Citations

Abstract Artificial intelligence (AI) models applied to mammography have been shown to improve breast cancer (BC) detection and risk estimation. The Transpara AI detection system has been associated with short and longer-term risk of invasive BC. Whether Transpara can identify changes in the breast associated with tamoxifen (TAM) and aromatase inhibitor (AIs) treatment is unknown. We compare changes in the Transpara malignancy score in the unaffected breast of BC cases using TAM or AIs to those of untreated women without cancer. Cases and controls were sampled from the Mayo Clinic Rochester Breast Screening Practice. Eligible cases were women with breast cancer treated with TAM and/or AIs for at least 8 months who had full field digital (FFDM) mammograms within two years prior to start of treatment (pretreatment mammogram). Controls did not have BC, were not using TAM, AIs, or postmenopausal hormones, and had at least two FFDM screening mammograms. Transpara scores (1-10) were calculated for the contralateral breast in cases and a randomly selected side for controls. Two controls were matched to each case on menopausal status at both mammograms, time between mammograms (< 6 months) and baseline Transpara score (±2 units). Conditional logistic regression was used to assess the association of treatment (case (TAM/AIs) vs. control) with change in Transpara score between the pretreatment mammogram and the mammogram taken closest to 13 months later. Change was classified as having a decrease in Transpara score between the two mammograms vs. no change or an increase. Models were adjusted for age and Transpara score at pretreatment mammogram, and time between the two mammograms. We performed analyses on all women combined and stratified by time on treatment, menopausal status, and treatment type (TAM vs. AIs). A total of 134 cases were identified, with 53 on TAM (21 premenopausal and 32 postmenopausal) and 81 on AIs (postmenopausal); 268 controls were matched to the cases. Characteristics of the study population are summarized (Table). Most case mammograms were obtained within six months prior to treatment start [median 2.63 months (interquartile range (IQR), 1.62, 5.72)] and median time on TAM/AIs was 10.9 months (IQR, 8.03, 16.6) at time of second mammogram. The median absolute change in Transpara score between the two mammograms was similar in cases [0 (IQR, -2, 1)] vs. controls [0 (IQR, -1.25, 1)]; 40.3% of cases and 39.2% of controls had any decrease. Conditional logistic models found no evidence for an association between TAM/AIs and decrease in Transpara score [odds ratio (OR) = 1.07; 95% confidence interval (CI), 0.65, 1.78]. When stratified by median time on treatment (10.9 months), there was suggestion of a stronger association for those on treatment for a longer duration (OR = 1.21; 95% CI, 0.61, 2.40 for >10.9 months vs. OR = 0.96; 95% CI, 0.43, 2.13 for < 10.9 months) but these results were not statistically significant. Similarly, odds ratios were stronger in postmenopausal (OR = 1.18; 95% CI, 0.67, 2.07) compared to premenopausal (OR = 0.91; 95% CI, 0.24, 3.45) women, and for AIs (OR = 1.21, 95% CI, 0.64, 2.29) vs. TAM (OR = 0.93; 95% CI, 0.39, 2.22) but none of these results reached statistical significance. In summary, we found no association between treatment with TAM/AIs and change in Transpara score. However, our study had limited power. Also, longer time on treatment as well as investigation of AI-based scores trained directly to assess BC risk may be necessary to identify relevant changes. Citation Format: Yvonne Wang, Christopher Scott, Matthew Jensen, Dan Hursh, Kathleen Brandt, Aaron Norman, Fang Fang Wu, Stacey Winham, Karla Kerlikowske, Celine Vachon. Changes in an artificial intelligence model score for breast cancer detection (Transpara) with tamoxifen and aromatase inhibitor treatment [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-09-04.

Abstract Background: Plant-based diet is recommended by multiple cancer survivorship guidelines and was reported to be associated with better survival among patients with non-metastatic colorectal cancer. However, the association between plant-based diet and survival in metastatic colorectal cancer is unknown. Methods: Using an NCI-sponsored systemic therapy trial conducted from 2005 to 2015 (CALGB/SWOG 80405), we included 1,279 patients who completed validated food frequency questionnaires at the initiation of treatment for metastatic colorectal cancer. To emphasize different impact of healthful plant foods, less healthful plant foods, and animal foods, we used 18 food groups to calculate three plant-based indexes (ranges: 18-90 points): overall plant-based diet index (PDI), healthful plant-based diet index (hPDI), and unhealthful plant-based diet index (uPDI). The primary outcome was overall survival, and the secondary outcome was progression-free survival. We estimated the associations of three indexes (quintiles) with survival using multivariable Cox proportional hazards regression. Results: Of 1,279 patients (median follow-up: 6.1 years), mean (SD) age at diagnosis was 58.8 (11.7) years, 57.4% were men, 85.6% were White, and 1,096 deaths and 1,201 events of progression occurred. The mean (SD) points of three indexes were 51.2 (6.3) for PDI, 51.1 (6.7) for hPDI, and 51.2 (8.1) for uPDI. Compared to the lowest quintile (Q1), the highest quintile (Q5) of PDI was significantly associated with better overall survival (HR: 0.80 [0.65-0.99]) and progression-free survival (HR: 0.80 [0.65-0.98]). Similar findings were observed for hPDI, but uPDI was not significantly associated with worse survival. Conclusions: Our findings suggest that plant-based diet is associated with better survival among patients with metastatic colorectal cancer, and plant-based dietary interventions should be considered for future trials in metastatic colorectal cancer. Table. Adjusted Associations of Plant-Based Diet with Survival in Metastatic Colorectal Cancer Q1 Q2 Q3 Q4 Q5 P for trend Overall Survival PDI 1.00 0.96 (0.80-1.16) 0.93 (0.77-1.14) 0.82 (0.67-0.99) 0.80 (0.65-0.99) 0.01 hPDI 1.00 0.95 (0.78-1.14) 0.94 (0.77-1.15) 0.86 (0.70-1.04) 0.84 (0.68-1.03) 0.07 uPDI 1.00 1.14 (0.95-1.39) 1.07 (0.87-1.31) 1.18 (0.97-1.45) 1.17 (0.95-1.45) 0.15 Progression-free Survival PDI 1.00 0.84 (0.70-1.01) 0.94 (0.78-1.14) 0.93 (0.77-1.12) 0.80 (0.65-0.98) 0.10 hPDI 1.00 0.86 (0.72-1.03) 0.83 (0.69-1.01) 0.80 (0.67-0.97) 0.80 (0.66-0.97) 0.03 uPDI 1.00 1.12 (0.94-1.34) 1.11 (0.91-1.34) 1.10 (0.91-1.34) 1.15 (0.94-1.41) 0.23 Citation Format: En Cheng, Fang-Shu Ou, Chao Ma, Alan P. Venook, Heinz-Josef Lenz, Eileen M. O’Reilly, Peter T. Campbell, Chaoyuan Kuang, Bette J. Caan, Kimmie Ng, Jeffrey A. Meyerhardt. Plant-based diet and survival among patients with metastatic colorectal cancer: Findings from CALGB/SWOG 80405 (Alliance) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2200.

PURPOSE The phase III Cancer and Leukemia Group B (CALGB)/SWOG 80405 trial found no difference in overall survival (OS) in patients with metastatic colorectal cancer receiving first-line chemotherapy in combination with either bevacizumab or cetuximab. We investigated the potential prognostic and predictive value of HER2 amplification and gene expression using next-generation sequencing (NGS) and NanoString data. PATIENTS AND METHODS Primary tumor DNA from 559 patients was profiled for HER2 amplification by NGS (FoundationOne CDx). Tumor tissue from 925 patients was tested for NanoString gene expression using an 800-gene panel. OS and progression-free survival (PFS) were the time-to-event end points. RESULTS High HER2 expression (dichotomized at median) was associated with longer PFS (11.6 v 10 months, P = .012) and OS (32 v 25.3 months, P = .033), independent of treatment. An OS benefit for cetuximab versus bevacizumab was observed in the high HER2 expression group ( P = .02), whereas a worse PFS for cetuximab was seen in the low-expression group ( P = .019). When modeled as a continuous variable, increased HER2 expression was associated with longer OS (hazard ratio [HR], 0.83 [95% CI, 0.75 to 0.93]; adjusted P = .0007) and PFS (HR, 0.82 [95% CI, 0.74 to 0.91]; adjusted P = .0002), reaching a plateau effect after the median. In patients with HER2 expression lower than median, treatment with cetuximab was associated with worse PFS (HR, 1.38 [95% CI, 1.12 to 1.71]; adjusted P = .0027) and OS (HR, 1.28 [95% CI, 1.02 to 1.59]; adjusted P = .03) compared with that with bevacizumab. A significant interaction between HER2 expression and the treatment arm was observed for OS ( P intx = .017), PFS ( P intx = .048), and objective response rate ( P intx = .001). CONCLUSION HER2 gene expression was prognostic and predictive in CALGB/SWOG 80405. HER2 tumor expression may inform treatment selection for patients with low HER2 favoring bevacizumab- versus cetuximab-based therapies.

Abstract Background: Streptococcus pneumoniae is the most common bacterial cause of community acquired pneumonia and the acute respiratory distress syndrome (ARDS). Some clinical trials have demonstrated a beneficial effect of corticosteroid therapy in community acquired pneumonia, COVID-19, and ARDS, but the mechanisms of this benefit remain unclear. The objective of this study was to investigate the effects of corticosteroids on the pulmonary biology of pneumococcal pneumonia in an observational cohort of mechanically ventilated patients and in a mouse model of bacterial pneumonia with Streptococcus pneumoniae. Methods: We studied gene expression with lower respiratory tract transcriptomes from a cohort of mechanically ventilated patients and in mice. We also carried out comprehensive physiologic, biochemical, and histological analyses in mice to identify the mechanisms of lung injury in Streptococcus pneumoniae with and without adjunctive steroid therapy. Results: Transcriptomic analysis identified pleiotropic effects of steroid therapy on the lower respiratory tract in critically ill patients with pneumococcal pneumonia, findings that were reproducible in mice. In mice with pneumonia, dexamethasone in combination with ceftriaxone reduced (1) pulmonary edema formation, (2) alveolar protein permeability, (3) proinflammatory cytokine release, (4) histopathologic lung injury score, and (5) hypoxemia but did not increase bacterial burden. Conclusions: The gene expression studies in patients and in the mice support the clinical relevance of the mouse studies, which replicate several features of pneumococcal pneumonia and steroid therapy in humans. In combination with appropriate antibiotic therapy in mice, treatment of pneumococcal pneumonia with steroid therapy reduced hypoxemia, pulmonary edema, lung permeability, and histologic criteria of lung injury, and also altered inflammatory responses at the protein and gene expression level. The results from these studies provide evidence for the mechanisms that may explain the beneficial effects of glucocorticoid therapy in patients with community acquired pneumonia from Streptococcus Pneumoniae.

ImportanceArginine deprivation using ADI-PEG20 (pegargiminase) combined with chemotherapy is untested in a randomized study among patients with cancer. ATOMIC-Meso (ADI-PEG20 Targeting of Malignancies Induces Cytotoxicity-Mesothelioma) is a pivotal trial comparing standard first-line chemotherapy plus pegargiminase or placebo in patients with nonepithelioid pleural mesothelioma.ObjectiveTo determine the effect of pegargiminase-based chemotherapy on survival in nonepithelioid pleural mesothelioma, an arginine-auxotrophic tumor.Design, Setting, and ParticipantsThis was a phase 2-3, double-blind randomized clinical trial conducted at 43 centers in 5 countries that included patients with chemotherapy-naive nonepithelioid pleural mesothelioma from August 1, 2017, to August 15, 2021, with at least 12 months’ follow-up. Final follow-up was on August 15, 2022. Data analysis was performed from March 2018 to June 2023.InterventionPatients were randomly assigned (1:1) to receive weekly intramuscular pegargiminase (36.8 mg/m2) or placebo. All patients received intravenous pemetrexed (500 mg/m2) and platinum (75-mg/m2 cisplatin or carboplatin area under the curve 5) chemotherapy every 3 weeks up to 6 cycles. Pegargiminase or placebo was continued until progression, toxicity, or 24 months.Main Outcomes and MeasuresThe primary end point was overall survival, and secondary end points were progression-free survival and safety. Response rate by blinded independent central review was assessed in the phase 2 portion only.ResultsAmong 249 randomized patients (mean [SD] age, 69.5 [7.9] years; 43 female individuals [17.3%] and 206 male individuals [82.7%]), all were included in the analysis. The median overall survival was 9.3 months (95% CI, 7.9-11.8 months) with pegargiminase-chemotherapy as compared with 7.7 months (95% CI, 6.1-9.5 months) with placebo-chemotherapy (hazard ratio [HR] for death, 0.71; 95% CI, 0.55-0.93; P = .02). The median progression-free survival was 6.2 months (95% CI, 5.8-7.4 months) with pegargiminase-chemotherapy as compared with 5.6 months (95% CI, 4.1-5.9 months) with placebo-chemotherapy (HR, 0.65; 95% CI, 0.46-0.90; P = .02). Grade 3 to 4 adverse events with pegargiminase occurred in 36 patients (28.8%) and with placebo in 21 patients (16.9%); drug hypersensitivity and skin reactions occurred in the experimental arm in 3 patients (2.4%) and 2 patients (1.6%), respectively, and none in the placebo arm. Rates of poststudy treatments were comparable in both arms (57 patients [45.6%] with pegargiminase vs 58 patients [46.8%] with placebo).Conclusions and RelevanceIn this randomized clinical trial of arginine depletion with pegargiminase plus chemotherapy, survival was extended beyond standard chemotherapy with a favorable safety profile in patients with nonepithelioid pleural mesothelioma. Pegargiminase-based chemotherapy as a novel antimetabolite strategy for mesothelioma validates wider clinical testing in oncology.Trial RegistrationClinicalTrials.gov Identifier: NCT02709512

Objective: To implement use of obstetric (OB) hospitalist telemedicine services (TeleOB) to support clinicians facing OB emergencies in low-resource hospital settings. Methods: TeleOB was staffed by OB hospitalists working at a tertiary maternity center. The service was available via real-time high-definition audio/video technology for providers at 17 outlying hospitals across a health system spanning two states. The initial 25 service activations are described. Results: TeleOB supported 17 deliveries, two postpartum emergency department (ED) consultations, and four antenatal ED consultations. In 10 of 17 (59%) deliveries, teleneonatology was jointly activated to support neonatal resuscitation. Sixteen (94%) deliveries occurred in multiparas, and five (29%) resulted from spontaneous preterm labor. Eighty percent (20/25) of activations occurred in facilities without maternity services. Conclusions: A TeleOB service staffed by OB hospitalists successfully supports hospitals in an integrated health care system. TeleOB is feasible for support of hospitals with no delivery facilities or with limited maternity care resources.