Re-irradiation For Recurrent Gliomas Research Articles

Survival Benefit of Re-Irradiating recurrent glioma Patients with VMAT Technique

Patients who have been treated with re irradiation for recurrent glioma reported survival benefits. Limited data are available for the outcomes after fractionated re-irradiation of 45Gy. This study aims to investigate whether re-irradiation of recurrent glioma with 45Gy dose can increase the overall survival of patients.

P17.01.A Reradiation by Glioblastoma recurrence with VMAT technique

Abstract Background Patients who have been treated with reirradiation for recurrent glioma reported survival benefits. This study aims to investigate whether re-irradiation of recurrent glioma with 45Gy dose can increase the overall survival of patients. Material and Methods A retrospective analysis of 35 patients re-irradiated for high-grade glioma recurrence between 2012 and 2020 was performed. All included patients met the following criteria: a) histopathological confirmation of primary brain cancer at initial diagnosis; b) a history of initial primary radiation; c) histological and/or imaging modality confirmation of recurrence. Outcome metrics included overall survival, prognostic factors for survival, and treatment-related toxicity. Results After the end of re-irradiation the median overall survival was 11 months (95% confidence interval, 7-14 months). From the patients evaluated in the current study after the end of re-irradiation the progression free survival was 6 months (3.8 - 8 months) while after the end of first radiation was 13 months (8 - 17.9 months). Our findings suggest that re-irradiation might prolong survival rates. Conclusion Recurrent Glioblastoma WHO IV is associated with a median overall survival of less than a year and the majority of patients have profound tumor-related symptoms .The results of this study suggest that re-irradiation may prolong the overall survival.

P05.04 Reradiation by reccurent gliomas with VMAT (Volumetric Modulated Arc Therapy) technique- survival benefit

Abstract BACKGROUND Patients who have been treated with reirradiation for recurrent glioma reported survival benefits. Limited data are available for the outcomes after fractionated re-irradiation. This study aims to investigate whether re-irradiation of recurrent glioma with 45Gy dose can increase the overall survival of patients. MATERIAL AND METHODS A retrospective analysis of 35 patients re-irradiated for high-grade glioma recurrence between 2012 and 2020 was performed. All included patients met the following criteria: a) histopathological confirmation of primary brain cancer at initial diagnosis; b) a history of initial primary radiation; c) histological and/or imaging modality confirmation of recurrence. Outcome metrics included overall survival, prognostic factors for survival, and treatment-related toxicity. RESULTS After the end of re-irradiation the median overall survival was 11 months (95% confidence interval, 7–14 months). From the patients evaluated in the current study after the end of re-irradiation the progression free survival was 6 months (3.8 - 8 months) while after the end of first radiation was 13 months (8 - 17.9 months). Our findings suggest that re-irradiation might prolong survival rates. CONCLUSION Recurrent Glioblastoma WHO IV is associated with a median overall survival of less than a year and the majority of patients have profound tumor-related symptoms.The results of this study suggest that re-irradiation may prolong the overall survival.

PO-1053 Validation of Modified Combs criteria in Indian cohort for re-irradiation in recurrent gliomas

PO-1053 Validation of Modified Combs criteria in Indian cohort for re-irradiation in recurrent gliomas

EP-1224 Re-Irradiation in Recurrent Gliomas: Treatment outcome and Prognostic factors

EP-1224 Re-Irradiation in Recurrent Gliomas: Treatment outcome and Prognostic factors

PO-0755 Patterns of Re-irradiation for Recurrent Gliomas and Validation of a Prognostic Score

PO-0755 Patterns of Re-irradiation for Recurrent Gliomas and Validation of a Prognostic Score

EP-1217 Reirradiation of recurrent gliomas with CyberKnife® SRS/SRT: a monoistitutional experience

EP-1217 Reirradiation of recurrent gliomas with CyberKnife® SRS/SRT: a monoistitutional experience

Re-irradiation for recurrent glioma: outcome evaluation, toxicity and prognostic factors assessment. A multicenter study of the Radiation Oncology Italian Association (AIRO).

The prognosis of glioma is dismal, and almost all patients relapsed. At recurrence time, several treatment options are considered, but to date there is no a standard of care. The Neurooncology Study Group of the Italian Association of Radiation Oncology (AIRO) collected clinical data regarding a large series of recurrent glioma patients who underwent re-irradiation (re-RT) in Italy. Data regarding 300 recurrent glioma patients treated from May 2002 to November 2017, were analyzed. All patients underwent re-RT. Surgical resection, followed by re-RT with concomitant and adjuvant chemotherapy was performed. Clinical outcome was evaluated by neurological examination and brain MRI performed, 1month after radiation therapy and then every 3months. Re-irradiation was performed at a median interval time (IT) of 16months from the first RT. Surgical resection before re-RT was performed in 19% of patients, concomitant temozolomide (TMZ) in 16.3%, and maintenance chemotherapy in 29%. Total doses ranged from 9Gy to 52.5Gy, with a median biological effective dose of 43Gy. The median, 1, 2year OS were 9.7months, 41% and 17.7%. Low grade glioma histology (p ≪ 0.01), IT > 12months (p = 0.001), KPS > 70 (p = 0.004), younger age (p = 0.001), high total doses delivered (p = 0.04), and combined treatment performed (p = 0.0008) were recorded as conditioning survival. our data underline re-RT as a safe and feasible treatment with limited rate of toxicity, and a combined ones as a better option for selected patients. The identification of a BED threshold able to obtain a greater benefit on OS, can help in designing future prospective studies.

P01.069 Re-irradiation for recurrent glioma: outcome evaluation, toxicity and prognostic factors assessment. A multicenter retrospective study by the Brain-Study-Group of the Radiation Oncology Italian Association (AIRO)

P01.069 Re-irradiation for recurrent glioma: outcome evaluation, toxicity and prognostic factors assessment. A multicenter retrospective study by the Brain-Study-Group of the Radiation Oncology Italian Association (AIRO)

Reirradiation for recurrent glioma

Reirradiation for recurrent glioma

Expert consensus on re-irradiation for recurrent glioma

PurposeTo investigate radiation oncologists’ opinions on important considerations to offering re-irradiation (re-RT) as a treatment option for recurrent glioma.Materials and methodsA survey was conducted with 13 radiation oncologists involved in the care of central nervous system tumor patients. The survey was comprised of 49 questions divided into 2 domains: a demographic section (10 questions) and a case section (5 re-RT cases with 5 to 6 questions representing one or several re-RT treatment dilemmas as may be encountered in the clinic). Respondents were asked to rate the relevance of various factors to offering re-RT, respond to the cases with a decision to offer re-RT vs. not, volume to be treated, margins to be employed, dose/fractionation suggested and any additional comments with respect to rationale in each scenario.ResultsSixty nine percent of responders have been practicing for greater than 10 years and 61% have re-RT 20 to 100 patients to date, with 54% seeing 2–5 re-RT cases per month and retreating 1–2 patients per month. Recurrent tumor volume, time since previous radiation therapy, previously administered dose to organs at risk and patient performance status were rated by the majority of responders (85%, 92%, 77%, and 69% respectively) as extremely relevant or very relevant to offering re-RT as an option.ConclusionThe experts’ practice of re-RT is still heterogeneous, reflecting the paucity of high-quality prospective data available for decision-making. Nevertheless, practicing radiation oncologists can support own decisions by referring to the cases found suitable for re-RT in this survey.

Re-irradiation for recurrent glioma- the NCI experience in tumor control, OAR toxicity and proposal of a novel prognostic scoring system

Purpose/objectivesDespite mounting evidence for the use of re-irradiation (re-RT) in recurrent high grade glioma, optimal patient selection criteria for re-RT remain unknown. We present a novel scoring system based on radiobiology principles including target independent factors, the likelihood of target control, and the anticipated organ at risk (OAR) toxicity to allow for proper patient selection in the setting of recurrent glioma.Materials/methodsThirty one patients with recurrent glioma who received re-RT (2008–2016) at NCI – NIH were included in the analysis. A novel scoring system for overall survival (OS) and progression free survival (PFS) was designed to include:1) target independent factors (age, KPS (Karnofsky Performance Status), histology, presence of symptoms), 2) target control, and 3) OAR toxicity risk. Normal tissue complication probability (NTCP) calculations were performed using the Lyman model. Kaplan-Meier analysis was performed for overall survival (OS) and progression free survival (PFS) for comparison amongst variables.ResultsNo patient, including those who received dose to OAR above the published tolerance dose, experienced any treatment related grade 3–5 toxicity with a median PFS and OS from re-RT of 4 months (0.5–103) and 6 months (0.7–103) respectively. Based on cumulative maximum doses the average NTCP was 25% (0–99%) for the chiasm, 21% (0–99%) for the right optic nerve, 6% (0–92%) for the left optic nerve, and 59% (0–100%) for the brainstem. The independent factor and target control scores were each statistically significant for OS and the combination of independent factors plus target control was also significant for both OS (p = 0.02) and PFS (p = 0.006). The anticipated toxicity risk score was not statistically significant.ConclusionOur scoring system may represent a novel approach to patient selection for re-RT in recurrent high grade glioma. Further validation in larger patient cohorts including compilation of doses to tumor and OAR may help refine this further for inclusion into clinical trials and general practice.

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

IntroductionFor about 30 years, researchers developed prognostic scores and searched for prognostic factors to predict outcomes for cancer patients. The “Combs Prognostic Score” for re-irradiation in recurrent glioma was recently validated and results showed that the score is a significant (p < .001) and reliable predictor for patients undergoing re-irradiation (re-RT). We sought to enhance the score and generated a novel scoring approach, taking into account the information on resection of recurrent tumors, KPS, and tumor volume.Patients and methodsThe prognostic score was generated based on 209 patients treated between 2002 and 2016 for recurrent glioma at the department of radiation oncology at the Klinikum rechts der Isar, Munich. To further enhance the previously validated Combs Prognostic Score, which uses the prognostic factors primary histology, time between primary RT and re-RT, and age, we added KPS, tumor volume (PTV) and re-resection into the scoring scheme.ResultsThe median follow-up time was 3.5 months. 67.5% were WHO IV gliomas with a median OS after re-RT of 7.9 months, 17.7% were WHO III gliomas with an OS of 11.3 months and 14.8% were WHO I/II gliomas with an OS of 14.7 months. Multivariate analyses confirmed the prognostic factors KPS (p < .001) and showed a tendency to significance for tumor volume (p = .067) and re-resection (p = .064). The new prognostic score demonstrated a high significance (p < .001).ConclusionThe “New Combs Prognostics Score” is a significant and useful tool to predict the overall effect of re-RT in patients with recurrence gliomas. This modified score offers an even better way to classify patients in clinical routine and prospective clinical trials investigating re-irradiation.

Validation of an established prognostic score after re-irradiation of recurrent glioma

Background: Re-irradiation (Re-RT) is offered widely in clinical routine, and has been established as a key element in the treatment of recurrent gliomas. At our center, generally re-resection is performed widely by an experienced neurosurgical team. Thus, Re-RT mostly offered to patients with macroscopic residuals or irresectable lesions, is applied later compared to other centers. Therefore, we sought to validate the Combs Prognostic Score developed in 2012 using our independent patient cohort.Patients and methods: We included 199 patients treated from 2002 until April 2016 for recurrent glioma at the Department of Radiation Oncology at the Klinikum Rechts der Isar, Munich. Different concepts of Re-RT were applied.Results: Median follow-up after Re-RT was 2.5 months. Median overall survival (OS) after Re-RT was 7.9 months for WHO IV gliomas, 11.3 months for WHO III gliomas, and 13.6 months for low-grade gliomas (WHO I/II). Univariate analyses confirmed the prognostic factors primary histology (p = 0.001), age (p = 0.002), and time between primary radiotherapy and Re-RT (p < 0.001). We also tested Karnofsky Performance Score (KPS), gender, and neurological symptoms before Re-RT as well as planning target volume and found only KPS also significant at p < 0.001. Comparing the prognostic score groups, the outcome was highly statistically significant at p < 0.001.Conclusion: In our analysis, we validated the Combs Prognostic Score. Validation in this independent large patient cohort confirms the significance of the score for glioma recurrences. Thus, the role of the Combs Prognostic Score might be an essential component of future clinical decision making and patient stratification.

Re-Irradiation for Recurrent Gliomas: Treatment Outcomes and Prognostic Factors.

PurposeThe aim of this study was to evaluate the efficacy of re-irradiation in patients with recurrent gliomas and to identify subgroups for whom re-irradiation for recurrent gliomas is most beneficial.Materials and MethodsWe retrospectively reviewed 36 patients with recurrent or progressive gliomas who received re-irradiation between January 1996 and December 2011. Re-irradiation was offered to recurrent glioma patients with good performance or at least 6 months had passed after initial radiotherapy (RT), with few exceptions.ResultsMedian doses of re-irradiation and initial RT were 45.0 Gy and 59.4 Gy, respectively. The median time interval between initial RT and re-irradiation was 30.5 months. Median overall survival (OS) and the 12-month OS rate were 11 months and 41.7%, respectively. In univariate analysis, Karnofsky performance status (KPS) ≥70 (p<0.001), re-irradiation dose ≥45 Gy (p=0.040), and longer time interval between initial RT and re-irradiation (p=0.040) were associated with improved OS. In multivariate analysis, KPS (p=0.030) and length of time interval between initial RT and re-irradiation (p=0.048) were important predictors of OS. A radiographically suspected mixture of radiation necrosis and progression after re-irradiation was seen in 5 patients.ConclusionRe-irradiation in conjunction with surgery could be a salvage treatment for selected recurrent glioma patients with good performance status and recurrence over a long time.

RT-08 * PROTON THERAPY (PT) LARGE-VOLUME RE-IRRADIATION FOR RECURRENT GLIOMA: OVERALL SURVIVAL (OS) AND TOXICITY OUTCOMES

BACKGROUND: The therapeutic benefit of targeting T2/FLAIR in addition to contrast-enhancing (CE) tumor during re-irradiation for recurrent glioma can be attenuated by augmented toxicity. Given its steep dose fall-off and narrow penumbrae, PT minimizes volume of brain parenchyma outside target volume, potentially permitting a less toxic delivery of large-volume re-irradiation. METHODS: From 2/2011 to 12/2013, 19 consecutive adult patients with recurrent glioma treated with PT re-irradiation at a single institution were retrospectively analyzed. Planning target volume (PTV) included T2/FLAIR and CE abnormalities. Covariates assessed were age, gender, KPS at time of PT, number of salvage treatments, grade at initial diagnosis, interval between prior radiotherapy and PT, PT dose, PT PTV, bevacizumab failure, concurrent use of temozolomide and/or bevacizumab, and post-PT radiation necrosis. OS time from PT start was estimated with Kaplan-Meier analysis; comparisons used log-rank statistic. Multivariate analysis used the Cox proportional hazards model. RESULTS: Median age was 42 and median KPS was 90. Median salvage treatments was 2 (range 1-9). Median interval between prior radiotherapy and PT was 36.1 months (mos) (range 6.9-162.9). 12 patients (63%) were bevacizumab-refractory. Median PT dose was 50.4 CGE and median PTV was 224.2 cc. 5 patients (26%) remain alive. Median OS was 9.4 mos overall, 6.6 mos amongst bevacizumab-refractory patients, and 12.3 mos amongst bevacizumab-naive patients. Prior bevacizumab failure (hazard ratio (HR) 3.79; P = 0.047), shorter interval since prior radiotherapy (HR 1.04; P = 0.02), and Grade 4 disease (HR 4.17; P = 0.03) were prognostic of inferior OS. One patient had grade 3 radiation necrosis in the setting of PT re-irradiation for progressive brainstem glioma. One patient had grade 2 radiation necrosis, and another had grade 2 stroke. No other grade ≥3 toxicities were observed. CONCLUSION: Large-volume PT re-irradiation for recurrent glioma is safe and associated with promising OS outcomes, particularly in the setting of bevacizumab-refractory tumors.

Overall Survival (OS) and Toxicity Outcomes Following Large-Volume Re-irradiation Using Proton Therapy (PT) for Recurrent Glioma

During re-irradiation for recurrent glioma, whether to target T2/FLAIR signal abnormality in addition to contrast-enhancing (CE) tumor remains controversial. While recent series have demonstrated improved tumor control when targeting T2/FLAIR abnormality, larger volume re-irradiation can increase neurotoxicity risk. Given its steep dose fall-off and narrow penumbrae, PT can minimize the volume of brain parenchyma outside the re-irradiation target volume and permit potentially safer delivery of large-volume re-irradiation. This study seeks to explore this hypothesis through a retrospective review of OS and toxicity outcomes of patients treated with large-volume PT re-irradiation. From February 2011 to November 2013, 18 consecutive adult patients with recurrent glioma treated with PT re-irradiation at a single institution were retrospectively analyzed. Planning target volume (PTV) included T2/FLAIR and CE abnormalities. Covariates assessed for OS prediction were age, gender, KPS at time of PT, number of pre-PT recurrences, grade at initial diagnosis, interval between PT and prior radiation therapy, PT dose, PT PTV, bevacizumab failure, concurrent use of temozolomide and/or bevacizumab, and post-PT radiation necrosis. OS time from PT start was estimated with Kaplan-Meier analysis; comparisons used log-rank statistic. Multivariate analysis used the Cox proportional hazards model. Median age was 43 and median KPS was 80. At initial diagnosis, 13 patients (72%) had grade 3-4 glioma and 4 (22%) had grade 2 glioma. One patient did not undergo biopsy for brainstem glioma. Median number of pre-PT recurrences was 2 (range 1-9). Median interval between PT and prior radiation therapy was 37.8 months (mos) (range 6.9-162.9). 11 patients (61%) failed prior bevacizumab therapy. Median PT dose was 50.4 CGE and median PTV was 232.5cc. 3 patients (17%) received concurrent temozolomide alone, 3 (17%) received concurrent bevacizumab alone, and 7 (39%) received both. 5 patients (28%) remain alive. Median OS was 9.4 mos overall, 7.4 mos amongst bevacizumab-refractory patients, and 12.4 mos amongst bevacizumab-naive patients. Prior bevacizumab failure (hazard ratio (HR) 5.41; P = 0.05) and shorter interval since prior radiation therapy (HR = 1.31 for each interval year; P = 0.038) were prognostic of inferior OS. Remaining factors were insignificant. One patient had grade 3 radiation necrosis in the setting of PT re-irradiation for progressive brainstem glioma. One patient had grade 2 radiation necrosis. No other grade ≥3 toxicities were observed. Large-volume PT re-irradiation for recurrent glioma is safe and associated with promising OS outcomes, particularly in the setting of bevacizumab-refractory tumors.

Re-irradiation for Recurrent Gliomas: Comparison of Multiple Fractionation Schedules

Re-irradiation for Recurrent Gliomas: Comparison of Multiple Fractionation Schedules

Re-irradiation for Recurrent Glioma: A Single Institution Review

Management of recurrent glioma is controversial and responses to standard therapeutic options are modest. There is limited evidence regarding the role of re-irradiation in these patients. The purpose of this study was to evaluate the outcomes and prognostic factors for patients treated with re-irradiation for recurrent gliomas.

Re-irradiation for Recurrent Gliomas: Treatment Outcomes and Prognostic Factors

Re-irradiation for Recurrent Gliomas: Treatment Outcomes and Prognostic Factors