Anand, Aman Raj

Background/Objectives: Adjuvant radiation for gynecologic malignancies often exposes organs at risk (OARs), such as the bone marrow, bowel, rectum, and bladder, to radiation, leading to toxicities that impact treatment tolerance and patient quality of life. Scanning proton beam therapy, particularly with Individual Field Simultaneous Optimization (IFSO), may offer dosimetric and biological advantages over volumetric modulated arc therapy (VMAT). This study evaluates the clinical impact of IFSO-based proton planning in post-operative gynecologic cancer patients. Materials and Methods: Fourteen patients receiving adjuvant proton therapy to 45 Gy in 25 fractions were retrospectively analyzed. Comparison VMAT plans were generated on the same datasets. Dose–volume metrics for key OARs and normal tissue complication probabilities (NTCPs) were compared using paired statistical tests. Robustness evaluations accounted for setup and range uncertainties. Results: Proton plans significantly reduced dose to bone marrow (V10Gy: 58% vs. 86%, p < 0.00001; V20Gy: 47% vs. 58%, p < 0.00001), small bowel (V20Gy: 21% vs. 56%, p < 0.00001), and femoral heads (left femoral head mean: 11Gy vs. 13Gy, p = 0.032; right femoral head mean: 11Gy vs. 13Gy, p = 0.022). NTCP modeling predicted significantly lower rates of bowel urgency (9.4% vs. 3.3%, p < 0.001) and hematologic toxicity (10.2% vs. 4.9%, p < 0.001) with proton therapy. Plans remained robust across uncertainty scenarios. Conclusions: IFSO-based scanning proton therapy provides clinically meaningful sparing of bone marrow and bowel, with the potential to reduce hematologic and gastrointestinal toxicities. These findings support its use in patients receiving adjuvant pelvic radiotherapy, particularly those undergoing extended field treatment or chemotherapy.

Objectives: Identifying patients’ advantageous radiotherapy modalities prior to CT simulation is challenging. This study aimed to develop a workflow using deep learning (DL)-predicted synthetic CT (sCT) for treatment modality comparison based solely on a diagnostic CT (dCT). Methods: A DL network, U-Net, was trained utilizing 46 thoracic cases from a public database to generate sCT images predicting planning CT (pCT) scans based on the latest dCT, and tested on 15 institutional patients. The sCT accuracy was evaluated against the corresponding pCT and a commercial algorithm deformed CT (MdCT) based on Mean Absolute Error (MAE) and Universal Quality Index (UQI). To determine advantageous treatment modality, clinical dose-volume histogram (DVH) metrics and Normal Tissue Complication Probability (NTCP) differences between proton and photon treatment plans were analyzed on the sCTs via concordance correlation coefficient (CCC). Results: The AI-generated sCTs closely resembled those of the commercial deformation algorithm in the tested cases. The differences in MAE and UQI values between the sCT-vs-pCT and MdCT-vs-pCT were 19.38 HU and 0.06, respectively. The mean absolute NTCP deviation between sCT and pCT was 1.54%, 0.21%, and 2.36% for esophagus perforation, lung pneumonitis, and heart pericarditis, respectively. The CCC between sCT and pCT was 0.90 for DVH metrics and 0.97 for NTCP, indicating moderate agreement for DVH metrics and substantial agreement. Conclusions: Radiation oncologists can potentially utilize this personalized sCT based approach as a clinical support tool to rapidly compare the treatment modality benefit during patient consultation and facilitate in-depth discussion on potential toxicities at a patient-specific level.

Abstract Purpose/Objectives: Proton therapy is under investigation in breast cancer as a strategy to reduce heart and lung exposure, which is associated with late cardiopulmonary adverse events and secondary malignancy. To date, studies investigating postmastectomy radiotherapy (PMRT) with protons have used conventional fractionation. We hypothesized that condensing treatment to 15 fractions would be safe based on evidence that breast cancer is more sensitive to higher dose fractions than surrounding normal tissues. Materials/Methods: We conducted a randomized non-inferiority phase II trial comparing conventional and hypofractionated proton PMRT with primary endpoint of 24-month complication rate (defined as grade 3 or higher late adverse events using CTCAE, v 4.0 and/or unplanned surgical intervention in patients undergoing mastectomy with reconstruction). With a 10% non-inferiority margin the study ensured 80% power and had a one sided-type I error rate of 0.05. Cardiotoxicity was assessed with serial transthoracic conventional and 2-dimensional speckle tracking echocardiography (2D-STE). Eligibility included age ≥ 18 years with non-inflammatory breast cancer resected by mastectomy with indications for PMRT. Assignment of treatments was balanced with respect to immediate breast reconstruction (IBR). Conventional fractionation group received 50 Gy in 25 fractions of 2 Gy, and hypofractionation group received 40.05 Gy in 15 fractions of 2.67 Gy (RBE 1.1). Target volume included the chest wall and axillary, supraclavicular, and internal mammary lymph nodes. All patients were treated with multi-field optimized pencil beam scanning (intensity modulated proton therapy). Results: Between 2016 and 2018, 82 patients were enrolled and randomized (41 conventional, 41 hypofractionation). Median patient age was 52 years. 32.9% were staged T3-T4 and 79.3% node positive at diagnosis. 57 of 82 patients (69.5%) elected IBR. The median mean heart dose was 0.49 Gy and the median ipsilateral lung volume receiving 40% of prescription or greater (V40%) was 13.6%. No significant changes on conventional or 2D-STE at end-of-treatment or 3-month follow-up compared to baseline were observed. The rate of ≥ grade 2 acute dermatitis was lower with hypofractionation (44% vs 15%, p = 0.006). Other ≥ grade 2 acute adverse events including esophagitis (0 vs 5%), infection (5% vs 2.4%) and skin hyperpigmentation (7.3% vs 4.8%) were not significantly different between the two arms. With a median follow-up of 38.3 months, the 24-month complication rate was conventional 14.6% vs hypofractionation 17.1% (absolute difference 2.4%, p=0.17, 95% CI [-, 15.7%]). In patients with IBR, 6 of 28 (21.4%) conventional and 7 of 29 (24.1%) hypofractionated patients developed complications (p =0.80). There was no significant difference in 3-year disease-free survival between the conventional (89.4%; 95% CI 80.0 – 99.8%) and hypofractionated (92.4%, 95% CI 84.5 – 100.0%) arms (p = 0.91). One local recurrence occurred in the hypofractionated arm simultaneous with regional and distant relapse. The remaining 6 recurrences were isolated distant events. Conclusions: Proton PMRT provided excellent locoregional control and normal tissue sparing. There were no subclinical echocardiographic changes indicative of radiation-induced cardiac dysfunction. Hypofractionation resulted in comparable disease control, tolerability and reconstruction outcomes as conventional fractionation. Although non-inferiority of hypofractionation could not be established based on the upper bound of the 95% confidence interval for complication rate being greater than 10%, both conventional and hypofractionation may be considered appropriate regimens for ongoing phase 3 randomized trials comparing photon and proton radiotherapy. Citation Format: Robert Mutter, Sharmila Giri, Briant Fruth, Nicholas Remmes, Aman Anand, Kathryn Ruddy, Hector Villarraga, Sebastian Santos Patarroyo, Elizabeth Yan, Kenneth Merrell, Lisa McGee, Tamara Vern-Gross, Bradley Stish, Robert Gao, Judy C. Boughey, Sean Park, Kimberly Corbin, Carlos Vargas. Phase II randomized trial of conventional versus hypofractionated post-mastectomy proton radiotherapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr GS4-05.

AbstractMonte Carlo (MC) simulation has been used to generate commissioning data for the beam modeling of treatment planning system (TPS). We have developed a method called radial projection (RP) for postprocessing of MC‐simulation‐generated data. We used the RP method to reduce the statistical uncertainty of the lateral profile of proton pencil beams with axial symmetry. The RP method takes advantage of the axial symmetry of dose distribution to use the mean value of multiple independent scores as the representative score. Using the mean as the representative value rather than any individual score results in substantial reduction in statistical uncertainty. Herein, we present the concept and step‐by‐step implementation of the RP method, as well as show the advantage of the RP method over conventional measurement methods for generating lateral profile. Lateral profiles generated by both methods were compared to demonstrate the uncertainty reduction qualitatively, and standard error comparison was performed to demonstrate the reduction quantitatively. The comparisons showed that statistical uncertainty was reduced substantially by the RP method. Using the RP method to postprocess MC data, the corresponding MC simulation time was reduced by a factor of 10 without quality reduction in the generated result from the MC data. We concluded that the RP method is an effective technique to increase MC simulation efficiency for generating lateral profiles for axially symmetric pencil beams.