Multi-institutional, randomized, double-blind, placebo-controlled trial to assess the efficacy of a mucoadhesive hydrogel (MuGard) in mitigating oral mucositis symptoms in patients being treated with chemoradiation therapy for cancers of the head and neck.

BACKGROUND: The objective of this trial was to determine how a mucoadhesive hydrogel (MuGard), a marketed medical device, would fare when tested with the strictness of a conventional multi-institutional, double-blind, randomized, placebo-controlled study format. METHODS: A total of 120 subjects planned to receive chemoradiation therapy (CRT) for treatment of head and neck cancers were randomized to receive either MuGard or sham control rinse (SC) during CRT. Subjects completed the validated Oral Mucositis Daily Questionnaire. Weight, opiate use, and World Health Organization (WHO) oral mucositis (OM) scores were recorded. Subjects who dosed at least once daily during the first 2.5 weeks of CRT were included in the efficacy analysis. RESULTS: Of 120 subjects enrolled, 78 (SC, N=41; MuGard, N=37) were eligible for efficacy analysis. Both cohorts were similar in demographics, baseline characteristics, primary tumor type, and planned CRT regimen. MuGard effectively mitigated OM symptoms as reflected by area under the curve of daily patient-reported oral soreness (P=.034) and WHO scores on the last day of radiation therapy (P=.038). MuGard was also associated with nonsignificant trends related to therapeutic benefit including opioid use duration, and OM scores (WHO criteria) at CRT week 4. Rinse compliance was identical between cohorts. No significant adverse events were reported, and the adverse event incidence was similar between cohorts. CONCLUSIONS: Testing MuGard, a rinse marketed as a device, in a standard clinical trial format demonstrated its superiority to SC in mitigating OM symptoms, delaying OM progression, and its safety and tolerability.

A technique of partial breast irradiation utilizing proton beam radiotherapy: comparison with conformal x-ray therapy.

PURPOSE: To develop a breast immobilization system and clinical technique to deliver partial breast irradiation with a proton beam and compare dose distributions using proton therapy and conformal x-rays. METHODS: A clinical technique to provide reproducible breast immobilization was developed. Breast immobilization begins by fitting each patient with a treatment brassiere. Patients are placed prone in a cylindrical polyvinyl chloride shell with the upper and lower body being supported and immobilized with Vac-Lok foam bead cushions. The upper chest and breast areas are immobilized with two-part expandable foam. After a treatment planning computed tomography scan, the lumpectomy cavity is outlined, and a clinical target volume is generated by adding 1cm in all dimensions. A three-dimensional treatment plan is developed with treatment typically given with 2 to 4 separate proton beams. The dose administered is 40 cobalt Gray equivalents (CGE) delivered in 10 daily fractions of 4 CGE with multiple fields treated each day. Proton and conformal x-ray plans were compared using dose-volume histogram analysis to determine volumes of normal breast tissue and skin treated with each technique. RESULTS: An institutional review board-approved clinical trial was developed using this technique, and 20 patients have completed treatment. All subjects were able to undergo the immobilization procedure and daily treatments without significant discomfort, and no treatment interruptions were encountered. There was no evidence of respiratory motion identified on treatment planning CT images or on daily set-up radiographs. Acute toxicity has been limited to occasional radiation dermatitis (Radiation Therapy Oncology Group grade 1-2). Proton plans were compared with 2 methods of photon partial breast irradiation, including reduced tangential fields and five-field conformal techniques. Ten treatment plans with dose-volume histogram analysis revealed that the use of proton beams provided a significant reduction in doses to the ipsilateral breast and skin while eliminating doses to the heart and lung tissues. CONCLUSIONS: A simple immobilization procedure provides accurate and reproducible breast positioning while simultaneously eliminating respiratory motion. The procedure has been well tolerated by the first 20 patients. Protons can provide substantial normal tissue protection compared with the use of conformal x-rays when used for partial breast treatment. We plan to continue enrollment and analyze long-term toxicity, local control, and survival.

Reducing toxicity from craniospinal irradiation: using proton beams to treat medulloblastoma in young children.

PURPOSE: We report on a radiation treatment technique that has reduced the dose to critical normal structures in children with medulloblastoma. PATIENTS AND METHODS: Three children between the ages of 3 and 4 with stage M2 or M3 medulloblastoma were treated between 2001 and 2003 with craniospinal irradiation using protons. Patients received 36 cobalt gray equivalent to the craniospinal axis, then 18 cobalt gray equivalent to the posterior fossa. The cranium was treated with opposed lateral fields. The spine was treated with three matched posteroanterior fields, with the beam stopping just beyond the thecal sac. The posterior fossa was then treated with alternating posteroanterior, right posterior oblique, and left posterior oblique fields, with the beam stopping just proximal to the cochlea. The use of general anesthesia and pre-porting with diagnostic-quality x-rays allowed precise patient positioning. RESULTS: Craniospinal irradiation delivered via conformal proton irradiation substantially reduced the dose to the cochlea and vertebral bodies and virtually eliminated the exit dose through thorax, abdomen, and pelvis. Despite concurrent chemotherapy, a clinically significant lymphocyte count reduction was not seen. Patients tolerated treatment well; acute side effects (e.g., nausea, decreased appetite, and odynophagia) were mild. All patients completed therapy without interruption. CONCLUSION: Our proton-beam technique for craniospinal irradiation of pediatric medulloblastoma has successfully reduced normal-tissue doses and acute treatment-related sequelae. This technique may be especially advantageous in children with a history of myelosuppression, who might not other wise tolerate irradiation.