patients reirradiated for high-grade glioma recurrence between 2007 and 2016 (including patients with initial low-grade glioma). Outcome metrics included overall survival (OS), prognostic factors for survival, and treatment-related toxicity.ResultsPatients (n = 118; median age 47 years; median Karnofsky performance status score: 80) were re-treated at a median of 28 months (range, 5-214 months) after initial radiation therapy. The median reirradiation dose was 41.4 Gy (range, 12.6-54.0 Gy) to a median lesion volume of 202 cm3 (range, 20-901 cm3). The median cumulative (initial radiation and reirradiation combined) potential maximum brainstem dose was 76.9 Gy (range, 5.0-108.3 Gy) and optic apparatus dose was 56.0 Gy (range, 4.5-90.9 Gy). Of the patients, 56% received concurrent temozolomide, 14%, bevacizumab, and 11%, temozolomide plus bevacizumab; 19% had no chemotherapy. The planned reirradiation was completed by 90% of patients. Median OS from the completion of reirradiation was 9.6 months (95% confidence interval [CI], 7.5-11.7 months) for all patients and 14.0, 11.5, and 6.7 months for patients with initial grade 2, 3, and 4 glioma, respectively. On multivariate analysis, better OS was observed with a >24-month interval between radiation treatments (hazard ratio [HR]: 0.3; 95% CI, 0.2-0.5; P < .001), reirradiation dose >41.4 Gy (HR: 0.6; 95% CI, 0.4-0.9; P = .03), and gross total resection before reirradiation (HR: 0.6, 95% CI, 0.3-0.9; P = .02). Radiation necrosis and grade ≥3 late neurotoxicity were both minimal (<5%). No symptomatic persistent brainstem or optic nerve/chiasm injury was identified.ConclusionsSalvage reirradiation, even at doses >41.4 Gy in conventional fractionation, along with chemotherapy, was safe and well tolerated with meaningful survival duration. These data provide information that may be useful in implementing safe reirradiation treatments for appropriately selected patients and guiding future studies to define optimal reirradiation doses, maximal safe doses to critical structures, and the role of systemic therapy.

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Section: Discussionsupporting

confidence: 88%

Re-irradiation for malignant glioma: Toward patient selection and defining treatment parameters for salvage

Shen

Kummerlowe

Redmond

et al. 2018

Advances in Radiation Oncology

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“…A significant benefit for patients who received an RT after second surgery was found (median OS after second surgery 8.5 vs. 13.4 months) [36]. This finding is in line with other reports [37][38][39]. Importantly, the indication for a second RT is re-thought currently.…”

Section: Recurrent Gliomasupporting

confidence: 83%

“…Importantly, the indication for a second RT is re-thought currently. While Re-RT classically was prescribed only in cases with a macroscopic tumor, newer approaches now investigate the value of a second RT even after GTR of a recurrent glioma [38,40,41]. This approach is supported by the efficacy of adjuvant RT in the primary situation, the efficacy of Re-RT in macroscopic disease as well as by the good safety profile of Re-RT with modern RT techniques.…”

Section: Recurrent Gliomamentioning

confidence: 99%

The algorithms of adjuvant therapy in gliomas and their effect on survival

Straube¹,

Schmidt‐Graf²,

Wiestler³

et al. 2019

J Neurosurg Sci

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The treatment of gliomas became more sophisticated during the last decades. As by now, adjuvant treatment after maximum safe resection is considered an important and effective treatment strategy in most gliomas, yet the decision is based on several factors. This review summarizes the available evidence for the current adjuvant treatment algorithms with a focus on the impact on the survival of glioma patients. The review is based on the current guidelines, but it also includes new insights which have not yet been included into the official guidelines.

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“…Still, all possibilities should be evaluated in newly diagnosed as well as recurrent patients, including surgery, radiotherapy and chemotherapy. Again, the extent of surgical resection is crucial [33] and the benefit of radiotherapy for recurrent GBM is evident for resected as well as unresected lesions [34][35][36][37].…”

Section: Current Treatment Of Gbmmentioning

confidence: 99%

The Role of miRNA for the Treatment of MGMT Unmethylated Glioblastoma Multiforme

Kirstein

Schmid

Combs

2020

Cancers

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Glioblastoma multiforme (GBM) is the most common high-grade intracranial tumor in adults. It is characterized by uncontrolled proliferation, diffuse infiltration due to high invasive and migratory capacities, as well as intense resistance to chemo- and radiotherapy. With a five-year survival of less than 3% and an average survival rate of 12 months after diagnosis, GBM has become a focus of current research to urgently develop new therapeutic approaches in order to prolong survival of GBM patients. The methylation status of the promoter region of the O6-methylguanine–DNA methyltransferase (MGMT) is nowadays routinely analyzed since a methylated promoter region is beneficial for an effective response to temozolomide-based chemotherapy. Furthermore, several miRNAs were identified regulating MGMT expression, apart from promoter methylation, by degrading MGMT mRNA before protein translation. These miRNAs could be a promising innovative treatment approach to enhance Temozolomide (TMZ) sensitivity in MGMT unmethylated patients and to increase progression-free survival as well as long-term survival. In this review, the relevant miRNAs are systematically reviewed.

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Moving Second Courses of Radiotherapy Forward

Cited by 14 publications

References 31 publications

Re-irradiation for malignant glioma: Toward patient selection and defining treatment parameters for salvage

Re-irradiation for malignant glioma: Toward patient selection and defining treatment parameters for salvage

The algorithms of adjuvant therapy in gliomas and their effect on survival

The Role of miRNA for the Treatment of MGMT Unmethylated Glioblastoma Multiforme

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