Patel, Samir H.

Abstract BACKGROUND Intensity‐modulated proton therapy (IMPT) demonstrates superior dose distribution over volumetric‐modulated arc therapy (VMAT) for sparing organs‐at‐risk (OARs) in ipsilateral radiotherapy. To determine a clinical benefit, assessment of patient‐reported outcomes (PRO) and physician‐reported toxicities alongside a dosimetric analysis is needed. METHODS Plans were analyzed for dosimetric differences. PROs were compared for patients undergoing ipsilateral curative‐intent radiotherapy for tonsil and salivary gland cancers with VMAT or IMPT from 2015 to 2020. Physician‐reported toxicities were compared. RESULTS In 40 patients, IMPT was associated with decreased dose to multiple OARs and less deterioration in the following PROs: pain, swallowing function, dry mouth, sticky saliva, sensory change, cough, speech, feeling ill, and social eating. Physician‐reported toxicities demonstrated less oral pain. CONCLUSION IMPT is associated with decreased dose to OARs and less patient‐reported acute deterioration in multiple head and neck domains. A strong consideration for IMPT in ipsilateral head and neck patients with cancer is warranted.

AbstractPurposeDue to the employment of quadratic programming using soft constraints to implement dose volume constraints and the “trial‐and‐error” procedure needed to achieve a clinically acceptable plan, conventional dose volume constraints (upper limit) are not adequately effective in controlling small and isolated hot spots in the dose/linear energy transfer (LET) distribution. Such hot spots can lead to adverse events. In order to mitigate the risk of brain necrosis, one of the most clinically significant adverse events in patients receiving intensity‐modulated proton therapy (IMPT) for base of skull (BOS) cancer, we propose per‐voxel constraints to minimize hot spots in LET‐guided robust optimization.Methods and materialsTen BOS cancer patients treated with IMPT were carefully selected by meeting one of the following conditions: (1) diagnosis of brain necrosis during follow‐up; and (2) considered high risk for brain necrosis by not meeting dose constraints to the brain. An optimizing structure (BrainOPT) and an evaluating structure (BrainROI) that both contained the aforementioned hot dose regions in the brain were generated for optimization and evaluation, respectively. Two plans were generated for every patient: one using conventional dose‐only robust optimization, the other using LET‐guided robust optimization. The impact of LET was integrated into the optimization via a term of extra biological dose (xBD). A novel optimization tool of per‐voxel constraints to control small and isolated hot spots in either the dose, LET, or combined (dose/LET) distribution was developed and used to minimize dose/LET hot spots of the selected structures. Indices from dose‐volume histogram (DVH) and xBD dose‐volume histogram (xBDVH) were used in the plan evaluation. A newly developed tool of the dose‐LET‐volume histogram (DLVH) was also adopted to illustrate the underlying mechanism. Wilcoxon signed‐rank test was used for statistical comparison of the DVH and xBDVH indices between the conventional dose‐only and the LET‐guided robustly optimized plans.ResultsPer‐voxel constraints effectively and efficiently minimized dose hot spots in both dose‐only and LET‐guided robust optimization and LET hot spots in LET‐guided robust optimization. Compared to the conventional dose‐only robust optimization, the LET‐guided robust optimization could generate plans with statistically lower xBD hot spots in BrainROI (VxBD,50 Gy[RBE], p = 0.009; VxBD,60 Gy[RBE], p = 0.025; xBD1cc, p = 0.017; xBD2cc, p = 0.022) with comparable dose coverage, dose hot spots in the target, and dose hot spots in BrainROI. DLVH analysis indicated that LET‐guided robust optimization could either reduce LET at the same dose level or redistribute high LET from high dose regions to low dose regions.ConclusionPer‐voxel constraint is a powerful tool to minimize dose/LET hot spots in IMPT. The LET‐guided robustly optimized plans outperformed the conventional dose‐only robustly optimized plans in terms of xBD hot spots control.

Malignant melanoma of the lacrimal sac is an exceptionally rare tumor with a poor prognosis. We report two cases of malignant melanoma of the lacrimal sac: a 73 year-old female treated with primary surgical resection and a 75 year-old male treated with surgical resection, adjuvant proton beam radiotherapy, and adjuvant immunotherapy. We discuss the role of post-operative proton beam therapy and recent advancements in immunotherapy. These cases highlight the importance of early diagnosis and multi-modality treatment in this aggressive malignancy.

AbstractBackgroundAggressive dose de‐escalated adjuvant radiation therapy (RT) in patients with human papillomavirus–associated oropharyngeal squamous cell carcinoma (HPV(+)OPSCC).MethodsPatients with HPV(+)OPSCC on a phase II clinical trial of primary surgery and neck dissection followed by dose de‐escalated RT (N = 79) were compared with a cohort of patients who received standard adjuvant therapy (N = 115). Local recurrence‐free, regional recurrence‐free, distant metastases‐free survival, and progression‐free survival (PFS) were assessed.ResultsOf 194 patients, 23 experienced progression at a median of 1.1 years following surgery (interquartile range [IQR] 0.7‐2.0; range 0.3‐5.4); 10 patients in the de‐escalated cohort and 13 patients in the standard cohort. The 3‐year PFS rate for the de‐escalated cohort was 87%, and in the standard cohort was 90% (hazard ratio [HR] 1.18, 95% confidence interval (CI) [0.50‐2.75]).ConclusionPatients with HPV(+)OPSCC who undergo surgical resection and neck dissection and meet criteria for adjuvant therapy can undergo aggressive dose de‐escalation of RT without increasing risk of progression locally, regionally or at distant sites.

Many American Indian (AI) and Alaska native (AN) patients do not complete guideline-concordant cancer care for the 4 most common cancers. Our aim was to better understand AI/AN attitudes toward radiation therapy (RT). Patients eligible for this survey study were AI/AN patients with cancer at the Phoenix Indian Medical Center who either received previous RT or were recommended to receive RT. An 18-item questionnaire was administered to each of the 50 participants from October 1, 2018, through February 15, 2019. Willingness to travel for RT was compared to respondent characteristics, concerns regarding RT, and obstacles to obtain RT. Duration of RT was important to 78% of patients: 24% would consider traveling 25 miles or more for a standard course, and 48% would travel that distance for a shorter course ( P < .001). The top-ranked barriers to RT were transportation, cost of treatment, and insurance compatibility. The top-ranked concerns about RT were adverse effects, cost of treatment, and fear of RT. Concerns about adverse effects were associated with the radiation team’s inability to explain the treatment ( P = .05). Transportation concerns were significantly associated with accessibility ( P = .02), communication with the RT team ( P = .02), and fear of RT ( P = .04). AI/AN patients are concerned about the adverse effects of RT and the logistics of treatment, particularly costs, transportation, and insurance compatibility. Use of culturally specific education and hypofractionation regimens may increase acceptance of RT for AI/AN patients with cancer, and this hypothesis will be tested in a future educational intervention-based study.

e13617 Background: Breast cancer (BC) is the most prevalent cancer of women in the United States (US). The incidence rates for BC among American Indian and Alaska Native (AI/AN) women vary across the US. A novel application of Bayesian disease mapping was applied to quantify potential inequities in 10-year BC incidence in New Mexico (NM) in order to better inform health equity initiatives within the AI/AN at-risk population. Methods: Surveillance, Epidemiology, and End Results Program (SEER) data from 2005 to 2014 were used to identify new cases of BC within the 33 counties in NM. Initially, a Poisson-gamma model was applied to quantify the reduction in risk of BC within the at-risk AI/AN population compared with the general at-risk population. To account for spatial variation and to address the small area estimation problem inherent in these data by borrowing strength globally and locally in NM, we applied Bayesian disease mapping to the counts of county-level BC cases. We quantified the disparity effect, as measured by the rate ratio (95% credible interval [CI]), comparing the incidence of BC between at-risk AI/AN and non-AI/AN women, and assessed if the rate ratio differed between counties. Markov chain Monte Carlo sampling was used to estimate posterior quantities and the deviance information criterion was used for model selection. Results: In 2010, 1,041,758 women were at-risk for BC of which 107,656 (10.3%) were AI/AN women. During the 10-year study period, 12,974 new BC cases were recorded in the general at-risk population. In the at-risk AI/AN population, the expected number of new cases during the 10-year study period, therefore, was 1,340.74; however, 597 incidence cases of BC were diagnosed in the at-risk AI/AN population resulting in a posterior mean for the true relative risk of 0.445 (95% CI: 0.410, 0.482). Based on the selected model that accounted for over dispersion and spatial correlation among the 33 counties, the posterior mean of the overall adjusted rate ratio was 0.405 (95% CI: 0.336, 0.478). The adjusted rate of BC in AI/AN women was 0.40 times the corresponding adjusted rate for women who were non-AI/AN. Further, the adjusted rate ratios were similar for each county. Conclusions: The novel application of Bayesian disease mapping to these data provided substantial evidence of a significant overall disparity effect in BC incidence within NM between at-risk AI/AN and non-AI/AN women, which was more marked than previous reports. Targeted state-wide health equity initiatives may lead to reducing disparities in BC incidence in AI/AN at-risk women.

Objectives: To report long-term outcomes of nonmelanoma skin cancer (NMSC) in immunosuppressed cardiac and liver transplant recipients (CLTR). Materials and Methods: The authors reviewed CLTR at the Mayo Clinic in Arizona from 1986 to 2013. Patient and tumor characteristics were recorded. Survival rates were calculated using the Kaplan-Meier method. Patient-specific and lesion-specific analyses were performed. Univariate and multivariate cox regressions were performed for comparisons. Results: Seven-hundred and forty-seven patients underwent cardiac (138) or liver (609) transplantation and of these, 97 patients (13%) developed 382 invasive NMSC. The median follow-up was 11 (range, 3 to 27) years for surviving patients. Primary treatment was mainly surgery alone. At 10 years, the local recurrence (LR) rate was 20% (95% confidence interval, 15%-28%), and 14% of patients had multiple LRs. At 10 years, LR rates were higher for T3/T4 tumors when compared with T1/T2 tumors (32.5% vs. 20%, P=0.05). At 10 years, overall survival was 79% (95% confidence interval, 64%-88%). On multivariate analysis, age 61 years and more demonstrated inferior overall survival (P<0.01). Conclusions: This is the first study describing the AJCC 8th edition stage-based patterns of recurrence and long-term outcomes of surgically managed NMSC in a large cohort of immunosuppressed CLTRs. T3 and T4 tumors recur more often than early stage tumors. Further study is required to identify factors related to recurrence and guide upfront treatment intensification in this high-risk population.

PurposeThe dose‐averaged linear energy transfer (LETd) for intensity‐modulated proton therapy (IMPT) calculated by one‐dimensional (1D) analytical models deviates from more accurate but time‐consuming Monte Carlo (MC) simulations. We developed a fast hybrid three‐dimensional (3D) analytical LETd calculation that is more accurate than 1D analytical model.MethodsWe used the Geant4 MC code to generate 3D LETd distributions of monoenergetic proton beams in water for all energies and used a customized error function to fit the LETd lateral profiles at various depths to the MC simulation. The 3D LETd calculation kernel was a lookup table of these fitted coefficients, and LETd was determined directly from spot energies and voxel coordinates during analytical dose calculations. We validated our new method by comparing the calculated LETd distributions to MC results using 3D Gamma index analysis with 3%/2 mm criteria in 12 patient geometries. The significance of the improvement in Gamma index analysis passing rates over the 1D analytical model was determined using the Wilcoxon rank‐sum test.ResultsThe passing rate of 3D Gamma analysis comparing LETd distributions from the hybrid 3D method and the 1D method to MC simulations was significantly improved from 94.0% ± 2.5% to 98.0% ± 1.0% (P = 0.0003). The typical time to calculate dose and LETd simultaneously using an Intel Xeon E5‐2680 2.50 GHz workstation was approximately 2.5 min.ConclusionsOur new method significantly improved the LETd calculation accuracy compared to the 1D method while maintaining significantly shorter calculation time even comparing with the GPU‐based fast MC code.