Dataset Information

Dosimetric feasibility analysis and presentation of an isotoxic dose-escalated radiation therapy concept for glioblastoma used in the PRIDE trial (NOA-28; ARO-2022-12).

ABSTRACT:

Background and purpose

The PRIDE trial (NOA-28; ARO-2022-12; NCT05871021) is scheduled to start recruitment in October 2023. Its primary objective is to enhance median overall survival (OS), compared to historical median OS rates, in patients with methylguanine methlyltransferase (MGMT) promotor unmethylated glioblastoma by incorporating isotoxic dose escalation to 75 Gy in 30 fractions. To achieve isotoxicity and counteract the elevated risk of radiation necrosis (RN) associated with dose-escalated regimens, the addition of protective concurrent bevacizumab (BEV) serves as an innovative approach. The current study aims to assess the dosimetric feasibility of the proposed concept.

Materials and methods

A total of ten patients diagnosed with glioblastoma were included in this dosimetric analysis. Delineation of target volumes for the reference plans adhered to the ESTRO-EANO 2023 guideline. The experimental plans included an additional volume for the integrated boost. Additionally, the 60 Gy-volume was reduced by using a margin of 1.0 cm instead of 1.5 cm. To assess the risk of symptomatic RN, the Normal Tissue Complication Probability (NTCP) was calculated and compared between the reference and experimental plans.

Results

Median NTCP of the reference plan (NTCP_ref) and of the experimental plan (NTCP_ex) were 0.24 (range 0.11-0.29) and 0.42 (range 0.18-0.54), respectively. NTCP_ex was a median of 1.77 (range 1.60-1.99) times as high as the NTXP_ref. In a logarithmic comparison, the risk of RN is enhanced by a factor of median 2.00 (range 1.66-2.35). The defined constraints for the organs at risk were feasible.

Conclusion

When considering the potential protective effect of BEV, which we hypothesized might reduce the risk of RN by approximately two-fold, achieving isotoxicity with the proposed dose-escalated experimental plan for the PRIDE trial seems feasible.

SUBMITTER: Bodensohn R

PROVIDER: S-EPMC10726217 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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Dosimetric feasibility analysis and presentation of an isotoxic dose-escalated radiation therapy concept for glioblastoma used in the PRIDE trial (NOA-28; ARO-2022-12).

Bodensohn Raphael R Fleischmann Daniel F DF Maier Sebastian H SH Anagnostatou Vasiliki V Garny Sylvia S Nitschmann Alexander A Büttner Marcel M Mücke Johannes J Schönecker Stephan S Unger Kristian K Hoffmann Elgin E Paulsen Frank F Thorwarth Daniela D Holzgreve Adrien A Albert Nathalie L NL Corradini Stefanie S Tabatabai Ghazaleh G Belka Claus C Niyazi Maximilian M

Clinical and translational radiation oncology 20231203

<h4>Background and purpose</h4>The PRIDE trial (NOA-28; ARO-2022-12; NCT05871021) is scheduled to start recruitment in October 2023. Its primary objective is to enhance median overall survival (OS), compared to historical median OS rates, in patients with methylguanine methlyltransferase (MGMT) promotor unmethylated glioblastoma by incorporating isotoxic dose escalation to 75 Gy in 30 fractions. To achieve isotoxicity and counteract the elevated risk of radiation necrosis (RN) associated with do ...[more]

PMID: 38116137

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Project description:BackgroundThe higher specificity of amino-acid positron emission tomography (AA-PET) in the diagnosis of gliomas, as well as in the differentiation between recurrence and treatment-related alterations, in comparison to contrast enhancement in T1-weighted MRI was demonstrated in many studies and is the rationale for their implementation into radiation oncology treatment planning. Several clinical trials have demonstrated the significant differences between AA-PET and standard MRI concerning the definition of the gross tumor volume (GTV). A small single-center non-randomized prospective study in patients with recurrent high grade gliomas treated with stereotactic fractionated radiotherapy (SFRT) showed a significant improvement in survival when AA-PET was integrated in target volume delineation, in comparison to patients treated based on CT/MRI alone.MethodsThis protocol describes a prospective, open label, randomized, multi-center phase II trial designed to test if radiotherapy target volume delineation based on FET-PET leads to improvement in progression free survival (PFS) in patients with recurrent glioblastoma (GBM) treated with re-irradiation, compared to target volume delineation based on T1Gd-MRI. The target sample size is 200 randomized patients with a 1:1 allocation ratio to both arms. The primary endpoint (PFS) is determined by serial MRI scans, supplemented by AA-PET-scans and/or biopsy/surgery if suspicious of progression. Secondary endpoints include overall survival (OS), locally controlled survival (time to local progression or death), volumetric assessment of GTV delineated by either method, topography of progression in relation to MRI- or PET-derived target volumes, rate of long term survivors (>1 year), localization of necrosis after re-irradiation, quality of life (QoL) assessed by the EORTC QLQ-C15 PAL questionnaire, evaluation of safety of FET-application in AA-PET imaging and toxicity of re-irradiation.DiscussionThis is a protocol of a randomized phase II trial designed to test a new strategy of radiotherapy target volume delineation for improving the outcome of patients with recurrent GBM. Moreover, the trial will help to develop a standardized methodology for the integration of AA-PET and other imaging biomarkers in radiation treatment planning.Trial registrationThe GLIAA trial is registered with ClinicalTrials.gov ( NCT01252459 , registration date 02.12.2010), German Clinical Trials Registry ( DRKS00000634 , registration date 10.10.2014), and European Clinical Trials Database (EudraCT-No. 2012-001121-27, registration date 27.02.2012).

Project description:PurposeThe role of radiotherapy for unresectable pancreatic cancer is controversial. A benefit of additional radiotherapy is supported by some observations. A dose-effect relationship was recently found by dose escalation employing image guided and intensity modulated radiotherapy.MethodsWe retrospectively evaluated 28 consecutive patients, all with history of extensive prior therapies for unresectable locally advanced/ recurrent pancreatic cancer (LAPC/LRPC). Treatment was delivered by helical tomotherapy after daily position verification with computed tomography. Dose to the planned target volume (PTV) was 51 Gy, while the dose to the macroscopic tumor was escalated by a simultaneous integrated boost to a median cumulative dose of 66 Gy (60-66 Gy). Concomitant chemotherapy consisted mainly of capecitabine (n = 23).Results10 of 28 patients presented acute toxicities > grade 2, one patient succumbed to gastrointestinal bleeding after treatment. No correlations of toxicities and dose volume histograms (DVH) of retrospectively delineated small bowel loops were observed, although average small bowel volume receiving ≥ 20 Gy was 374 ml. DVH analyses revealed a correlation of splenic parameters and acute toxicity: Vomiting, anorexia, dehydration, hematologic toxicity, fatigue, combined gastro-intestinal toxicity wit R-values between 0.392 and 0.561 (all p-values > 0.05). Only one patient developed late toxicities > grade 2. With an average follow-up time in surviving patients of 14 months median overall survival time was 19 months and median time to local recurrence 13 months. In 8 patients with available imaging of local recurrence: 5 in field recurrences, 2 marginal recurrences and one lymph node recurrence outside the high dose radiation field were observed. In univariate analysis only ΔCA-19-9 during radiotherapy was associated with local control (p = 0.029) and overall survival (p = 0.049).ConclusionDose escalated normo-fractionated radiotherapy for LAPC/LRPC seems feasible and suitable to prolong local control and in consequence long-term survival. However, in-field local progression is still frequently observed and possibilities to increase the local effectiveness should be evaluated. Exposure of the spleen was predictive for acute toxicity and should be further investigated.

Dataset Information

Dosimetric feasibility analysis and presentation of an isotoxic dose-escalated radiation therapy concept for glioblastoma used in the PRIDE trial (NOA-28; ARO-2022-12).

Background and purpose

Materials and methods

Results

Conclusion

Publications

Dosimetric feasibility analysis and presentation of an isotoxic dose-escalated radiation therapy concept for glioblastoma used in the PRIDE trial (NOA-28; ARO-2022-12).

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