Intensity Modulated Proton Therapy for Bilateral Breast or Chest Wall and Comprehensive Nodal Irradiation for Synchronous Bilateral Breast Cancer: Initial Clinical Experience and Dosimetric Comparison.

Purpose: Synchronous bilateral breast cancer (SBBC) poses distinct challenges for radiation therapy planning. We report our proton therapy experience in treating patients with SBBC. We also provide a dosimetric comparison of intensity modulated proton therapy (IMPT) versus photon therapy. Methods and Materials: Patients with SBBC who received IMPT at our institution were retrospectively analyzed. The clinical target volume (CTV) included the breast or chest wall and comprehensive regional lymph nodes, including axilla, supraclavicular fossa, and the internal mammary chain. Intensity modulated proton therapy and volumetric modulated arc therapy (VMAT) plans were generated with the goal that 90% of the CTV would recieve at least 90% of the prescription dose (D90>=90%). Comparisons between modalities were made using the Wilcoxon signed rank test. Physician-reported acute toxic effects and photography were collected at baseline, end of treatment, and each follow-up visit. Results: Between 2015 and 2018, 11 patients with SBBC were treated with IMPT. The prescription was 50 Gy in 25 fractions. The median CTV D90 was 99.9% for IMPT and 97.6% for VMAT (P = .001). The mean heart dose was 0.7 Gy versus 7.2 Gy (P = .001), the total lung mean dose was 7.8 Gy versus 17.3 Gy (P = .001), and the total lung volume recieving 20 Gy was 13.0% versus 27.4% (P = .001). The most common acute toxic effects were dermatitis (mostly grade 1-2 with 1 case of grade 3) and grade 1 to 2 fatigue. The most common toxic effects at the last-follow up (median, 32 months) were grade 1 skin hyperpigmentation, superficial fibrosis, and extremity lymphedema. No nondermatologic or nonfatigue adverse events of grade >1 were recorded. Conclusions: Bilateral breast and/or chest wall and comprehensive nodal IMPT is technically feasible and associated with low rates of severe acute toxic effects. Treatment with IMPT offered improved target coverage and normal-tissue sparing compared with photon therapy. Long-term follow-up is ongoing to assess efficacy and toxic effects.

Radiation biology considerations of proton therapy for gastrointestinal cancers.

Clinical enthusiasm for proton therapy (PT) is high, with an exponential increase in the number of centers offering treatment. Attraction for this charged particle therapy modality stems from the favorable proton dose distribution, with low radiation dose absorption on entry and maximum radiation deposition at the Bragg peak. The current clinical convention is to use a fixed relative biological effectiveness (RBE) value of 1.1 in order to correct the physical dose relative to photon therapy (i.e., proton radiation is 10% more biologically effective then photon radiation). In recent years, concerns about the potential side effects of PT have emerged. Various studies and review articles have sought to better quantify the RBE of PT and shine some light on the complexity of this problem. Reduction in biologic hot spots of non-target tissue is paramount in proton radiation therapy (RT) planning as the primary benefit of proton RT is a reduction in organ at risk (OAR) irradiation. New and emerging clinical data is in support of variable proton biological effectiveness and demonstrate late toxicity, presumably associated with high biological dose, to OAR. Overall, PT has promise to treat many cancer sites with similar efficacy as conventional RT but with fewer acute and late toxicities. However, further knowledge of biologic effective dose and its impact on both cancer and adjacent OAR is paramount for effective and safe treatment of patients with PT.

Electrocardiogram-Gated Computed Tomography with Coronary Angiography for Cardiac Substructure Delineation and Sparing in Patients with Mediastinal Lymphomas Treated with Radiation Therapy.

PURPOSE: (1) Demonstrate feasibility of electrocardiogram-gated computed tomography with coronary angiography (E-CTA) in treatment planning for mediastinal lymphoma and (2) assess whether inclusion of cardiac substructures in the radiation plan optimization (CSS optimization) results in increased cardiac substructure sparing. METHODS AND MATERIALS: Patients with mediastinal lymphomas requiring radiation therapy were prospectively enrolled in an observational study. Patients completed a treatment planning computed tomography scan and E-CTA in the deep inspiration breath hold position. Avoidance structures (eg, coronary arteries and cardiac valves) were created in systole and diastole and then merged into a single planning organ-at-risk volume based on a cardiac substructure contouring atlas. In the photon cohort, 2 volumetric modulated arc therapy plans were created per patient with and without CSS optimization. Dosimetric endpoints were compared. RESULTS: In the photon cohort, 7 patients were enrolled. For all 7 patients, the treating physician elected to use the CSS optimization plan. At the individual level, 2 patients had reductions of 10.8% and 16.2% of the right coronary artery receiving at least 15 Gy, and 1 had a reduction of 9.6% of the left anterior descending artery receiving 30 Gy. No other differences for coronary arteries were detected between 15 and 30 Gy. Conversely, 5 of 7 patients had >10% reductions in dose between 15 to 30 Gy to at least 1 cardiac valve. The greatest reduction was 22.8% of the aortic valve receiving at least 30 Gy for 1 patient. At the cohort level, the maximum, mean, and 5-Gy increment analyses were nominally similar between planning techniques for all cardiac substructures and the lungs. CONCLUSIONS: Cardiac substructure delineation using E-CTA was feasible, and inclusion in optimization led to modest improvements in sparing of radiosensitive cardiac substructures for some patients.