The Florida-California CaRE2 Health Equity Center advances its mission to eliminate cancer health disparities through a multifaceted approach that promotes innovation in cancer research. Funded by a Florida Department of Health Innovation Award to UF, the Florida-based CaRE2 research team is directly collaborating to implement this innovative project. One of the first activities was to develop materials designed to increase awareness of the RadTox test - a test using small amounts of blood to assess whether one’s tumor is responding to the current cancer treatment. Having educational materials in Spanish is essential for enabling Spanish-speaking individuals to consider participating in cancer-related research. Recognizing the importance of language access, CaRE2 bi-lingual team members translated materials into Spanish with CaRE2 tri-institutional investigators indirectly involved back-translating information to ensure accurate information transfer. The other key collaborative effort is information sharing to reach a broader community beyond clinical populations in collaboration with the industry partner, DiaCarta. The CaRE2 Health Equity Center’s is leveraging several resources to inform the community about this project, including our community contact registry, community events direct outreach, and collegial connections. With more than 1,408 adults enrolled from CaRE2’s communities, the contact registry enhances the capacity to inform more people about this test and involvement opportunities. Information also is shared at English and Spanish-speaking community events held in CaRE2’s immediate catchment areas. Additionally, CaRE2 investigators continue to leverage institutional, community, and industry partnerships, resulting in a network filled with varying perspectives and expertise partnering on this innovative project. Since October 2024, 1,116 CaRE2 contact registry members who are Florida residents and 20 people attending three community events received CaRE2 and IRB approved materials about this new test. So far 1,200 individuals have responded to seek and give additional information from the study REDCap site. CaRE2 investigators also partner to assist with sharing this information through mass media in local and statewide outlets, leading to additional opportunities to collaborate on this innovative research study. CaRE2 continues to leverage our capacity by involving our tri-institutional team and co-investigators not directly involved with this project to review materials for population-relevance and fidelity and suggest additional strategies to inform the broader population about this novel test. Given our continued success, CaRE2 recommends using multifaceted approaches to address cancer health disparities and create community-centered solutions that leverage existing human capacity and resources. Nazleen Del Rio, Brooke Hensel, Ileana Guzman, Sandra Suther, Fern J. Webb, Paul Okunieff, Diana Wilkie. Leveraging partnerships through a Florida Innovation Grant: A collaborative approach by the Care2 Health Equity Center [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4974.

We profile a technology transfer process between two partnering research institutions and the early outcomes. The Partnerships to Advance Cancer Health Equity (PACHE) program seeks to increase cancer research at HBCUs via collaborations with NCI-designated cancer centers. One such partnership, the Florida-California Cancer Research Education and Engagement (CaRE2) Health Equity Center, completed a series of studies with Patient Derived Xenograft (PDX) models to test novel compounds and delivery systems as treatment for pancreatic cancer. PDX models involve the implantation of human tumor tissues into immune incompetent mice for studies that mirror the human context. Few pancreatic cancer PDX models exist for Black patients, at high risk for pancreatic cancer incidence and mortality. For early studies, the cancer center Tissue Modeling & Drug Development Core (TMDDC) shipped the PDX models to the HBCU after implantation in the 25 mice needed for each study. To increase research capacity at the HBCU after these successful studies, the HBCU investigators, students, and a veterinarian were trained at the cancer center lab to implant the PDX tumor tissue in immune incompetent mice. The TMDDC shipped frozen PDX tumor tissue from a Black male patient to the HBCU, which the veterinarian implanted in 3 mice (Generation 1; Gen1). Tumor growth occurred in 1 of 3 mice (33%). The Gen1 tumor is now being expanded by implantation into 5 additional mice (Gen2) for future implantation in the 25 mice (Gen3) that are needed for the planned studies. The TMDDC shipped tissue from a Black female patient’s PDX tumor to the HBCU for replication of Gen1-3 procedures. In support of 2 CaRE2 projects, the 50 mice (25 from a Black male, 25 from a Black female) with the Gen3 PDX tumors will be used at the HBCU to (1) test effects of a modified gemcitabine compound delivered by nanotechnology, and (2) test a cfDNA biomarker of tumor response. Two postbaccalaureate trainees (1 at cancer center, 1 at HBCU) worked with the TMDDC at each institution as part of the technology transfer from the cancer center to the HBCU. The trainees’ important contribution to the technology transfer process involved documentation of the standard operating procedures for receiving the PDX tissues, implementing the expansion Gen1-3 steps for research at the HBCU, and building a well-annotated, living repository of pancreatic PDX tissues at the HBCU for ongoing cancer health disparities research studies and for training of the HBCU graduate students in the use of these technologies. This successful technology transfer enables cutting edge training for the HBCU students and facilitates their success as they enter the cancer health disparities research workforce. Furthermore, this project demonstrates the hallmark of a successful PACHE partnership, specifically the complementary collaboration among the CaRE2 Projects, Research Education Core, TMDDC, and Administrative Core to enable this technology transfer to the HBCU. Teni O. Akin-Olugbemi (equal contribution), De'llaijah Lucas (equal contribution), Romell Stone, Esther Frimpong, Raviteja Bulusu, Hernan Flores-Rozas, Edward Agyare, Tanise Jackson, Renee Reams, Seth Ablordeppey, Brooke Hensel, Jose Trevino, Steven J. Hughes, Han Song, Christina Gobin, Bodour Salhia, Paul Okunieff, Kristianna Fredenburg, John M. Allen, Bereket Mochona, Diana J. Wilkie. PDX technology transfer: NCI cancer center to HBCU [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 45.

Aim Availability of pancreatic ductal adenocarcinoma (PDAC) xenografts is a recognized medical research need. Patient-derived xenograft (PDX) mouse models are a valuable tool for studying PDAC, as they preserve the molecular, histological, and often stromal features of the primary tumor. However, access to PDX technologies is nationally limited, particularly at Historically Black Colleges and Universities (HBCUs). We aimed to establish a self-sustained PDX biorepository at Florida A&M University (FAMU), a HBCU, through a partnership with two NCI-designated cancer centers and the CaRE 2 Health Center. Methods FAMU faculty and trainees received training in xenograft implantation, tumor excision, cryopreservation, and biorepository management. The University of Florida shipped frozen tumor tissues from two PDAC patients to FAMU; one was implanted at FAMU and serially passaged across generations for experimental needs and to produce reproducible early generation PDX. Trainees gained experience in both laboratory and translational workflows and participated in documenting standard operating procedures for sustaining the biorepository. Results Engraftment success was observed across murine generations (G): G0 (66%, mean volume 196.5 mm 3 ), G1 (50%, 283.0 mm 3 ), G2 (60%, 321.4 mm 3 ), and G3 (80%, 416.3 mm 3 ). All viable tumors were cryopreserved and archived in FAMU’s newly established PDX biorepository. The repository now supports two active PDAC projects focused on drug response and biomarker discovery and can passage the second PDAC tumor. Conclusion Our successful collaboration and transfer of advanced cancer modeling technology to a HBCU strengthens FAMU’s institutional research capacity. The collaboration also offers translational cancer research training, preparing trainees for careers in oncology medicine and biomedical science.

Optimal triage biodosimetry would include risk stratification within minutes, and it would provide useful triage despite heterogeneous dosimetry, cytokine therapy, mixed radiation quality, race, and age. For regulatory approval, the U.S. Food and Drug Administration (FDA) Biodosimetry Guidance requires suitability for purpose and a validated species-independent mechanism. Circulating cell-free DNA (cfDNA) concentration assays may provide such triage information. To test this hypothesis, cfDNA concentrations were measured in unprocessed monkey plasma using a branched DNA (bDNA) technique with a laboratory developed test. The cfDNA levels, along with hematopoietic parameters, were measured over a 7-day period in Rhesus macaques receiving total body radiation doses ranging from 1 to 6.5 Gy. Low-dose irradiation (0-2 Gy) was easily distinguished from high-dose whole-body exposures (5.5 and 6.5 Gy). Fold changes in cfDNA in the monkey model were comparable to those measured in a bone marrow transplant patient receiving a supralethal radiation dose, suggesting that the lethal threshold of cfDNA concentrations may be similar across species. Average cfDNA levels were 50 +/- 40 ng/mL [+/- 1 standard deviation (SD)] pre-irradiation, 120 +/- 13 ng/mL at 1 Gy; 242 +/- 71 ng/mL at 2 Gy; 607 +/- 54 at 5.5 Gy; and 1585 +/- 351 at 6.5 Gy (+/- 1 SD). There was an exponential increase in cfDNA concentration with radiation dose. Comparison of the monkey model with the mouse model and the Guskova model, developed using Chernobyl responder data, further demonstrated correlation across species, supporting a similar mechanism of action. The test is available commercially in a Clinical Laboratory Improvement Amendments (CLIA) ready form in the U.S. and the European Union. The remaining challenges include developing methods for further simplification of specimen processing and assay evaluation, as well as more accurate calibration of the triage category with cfDNA concentration cutoffs. (C) 2024 by Radiation Research Society

Purpose: In breast cancer, improved treatment approaches that reduce injury to lung tissue and early diagnosis and intervention for lung toxicity are increasingly important in survivorship. The aims of this study are to (1) compare lung tissue radiographic changes in women treated with conventional photon radiation therapy and those treated with proton therapy (PT), (2) assess the volume of lung irradiated to 5 Gy (V5) and 20 Gy (V20) by treatment modality, and (3) quantify the effects of V5, V20, time, and smoking history on the severity of tissue radiographic changes. Patients and Methods: A prospective observational study of female breast cancer patients was conducted to monitor postradiation subclinical lung tissue radiographic changes. Repeated follow-up x-ray computed tomography scans were acquired through 2 years after treatment. In-house software was used to quantify an internally normalized measure of pulmonary tissue density change over time from the computed tomography scans, emphasizing the 6- and 12 -month time points. Results: Compared with photon therapy, PT was associated with significantly lower lung V5 and V20. Lung V20 (but not V5) correlated significantly with increased subclinical lung tissue radiographic changes 6 months after treatment, and neither correlated with lung effects at 12 months. Significant lung tissue density changes were present in photon therapy patients at 6 and 12 months but not in PT patients. Significant lung tissue density change persisted at 12 months in ever -smokers but not in never -smokers. Conclusion: Patients treated with PT had significantly lower radiation exposure to the lungs and less statistically significant tissue density change, suggesting decreased injury and/or improved recovery compared to photon therapy. These findings motivate additional studies in larger, randomized, and more diverse cohorts to further investigate the contributions of treatment modality and smoking regarding the short- and long-term radiographic effects of radiation on lung tissue.

524 Background: Alliance A011202 is evaluating the efficacy of axillary lymph node dissection (ALND) compared to regional nodal irradiation (RNI) for patients with cN1 breast cancer who receive neoadjuvant chemotherapy (NCTX) that becomes ycN0 but remains pN+. In the absence of its publication, level I guidance does not exist regarding the optimal axillary surgery for patients receiving NCTX. We sought to evaluate outcomes across two national contemporary clinical NCTX trials based on axillary and breast response to NCTX, particularly if more aggressive surgery was associated with more favorable outcomes. Methods: With IRB approval (IRB201802781), we obtained data from NCTX trials NSABP B40 and B41. B40 enrolled women with HER2- disease, and B41 enrolled those with HER2+ disease. RNI and axillary surgery were selected at physician discretion and not protocolled. Patients received sentinel lymph node biopsy (SLNB), SLNB+ALND (S+ALND), or ALND. We examined outcomes of locoregional recurrence (LRR), distant recurrence (DR), disease free survival (DFS), and overall survival (OS). Univariable and multivariable analyses of B40 and B41 data were performed to evaluate the associations of axillary surgery with the outcomes above, adjusting for age, tumor subtype, mastectomy or not, breast pathologic complete response (pCR), axillary pCR, tumor subtype, regional nodal irradiation, and grade. Kaplan-Meier estimation was used for OS and DFS, with cumulative incidence function for LRR and DR. Results: Median follow-up for studies B40 and B41 were 4.5 and 5.1 years, respectively, including 1154 and 504 patients for analysis. A total of 786 (47%) patients were cN+, and of those, 377 had a pcR (48%). 440 (27%), 505 (31%), and 663 (41%) patients had SLNB, S+ALND, and ALND respectively. 855 (52%) and 803 (48%) patients had mastectomy and lumpectomy, respectively. 783 (51%) received RNI. For the 518 ypN+ patients on B40, 7/25 (SLNB), 69/234 (S+ALND), and 107/259 (ALND) experienced an event. DFS at 5 years was 71%, 68%, and 56% for the SLNB, S+ALND, and ALND groups respectively with ypN+ on B40. For the 112 ypN+ patients on B41, 3/6, 15/43, and 27/63 experienced an event. DFS at 5 years was 50%, 64%, and 55% for the SLNB, S+ALND, and ALND groups, respectively, with ypN+ on B41. In multivariable analyses for the combined population of B40 and B41 for LRR, DR, DFS, and OS, SLNB was never associated with a higher chance of relapse or inferior survival (HR > 1) compared to S+ALND or ALND. Conclusions: Among women prospectively treated on national trials with NCTX and axillary surgery and RNI selected at physician discretion, receipt of SLNB alone was not associated with a higher likelihood of recurrence compared to S+ALND or ALND. Anticipated results of A011202 will provide level I guidance on axillary surgery for patients with cN1 disease converting to cN0 post-NCTX.

Introduction The Florida-California Cancer Research, Education, and Engagement (CaRE 2 ) Health Equity Center is a triad partnership committed to increasing institutional capacity for cancer disparity research, the diversity of the cancer workforce, and community empowerment. This article provides an overview of the structure, process innovations, and initial outcomes from the first 4 years of the CaRE 2 triad partnership. Methods CaRE 2 serves diverse populations in Florida and California using a “molecule to the community and back” model. We prioritize research on the complex intersection of biological, environmental, and social determinants health, working together with scientific and health disparities communities, sharing expertise across institutions, bidirectional training, and community outreach. Partnership progress and outcomes were assessed using mixed methods and four Program Steering Committee meetings. Results Research capacity was increased through development of a Living Repository of 81 cancer model systems from minority patients for novel cancer drug development. CaRE 2 funded 15 scientific projects resulting in 38 publications. Workforce diversity entailed supporting 94 cancer trainees (92 URM) and 34 ESIs (32 URM) who coauthored 313 CaRE 2 -related publications and received 48 grants. Community empowerment was promoted via outreaching to more than 3000 individuals, training 145 community cancer advocates (including 28 Community Scientist Advocates), and publishing 10 community reports. CaRE 2 members and trainees together have published 639 articles, received 61 grants, and 57 awards. Conclusion The CaRE 2 partnership has achieved its initial aims. Infrastructure for translational cancer research was expanded at one partner institution, and cancer disparities research was expanded at the two cancer centers.

The potential disparities in palliative care delivery for underrepresented minorities with breast cancer are not well known. We sought to determine whether race and ethnicity impact the receipt of palliative care for patients with metastatic breast cancer (MBC). We retrospectively reviewed the National Cancer Database for female patients diagnosed with stage IV breast cancer between 2010 and 2017 who received palliative care following diagnosis of MBC to assess the proportion of patients who received palliative care, including non–curative-intent local–regional or systemic therapy. Multivariable logistic regression analysis was performed to identify variables associated with receiving palliative care. 60,685 patients were diagnosed with de novo MBC. Of these, only 21.4

BACKGROUND Epidemiologic evidence reporting the role of frailty in survival among older adults with a prior cancer diagnosis is limited. METHODS A total of 2050 older adults (≥60 years old) surviving for at least 1 year after a cancer diagnosis and 9474 older adults without a cancer history from the National Health and Nutrition Examination Survey (1999‐2014) were included for analysis. The exposure variable, a 45‐item frailty index (FI), was categorized on the basis of validated cutoffs (FI ≤ 0.10 [fit], 0.10 < FI ≤ 0.21 [prefrail], and FI > 0.21 [frail]). All‐cause mortality was ascertained via the National Death Index. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) and 95% confidence interval (CIs) for the FI, and this was followed by restricted cubic splines depicting dose‐response curves. RESULTS For older cancer survivors, the mean age at the baseline was 72.6 years (SD, 7.1 years); 5.9% were fit, 38.2% were prefrail, and 55.9% were frail. Older adults without a cancer history were slightly younger (mean age, 70.0 years) and less frail (47.9% were frail). At each level of the FI, cancer survivors (1.9 per 100 person‐years for FI ≤ 0.10, 3.4 per 100 person‐years for 0.10 < FI ≤ 0.21, and 7.5 per 100 person‐years for FI > 0.21) had higher mortality than their cancer‐free counterparts (1.4 per 100 person‐years for FI ≤ 0.10, 2.4 per 100 person‐years for 0.10 < FI ≤ 0.21, and 5.4 per 100 person‐years for FI > 0.21). The multivariable model suggested a positive association between the FI and all‐cause mortality for survivors (aHR for FI > 0.21 vs FI ≤ 0.10, 2.80; 95% CI, 1.73‐4.53) and participants without a cancer history (aHR for FI > 0.21 vs FI ≤ 0.10, 2.75; 95% CI, 2.29‐3.32). Restricted cubic splines indicated that all‐cause mortality risk increased with the FI in a monotonic pattern. CONCLUSIONS Frailty is associated with a higher risk of death in older cancer survivors and the elderly without a cancer history.;

Purpose: There is a lack of level I evidence to guide radiation therapy recommendations for patients receiving neoadjuvant chemotherapy for breast cancer. We used 4 neoadjuvant chemotherapy trials to determine which patients benefit from regional nodal irradiation (RNI). Methods and Materials: We obtained data from the NSABP (National Surgical Adjuvant Breast and Bowel Project) B-18, B-27, B-40, and B-41 clinical trials. B-40 and B-41 allowed RNI at physician's discretion. We evaluated locoregional recurrence (LRR), distant recurrence, disease-free survival, and overall survival (OS). Kaplan-Meier, Peto-Peto, chi(2), Fisher exact, and Wilcoxon rank-sum tests were used for survival estimates and comparison. Results: Median follow-up for B-18, B-27, B-40, and B-41 was 13.7, 9.7, 4.5, and 5.1 years, respectively, including 742, 2254, 1154, and 504 patients for analysis. On multivariable analysis, factors significantly associated with RNI included tumor size, ypN status, and tumor subtype; Hispanic patients were less likely to receive RNI. Patients with ypN+HER2+ disease who received RNI had improved OS. B-40 patients with ypN+HR+ disease had improved LRR. On multivariable analysis for the B-40 and B-41 study population, RNI was not associated with significantly improved OS, disease-free survival, distant recurrence, or LRR. Conclusions: RNI was associated with a clinical benefit for patients with ypN+HER2+ and ypN+HR+ disease. RNI was not significantly associated with a clinically beneficial outcome for the entire cohort. Prospective phase 3 clinical trials are needed to establish guidelines for patients who should receive RNI after neoadjuvant treatment, and action is necessary to eliminate the disparity in care delivery shown for Hispanic women. (C) 2022 Elsevier Inc. All rights reserved.

Purpose/Objective(s)The Breast Cancer Lung Late Effects (BELLE) study prospectively enrolled patients with breast cancer who received adjuvant photon (XRT) or proton (PT) radiotherapy (RT) to evaluate potential early markers of induced lung injury, including pulmonary function tests (PFTs).Materials/MethodsPatients ≥18 years with AJCC 8th edition anatomic stage II-III or greater breast cancer were enrolled into the BELLE study between May 27, 2016 and May 26, 2020. All patients underwent clinical evaluation, computed tomography imaging, PFTs, and QoL questionnaires at baseline, 6 months, and 12 months relative to RT start. Fisher's exact tests and Kruskal-Wallis rank sum tests were used to compare the XRT and PT groups.ResultsA total of 37 patients were included in the final analysis (XRT, n=21; PT, n=16). Median age at diagnosis was 51 years (range, 31-76); 26 patients identified as white (70.3%), 8 as Black (21.6%), and 3 other (7.1%). Most patients did not have pre-existing respiratory disease (83.8%) or prior smoking history (62.2%), while 35.1% were former smokers and 1 was a current smoker (2.7%). The median BMI was 29.4 (range, 18.9-44.2). Most patients received chemotherapy (75.7%) and regional nodal irradiation (RNI; 78.4%). Median lung V20 was 25.3% (range, 5.6-39.7) and median lung V5 was 59.6% (range, 29.7-86.4). XRT patients had more pre-existing respiratory disease and were less likely to receive RNI (p=0.027 and p=0.006, respectively). There was no statistically significant difference between the XRT and PT cohorts for median lung V20 or V5. The median FEV1/FVC ratio at baseline, 6 months, and 12 months were not significantly different between the XRT and PT cohorts (80.2 % vs 81.5%, p=0.81; 79.3% vs 81.3%, p=0.95; and 80.6% vs 79.4% p>0.99, respectively). Similarly, the median FVC values at baseline, 6 months, and 12 months were not significantly different between the XRT and PT cohorts (3.4 L vs 3.1 L, p=0.76; 3.2 L vs 3.0 L, p=0.38; and 3.5 L vs 3.0 L, p=0.23, respectively). While the median DLCO at baseline was significantly worse for the PT cohort (91% vs 76%, p=0.005), there was no difference between cohorts at 6 and 12 months (79.0% vs 78.0%, p=0.38; 89.0% vs 84.0%, p=0.80, respectively). Four patients developed radiation pneumonitis (RP) within a year of RT including 3 with transient grade 1 (n=1 PT; n=2 XRT) and 1 with grade 3 (XRT).ConclusionDespite high variability among patients across all PFT parameters, the median FEV1/FVC ratio and FVC were stable over time and did not cross the threshold for concern of restrictive lung disease in either cohort. Although DLCO decreased at 6 months in the XRT cohort, both cohorts showed improvement at one year without diagnosis of restrictive lung disease. Utilizing PFTs as an early marker of RT-induced lung injury, neither patients treated with XRT nor PT exhibited sustained PFT abnormalities with 1 year of follow-up.

Breast cancer-related lymphedema (BCRL) is a source of postoperative morbidity for breast cancer survivors. Lymphatic microsurgical preventive healing approach (LYMPHA) is a technique used to prevent BCRL at the time of axillary lymph node dissection (ALND). We report the 5-year experience of a breast surgeon trained in LYMPHA and investigate the outcomes of patients who underwent LYMPHA following ALND for treatment of cT1–4N1–3M0 breast cancer. A retrospective review of patients with cT1–4N1–3M0 breast cancer was performed in patients who underwent ALND with and without LYMPHA. Diagnosis of BCRL was made by certified lymphedema therapists. Descriptive statistics and lymphedema surveillance data were analyzed using results of Fisher’s exact or Wilcoxon rank-sum tests. Logistic regression and propensity matching were performed to assess the reduction of BCRL occurrence following LYMPHA. In a 5-year period, 132 patients met inclusion criteria with 76 patients undergoing LYMPHA at the time of ALND and 56 patients undergoing ALND alone. Patients who underwent LYMPHA at the time of ALND were significantly less likely to develop BCRL than those who underwent ALND alone (p = 0.045). Risk factors associated with BCRL development were increased patient age (p = 0.007), body mass index (BMI) (p = 0.003), and, in patients undergoing LYMPHA, number of positive nodes (p = 0.026). LYMPHA may be successfully employed by breast surgeons trained in lymphatic–venous anastomosis at the time of ALND. While research efforts should continue to focus on prevention and surveillance of BCRL, LYMPHA remains an option to reduce BCRL and improve patient quality of life.

Tyrosine kinase inhibitors (TKIs), VEGF/VEGF receptor inhibitors (VEGFIs) and immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced cancers including non-small-cell lung cancer (NSCLC). This study aims to evaluate the utility of plasma cell-free DNA (cfDNA) as a prognostic biomarker and efficacy predictor of chemotherapy (CT) with or without these precision therapies in NSCLC patients. Peripheral cfDNA levels in 154 NSCLC patients were quantified before and after the first target cycle of chemotherapy. The correlations of cfDNA with tumor burden, clinical characteristics, progression-free survival (PFS)/disease-free survival (DFS), objective response ratio (ORR), and therapy regimens were analyzed respectively. Baseline cfDNA, but not post-chemotherapeutic cfDNA, positively correlates with tumor burden. Notably, cfDNA kinetics (cfDNA Ratio, the ratio of post-chemotherapeutic cfDNA to baseline cfDNA) well distinguished responsive individuals (CR/PR) from the non-responsive (PD/SD). Additionally, cfDNA Ratio was found negatively correlated with PFS in lung adenocarcinoma (LUAD), but not lung squamous-cell carcinoma (LUSC) which may be due to a limited number of LUSC patients in this cohort. LUAD patients with low cfDNA Ratio have prolonged PFS and improved ORR, compared to those with high cfDNA Ratio. When stratified by therapy regimen, the predictive value of cfDNA Ratio is significant in patients with chemotherapy plus VEGFIs, while more patients need be included to validate the value of cfDNA Ratio in other regimens. Thus, the kinetics of plasma cfDNA during chemotherapy may function as a prognostic biomarker and efficacy predictor for NSCLC patients.

Objectives: Increasing the percentage of academic faculty who are female and/or an under-represented minority (URM) is a goal in radiation oncology. When studying diversity changes in our University Radiation Oncology Department, we found that increases in resident diversity preceded changes in faculty diversity in every major category. To illustrate these findings, we plotted resident versus faculty diversity each year over the 52-year history of our program. Materials and Methods: Plots were generated of the percent of residents versus faculty in our program each year between 1967 and 2020 in the following categories: female, URM, and people of color. Results: By 1995, substantial levels of diversity were present among both residents and faculty with approximate median annual values between 1995 and 2020 of 30% female for both residents and faculty, 15% URM for both residents and faculty, and 30% persons of color for residents and 15% for faculty. In all analyses, increase in resident diversity preceded an increase in faculty diversity and, in the great majority of years, resident diversity was greater than faculty diversity. Conclusion: Our experience suggests that it may be easier to increase resident than faculty diversity and that increases in resident diversity may facilitate increasing faculty diversity.

Multiple competing normal tissue complication probability (NTCP) models have been proposed for predicting symptomatic radiation-induced lung injury in human. In this paper we tested the efficacy of four common NTCP models applied quantitatively to sub-clinical X-ray computed tomography (CT)-density changes in the lung following radiotherapy. Radiotherapy planning datasets and follow-up chest CTs were obtained in eight patients treated for targets within the lung or hilar region. Image pixel-wise radiation dose exposure versus change in observable CT Hounsfield units was recorded for early (2–5 months) and late (6–9 months) time-points. Four NTCP models, Lyman, Logistic, Weibull and Poisson, were fit to the population data. The quality of fits was assessed by five statistical criteria. All four models fit the data significantly (p < 0.05) well at early, late and cumulative time points. The Lyman model fitted best for early effects while the Weibull Model fitted best for late effects. No significant difference was found between the fits of the models and with respect to parameters D 50 and γ 50 . The D 50 estimates were more robust than γ 50 to image registration error. For analyzing population-based sub-clinical CT pixel intensity-based dose response, all four models performed well.

Level I evidence demonstrates that regional nodal irradiation (RNI) improves outcomes and decreases distant recurrence (DR) in women with high-risk node-negative (cN0) and -positive (cN+) breast cancer treated with adjuvant chemotherapy (CTX). Evidence to refine the indication of RNI in the neoadjuvant CTX (NCTX) setting awaits completion of NSABP-51, which enrolls cN+ women with axillary pathologic complete response (apCR). We hypothesized that lack of breast pCR (bpCR) portends worse outcome and identifies a high-risk population, and should not be used without level I evidence to justify foregoing radiation on apCR status alone. We obtained data from NCTX trials NSABP B18, B27, B40, and B41. B18 and B27 did not include HER2-directed therapy, B40 enrolled women with HER2- disease, and B41 enrolled those with HER2+ disease. B40 and B41 allowed RNI at the physicians' discretion. We evaluated locoregional recurrence (LRR), DR, disease-free survival (DFS), and overall survival (OS) among 4 strata of pCR: ypT0/ypN0; ypT+/ypN0; ypT0/ypN+; ypT+/ypN+. Kaplan-Meier estimated OS and DFS and cumulative incidence plots estimated LRR and DR. A log-rank or Peto-Peto (when proportional hazards assumption did not hold) test was used for survival comparison. Gray's test was used for cumulative incidence function (CIF) comparison. A stepdown Bonferroni adjustment was used for multiple comparison adjustment. Chi-squared or Fisher exact tests were used to compare categorical variables and Wilcoxson rank-sum test for continuous variables. Median follow-up for B18, B27, B40, and B41 was 13.7, 9.7, 4.5, and 5.1 years, respectively, and included 742, 2254, 1154, and 504 women for analysis. cN+ women with apCR in B18 and B27 (combined) with bpCR had better OS than those without bpCR (p = 0.02) with 5-year OS rates (95% CI) of 90% (85%, 96%) vs 80% (75%, 86%). For B40 and B41, RNI was discretionary but administered more commonly to those with larger tumors (median [IQR]: 5.0 [3] vs 4.0 [3] cm, p<0.01) and those without bpCR (68% vs 58%, p<0.01) or apCR (54% vs 26%, p<0.01). cN+ women in B40 and B41 (combined) with apCR with bpCR had better OS than those without bpCR (p = 0.008) with 5-year OS rates (95% CI) of 96% (93% - 99%) vs 86% (80% - 93%), and reduced CIF of DR (p = 0.02) with 5-year CIF rates (95% CI) of 8% (5% - 12%) vs 14% (9% - 21%). In women with cN+ypN0 on B-18 and B-27 for which no HER2-directed therapy was offered, residual breast disease was associated with worse OS than bpCR. While in the modern NCTX trials cN+ women with higher risk disease received RNI with HER2-directed therapy, ypN0 women with residual breast disease continue to demonstrate worse survival and DR than women with bpCR, despite apCR. In the absence of level I data, we advise caution in omitting RNI off trial in women with cN+ ypN0 disease with residual breast disease.