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Significance: Achieving pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) is a significant predictor of increased likelihood of survival in breast cancer patients. Early prediction of pCR is of high clinical value as it could allow personalized adjustment of treatment regimens in non-responding patients for improved outcomes., Aim: We aim to assess the association between hemoglobin-based functional imaging biomarkers derived from diffuse optical tomography (DOT) and the pathological outcome represented by pCR at different timepoints along the course of NACT., Approach: Twenty-two breast cancer patients undergoing NACT were enrolled in a multimodal DOT and X-ray digital breast tomosynthesis (DBT) imaging study in which their breasts were imaged at different compression levels. Logistic regressions were used to study the associations between DOT-derived imaging markers evaluated after the first and second cycles of chemotherapy, respectively, with pCR status determined after the conclusion of NACT at the time of surgery. Receiver operating characteristic curve analysis was also used to explore the predictive performance of selected DOT-derived markers., Results: Normalized tumor HbT under half compression was significantly lower in the pCR group compared to the non-pCR group after two chemotherapy cycles ( p = 0.042 ). In addition, the change in normalized tumor StO 2 upon reducing compression from full to half mammographic force was identified as another potential indicator of pCR at an earlier time point, i.e., after the first chemo cycle ( p = 0.038 ). Exploratory predictive assessments showed that AUCs using DOT-derived functional imaging markers as predictors reach as high as 0.75 and 0.71, respectively, after the first and second chemo cycle, compared to AUCs of 0.50 and 0.53 using changes in tumor size measured on DBT and MRI., Conclusions: These findings suggest that breast DOT could be used to assist response assessment in women undergoing NACT, a critical but unmet clinical need, and potentially enable personalized adjustments of treatment regimens., (© 2024 The Authors.)

Introduction: We evaluated the risk factors and outcomes for patients who experienced hepatotoxicity after use of sotorasib in KRAS G12C mutated NSCLC., Methods: Retrospective review of medical records of patients with KRAS G12C mutated NSCLC who received sotorasib between May 28th, 2021, and December 31st, 2021 across all Mayo Clinic sites, with follow up until December 31st, 2022., Results: Thirty-one patients received sotorasib as standard of care treatment. Grade 3 or higher hepatoxicity was seen in 32% (10/31) patients presenting at a median of 51 days (range, 27-123) of sotorasib initiation. Baseline demographics were comparable between patients with and without ≥grade 3 hepatotoxicity, except for presence of CNS metastases and time from prior immune checkpoint inhibitor (ICI) treatment. Improvement in liver tests was observed in all patients after stopping sotorasib, and it was restarted at a lower dose in 8 patients. Despite dose reduction, hepatotoxicity requiring sotorasib discontinuation occurred in 2 patients. Twenty-eight of 31 patients had received prior ICI. Median time from prior ICI therapy was 69 days (range, 4-542). Rates of ≥grade 3 hepatoxicity were 75% (3/4), 64% (7/11) and 0% (0/13) for patients who received ICI within 30 days, 31-90 days and >90 days. None of the 3 patients without prior ICI exposure developed hepatoxicity. The median PFS and OS were 3.9 months and 9.9 months respectively., Conclusion: One-third of patients developed grade 3 or higher sotorasib induced hepatotoxicity. Risk of hepatotoxicity was higher in patients who received sotorasib within 90 days of ICI treatment., Competing Interests: Declaration of Competing Interest A.D.: Consulting/advisor board for: Amgen, and Sanofi; S.R: None; R.B: None; C.S: None; Y.A: None A.P: None; R.M: Consulting/advisory board for: AstraZeneca, Turning Point Therapeutics, Janssen, Takeda ; Y.L: Consulting/advisory board for: AstraZeneca Pharmaceuticals, Janssen Pharmaceutical, Lilly Oncology, Turning point therapeutics, Honoraria: clarion health care, Research Funding Support: Merck, MacroGenics, Tolero Pharmaceuticals, AstraZeneca, Vaccinex, Blueprint Medicines, Harpoon Therapeutics, Sun Pharma Advanced Research, Bristol-Myers Squibb, Kyowa Pharmaceuticals, Tesaro, Bayer HealthCare, Mirati Therapeutics, Daiichi Sankyo; Y.Z: None; V.E: Consulting/advisory board for: AstraZeneca, Daiichi Sanyo, Jazz Pharmaceuticals, Bayer, Pfizer, and Novocure; P.S: None; A.S: None; N.M: None; C.H: None; K.L: Consulting/advisory board: Boehringer Ingelheim Pharmaceuticals, Amgen, AstraZeneca, Targeted Oncology, Takeda, Jazz Pharmaceuticals, Mirati Therapeutics, Janssen, and Regeneron. CME activities: OncLive and MJH Life Sciences. Research support (to institution): AstraZeneca and Mirati Therapeutics; A.A: None; J.M: None; AMS: Direct research funding: National Cancer institute, Department of Defense, Mark Foundation, Novartis, and Verily; Honoraria to institution for participation in advisory boards: AbbVie, BeiGene, BMS, Genentech, Inc., Janssen; Travel support: Shanghai Roche, and non-remunerated member of the Mesothelioma Applied Research Foundation Board of Directors and Friends of Patan Hospital.; Z.C: None; A.D: Advisory board: TP Therapeutics, Guardant Health, Chromacode, Anheart Therapeutics. Clinical trial support: Novartis, Syntrix Therapeutics, Sorrento Therapeutics, Anheart Therapeutics, Merck; Honoraria: Roche/Genentech, Intellisphere., (Copyright © 2023. Published by Elsevier Ltd.)