Mary Bird Perkins Cancer Center

Abstract Multi‐dimensional detector arrays have been adopted in radiation therapy clinics by medical physicists for various types of measurements. Typical applications of such devices include plan quality assurance (QA) measurements, periodic QA measurements for constancy checks of beam flatness and symmetry, as well as dose and beam quality constancy checks for linear accelerators (linacs). The multi‐dimensional arrays vary in terms of their size, detector types, and usage. This report provides guidelines to the users on initial and ongoing performance assessments that should be performed to ensure proper functionality of ion chamber and diode multi‐detector arrays that are positioned on the linac couch or gantry mounts and used for patient‐specific quality assurance (PSQA) and machine QA. The characteristics of the most common detector arrays are provided in this report along with their intended use. After reading this report, the user should understand how to assess the detector array's performance and proceed with its use. The report describes the most relevant array parameters for testing and offers detailed test instructions and frequencies. Test results from the TG members and other clinical users are presented in a table. The tolerances for the parameters with some statistics are recommended based on those test results and other publications. This report is not intended to provide a comprehensive review of linac quality assurance procedures or patient‐specific Intensity Modulated Radiation Therapy (IMRT) QA.

A. J. Olszewski, K. Aizawa, Y. H. Karimi, D. Sano, S. Y. Oh, A. Neuhof, D. Bouyoucef-Cherchalli, J. Wang, A. SyBing, M. Rodriguez, and V. T. G. Lin equally contributing author. Introduction: Although advances in adaptive, T cell-engaging immunotherapy have improved the prognosis of patients (pts) with relapsed/refractory diffuse large B cell lymphoma (R/R DLBCL), activation of innate immunity is a novel therapeutic approach. Maplirpacept is a recombinant SIRPα-blocking fusion protein designed to enhance phagocytosis and antitumor activity by disrupting inhibitory CD47-SIRPα signaling and has shown preliminary efficacy against DLBCL. This Phase 1b/2 study (NCT05626322) aimed to evaluate the safety, tolerability, and clinical benefits of the maplirpacept, tafasitamab, and lenalidomide combination in R/R DLBCL pts who are ineligible for high-dose chemotherapy (HDC) and/or autologous stem cell transplantation (ASCT). Results from the Ph1b trial are presented. Methods: Pts were aged ≥ 18 years with histologically confirmed R/R DLBCL, had ≥ 1 line of prior systemic treatment (tx; including an anti-CD20 containing regimen), and were not candidates for HDC/ASCT. Pts received maplirpacept IV 4 mg/kg, 10 mg/kg or 18 mg/kg + tafasitamab IV 12 mg/kg + lenalidomide 25 mg orally. For Ph1b, the primary objective was evaluation of dose-limiting toxicities (DLTs) during the 28-day DLT observation period; secondary objectives were safety, antitumor activity, pharmacokinetics (PK) and immunogenicity. Results: At data cut-off (December 13, 2024), 6 pts were evaluable for safety, and 5 were evaluable for DLTs. Median age was 58.5 years (range 40–81), 3 pts were male, 2 had bulky disease (longest diameter ≥ 7.5 cm), 3 had > 1 prior lymphoma-directed tx. No pts experienced DLT. Tx-emergent adverse events (TEAEs) of grade (G) ≥ 3 experienced by ≥ 2 pts were neutropenia (4 pts), thrombocytopenia, sepsis, and urinary tract infection (2 pts each). Maplirpacept tx-related AEs (TRAEs) G ≥ 3 were neutropenia (2 pts), thrombocytopenia and anemia (1 pt each). Three pts experienced serious AE (SAE); sepsis was the only SAE reported in > 1 pt. One TR-SAE (leukemia) resulted in death, unrelated to maplirpacept; a second death (cardiac arrest) occurred > 28 days after the last tx dose and was deemed unrelated to study tx. No TEAEs led to study tx discontinuation. TRAEs leading to dose interruption of maplirpacept were reported in 2 pts. Objective responses were observed in 4 pts, and all were complete responses; 1 pt had stable disease. The median duration of response was 9.6 mos; median progression free survival was 11.4 mos; median duration of tx with maplirpacept was 37 wks. Maplirpacept PK concentrations were consistent with previous datasets. No pts experienced anti-drug antibodies. Conclusions: Addition of maplirpacept to tafasitamab and lenalidomide showed clinical activity and tolerable safety profile in pts with R/R DLBCL. Although this trial was discontinued due to enrollment challenges, further development of maplirpacept for R/R DLBCL continues in NCT05896163. A genAI tool (Feb25; Pfizer; GPT-4o) developed draft 1; authors assume content responsibility. Research funding declaration: The study is sponsored by Pfizer. Medical writing support was provided by Haniya Javaid, BSc, of Engage Scientific Solutions, and funded by Pfizer. A Pfizer proprietary AI tool was used with author review to develop the first draft (February 2025); authors take full responsibility for the content. Keyword: immunotherapy Potential sources of conflict of interest: A. J. Olszewski Consultant or advisory role: Genmab, Blue Cross and Blue Shield of Rhode Island, Schrodinger, ADC Therapeutics, BeiGene, Bristol-Myers Squibb Other remuneration: Research Funding: Genentech/Roche, Precision Biosciences, Genmab, Artiva, Pfizer, Kymera Y. H. Karimi Consultant or advisory role: Yes Honoraria: Yes Other remuneration: Speakers Bureau, and Research Funding A. Neuhof Employment or leadership position: Pfizer employee Stock ownership: Yes D. Bouyoucef-Cherchalli Employment or leadership position: Pfizer employee Stock ownership: Yes J. Wang Employment or leadership position: Pfizer employee A. SyBing Employment or leadership position: Pfizer employee M. Rodriguez Employment or leadership position: Pfizer employee Stock ownership: Yes

Backgroundand Purpose:This study aimed to develop and evaluate an efficient method to automatically segment T1- and T2-weighted brain magnetic resonance imaging (MRI) images. We specifically compared the segmentation performance of individual convolutional neural network (CNN) models against an ensemble approach to advance the accuracy of MRI-guided radiotherapy (RT) planning.Materials and Methods. The evaluation was conducted on a private clinical dataset and a publicly available dataset (HaN-Seg). Anonymized MRI data from 55 brain cancer patients, including T1-weighted, T1-weighted with contrast, and T2-weighted images, were used in the clinical dataset. We employed an EDL strategy that integrated five independently trained 2D neural networks, each tailored for precise segmentation of tumors and organs at risk (OARs) in the MRI scans. Class probabilities were obtained by averaging the final layer activations (Softmax outputs) from the five networks using a weighted-average method, which were then converted into discrete labels. Segmentation performance was evaluated using the Dice similarity coefficient (DSC) and Hausdorff distance at 95% (HD95). The EDL model was also tested on the HaN-Seg public dataset for comparison.Results. The EDL model demonstrated superior segmentation performance on both the clinical and public datasets. For the clinical dataset, the ensemble approach achieved an average DSC of 0.7 ± 0.2 and HD95 of 4.5 ± 2.5 mm across all segmentations, significantly outperforming individual networks which yielded DSC values ≤0.6 and HD95 values ≥14 mm. Similar improvements were observed in the HaN-Seg public dataset.Conclusions. Our study shows that the EDL model consistently outperforms individual CNN networks in both clinical and public datasets, demonstrating the potential of ensemble learning to enhance segmentation accuracy. These findings underscore the value of the EDL approach for clinical applications, particularly in MRI-guided RT planning.

The longitudinal experience of patients is critical to the development of interventions to identify and reduce financial hardship. To evaluate financial hardship over 12 months in patients with newly diagnosed colorectal cancer (CRC) undergoing curative-intent therapy. This prospective, longitudinal cohort study was conducted between May 2018 and July 2020, with time points over 12 months. Participants included patients at National Cance Institute Community Oncology Research Program sites. Eligibility criteria included age at least 18 years, newly diagnosed stage I to III CRC, not started chemotherapy and/or radiation, treated with curative intent, and able to speak English. Data were analyzed from December 2022 through April 2023. The primary end point was financial hardship, measured using the Comprehensive Score for Financial Toxicity (COST), which assesses the psychological domain of financial hardship (range, 0-44; higher score indicates better financial well-being). Participants completed 30-minute surveys (online or paper) at baseline and 3, 6, and 12 months. A total of 450 participants (mean [SD] age, 61.0 [12.0] years; 240 [53.3%] male) completed the baseline survey; 33 participants (7.3%) were Black and 379 participants (84.2%) were White, and 14 participants (3.1%) identified as Hispanic or Latino and 424 participants (94.2%) identified as neither Hispanic nor Latino. There were 192 participants (42.7%) with an annual household income of $60 000 or greater. There was an improvement in financial hardship from diagnosis to 12 months of 0.3 (95% CI, 0.2 to 0.3) points per month (P < .001). Patients with better quality of life and greater self-efficacy had less financial toxicity. Each 1-unit increase in Functional Assessment of Cancer Therapy-General (rapid version) score was associated with an increase of 0.7 (95% CI, 0.5 to 0.9) points in COST score (P < .001); each 1-unit increase in self-efficacy associated with an increase of 0.6 (95% CI, 0.2 to 1.0) points in COST score (P = .006). Patients who lived in areas with lower neighborhood socioeconomic status had greater financial toxicity. Neighborhood deprivation index was associated with a decrease of 0.3 (95% CI, -0.5 to -0.1) points in COST score (P = .009). These findings suggest that interventions for financial toxicity in cancer care should focus on counseling to improve self-efficacy and mitigate financial worry and screening for these interventions should include patients at higher risk of financial burden.

Late cardiac toxicity is a potentially lethal complication of cancer therapy, yet the pathogenic mechanism remains largely unknown, and few treatment options exist. Here we report DNA-damaging agents such as radiation and anthracycline chemotherapies inducing delayed cardiac inflammation following therapy due to activation of cGAS- and STING-dependent type I interferon signaling. Genetic ablation of cGAS-STING signaling in mice inhibits DNA damage-induced cardiac inflammation, rescues late cardiac functional decline, and prevents death from cardiac events. Treatment with a STING antagonist suppresses cardiac interferon signaling following DNA-damaging therapies and effectively mitigates cardiac toxicity. These results identify a therapeutically targetable, pathogenic mechanism for one of the most vexing treatment-related toxicities in cancer survivors.

Objective. Patients who receive proton beam therapy are exposed to unwanted stray neutrons. Stray radiations increase the risk of late effects in normal tissues, such as second cancers and cataracts, and may cause implanted devices such as pacemakers to malfunction. Compared to therapeutic beams, little attention has been paid to modeling stray neutron exposures. In the past decade, substantial progress was made to develop semiempirical models of stray neutron dose equivalent, but models to routinely calculate neutron absorbed dose and kerma are still lacking. The objective of this work was to develop a new physics based analytical model to calculate neutron spectral fluence, kerma, and absorbed dose in a water phantom. Approach. We developed the model using dosimetric data from Monte Carlo simulations and neutron kerma coefficients from the literature. The model explicitly considers the production, divergence, scattering, and attenuation of neutrons. Neutron production was modeled for 120–250 MeV proton beams impinging on a variety of materials. Fluence, kerma and dose calculations were performed in a 30 × 180 × 44 cm3 phantom at points up to 43 cm in depth and 80 cm laterally. Main Results. Predictions of the analytical model agreed reasonably with corresponding values from Monte Carlo simulations, with a mean difference in average energy deposited of 20%, average kerma coefficient of 21%, and absorbed dose to water of 49%. Significance. The analytical model is simple to implement and use, requires less configuration data that previously reported models, and is computationally fast. This model appears potentially suitable for integration in treatment planning system, which would enable risk calculations in prospective and retrospective cases, providing a powerful tool for epidemiological studies and clinical trials.

e16272 Background: Localized pancreatic adenocarcinoma (PDAC) includes resectable, borderline resectable, and locally advanced cancers. In potentially resectable pancreatic cancer, the role of neoadjuvant therapy is evolving and guidelines from expert groups are conflicting. Although limited, randomized trials have shown that neoadjuvant chemotherapy (NCT) can provide survival benefits in patients with localized PDAC. Studies have compared FOLFIRINOX (FFN) with Gemcitabine plus nab-Paclitaxel (G-nP) as first-line NCT for PDAC, but no consensus has been established. As a result, we performed an updated meta-analysis to assess the difference in overall survival between two chemotherapy regimens. Methods: PubMed, EMBASE, and Cochrane databases were systematically reviewed from inception to December 2021 to identify studies comparing FFN with G-nP in the neoadjuvant settings for localized PDAC. The primary outcome was the overall survival of patients and secondary endpoints were RECIST partial or complete response, resection rate and R0 resection. The effectiveness of FOLFIRINOX and G-nP in terms of overall survival in patients with localized PDAC was compared using hazard ratios (HR) and 95% confidence intervals (CI). In addition, the heterogeneity of the studies was evaluated using Cochrane's Q test of heterogeneity and the I2 statistic. Pooled analysis of HR was performed with Stata 17 METAN using random effect model and P of 0.05 was considered statistically significant. Results: We identified 10 studies that met our inclusion criteria. All studies were retrospective and 5 of them were carried out in the United States. The total numbers of patients preoperatively treated with FOLFIRINOX versus G-nP were 988 and 719, respectively. In this meta-analysis compared to G-nP, neoadjuvant FFN was associated with significant prolonged overall survival (HR = 0.72, 95% CI: 0.63–0.82, P &lt; 0.001). FFN group had a significantly higher RECIST partial and complete response rate than the G-nP group, with an OR of 1.65 (95 % CI 1.02-2.68, p = 0.04). For resection rate and R0 resection, FFN group had ORs of 1.65 (95% CI 0.94-2.90, p = 0.08) and 1.91 (95% CI 0.95-3.81, P = 0.07) respectively, both outcomes were statistically insignificant. Conclusions: Results of our meta-analysis show that for localized pancreatic cancer, neoadjuvant treatment with FFN was associated with better survival than G-nP. One limitation to our current study was that all included studies were designed retrospectively. Further randomized clinical trials are needed to explore the ideal neoadjuvant chemotherapy for PDAC.[Table: see text]