Modification and optimization of an established prognostic score after re-irradiation of recurrent glioma

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

doi:10.1371/journal.pone.0180457

Cited by 37 publications

(44 citation statements)

References 27 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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“…The importance of the interval-factor is in line with former reports of re-RT. It can be assumed that the time of the first relapses after the primary treatment is an indicator of the biological behaviour of the tumour [25,38,39]. In our patient group, the median survival according to the histopathological grade was higher than in other reported studies (the median survival is around 55-60 months for grade 2 and 18-26 months for grade 3 tumours).…”

Section: Discussioncontrasting

confidence: 51%

“…Well-defined prognostic factors are established for glial tumours; however, the factors influencing the outcome of re-RT are less known. Different factors are considered to influence the efficacy of the survival after re-RT, such as age, performance status, histological grading and the length of the interval between the 1st and the 2nd course of RT [38,39]. A recent meta-analysis and appraisal summarizes the radiation parameters and outcomes of fractionated re-RT from studies published from 1999 to 2018 [17,40].…”

Section: Discussionmentioning

confidence: 99%

Low Fraction Size Re-irradiation for Large Volume Recurrence of Glial Tumours

Dobi

Darázs

Fodor

et al. 2020

Pathol. Oncol. Res.

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The aim of the present study was to evaluate the efficacy of re-irradiation (re-RT) in patients with advanced local relapses of glial tumours and to define the factors influencing the result of the hyper-fractionated external beam therapy on progression after primary management. We have analysed the data of 55 patients with brain tumours (GBM: 28) on progression, who were reirradiated between January 2007 and December 2018. The mean volume of the recurrent tumour was 118 cm 3 , and the mean planning target volume (PTV) was 316 cm 3 , to which 32 Gy was delivered in 20 fractions at least 7.7 months after the first radiotherapy, using 3D conformal radiotherapy (CRT) or intensity modulated radiotherapy (IMRT). The median overall survival (mOS) from the re-RT was 8.4 months, and the 6-month and the 12-month OS rate was 64% and 31%, respectively. The most important factors by univariate analysis, which significantly improved the outcome of re-RT were the longer time interval between the diagnosis and second radiotherapy (p = 0.029), the lower histology grade (p = 0.034), volume of the recurrent tumour (p = 0.006) and Karnofsky performance status (KPS) (p = 0.009) at the re-irradiation. Our low fraction size re-irradiation ≥ 8 months after the first radiotherapy proved to be safe and beneficial for patients with large volume recurrent glial tumours.

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“… and its modification by Kessel et al. based on a large independent, multicenter cohort of 565 patients. This is the largest validation cohort existing.…”

Section: Discussionmentioning

confidence: 99%

Re‐irradiation of recurrent gliomas: pooled analysis and validation of an established prognostic score—report of the Radiation Oncology Group (ROG) of the German Cancer Consortium (DKTK)

et al. 2018

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The heterogeneity of high‐grade glioma recurrences remains an ongoing challenge for the interdisciplinary neurooncology team. Response to re‐irradiation (re‐RT) is heterogeneous, and survival data depend on prognostic factors such as tumor volume, primary histology, age, the possibility of reresection, or time between primary diagnosis and initial RT and re‐RT. In the present pooled analysis, we gathered data from radiooncology centers of the DKTK Consortium and used it to validate the established prognostic score by Combs et al. and its modification by Kessel et al. Data consisted of a large independent, multicenter cohort of 565 high‐grade glioma patients treated with re‐RT from 1997 to 2016 and a median dose of 36 Gy. Primary RT was between 1986 and 2015 with a median dose of 60 Gy. Median age was 54 years; median follow‐up was 7.1 months. Median OS after re‐RT was 7.5, 9.5, and 13.8 months for WHO IV, III, and I/II gliomas, respectively. All six prognostic factors were tested for their significance on OS. Aside from the time from primary RT to re‐RT (P = 0.074) and the reresection status (P = 0.101), all factors (primary histology, age, KPS, and tumor volume) were significant. Both the original and new score showed a highly significant influence on survival with P < 0.001. Both prognostic scores successfully predict survival after re‐RT and can easily be applied in the routine clinical workflow. Now, further prognostic features need to be found to even improve treatment decisions regarding neurooncological interventions for recurrent glioma patients.

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Modification and optimization of an established prognostic score after re-irradiation of recurrent glioma

Cited by 37 publications

References 27 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

Low Fraction Size Re-irradiation for Large Volume Recurrence of Glial Tumours

Re‐irradiation of recurrent gliomas: pooled analysis and validation of an established prognostic score—report of the Radiation Oncology Group (ROG) of the German Cancer Consortium (DKTK)

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