Dataset Information

Glioblastoma radiotherapy using Intensity modulated Radiotherapy (IMRT) or proton Radiotherapy-GRIPS Trial (Glioblastoma Radiotherapy via IMRT or Proton BeamS): a study protocol for a multicenter, prospective, open-label, randomized, two-arm, phase III study.

ABSTRACT:

Background

Radiation therapy is an integral part of the multimodal primary therapy of glioblastomas. As the overall prognosis in this tumor entity remains unfavorable, current research is focused on additional drug therapies, which are often accompanied by increases in toxicity. By using proton beams instead of photon beams, it is possible to protect large parts of the brain which are not affected by the tumor more effectively. An initial retrospective matched-pair analysis showed that this theoretical physical benefit is also clinically associated with a reduction in toxicity during therapy and in the first few months thereafter.

Methods/design

The GRIPS trial is a multicenter, prospective, open-label, randomized, two-arm, phase III study using either intensity modulated photon radiation techniques (standard arm) or proton beam radiotherapy (experimental arm). Additionally, patients are stratified according to "fractionation scheme" (normofractionated/hypofractionated), "subventricular zone involvement" (yes/no) and concurrent chemotherapy (yes/no) and the planned case number is 326 patients. Radiation therapy is performed with a dose of 30 × 2 Gy(RBE) or 33 × 1.8 Gy(RBE), or for patients treated according to the hypofractionation protocol with 15 × 2.67 Gy(RBE). A possible administration of additional chemotherapy (concurrent or adjuvant) or tumor treating fields is applied in dosage and frequency according to the therapy standard outside of this study. The primary endpoint is the cumulative rate of toxicity CTC grade 2 and higher in the first 4 months. Secondary endpoints include overall survival, progression-free survival, quality of life, and neurocognition.

Discussion

Aim of the GRIPS study is to prospectively assess whether the theoretical physical advantage of proton beam radiotherapy will translate into a clinical reduction of toxicity during and in the first months after therapy. Trial registration ClinicalTrials (NCT): NCT04752280.

SUBMITTER: Konig L

PROVIDER: S-EPMC8691033 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Owing to its physical properties, intensity-modulated proton therapy (IMPT) used for patients with oropharyngeal carcinoma has the ability to reduce the dose to organs at risk compared to intensity-modulated radiotherapy (IMRT) while maintaining adequate tumor coverage. Our aim was to compare the clinical outcomes of these two treatment modalities.We performed a 1:2 matching of IMPT to IMRT patients. Our study cohort consisted of IMPT patients from a prospective quality of life study and consecutive IMRT patients treated at a single institution during the period 2010-2014. Patients were matched on unilateral/bilateral treatment, disease site, human papillomavirus status, T and N status, smoking status, and receipt of concomitant chemotherapy. Survival analyzes were performed using a Cox model and binary toxicity endpoints using a logistic regression analysis.Fifty IMPT and 100 IMRT patients were included. The median follow-up time was 32months. There were no imbalances in patient/tumor characteristics except for age (mean age 56.8years for IMRT patients and 61.1years for IMPT patients, p-value=0.010). Statistically significant differences were not observed in overall survival (hazard ratio (HR)=0.55; 95% confidence interval (CI): 0.12-2.50, p-value=0.44) or in progression-free survival (HR=1.02; 95% CI: 0.41-2.54; p-value=0.96). The age-adjusted odds ratio (OR) for the presence of a gastrostomy (G)-tube during treatment for IMPT vs IMRT were OR=0.53; 95% CI: 0.24-1.15; p-value=0.11 and OR=0.43; 95% CI: 0.16-1.17; p-value=0.10 at 3months after treatment. When considering the pre-planned composite endpoint of grade 3 weight loss or G-tube presence, the ORs were OR=0.44; 95% CI: 0.19-1.0; p-value=0.05 at 3months after treatment and OR=0.23; 95% CI: 0.07-0.73; p-value=0.01 at 1year after treatment.Our results suggest that IMPT is associated with reduced rates of feeding tube dependency and severe weight loss without jeopardizing outcome. Prospective multicenter randomized trials are needed to validate such findings.

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Project description:Coplanar extended-field intensity-modulated radiation therapy (EF-IMRT) targeting the whole-pelvic and para-aortic lymph nodes in patients with advanced cervical cancer results in impaired creatinine clearance. An improvement in renal function cannot be expected unless low-dose (approximately 10 Gy) kidney exposure is reduced. The dosimetric method should be considered during EF-IMRT planning to further reduce low-dose exposure to the kidneys. To assess the usefulness of non-coplanar EF-IMRT with kidney-avoiding beams to spare the kidneys during cervical carcinoma treatment in dosimetric analysis between non-coplanar and coplanar EF-IMRT, we compared the doses of the target organ and organs at risk, including the kidney, in 10 consecutive patients. To estimate the influence of EFRT on renal dysfunction, creatinine clearance values after treatment were also examined in 18 consecutive patients. Of these 18 patients, 10 patients who were included in the dosimetric analysis underwent extended field radiation therapy (EFRT) with concurrent chemotherapy, and eight patients underwent whole-pelvis radiation therapy with concurrent chemotherapy to treat cervical carcinoma between April 2012 and March 2015 at our institution. In the dosimetric analysis, non-coplanar EF-IMRT was effective at reducing low-dose (approximately 10 Gy) exposure to the kidneys, thus maintaining target coverage and sparing other organs at risk, such as the small bowel, rectum, and bladder, compared with coplanar EF-IMRT. Renal function in all 10 patients who underwent EFRT, including coplanar EF-IMRT (with kidney irradiation), was low after treatment, and differed significantly from that of the eight patients who underwent WPRT (no kidney irradiation) 6 months after the first day of treatment (P = 0.005). In conclusion, non-coplanar EF-IMRT should be considered in patients with advanced cervical cancer, particularly in patients with a long life expectancy or with pre-existing renal dysfunction.