External beam re-irradiation, combination chemoradiotherapy, and particle therapy for the treatment of recurrent glioblastoma.
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ABSTRACT:
SUBMITTER: Taunk NK
PROVIDER: S-EPMC4998049 | biostudies-literature | 2016
REPOSITORIES: biostudies-literature
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Project description:PurposeTo evaluate the clinical outcomes and treatment related toxicities of charged particle-based re-irradiation (reRT; protons and carbon ions) for the definitive management of recurrent or second primary skull base and head and neck tumors.Materials and methodsThe Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were applied for the conduct of this systematic review. Published work in English language evaluating the role of definitive charged particle therapies in the clinical setting of reRT for recurrent or second primary skull base and head and neck tumors were eligible for this analysis.ResultsA total of 26 original studies (15 protons, 10 carbon ions, and 1 helium/neon studies) involving a total of 1,118 patients (437 with protons, 670 with carbon ions, and 11 with helium/neon) treated with curative-intent charged particle reRT were included in this systematic review. All studies were retrospective in nature, and the majority of them (n=23, 88 %) were reported as single institution experiences (87% for protons, and 90% for carbon ion-based studies). The median proton therapy reRT dose was 64.5 Gy (RBE 1.1) (range, 50.0 - 75.6 Gy ), while the median carbon ion reRT dose was 53.8 Gy (RBE 2.5 - 3.0) (range, 44.8 - 60 Gy ). Induction and/or concurrent chemotherapy was administered to 232 (53%) of the patients that received a course of proton reRT, and 122 (18%) for carbon ion reRT patients. ReRT with protons achieved 2-year local control rates ranging from 50% to 86%, and 41% to 92% for carbon ion reRT. The 2-year overall survival rates for proton and carbon ion reRT ranged from 33% to 80%, and 50% to 86% respectively. Late ≥ G3 toxicities ranged from 0% to 37%, with brain necrosis, ototoxicity, visual deficits, and bleeding as the most common complications. Grade 5 toxicities for all treated patients occurred in 1.4% (n= 16/1118) with fatal bleeding as the leading cause.ConclusionsBased on current data, curative intent skull base and head and neck reRT with charged particle radiotherapy is feasible and safe in well-selected cases, associated with comparable or potentially improved local control and toxicity rates compared to historical reRT studies using photon radiotherapy. Prospective multi-institutional studies reporting oncologic outcomes, toxicity, and dosimetric treatment planning data are warranted to further validate these findings and to improve the understanding of the clinical benefits of charged particle radiotherapy in the reRT setting.
| S-EPMC8270105 | biostudies-literature
Project description:BackgroundHypofractionated stereotactic radiotherapy (hFSRT) is a salvage option for recurrent glioblastoma (GB) which may synergize anti-PDL1 treatment. This phase I study evaluated the safety and the recommended phase II dose of anti-PDL1 durvalumab combined with hFSRT in patients with recurrent GB.MethodsPatients were treated with 24 Gy, 8 Gy per fraction on days 1, 3, and 5 combined with the first 1500 mg Durvalumab dose on day 5, followed by infusions q4weeks until progression or for a maximum of 12 months. A standard 3 + 3 Durvalumab dose de-escalation design was used. Longitudinal lymphocytes count, cytokines analyses on plasma samples, and magnetic resonance imaging (MRI) were collected.ResultsSix patients were included. One dose limiting toxicity, an immune-related grade 3 vestibular neuritis related to Durvalumab, was reported. Median progression-free interval (PFI) and overall survival (OS) were 2.3 and 16.7 months, respectively. Multi-modal deep
learning-based analysis including MRI, cytokines, and lymphocytes/neutrophil ratio isolated the patients presenting pseudoprogression, the longest PFI and those with the longest OS, but statistical significance cannot be established considering phase I data only.ConclusionCombination of hFSRT and Durvalumab in recurrent GB was well tolerated in this phase I study. These encouraging results led to an ongoing randomized phase II. (ClinicalTrials.gov Identifier: NCT02866747).
| S-EPMC10485381 | biostudies-literature
Project description:PurposeThe value of O-(2-[18F]fluoroethyl)-L-tyrosine (FET)-positron emission tomography (PET)-radiomics in the outcome assessment of patients with recurrent glioblastoma (rGBM) has not been evaluated until now. The aim of this study was to evaluate whether a prognostic model based on FET-PET radiomics features (RF) is feasible and can identify rGBM patients that would most benefit from re-irradiation.MethodsWe prospectively recruited rGBM patients who underwent FET-PET before re-irradiation (GLIAA-Pilot trial, DRKS00000633). Tumor volume was delineated using a semi-automatic method with a threshold of 1.8 times the standardized-uptake-value of the background. 135 FET-RF (histogram parameters, shape and texture features) were extracted. The analysis involved the characterization of tumor and non-tumor tissue with FET-RF and the evaluation of the prognostic value of FET-RF for time-to-progression (TTP), overall survival (OS) and recurrence location (RL).ResultsThirty-two rGBM patients constituted our cohort. FET-RF discriminated significantly between tumor and non-tumor. The texture feature Small-Zone-Low-Gray-Level-Emphasis (SZLGE) showed the best performance for the prediction of TTP (p = 0.001, satisfying Bonferroni-multiple-test significance level). Additionally, two radiomics signatures could predict TTP (TTP-radiomics-signature, p = 0.001) and OS (OS-radiomics-signature, p = 0.038). SZLGE and the TTP-radiomics-signature additionally predicted RL. Specifically, high values for TTP-radiomics-signature and for SZLGE indicated not only earlier progression, but also a RL within the initial FET-PET active volume.ConclusionOur findings suggest that FET-PET radiomics could contribute to the prognostic assessment and selection of rGBM-patients benefiting from re-irradiation. Trial registration DRKS00000633. Registered on 8th of December in 2010. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00000633 .
| S-EPMC7931514 | biostudies-literature
Project description:To investigate whether cerebral blood volume (CBV), peak height (PH), and percentage of signal intensity recovery (PSR) measurements derived from the results of T2-weighted dynamic susceptibility-weighted contrast material-enhanced (DSC) magnetic resonance (MR) imaging performed after external beam radiation therapy (EBRT) can be used to distinguish recurrent glioblastoma multiforme (GBM) from radiation necrosis.Fifty-seven patients were enrolled in this HIPAA-compliant institutional review board-approved retrospective study after they received a diagnosis of GBM, underwent EBRT, and were examined with DSC MR imaging, which revealed progressive contrast enhancement within the radiation field. A definitive diagnosis was established at subsequent surgical resection or clinicoradiologic follow-up. Regions of interest were retrospectively drawn around the entire contrast-enhanced region. This created T2-weighted signal intensity-time curves that produced three cerebral hemodynamic MR imaging measurements: CBV, PH, and PSR. Welch t tests were used to compare measurements between groups.Mean, maximum, and minimum relative PH and relative CBV were significantly higher (P < .01) in patients with recurrent GBM than in patients with radiation necrosis. Mean, maximum, and minimum relative PSR values were significantly lower (P < .05) in patients with recurrent GBM than in patients with radiation necrosis.These findings suggest that DSC perfusion MR imaging may be used to differentiate recurrent GBM from EBRT-induced radiation necrosis.
| S-EPMC2770116 | biostudies-literature
Project description:The combination of re-irradiation and bevacizumab has emerged as a potential therapeutic strategy for patients experiencing their first glioblastoma multiforme (GBM) recurrence. This study aims to assess the effectiveness of the re-irradiation and bevacizumab combination in treating second-progression GBM patients who are resistant to bevacizumab monotherapy. This retrospective study enrolled 64 patients who developed a second progression after single-agent bevacizumab therapy. The patients were divided into two groups: 35 underwent best supportive care (none-ReRT group), and 29 received bevacizumab and re-irradiation (ReRT group). The study measured the overall survival time after bevacizumab failure (OST-BF) and re-irradiation (OST-RT). Statistical tests were used to compare categorical variables, evaluate the difference in recurrence patterns between the two groups, and identify optimal cutoff points for re-irradiation volume. The results of the Kaplan-Meier survival analysis indicated that the re-irradiation (ReRT) group experienced a significantly higher survival rate and longer median survival time than the non-ReRT group. The median OST-BF and OST-RT were 14.5 months and 8.8 months, respectively, for the ReRT group, while the OST-BF for the none-ReRT group was 3.9 months (p < 0.001). The multivariable analysis identified the re-irradiation target volume as a significant factor for OST-RT. Moreover, the re-irradiation target volume exhibited excellent discriminatory ability in the area under the curve (AUC) analysis, with an optimal cutoff point of greater than 27.58 ml. These findings suggest that incorporating re-irradiation with bevacizumab therapy may be a promising treatment strategy for patients with recurrent GBM resistant to bevacizumab monotherapy. The re-irradiation target volume may serve as a valuable selection factor in determining which patients with recurrent GBM are likely to benefit from the combined re-irradiation and bevacizumab treatment modality.
| S-EPMC10256803 | biostudies-literature
Project description:Although there is still no standard treatment for recurrent glioblastoma multiforme (rGBM), re-irradiation could be a therapeutic option. We retrospectively evaluated the efficacy and safety of re-irradiation using helical TomoTherapy (HT) with a simultaneous integrated boost (SIB) technique in patients with rGBM. 24 patients with rGBM underwent HT-SIB. A total dose of 20 Gy was prescribed to the Flair (fluid-attenuated inversion recovery) planning tumor volume (PTV) and 25 Gy to the PTV-boost (T1 MRI contrast enhanced area) in 5 daily fractions to the isodose of 67% (maximum dose within the PTV-boost was 37.5 Gy). Toxicity was evaluated by converting the 3D-dose distribution to the equivalent dose in 2 Gy fractions on a voxel-by-voxel basis. Median follow-up after re-irradiation was 27.8 months (range 1.6-88.5 months). Median progression-free survival (PFS) was 4 months (95% CI 2.0-7.9 months), while 6-month PFS was 41.7% (95% CI 22.2-60.1 months). Median overall survival following re-irradiation was 10.7 months (95% CI 7.4-16.1 months). There were no cases of re-operation due to early or late toxicity. Our preliminary results suggest that helical TomoTherapy with the proposed SIB technique is a safe and feasible treatment option for patients with rGBM, including those large disease volumes, reducing toxicity.
| S-EPMC7653937 | biostudies-literature
Project description:PurposeTo report an analysis of treatment outcomes of a cohort of patients re-irradiated for locally recurrent refractory breast cancer (LRRBC).Patients and methodsBetween 2008 and 2013, 47 women (mean age = 60 years) were re-irradiated for LRRBC. Outcomes were measured using Kaplan-Meier log rank to compare curves and Cox regression for multivariate analysis. Outcomes included overall survival (OS), time to re-treatment, survival without systemic progression, and survival without local recurrence.ResultsFifty-six instances of re-irradiation were completed and analyzed. The mean cumulative 2 Gy equivalent dose (EQD2) to the whole breast and tumour cavity (?/? = 3) was 99.8 Gy and 109.1 Gy, respectively. Most patients initially had significant symptoms before RT due to local recurrence. The median time to re-treatment and to systemic failure was 41 and 50 months, respectively. Median follow-up for OS was 17 months and OS was 0.73 (SE = 0.07) at 1 year and 0.67 (SE = 0.07) at 2 years. Local control was 0.62 (SE = 0.07) and 0.5 (0.08) at 1 and 2 years, respectively. Acute radiation dermatitis was G1-2, G3 and G4 in 45, 4 and 1 cases, respectively. One patient presented with necrosis. The most common long term toxicity was G3 fibrosis (n = 4) and telangiectatic changes (n = 3). Multivariable analysis indicated that skin involvement (Hazard Ratio = 6.6 (1.4-31), p = 0.016) and time to local recurrence <2yr (HR 3.1 (1.04-9.7) p = 0.042) predicted local recurrence.ConclusionHigh dose re-irradiation is feasible for locally RRBC. This approach can have a significant benefit in this very high-risk group.
| S-EPMC4741508 | biostudies-literature
Project description:BackgroundThe goal of this study was to evaluate outcomes in children with relapsed, molecularly characterized intracranial ependymoma treated with or without craniospinal irradiation (CSI) as part of a course of repeat radiation therapy (re-RT).MethodsThis was a retrospective cohort study of 31 children. Patients with distant relapse received CSI as part of re-RT. For patients with locally recurrent ependymoma, those treated before 2012 were re-irradiated with focal re-RT. In 2012, institutional practice changed to offer CSI, followed by boost re-RT to the site of resected or gross disease.ResultsMedian follow-up was 5.5 years. Of 9 patients with distant relapse after initial RT, 2-year freedom from progression (FFP) and overall survival (OS) were 12.5% and 62.5%, respectively. There were 22 patients with local failure after initial RT. In these patients, use of CSI during re-RT was associated with improvement in 5-year FFP (83.3% with CSI vs 15.2% with focal re-RT only, P = 0.030). In the subgroup of patients with infratentorial primary disease, CSI during re-RT also improved 5-year FFP (100% with CSI, 10.0% with focal re-RT only, P = 0.036). Twenty-three patients had known molecular status; all had posterior fossa group A tumors (n = 17) or tumors with a RELA (v-rel avian reticuloendotheliosis viral oncogene homolog A) fusion (n = 6). No patient developed radiation necrosis after fractionated re-RT, though almost all survivors required assistance throughout formal schooling. Five out of 10 long-term survivors have not developed neuroendocrine deficits.ConclusionsRe-irradiation with CSI is a safe and effective treatment for children with locally recurrent ependymoma and improves disease control compared with focal re-irradiation, with the benefit most apparent for those with infratentorial primary tumors.
| S-EPMC6422429 | biostudies-literature
Project description:The vast majority of our knowledge regarding cancer radiobiology and the activation of radio-resistance mechanisms emerged from studies using external beam radiation therapy (EBRT). Yet, less is known about the cancer response to internal targeted radionuclide therapy (TRT). Our comparative proteomics and phosphoproteomics study analyzed response to TRT with lutetium-177 labeled minigastrin analogue [177Lu]Lu-PP-F11N (β- emitter) in comparison to EBRT (ɣ-rays) in CCKBR-positive cancer cells.
2022-09-07 | PXD036034 | Pride
Project description:PurposeGlioblastomas (GBM) are the most common malignant primary brain tumors in adults and have a dismal prognosis. Patients frequently suffer from local tumor recurrences, with limited therapeutic options. Re-irradiation represents a possible intervention, but given the recent 5th edition of the World Health Organization classification of central nervous system tumors, studies in isocitrate dehydrogenase wild type (IDH-wt) cohorts undergoing a second course of radiotherapy remain limited. Herein, we sought to describe our institutional experience and outcomes after GBM IDH-wt re-irradiation.Materials and methodsGBM patients with confirmed IDH-wt status undergoing re-irradiation were included in this single-center, retrospective analysis.ResultsA total of 88 patients were analyzed. The median clinical and radiographic follow-up periods were 4.6 months and 4.4 months, respectively. Most patients had a Karnofsky performance status of at least 80% (n = 57). The median biologically effective dose and 2 Gy equivalent dose (EQD2) for re-irradiations, assuming an α/β ratio of 10 Gy for GBM, were 51.4 and 42.8 Gy, respectively. In total, 71 deaths were recorded. The median overall survival (OS) was 8.0 months. Multivariable Cox regression of OS revealed a positive influence of gross total resection vs. biopsy or no resection (hazard ratio: 0.43, p = 0.02). The median progression-free survival (PFS) was 5.9 months. The multivariable Cox regression for PFS did not detect any significant factors. No clear evidence of radiation necrosis was recorded during the available follow-up. However, only a minority (n = 4) of patients underwent surgery after re-irradiation, none showing histopathological proof of radiation necrosis.ConclusionThe prognosis for recurrent IDH-wt GBM after re-irradiation is poor. Patients who are amenable and able to undergo re-resection may have a favorable OS. A second course of radiotherapy with a moderate cumulative EQD2 and small- to medium-sized planning target volumes appeared safe regarding the occurrence of radiation necrosis.
| S-EPMC10369398 | biostudies-literature