Estimating the tolerance of brachial plexus to hypofractionated stereotactic body radiotherapy: a modelling-based approach from clinical experience.

BACKGROUND: Brachial plexopathy is a potentially serious complication from stereotactic body radiation therapy (SBRT) that has not been widely studied. Therefore, we compared datasets from two different institutions and generated a brachial plexus dose-response model, to quantify what dose constraints would be needed to minimize the effect on normal tissue while still enabling potent therapy for the tumor. METHODS: Two published SBRT datasets were pooled and modeled from patients at Indiana University and the Richard L. Roudebush Veterans Administration Medical Center from 1998 to 2007, as well as the Karolinska Institute from 2008 to 2013. All patients in both studies were treated with SBRT for apically located lung tumors localized superior to the aortic arch. Toxicities were graded according to Common Terminology Criteria for Adverse Events, and a probit dose response model was created with maximum likelihood parameter fitting. RESULTS: This analysis includes a total of 89 brachial plexus maximum point dose (Dmax) values from both institutions. Among the 14 patients who developed brachial plexopathy, the most common complications were grade 2, comprising 7 patients. The median follow-up was 30 months (range 6.1-72.2) in the Karolinska dataset, and the Indiana dataset had a median of 13 months (range 1-71). Both studies had a median range of 3 fractions, but in the Indiana dataset, 9 patients were treated in 4 fractions, and the paper did not differentiate between the two, so our analysis is considered to be in 3-4 fractions, one of the main limitations. The probit model showed that the risk of brachial plexopathy with Dmax of 26 Gy in 3-4 fractions is 10%, and 50% with Dmax of 70 Gy in 3-4 fractions. CONCLUSIONS: This analysis is only a preliminary result because more details are needed as well as additional comprehensive datasets from a much broader cross-section of clinical practices. When more institutions join the QUANTEC and HyTEC methodology of reporting sufficient details to enable data pooling, our field will finally reach an improved understanding of human dose tolerance.

Potential Clinical Significance of Overall Targeting Accuracy and Motion Management in the Treatment of Tumors That Move With Respiration: Lessons Learnt From a Quarter Century of Stereotactic Body Radiotherapy From Dose Response Models.

OBJECTIVE: To determine the long-term normal tissue complication probability with stereotactic body radiation therapy (SBRT) treatments for targets that move with respiration and its relation with the type of respiratory motion management (tracking vs. compression or gating). METHODS: A PubMed search was performed for identifying literature regarding dose, volume, fractionation, and toxicity (grade 3 or higher) for SBRT treatments for tumors which move with respiration. From the identified papers logistic or probit dose-response models were fitted to the data using the maximum-likelihood technique and confidence intervals were based on the profile-likelihood method in the dose-volume histogram (DVH) Evaluator. RESULTS: Pooled logistic and probit models for grade 3 or higher toxicity for aorta, chest wall, duodenum, and small bowel suggest a significant difference when live motion tracking was used for targeting tumors with move with respiration which was on the average 10 times lower, in the high dose range. CONCLUSION: Live respiratory motion management appears to have a better toxicity outcome when treating targets which move with respiration with very steep peripheral dose gradients. This analysis is however limited by sparsity of rigorous data due to poor reporting in the literature.

Phase III study of pentosanpolysulfate (PPS) in treatment of gastrointestinal tract sequelae of radiotherapy.

OBJECTIVES: To evaluate the effectiveness of pentosanpolysulfate (PPS) in the treatment of gastrointestinal tract sequelae of radiotherapy. METHODS: Eligible patients were those with grade 1 to 3 radiation related proctitis, diarrhea and/or melena. At least 4 weeks had to elapse since the completion of the radiotherapy course. Patients with bleeding diathesis or ulcers, and patients receiving anticoagulants or chemotherapy were excluded. Stratification criteria included the type of sequelae (proctitis, diarrhea, melena), the severity grade and the onset (<3 months post-RT, >3 months post-RT). Patients were randomized to one of the following arms: 100 mg PPS 3 times per day (300 mg/day), 200 mg PPS 3 times per day (600 mg/day), or placebo 3 times per day. If there was no improvement in symptoms after 2 months, the protocol treatment was discontinued. If the symptoms improved or resolved, the protocol treatment was continued for additional 4 months. Patients under treatment were evaluated monthly, than every 2 to 3 months for the next 18 months. A symptom assessment questionnaire was used to measure quality of life endpoints. RESULTS: From June 1999 to March 2001 180 patients were accessioned from 34 institutions. A total of 168 were analyzable. Neither the best observed response within 3 months for the entire population, nor the response rate within sequelae category or the quality of life measures differed significantly between the 3 arms of the study. CONCLUSION: Administration of PPS has not been associated with an improvement in the clinical course of radiation related morbidity of the gastrointestinal tract.