Search

Purpose/Objectives: Retrospective analysis suggests that dose escalation to a biologically effective dose of more than 70 Gy may improve overall survival in patients with pancreatic ductal adenocarcinoma (PDAC), but such treatments in practice are limited by proximity of organs at risk (OARs). We hypothesized that CT-guided online adaptive radiotherapy (OART) can account for interfraction movement of OARs and allow for safe delivery of ablative doses. Materials/Methods: This is a single institution retrospective analysis of patients with PDAC treated with OART on the Ethos platform (Varian Medical Systems, a Siemens Healthineers Company, Palo Alto). All patients were treated to 40 Gy in 5 fractions. PTV overlapping with a 5 mm planning risk volume expansion on the stomach, duodenum and bowel received 25 Gy. Initial treatment plans were created conventionally. For each fraction, PTV and OAR volumes were recontoured with AI assistance after initial cone beam CT (CBCT). The adapted plan was calculated, underwent QA, and then compared to the scheduled plan. A second CBCT was obtained prior to delivery of the selected plan. Total treatment time (first CBCT to end of radiation delivery) and active physician time (first to second CBCT) were recorded. PTV_4000 V95 %, PTV_2500 V9 5%, and D0.03 cc to stomach, duodenum and bowel were reported for scheduled (S) and adapted (A) plans. CTCAEv5.0 toxicities were recorded. Statistical analysis was performed using a two-sided T test and α of 0.05. Results: 21 patients with unresectable or locally-recurrent PDAC were analyzed, with a total of 105 fractions. Average total time was 29 min and 16 s (16:36–49:40) and average active physician time was 19:41 min (9:25–39:34). All fractions were treated with adapted plans. 97 % of adapted plans met PTV_4000 V95.0 % >95.0 % coverage goal and 100 % of adapted plans met OAR dose constraints. Median follow up was 6.6 months. Only 1 patient experienced acute grade 3+ toxicity directly attributable to radiation. Only 1 patient experienced late grade 3+ toxicity directly attributable to radiation. Conclusions: Daily CT-based OART was associated with significantly reduced dose OARs while achieving superior PTV coverage. Given the relatively quick total treatment time, radiation delivery was generally well tolerated and easily incorporated into the clinic workflow. Our initial clinical experience demonstrates OART allows for safe dose escalation in the treatment of PDAC.

Purpose: The emerging online adaptive radiation therapy (OART) treatment strategy based on cone beam computed tomography allows for real-time replanning according to a patient's current anatomy. However, implementing this procedure requires a new approach across the patient's care path and monitoring of the “black box” adaptation process. This study identifies high-risk failure modes (FMs) associated with AI-driven OART and proposes an interdisciplinary workflow to mitigate potential medical errors from highly automated processes, enhance treatment efficiency, and reduce the burden on clinicians. Methods and Materials: An interdisciplinary working group was formed to identify safety concerns in each process step using failure mode and effects analysis (FMEA). Based on the FMEA results, the team designed standardized procedures and safety checklists to prevent errors and ensure successful task completion. The Risk Priority Numbers (RPNs) for the top twenty FMs were calculated before and after implementing the proposed workflow to evaluate its effectiveness. Three hundred seventy-four adaptive sessions across 5 treatment sites were performed, and each session was evaluated for treatment safety and FMEA assessment. Results: The OART workflow has 4 components, each with 4, 8, 13, and 4 sequentially executed tasks and safety checklists. Site-specific template preparation, which includes disease-specific physician directives and Intelligent Optimization Engine template testing, is one of the new procedures introduced. The interdisciplinary workflow significantly reduced the RPNs of the high-risk FMs, with an average decrease of 110 (maximum reduction of 305.5 and minimum reduction of 27.4). Conclusions: This study underscores the importance of addressing high-risk FMs associated with AI-driven OART and emphasizes the significance of safety measures in its implementation. By proposing a structured interdisciplinary workflow and integrated checklists, the study provides valuable insights into ensuring the safe and efficient delivery of OART while facilitating its effective integration into clinical practice.

Purpose: A scoring mechanism called the scorecard that objectively quantifies the dosimetric plan quality of pancreas stereotactic body radiation therapy treatment plans is introduced. Methods and Materials: A retrospective analysis of patients with pancreatic ductal adenocarcinoma receiving stereotactic body radiation therapy at our institution between November 2019 and November 2020 was performed. Ten patients were identified. All patients were treated to 36 Gy in 5 fractions, and organs at risk (OARs) were constrained based on Alliance A021501. The scorecard awarded points for OAR doses lower than those cited in Alliance A021501. A team of 3 treatment planners and 2 radiation oncologists, including a physician resident without plan optimization experience, discussed the relative importance of the goals of the treatment plan and added additional metrics for OARs and plan quality indexes to create a more rigorous scoring mechanism. The scorecard for this study consisted of 42 metrics, each with a unique piecewise linear scoring function which is summed to calculate the total score (maximum possible score of 365). The scorecard-guided plan, the planning and optimization for which were done exclusively by the physician resident with no prior plan optimization experience, was compared with the clinical plan, the planning and optimization for which were done by expert dosimetrists, using the Sign test. Results: Scorecard-guided plans had, on average, higher total scores than those clinically delivered for each patient, averaging 280.1 for plans clinically delivered and 311.7 for plans made using the scorecard (P = .003). Additionally, for most metrics, the average score of each metric across all 10 patients was higher for scorecard-guided plans than for clinically delivered plans. The scorecard guided the planner toward higher coverage, conformality, and OAR sparing. Conclusions: A scorecard tool can help clarify the goals of a treatment plan and provide an objective method for comparing the results of different plans. Our study suggests that a completely novice treatment planner can use a scorecard to create treatment plans with enhanced coverage, conformality, and improved OAR sparing, which may have significant effects on both tumor control and toxicity. These tools, including the scorecard used in this study, have been made freely available.

Purpose: Adaptive magnetic resonance imaging–guided linear accelerators (aMRI-LINACs) are an emerging technology with the potential to improve radiation treatment for cancer through improved visualization and adaptive treatment. Given the competing forces of the increased cost, knowledge, and staff required for aMRI-LINAC therapy, it is unpredictable how rapidly and for whom aMRI-LINAC therapy is being adopted. Therefore, given that aMRI-LINAC therapy was granted approval from the Food and Drug Administration in late 2017, we evaluated the National Cancer Database (NCDB) to obtain a nationwide view of early aMRI-LINAC adoption in 2018 to 2019. Methods and Materials: Forty-three disease sites were aggregated. A sample of patients who underwent intensity modulated radiation therapy (IMRT) from 2018 to 2019 were matched 1:1 by stage for the top 4 cancer sites. We then compared 9 characteristics of interest (age, % White [vs non-White], % residing in metro areas, % living in the greatest income quartile, % insured by Medicare, % uninsured or unknown insurance status, % treated at a comprehensive cancer center or academic center, % with no recorded Charlson-Deyo comorbidities, and % residing in an area with highest educational) between the 2 samples (aMRI-LINAC and matched IMRT). Results: Only 171 patients were recorded as having been treated with aMRI-LINACs in the NCDB in 2018 to 2019. Fifty-six percent were male, 89% White, and 54% enrolled in Medicare. The most common sites of disease treated were lung (33 patients), pancreas (30 patients), prostate (29 patients), and breast (23 patients). There were no significant differences between aMRI-LINAC- and IMRT-matched patients except that patients with lung or breast cancer treated with aMRI-LINAC were significantly more likely to be treated at a comprehensive cancer center or academic center. Conclusions: aMRI-LINAC adoption recorded in the NCDB after Food and Drug Administration approval was potentially underreported, slow, and attributed to academic sites of practice. Further longitudinal study will be needed to assess how practice patterns evolve with greater adoption.

Patients with pancreatic ductal adenocarcinoma (PDAC) have a grim prognosis despite complete surgical resection and intense systemic therapies. While immunotherapies have been beneficial with many different types of solid tumors, they have almost uniformly failed in the treatment of PDAC. Understanding how therapies affect the tumor immune microenvironment (TIME) can provide insights for the development of strategies to treat PDAC. We used quantitative multiplexed immunofluorescence (qmIF) quantitative spatial analysis (qSA), and immunogenomic (IG) analysis to analyze formalin-fixed paraffin embedded (FFPE) primary tumor specimens from 44 patients with PDAC including 18 treated with neoadjuvant chemoradiation (CRT) and 26 patients receiving no treatment (NT) and compared them with tissues from 40 treatment-naïve melanoma patients. We find that relative to NT tumors, CD3+ T cell infiltration was increased in CRT treated tumors (p = .0006), including increases in CD3+CD8+ cytotoxic T cells (CTLs, p = .0079), CD3+CD4+FOXP3− T helper cells (Th, p = .0010), and CD3+CD4+FOXP3+ regulatory T cells (Tregs, p = .0089) with no difference in CD68+ macrophages. IG analysis from micro-dissected tissues indicated overexpression of genes involved in antigen presentation, T cell activation, and inflammation in CRT treated tumors. Among treated patients, a higher ratio of Tregs to total T cells was associated with shorter survival time (p = .0121). Despite comparable levels of infiltrating T cells in CRT PDACs to melanoma, PDACs displayed distinct spatial profiles with less T cell clustering as defined by nearest neighbor analysis (p

Purpose: Intraoperative radiation therapy (IORT) as a form of accelerated partial breast irradiation (APBI) is controversial given the limited evidence to support its efficacy. However, it remains an attractive option for low-risk patients with ductal carcinoma in situ (DCIS), who derive a small absolute benefit in local control with standard whole breast irradiation (WBI). We examine how the American Society for Therapeutic Radiation Oncology (ASTRO) APBI consensus guidelines (CG) may be applied to the preoperative selection of patients with DCIS for IORT and determine treatment outcomes by CG group. Methods and Materials: We identified patients with biopsy-proven pure DCIS enrolled in an institutional prospective registry IORT database using the Zeiss Intrabeam® device between September 2013 and February 2017. Based on available preoperative clinicopathologic information, patients were deemed suitable, cautionary, or unsuitable for IORT according to the ASTRO CG. Change in CG group based on final pathologic diagnosis was determined, and additional therapy was recommended for unsuitable patients. Outcome in terms of ipsilateral breast tumor recurrence was determined. Results: A total of 61 DCIS lesions in 60 patients were treated with IORT. Preoperatively, 21 patients (35%) were suitable and 36 (59%) were cautionary. Four (6%) were unsuitable because of lesion size but declined WBI. Final pathologic diagnosis changed the CG grouping of 10 patients (16%) because of either occult high-grade disease in 2 (3%) or close/positive margins in 8 (13%). Ultimately 12 patients total were considered unsuitable, of whom 8 (66%) accepted additional WBI after IORT. At a median follow-up of 2.2 years, ipsilateral breast tumor recurrence was identified among 2 suitable, 1 cautionary, and no unsuitable patients. Conclusion: Further investigation is necessary to refine selection of patients with DCIS who may be optimally treated with IORT alone. High acceptance of additional therapy among unsuitable patients resulted in excellent outcomes. The use of biomarkers in addition to traditional clinical and pathologic factors may help to better select patients for IORT.

Comprehensive patient education is necessary for shared decision-making. While patient–provider conversations primarily drive patient education, patients also use published materials to enhance their understanding. In this investigation, we evaluated the readability of 2585 patient education materials published in high-impact medical journals from 1998 to 2018 and compared our findings to readability recommendations from national groups. For all materials, mean readability grade levels ranged from 11.2 to 13.8 by various metrics. Fifty-four (2.1%) materials met the American Medical Association recommendation of sixth grade reading level, and 215 (8.2%) met the National Institutes of Health recommendation of eighth grade level. When stratified by journal and material type, general medical education materials from Annals of Internal Medicine were the most readable ( P < .001), with 79.8% meeting the eighth grade level. Readability did not differ significantly over time. Efforts to standardize publication practice with the incorporation of readability evaluation during the review process may improve patients’ understanding of their disease processes and treatment options.

Background: Treatment for adult Philadelphia chromosome+ acute lymphoblastic leukemia includes using dasatinib, a tyrosine kinase inhibitor. Cutaneous squamous cell carcinomas and keratoacanthomas are common findings in patients treated with BRAF inhibitors of tyrosine kinases. No documentation of dasatinib inducing multiple keratoacanthomas, squamous cell carcinomas type during treatment of Philadelphia chromosome+ acute lymphoblastic leukemia is currently available. Case: A 77-year-old Caucasian male presented to the dermatology clinic two months after starting treatment with dasatinib for Philadelphia chromosome positive+ acute lymphoblastic leukemia. Biopsies confirmed the lesions on the arms, chest, legs and back as keratoacanthoma (KA) type of squamous cell carcinomas (SCCs). The cutaneous lesions were surgically removed and no new or recurrent lesions were detected since their initial rapid onset despite continued dasatinib therapy. Conclusion: This report of the rapid onset of keratoacanthoma type squamous cell carcinomas in a patient with Philadelphia chromosome+ acute lymphoblastic leukemia treated with dasatinib is presumed to be the first due to the rarity of adult Philadelphia chromosome+ acute lymphoblastic leukemia. This report documents another tyrosine kinase inhibitor that is associated with the eruption of keratoacanthomas, and adds to the literature regarding the regularity of this relatively common side effect, which may have treatment other than surgery if only a few lesions are present.

IntroductionMastectomy is the current standard of care for ipsilateral breast tumor recurrences after prior whole breast irradiation (WBI). We report our single-institution experience with breast-conserving surgery (BCS) followed by intraoperative radiotherapy (IORT) as an alternative to salvage mastectomy for new or recurrent breast cancers that develop in the setting of prior thoracic radiation.MethodsWe performed an IRB-approved retrospective review of patients treated with breast IORT between September 2013 and November 2016. We identified 12 patients who declined salvage mastectomy for their breast cancer after prior thoracic radiation. IORT was delivered using the Intrabeam™ device (Carl Zeiss, Germany). A dose of 20 Gy was prescribed to the lumpectomy cavity surface using 50 kV X-rays. We graded both acute and late treatment-related breast toxicities using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Local control, mastectomy-free survival, distant metastasis, and overall survival were determined.ResultsOur study included nine patients who developed a new or recurrent ipsilateral breast cancer after prior WBI for early-stage breast cancer, two patients with primary breast cancer after mantle-field radiation for Hodgkin’s lymphoma, and one patient with a synchronous stage III non-small cell lung cancer treated with definitive radiation to the ipsilateral lung and mediastinum. The median time from prior radiation to presentation was 18 years (range: 2 months to 46 years). All patients successfully underwent partial breast reirradiation with IORT and were able to preserve their breast. At a median follow-up of 14 months (4–25 months), there were no local or distant recurrences. There was a single non-cancer-related death. In the acute setting, we observed grade 1 toxicity in 58% (n = 7), grade 2 toxicity in 17% (n = 2), and no grade 3 or higher toxicity. In the late setting, at least 3 months after IORT, we observed grade 1 hyperpigmentation and/or fibrosis in 50% (n = 6), symptomatic seroma requiring drainage in 33% (n = 4). A single patient developed an abscess requiring hospitalization and intravenous antibiotic therapy.ConclusionBCS with IORT is a feasible salvage option for patients who present with localized breast cancer after prior thoracic radiation treatment. Continued follow-up of these patients is warranted given the incidence of delayed toxicity.