Browse Articles
Discover research articles across all indexed journals
Point-of-care cancer screening using saliva transmission spectroscopy and machine learning.
e22526 Background: Tier-1 cancer screening would benefit from point-of-care (POC) testing that is rapid, inexpensive, and highly specific to minimize unnecessary downstream workup. We evaluated saliva transmission hyperspectral spectroscopy combined with machine learning algorithms as a POC screening approach. Methods: Saliva was collected from outpatient consented participants in a lung cancer clinic (n = 99) and a high-risk clinic (n = 152) on an IRB-approved protocol (PREDICT NCT05802069). Two drops of saliva were scanned in ~3 seconds on a ProSpectral hyperspectral spectrophotometric device to acquire transmission spectra. Cancer status and stage were abstracted from the electronic health record and categorized as cancer-positive, hereditary cancer-predisposition but without diagnosis, no evidence of disease (NED) while on treatment, and NED at least 2 months after treatment completion. Spectra and labels were used to train and validate a Pattern Discovery Engine (PDE) classifier, which yields a human-readable symbolic equation in the spectral domain; operating thresholds were calibrated to tune specificity for low false-positive tier-1 operation. Results: Across clinically relevant labeling i.e., cancer-positive (n = 99 patients), hereditary cancer-predisposition but without diagnosis (n = 86), no evidence of disease (NED) while on treatment (n = 16), and NED at least 2 months after treatment completion (n = 50), models achieved high median balanced accuracy and maintained discrimination under very high specificity settings suitable for tier-1 screening (very few false positives). At comparable cohort scale, discrimination exceeded that reported for sequencing-based cfDNA methylation blood assays, while reducing time-to-signal from centralized laboratory workflows (~2-week turnaround) to seconds at the POC and avoiding reagent costs. Saturation analysis indicates that Specificity > 98% is likely attainable with fewer than 500 samples, providing a path to a clinically actionable screening protocol in subsequent phases of work. Conclusions: Saliva transmission hyperspectral spectroscopy with the PDE supports a practical, near-real-time POC paradigm for early cancer screening and triage. Ongoing work will attribute discriminative spectral regions and identify contributing analytes and host-response biomarkers using orthogonal assays (e.g., fractionation and targeted mass spectrometry), improving interpretability and enabling prospective validation. Samples Balanced Accuracy Sensitivity Specificity F1-Score 251 61% 44% 91% 0.55
Impact of social marginalization on stage at presentation and survival for invasive lobular versus ductal breast carcinoma.
641 Background: We aim to determine how indices of social marginalization impact stage at diagnosis, health services use, and overall survival comparing invasive ductal (IDC), pure (pILC) and mixed lobular (mILC) breast carcinoma (ILC) between 2005 and 2025 in the province of Ontario, Canada. Methods: Using population-based administrative healthcare datasets at Institute of Clinical Evaluative Sciences (ICES) Ontario, we identified all cases of IDC, pILC and mILC in Ontario, Canada between 2005 and 2025 using ICD-O-3 codes. We compared prior healthcare utilization between groups. We further compared clinical and healthcare utilization measures between four Ontario Marginalization (ON-MARG) indices: household and dwellings (includes % living alone, housing density), material resources (includes unemployment and education level), age and labour force (includes % seniors and not participating in the work force), and racialized and newcomer populations (includes % of recent immigrants). Using a multivariable Cox proportional hazards regression analysis incorporating sociodemographic, tumour and treatment factors, we assessed the impact of social marginalization indices on survival for the overall cohort and for ILC cases. Statistical analysis was performed using SAS and P values < 0.05 were significant. Results: We identified 16,122 (9%) pILC, 7,284 (4%) mILC and 156,870 (87%) IDC cases. At diagnosis, increasing marginalization for household and dwellings, material resources, and age and labour force correlated with less likelihood to having had a mammogram within 1 and 5 years prior to diagnosis (P < .0001). Increasing marginalization in these three quintiles correlated with worse clinical stage at diagnosis for both IDC and ILC (P < .001). Patients diagnosed with pure ILC breast cancer had 1.14 times (95%CI: 1.11 - 1.18) the likelihood of mortality in the follow-up relative to females diagnosed with IDC breast cancer. Increasing marginalization in the ON-MARG indices had a worse mortality for the overall cohort and for ILC cases, except for the racialized and newcomer populations quintile (P < .0001). Conclusions: In Ontario, Canada, the indices of social marginalization found to be associated with worse survival after a breast cancer diagnosis were household and dwellings, material resources, age and labour force but not racialized and newcomer populations. These findings highlight personalized risk factors for worse stage at presentation and survival for both IDC and ILC, independent of clinical and treatment factors.
Natural language processing (NLP) to identify neoplastic fever in the electronic medical record (EMR).
e13679 Background: Neoplastic fever (also known as “tumor fever”; TF), is a rare but challenging condition that can be difficult to distinguish from infectious or treatment-related causes of fever. TF can lead to potentially unnecessary diagnostic testing and antibiotic use, as well as physical and psychological distress for patients. While treating the underlying cancer is the gold standard, this may not be successful or sufficient. Further, the inability to prospectively identify individuals with TF limits research to improve prevalence estimates, non-cancer directed therapy and patient quality of life. Therefore, our goal was to develop and validate an NLP algorithm to identify TF from the clinical notes of a retrospective cohort of adult cancer patients. Methods: Research was approved by the Fred Hutchinson Cancer Center Institutional Review Board. Unstructured clinical notes were extracted from the EMR among patients in the Adult Oncology Program with both ICD10 cancer-related diagnoses with at least two outpatient office visits within a 6-month period between January 1, 2018 and December 31, 2024. The study team developed the annotation schema iteratively with clinical and NLP experts for TF and related clinical entities. Annotations occurred over multiple rounds using the MedTator software. Inter-annotator agreement was assessed using F1 scoring and Cohen’s kappa coefficient, with acceptable inter-annotator agreement (AIAA) defined as F1 score of ≥.8. Results: 354,245 clinical notes for 26,774 individuals were identified during the study period. Of these, 117,545 (~33.18%) notes had a term related to TF (e.g. "tumor fever", "neoplastic fever", "fever", "sweating"). 341 charts were annotated from 89 patients for the final gold standard corpus. AIAA was achieved with overall F1 score of .83 (see Table 1) across all entity and relation types. Training and evaluation of NLP models is ongoing. Full results will be presented. Conclusions: Our results suggest NLP can be used to identify true cases of tumor fever in the EMR. To our knowledge, this is the first gold standard annotated corpus specifically designed for tumor fever detection in clinical notes. This resource addresses a critical gap in oncology-focused NLP, providing a foundation for developing and evaluating automated methods to identify tumor fever from EHR data and supporting future research aimed at improving diagnostic accuracy and treatment of tumor fever. Inter-annotator agreement, precision and recall for tumor fever-related annotation labels. Annotation Label F1 Precision Recall True Positive False Positive False Negative OVERALL 0.8263 0.7565 0.9103 2181 702 215 FEVER 0.9433 0.9252 0.9620 507 41 20 FEVER SYMPTOMS 0.9236 0.8788 0.9732 145 20 4 NEOPLASM 0.7874 0.6889 0.9186 722 326 64 CANCER SIGN 0.7457 0.6643 0.8498 566 286 100 NEGATION 0.8078 0.8240 0.7923 103 22 27 TUMOR FEVER 0.9753 0.9517 1.0000 138 7 0
Symptom-based individual risk prediction for late mortality: A report from the Childhood Cancer Survivor Study study (CCSS).
10050 Background: Survivors of childhood cancer face a higher risk of late mortality than the general population. Yet no prior study has integrated patient-reported symptoms and social determinants of health with treatment exposures to predict late mortality risks. Methods: A total of 9,569 survivors from the CCSS cohort who completed two surveys (baseline [T1], follow-up [T2]) reported 37 symptoms spanning 10 domains (cardiac, pulmonary, sensory, musculoskeletal, nausea, pain, fatigue, memory, anxiety, depression) at T1 and T2. Additional predictors included sociodemographic and lifestyle factors, address-linked Area Deprivation Index, and treatment exposures. Standardized mortality ratios (SMRs) were calculated, stratified by individual symptoms and domains at T2 and T1-T2 change, to compare mortality rates between survivors and the general population five years after T2. Multivariable Cox proportional hazards models with LASSO regularization were used to predict 5-year health-related and cause-specific late mortality (cardiac, pulmonary, subsequent neoplasm) after T1 and T2. The dataset was randomly split into training and test datasets in a 7:3 ratio, and prediction performance was assessed using the area under the receiver operating characteristic curve (AUC). Results: Among 9,569 survivors (52.4% female), the median age at T1 and T2 was 27.1 and 36.9 years; median years from diagnosis to T1 and T2 were 16.6 and 26.3, respectively. Acute lymphoblastic leukemia (31.3%) and Hodgkin lymphoma (15.3%) were the most frequently observed primary diagnoses. Compared with the sex/age/race/calendar year-matched general population, survivors had significantly higher health-related mortality 5 years after T2, with SMR of 4.21 (95%CI 3.76-4.70). Presence of cardiac and pulmonary symptom domains at T2, and their persistence and worsening from T1 to T2, were associated with >10-fold higher SMRs. Presence, persistence, and worsening of individual symptoms, including angina pectoris, chronic cough, and trouble breathing, were also associated with SMRs >10. For 5-year health-related mortality after T2, the symptom-based model yielded an AUC of 0.79 (95%CI 0.75-0.84), surpassing the symptom-agnostic model (AUC 0.76, 95%CI 0.71-0.81) and the T1 model (AUC 0.73, 95%CI 0.67-0.79). Cause-specific models also showed strong prediction performance, with symptom-based AUCs of 0.87 for cardiac, 0.89 for pulmonary, and 0.78 for subsequent neoplasms mortality. Conclusions: Adult survivors of childhood cancer experience elevated SMRs, with the greatest excess late mortality observed in those reporting cardiopulmonary symptoms. Longitudinal symptom-based models yielded the highest predictive performance, outperforming single-time-point and symptom-agnostic models. Incorporating symptom data can strengthen mortality prediction and inform targeted survivorship care.
Final results of a phase II study of fluorouracil (FU), leucovorin (LV), and nanoliposomal irinotecan (nal-IRI) in previously treated biliary tract cancer (NAPOLI-2).
4122 Background: BTCs are rare and aggressive malignancies. The first-line standard of care regimen for advanced BTC (aBTC) is gemcitabine (GEM), cisplatin, and an immune checkpoint inhibitor. Although FOLFOX is a preferred second-line treatment, it is limited by neuropathy. Nal-IRI contains IRI free base in liposome nanoparticles, which shelter IRI from conversion to its active metabolite (SN-38) and increase intratumoral SN-38 compared with IRI alone. The NAPOLI-1 trial of FU/LV/nal-IRI vs. FU/LV in second-line advanced pancreatic adenocarcinoma showed an overall survival (OS) benefit. The NIFTY trial (South Korea) demonstrated median OS (mOS) benefit of FU/LV/nal-IRI over FU/LV in a second-line aBTC population (8.6 vs. 5.3 months [mo], HR 0.68, 95% CI 0.48-0.95); however, the NALIRICC trial (Germany) did not (6.9 vs. 8.2 mo, HR 1.08, 95% CI 0.68-1.72). We sought to characterize second-line FU/LV/nal-IRI efficacy in US patients (pts) with second-line aBTC. Methods: This was a single-arm, open-label, multicenter phase II study of pts with aBTC previously treated with GEM/platinum chemotherapy. Pts received nal-IRI 70 mg/m 2 IV over 90 minutes, LV 400 mg/m 2 IV over 30 minutes every 14 days, and FU 2400 mg/m 2 IV over 46 hours every 14 days. The primary objective was to determine progression-free survival rate at 4 mo (PFS 4mo ) using RECIST v. 1.1 criteria. Median PFS reported for pts receiving second-line 5-FU doublet chemotherapy was 3 mo with a PFS of 30%. FU/LV/nal-IRI was of interest if it could increase the PFS 4mo to 50% or higher. Using a one-sided α of 0.05 and 80% power, 17 of 39 evaluable pts had to be progression-free at 4 mo to detect a difference in PFS 4mo between 30% and 50%. Results: Forty-eight pts were enrolled: median age 64.5 years; 69% women; 27% gallbladder primary; 54% intra- and 19% extrahepatic. Ten pts came off study due to toxicity without disease progression before 4 mo on study and were replaced to evaluate the PFS 4mo endpoint. Of 38 evaluable pts, 18 pts (PFS 4mo 47%) were alive and progression-free at 4 mo, meeting the primary endpoint. With a median follow-up of 7.1 mo, median time to disease progression or study discontinuation due to toxicity for all pts was 2.3 mo (95% CI 1.8-4.6, PFS 4mo 38%), and for pts evaluable for the primary endpoint, median PFS was 3.5 mo (95% CI 1.8-5.5). Five pts (10%) had PFS beyond 12 mo. mOS for all pts was 7.9 mo (95% CI 5.7-11.7). Of 41 evaluable pts, the response rate was 2% (1 PR), and the disease control rate was 54%. Adverse events (AEs) were consistent with known toxicities from the FU/LV/nal-IRI regimen. Conclusions: FU/LV/nal-IRI is an effective second-line regimen for aBTC in US pts. There was significant early toxicity as 21% of pts came off study due to AEs before 4 mo. Correlative studies, including longitudinal analyses of circulating tumor DNA using banked blood specimens, are planned (NCT04005339). Clinical trial information: NCT04005339 .
Antibody-encapsulated actinomycin D for targeted cancer treatments.
e13019 Background: HER2 is overexpressed in 15-20% of breast cancers and other cancers, and HER2-targeted therapies have revolutionized cancer treatment in the past 20 years. Trastuzumab (Tr) has demonstrated efficacy on HER2+ breast cancer and advanced gastric cancer. Recently, Tr-based antibody drug conjugates (ADCs), trastuzumab emtansine and trastuzumab deruxtecan, have emerged as a new class of anti-HER2 therapies by combining targeted antibodies with cytotoxic agents via linkers. However, ADC approach faces great challenges, in vivo instability, complicated manufacturing, limited cytotoxic payloads and suboptimal payload release, etc. Smarter and better designs are urgently needed. Methods: Our patented single protein encapsulation (SPE) platform, allowing encapsulation of small-molecule drugs by a single protein (albumins or globulins) without artificial nanoparticles and chemical modifications to drugs and proteins, has achieved great success in development of 2 drug products, SPEDOX-6 under clinical trial (NCT0764018) and SPESN38-8 (IND #: 164346) under IND-enabling study based on albumin, which have prompted us to utilize antibody, such as Tr, to encapsulate cytotoxic payload, like actinomycin D (ACT), forming antibody encapsulated drugs (AEDs). We have successfully developed Tr-ACT2 as a first-in-class AED drug, featuring each Tr molecule to encapsulate two ACT molecules without linkers. Tr-ACT2 was well characterized by UV, fluorescence, membrane dialysis, particle size distribution, and molecular docking. In vitro and in vivo anticancer efficacy of Tr-ACT2 against various HER2+ & HER2- cancers were evaluated. Results: Tr-ACT2 has been investigated in following. In vitro cytotoxicity of Tr-ACT2 against human breast cancers, HER2+ (SKBR3, JIMT1) and HER2- (BT549, MDA-MB-231) and A549 (NSCLC, HER2-), was evaluated, leading to a time-dependent and significant reduction in cell viability. Notably, Tr-ACT2's cytotoxic activity appeared to be independent of HER2 levels. Internalization study on Tr-ACT2 demonstrated that early-stage internalization of Tr-ACT2 is HER2 dependent, but rate of late-stage internalization of Tr-ACT2 is not limited by HER2 levels, confirming that Tr-ACT2 could be effectively internalized into both HER2+ and HER2- cancer cells. In vivo anticancer efficacy of Tr-ACT2 at 1 mg/kg vs irinotecan at 50 mg/kg using A549 mouse model has been evaluated, showing that Tr-ACT2 was significantly more effective in suppressing growth of A549 than irinotecan. Conclusions: We successfully developed first-in-class AED nanocomplex, Tr-ACT2, as a potent anticancer agent, demonstrating that the SPE technology can be applied to monoclonal antibody for encapsulating small-molecule drugs without covalent conjugation and marking a significant advancement in antibody-based therapeutics. Newly-created AEDs have great potentials for not only replacing, but also expanding ADC approaches due to SPE’s significant advantages.
Prevention of paclitaxel-induced neurotoxicity with lithium: Results from a multicenter, randomized, double-blind, placebo-controlled phase 2 trial (PREPARE).
12129 Background: Chemotherapy-induced neurotoxicity is a frequent adverse effect of paclitaxel (PTX). It reduces quality of life and often necessitates treatment modifications. The objective of this clinical trial was to determine the safety and efficacy of lithium (Li + ) co-treatment on chemotherapy-induced neurotoxicity in breast cancer patients treated with PTX. Methods: Multicenter, randomized, double-blind, placebo-controlled phase-2 trial (parallel-group design) conducted in eight primary care centers in Germany between August 2022 and July 2024. Eligible breast cancer patients aged 18-70 years, with no pre-existing polyneuropathy and to be treated with PTX were randomized 1:1 to either oral Li + or placebo with sham dose adjustments. The intervention started 10-14 days prior to the first and lasted until three days after the last PTX infusion. Results: A total of 94 patients were enrolled, 86 patients were randomized and 78 were analyzed according to the intention-to-treat principle. Targeted Li + trough serum concentrations of 0.5 to 0.8mmol/l were reliably reached prior to PTX therapy. The total neuropathy score reduced (TNSr) was 0.5 points higher in the placebo group than in the Li + group (95% CI 1.6 to -0.6, not significant), while serum neurofilament light chain levels showed no difference. Structural MRI showed slightly higher total intracranial volume in the Li⁺ group, but no difference in hippocampal volume. Cognitive testing using the CANTAB indicated a strong trend towards better performance in hippocampus-dependent tasks, including delayed matching to sample and spatial working memory for the Li + group. The patient reported outcome measures (PROM) completion rates were high (baseline 99%, endpoint 95%). Patients receiving Li⁺ consistently reported higher quality of life and less pain scores on the EORTC QLQ-C30 during and after therapy, with between-group differences of 11 AU (95% CI 18 to 4) for global health status and -14 AU (95% CI −27 to -0.2) for pain, exceeding established minimal clinically important differences. The latter finding was supported by a lower reported intake of pain medication in the Li + group of 54% vs 70% in the placebo group. Eleven serious adverse events were reported in the trial, six in the placebo group and five in the Li + group. Patients in the Li + group experienced fewer adverse events compared to patients in the placebo group with a relative risk reduction of 26% for any CTCAE grade and 45% for grade ≥ 3. Conclusions: Among breast cancer patients receiving PTX chemotherapy co-treatment with Li + was not superior to placebo for the development of polyneuropathy as measured by TNSr. However, there were better patient-reported outcomes including quality of life and pain, as well as lower rates of adverse events. These observations warrant confirmation in a larger phase-3 interventional trial. Clinical trial information: DRKS00027165.
Prognostic value of an MRI-derived recurrence assay in women with hormone receptor–positive, HER2-negative breast cancer: A retrospective, multi-center analysis.
560 Background: Patients (pts) with early stage hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer (BC) remain at both short and long term risk of recurrence. While clinico-pathological and gene-based biomarkers provide insight into early and late recurrence risk, additional prognostic tools are needed. We previously developed (Saha et al. Clin Cancer Res , 2025) a new breast MRI image-based artificial intelligence prognostic tool (TumorSight Risk) composed of both radiographic and clinical information. Here we sought to validate this tool in an independent cohort. Methods: In this multi-center, blinded, prospective/retrospective validation study, we sought to validate the 5-year recurrence-free survival (RFS) according to pre-defined risk scores (0-100) and categories (“high” or “low”) via pre-specified cutoff (≥47) for pts with HR+/HER2- BC. Kaplan-Meier and Cox regression analyses were then used to assess the unadjusted and adjusted association between risk category/score and the 5-year RFS. Results: 2,129 pts with HR+/HER2- BC diagnosed between January 1, 2010, and December 31, 2024, who underwent breast MRI prior to surgery (no neoadjuvant therapy) were included from four institutions. Median age was 57 years, 16% were Black, 15% had grade 3 disease, 93% were clinical T1 or T2, and 85%/15% were clinical N0/N1. At a median follow up of 6.24 years, the unadjusted hazard ratio (HR) for RFS comparing low (n=1808) and high risk (n=321) pts was 2.71 (95% CI = 1.95 – 3.76, p = 3x10 -9 ). The estimated 5 year RFS rate according to risk score (low and high) was 95.5% (95% CI: 94.63 – 96.3%) and 89.6% (95% CI = 86.4 – 92.6%) while the 10 year RFS estimates were 88.9% (95% CI = 86.5 - 90.9%) and 69.6% (95% CI = 59.1 – 77.9%). Univariate subgroup analysis demonstrated that the risk score was prognostic by age (< 50 vs. ≥50 years), pathologic nodal status, grade, and surgery type, regardless of chemo-, endocrine, or radiation therapy administration. The observed continuous risk score was strongly associated with risk of recurrence, with a 22% increase in relative risk per 10-unit change in risk score (0-100), translating to a 2.4% (95% CI = 1.2 – 4.5%) and 25.5% (95% CI = 15.4 – 40.4%) risk of recurrence at 5-years for pts at the lowest (0-9) versus highest (90-100) risk score. The prognostic association between risk score and RFS remained after adjusting for pathologic T- and N-stage, grade, age, race, and treatment (p = 0.002). Conclusions: TumorSight Risk is a new image-based biomarker for HR+/HER2- BC that provides prognostic information independent of standard clinico-pathological parameters. Given the ready availability of breast MRI in most pts with BC, TumorSight Risk may be a convenient tool for estimating risk for recurrence.
Associations between chronic pain, depression, and social vulnerability in US adults with colon cancer.
e15698 Background: Chronic pain is a frequent and disabling sequela of colon cancer treatment, yet nationally representative U.S. data evaluating the contribution of social vulnerability and mental health remain limited. We examined associations between social determinants of health, psychosocial factors, and chronic pain among adults with colon cancer. Methods: We conducted a cross-sectional analysis of pooled 2021 and 2023 National Health Interview Survey data accessed through IPUMS, identifying adults aged ≥18 years with self-reported history of colon cancer. Chronic pain was defined as pain occurring on most or every day for ≥3 months. Social vulnerability indicators included federal poverty status, food insecurity, delayed or forgone medical care due to cost, and lack of a usual source of care. Psychosocial variables included self-reported lifetime depression and anxiety. Multivariable logistic regression models estimated adjusted odds ratios (aORs) and 95% confidence intervals (CIs), adjusting for age, sex, and race/ethnicity. Interaction terms tested effect modification by depression and anxiety across poverty strata. Model discrimination was assessed using receiver operating characteristic (ROC) curves, and calibration was evaluated with Hosmer-Lemeshow goodness-of-fit tests. Survey-weighted sensitivity analyses incorporating NHIS sampling weights, strata, and primary sampling units were performed to assess robustness. Results: Among 380 adults with colon cancer, median age was 62 years (interquartile range, 54–71), 54% were female, and 32% identified as racial or ethnic minority groups. Overall, 207 individuals (54%) reported chronic pain. In adjusted analyses, female sex (aOR 2.16, 95% CI 1.33–3.56) and depression (aOR 3.72, 95% CI 1.97–7.24) were independently associated with higher odds of chronic pain. Living below the federal poverty level was associated with lower odds of chronic pain compared with ≥200% of the poverty threshold (aOR 0.23, 95% CI 0.08–0.59). Anxiety was not independently associated with pain after adjustment. Poverty-by-depression and poverty-by-anxiety interactions were nonsignificant. The final model demonstrated moderate discrimination (AUC 0.72) and adequate calibration (Hosmer-Lemeshow P = .27). Survey-weighted sensitivity analyses yielded consistent effect estimates, with depression remaining the strongest predictor of chronic pain. Conclusions: More than half of U.S. adults with colon cancer reported chronic pain. Depression was strongly associated with pain burden, independent of demographic and socioeconomic factors. These findings support integrating routine psychosocial screening and mental health services into survivorship care to mitigate long-term pain-related morbidity.
Does resection of cavity shave margins impact survival in breast cancer patients?
513 Background: Randomized controlled trials have shown that resection of cavity shave margins (CSM) halves the margin positivity and re-excision rate in breast cancer (bc) patients (pts), but the impact on overall (OS) and disease-free survival (DFS) remains unclear. Methods: Between Oct 21, 2011 and Nov 25, 2013, the SHAVE trial enrolled 235 pts in a single center study. Between Jul 28, 2016 and Apr 13, 2018, SHAVE2 enrolled 396 pts across 9 other US sites. Both studies were similar in their study criteria and methods. Pts ≥ 18 years of age, with planned partial mastectomy (PM) for stage 0-3 bc were eligible. Surgeons performed their standard PM with excision of selective margins as needed based on gross evaluation and specimen radiograph. Pts were then randomized intraoperatively to either “shave” or “no shave” arms. In the former, surgeons were instructed to take additional CSM from ≥4 faces of the cavity; in the latter, to close. Pts were followed for a median of 60.4 months (mo). Results: Across both studies (n = 631), the median pt age was 64 (range; 29-94), and the median invasive tumor size was 1 cm (range; 0-8 cm). Forty pts had no further disease at the time of PM either due to all disease being removed in the core biopsy or due to neoadjuvant chemotherapy. Before randomization, margin positivity was similar between the “shave” and “no shave” arms (37.8% vs. 34.8%, p = 0.457). After randomization, the “shave” group had a significantly lower positive margin rate (14.0% vs. 34.8%, p < 0.001) and re-excision rate (9.2% vs. 24.1%, p < 0.001). In the “shave” arm, 13.3% of those with negative margins prior to randomization had cancer found in the CSM. Pts in the “shave” arm were less likely to have positive final margins (after re-excision where performed; 6.3% vs. 15.8%, p < 0.001). Both groups had similar rates of radiation therapy (XRT) (82.8% vs. 81.8%, p = 0.831). Local recurrence rates were nearly identical at a median follow-up of 60.4 mo (1.3% vs. 1.6%, p = 1.000). 5-year DFS (91.9% vs. 92.6%, p = 0.820) and OS were not significantly different between groups (93.5% vs. 93.5%, p = 0.841). On Cox proportional hazard modelling, including randomization arm, final margin (after re-excision), and use of XRT, only the use of XRT significantly improved DFS (5 yr DFS 86.3% vs. 94.4%, HR: 0.47; 95% CI: 0.256-0.865, p = 0.015). Conclusions: While CSM reduced margin positivity and re-excision rates, it does not have an impact on DFS or OS at a median of 60.4 mo of surveillance; only the use of XRT significantly improved DFS. Although resection of CSM removed additional disease in 13.3% of margin-negative pts and was associated with a lower final positive margin rate, this did not translate into lower local recurrence rates. These results suggest that XRT may effectively manage small-volume residual disease that remains after PM. Clinical trial information: NCT01452399 ; NCT02772731 .
Age-related immune toxicity and treatment outcomes in triple-negative breast cancer treated with pembrolizumab.
e12710 Background: Tolerability and treatment completion of pembrolizumab added to neoadjuvant chemotherapy for triple-negative breast cancer (TNBC) varies across age groups. This study evaluated age-related patterns in immune-related adverse events (irAEs), pembrolizumab exposure, and clinical outcomes in TNBC treated with the KEYNOTE-522 regimen. Methods: We retrospectively analyzed consecutive TNBC patients treated with neoadjuvant ± adjuvant pembrolizumab from 2020–2025 at a multicenter single, academic, healthcare network. Patients were stratified by median age (53 years). Clinical, pathological, treatment, and toxicity data were abstracted. Outcomes included irAE incidence, treatment completion, pathological complete response (pCR), overall survival (OS) and progression free survival (PFS). Survival was assessed using Kaplan–Meier and multivariable Cox regression. Results: Among 125 patients, 36.8% developed immune-related adverse events (irAEs), including 15.2% with grade ≥3 toxicity. Younger patients had a higher incidence of irAEs than older patients (51% vs 31%; OR 2.19, 95% CI 1.05–4.43; p = 0.0326), developed toxicity earlier (mean 5.8 vs 7.2 cycles), and required systemic corticosteroids more frequently (OR 2.57, 95% CI 1.07–6.25; p = 0.0379). Younger patients received fewer neoadjuvant pembrolizumab doses (mean 6.17 vs 7.0) and were less likely to proceed to adjuvant pembrolizumab (OR 0.16, 95% CI 0.07–0.35; p < 0.0001). Despite reduced treatment exposure, pCR rates did not differ by age, and pCR was not associated with number of pembrolizumab doses received. OS did not differ by age alone (log-rank p = 0.4084). Achieving pCR was associated with markedly improved OS (HR 0.10, 95% CI 0.02–0.56; log-rank p = 0.0081) and PFS (HR 0.06, 95% CI 0.009–0.49; log-rank p = 0.0080), with this survival benefit significant in older patients (log-rank p = 0.0369) but not younger patients (log-rank p = 0.1537). Completion of adjuvant pembrolizumab improved OS (HR 0.17, 95% CI 0.04–0.75; log-rank p = 0.0193) and PFS (HR 0.17, 95% CI 0.03–0.89; log-rank p = 0.0360) overall, with benefit confined to older patients (log-rank p = 0.0258). On multivariable analysis, pCR was the strongest predictor of improved OS (HR 0.04, 95% CI 0.002–0.27; p < 0.01), while development of irAEs was associated with increased mortality risk (HR 7.95, 95% CI 1.27–70.78; p < 0.05). Conclusions: Age significantly influenced irAE risk, timing, and pembrolizumab feasibility. Younger patients maintained similar pCR and OS despite reduced treatment exposure, suggesting adequate immune activation may occur with shorter therapy. However, older patients derived greater survival benefit from completing the full regimen. Age-adapted immunotherapy strategies in early-stage TNBC should be evaluated.
Timing of central nervous system metastases occurrence in patients with metastatic breast cancer treated with CDK 4/6 inhibitors: A single institution real-world analysis.
e13068 Background: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) are standard first-line treatment for patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC). Patients with CNS metastases in HR+/HER2- MBC remain underrepresented in clinical trials, and a major unmet clinical need despite advances in systemic therapy; real-world data (RWD) are needed to better understand their patterns of occurrence. Methods: Data were extracted from medical records of HR+/HER2- MBC patients treated with CDK4/6i at the University Hospital Centre Zagreb from April 2018 to December 2025. Patients were stratified by timing of CNS metastases development: at baseline, during CDK4/6i treatment, or in later lines (after progression on CDK4/6i therapy). Median real-world progression-free survival (rwPFS) was estimated using the Kaplan-Meier method. Results: Among 442 HR+/HER2- MBC patients, 49 (11%) developed CNS metastases (radiologically and/or histologically confirmed) during the course of metastatic disease. Median rwPFS in 14 patients with baseline CNS metastases treated with CDK4/6i was 12.5 months (95% CI, 6-22 months). Median rwPFS in 17 patients who developed CNS metastases during CDK4/6i therapy was 30 months (95% CI, 25-50 months). Among them, 10 patients had isolated CNS progression and continued CDK4/6i beyond CNS progression, achieving a median rwPFS of 7 months (95% CI, 6-13 months), while 7 patients had both systemic and CNS progression and subsequently received chemotherapy. In patients with baseline CNS metastases abemaciclib was the most frequently used CDK4/6i, and ribociclib in those who developed CNS metastases during CDK4/6i therapy. In 18 patients who developed CNS metastases in later lines, after progression on CDK4/6i therapy, median rwPFS on CDK4/6i was 18 months (95% CI, 12-25 months), 56% progressed within 12 months. Conclusions: Favourable median rwPFS was observed in patients with CNS metastases treated with CDK4/6i, whether present at baseline or developed during therapy. Continuation of CDK4/6i beyond CNS progression, may in isolated cases provide meaningful disease control. These findings are consistent with PFS reported in pivotal randomized trials. Further research is needed to identify biomarkers predictive of CNS progression. Clinicopathological and molecular characteristics of patients with CNS metastases. Baseline CNSmetastases (n=14) CNS progression duringCDK4/6i therapy (n=17) CNS metastases after progression on CDK4/6i therapy (n=18) Lobular tumour histology, n(%) 6 (43%) 4 (24%) 5 (28%) PIK3CA mt, n(%) 5 (35%) 4 (24%) 5 (28%) PR negative, n(%) 3 (21%) 10 (59%) 7 (39%) HER2 low (1+ or 2+), n(%) 4 (29%) 5 (29%) 5 (28%) gBRCA 1 or 2 mt, n(%) 0 2 (12%) 1 (5%) Median rwPFS months, (95% CI) 12.5 (6-22) 30 (25-50) 18 (12-25)
Real-world outcomes of bruton tyrosine kinase inhibitors versus venetoclax in chronic lymphocytic leukemia.
e18616 Background: Bruton tyrosine kinase inhibitors (BTKi) and venetoclax-based regimens have transformed the frontline management of chronic lymphocytic leukemia (CLL). BTKi are typically administered continuously, whereas venetoclax offers a fixed-duration, time-limited regimen. Real-world comparative effectiveness data between these treatment strategies remain limited. Methods: We performed a retrospective analysis using the TriNetX database, including patients aged ≥18 years diagnosed with CLL. Patients were divided into two cohorts based on the first-line therapy with either a BTKi (ibrutinib, acalabrutinib, or zanubrutinib, plus obinutuzumab) (BTKi group) or VenG (venetoclax plus obinutuzumab) (VenG group). Propensity score matching (PSM) was performed to balance baseline demographics. The primary outcome was 3-year overall survival (OS). Secondary outcomes included the rate of complete response (CR), all-cause intensive care unit (ICU) admission, atrial fibrillation, major bleeding, infection, and tumor lysis syndrome (TLS). Outcomes were analyzed using Kaplan-Meier survival estimates and measures of association. Results: Baseline characteristics were well-balanced following PSM. A total of 732 patients were included in each group. The mean age at index was 69.8 ± 9.8 years in the VenG group and 69.8 ± 11 years in the BTKi group. Males comprised 66.1% of the VenG group and 64.8% of the BTKi group, while females accounted for 33.9% and 35.2%, respectively. The majority of patients were White (81.3% in the VenG group and 81.1% in the BTKi group), followed by African American (8.9% vs 8.7%) and Asian (1.9% vs 1.6%). BTKi exposure included acalabrutinib (n = 351), ibrutinib (n = 343), and zanubrutinib (n = 82). VenG use was associated with a statistically significant improvement in 3-year OS compared to the BTKi group (p < 0.0001), with a hazard ratio (HR) of 0.54 (95% CI: 0.41–0.71). CR were more frequently observed in the VenG group compared to the BTKi group (17.4% vs. 9.4%, p < 0.0001). There were also significant differences between groups in the rate of major bleeding (4.5% vs. 7.4%, p = 0.0275). However, the VenG group showed a higher incidence of TLS (5.8% vs. 3.1%, p = 0.0153). There was no significant difference in rates of all-cause ICU admission (7.5% vs. 9.3%, p = 0.2287), atrial fibrillation (7.3% vs. 7.9%, p = 0.6949), and infection (19.9% vs. 17.3%, p = 0.2905). Conclusions: In this study, VenG therapy was associated with significantly improved OS and higher CR rates compared with continuous BTKi therapy. VenG also demonstrated lower rates of major bleeding, while rates of ICU admission, atrial fibrillation, and infection were comparable. The higher incidence of TLS with VenG highlights the importance of risk stratification and prophylactic measures. Overall, the results support the VenG regimen as an effective frontline treatment option.
KANDLELIT-014: A phase 2 study of MK-1084 as monotherapy and in combination with cetuximab in <i>KRAS</i> G12C-mutant advanced solid tumors.
TPS3185 Background: KRAS is one of the most frequently mutated oncogenes in human cancers, with the G12C mutant isoform accounting for ~15% of all KRAS mutations. Despite their promising antitumor activity and manageable safety profile in advanced solid tumors, first-generation KRAS G12C inhibitors are often limited by acquired resistance in the monotherapy setting. MK-1084 is a next-generation, highly potent and selective KRAS G12C–GDP covalent inhibitor that exerts downstream regulation of the MAPK pathway. EGFR-mediated reactivation of RAS-MAPK signaling is proposed as a key driver of resistance to KRAS G12C inhibitors, particularly in colorectal cancer (CRC). The combination of KRAS G12C inhibitors and EGFR-targeted monoclonal antibodies has demonstrated clinical benefit in KRAS G12C-mutated CRC and non-small cell lung cancer (NSCLC), supporting the potential of this mutation as a clinically-relevant target across tumor types. KANDLELIT-014 (NCT07209111) is a phase 2, randomized, open-label, multicenter, tumor-agnostic study of MK-1084 as monotherapy and in combination with EGFR inhibitor cetuximab in participants with previously treated advanced solid tumors harboring a KRAS G12C mutation. Methods: Eligible participants are aged ≥18 years with histological or blood-based KRAS G12C-mutated locally advanced unresectable or metastatic solid tumors (other than CRC) that have progressed on or following standard-of-care systemic treatment, or for whom no satisfactory alternative treatment options are available. Additional eligibility criteria include an ECOG PS score of 0 or 1 and measurable disease per RECIST v1.1. Participants were excluded if they had uncontrolled, significant cardiovascular or cerebrovascular diseases; an additional progressive active malignancy that required treatment within the past 3 years; or active CNS metastases, carcinomatous meningitis, or primary brain tumors. Participants will be randomly assigned 1:1 to receive MK-1084 100 mg orally once daily as monotherapy (Arm 1) or in combination with cetuximab 500 mg/m 2 intravenously every 2 weeks (Arm 2) until discontinuation criteria are met. Randomization will be stratified according to the following tumor groups: NSCLC, pancreatic ductal adenocarcinoma, endometrial cancer, biliary tract cancer, and other solid tumors. The primary end points are ORR per RECIST v1.1 as assessed by blinded independent central review (BICR), safety, and tolerability. Key secondary end points include OS, DOR per RECIST v1.1 by BICR, and PFS per RECIST v1.1 by BICR. Imaging will be performed every 6 weeks until Week 18, every 8 weeks until Week 50, and every 12 weeks thereafter until disease progression or discontinuation. AEs will be evaluated from randomization to 30 days after the last dose of study treatment per NCI CTCAE v5.0. This global study is actively enrolling. Clinical trial information: NCT07209111 .
Impact of first-line comprehensive genomic profiling on survival outcomes for patients with advanced solid tumors who received molecularly-matched therapies: 3-year follow-up of the prospective FIRST-Dx study.
3134 Background: Comprehensive genomic profiling (CGP) by next-generation sequencing has been reimbursed in Japan since 2019. However, only 8.2% of patients (pts) had received molecularly-matched treatments. One major reason for this limited drug accessibility is that CGP is covered only after progression with standard of care (SoC). We previously reported that first-line CGP using FoundationOne CDx in advanced solid tumors (FIRST-Dx study) could identify molecular-based recommended therapy (MBRT) for 61% of pts (105/172), and 22.7% (39/172) could be treated by MBRT (JAMA Netw Open 2023, Cancer Sci 2025). To evaluate the impact of the first-line CGP test on survival outcomes, a 3-year follow-up analysis was conducted. Methods: The FIRST-Dx study was a multi-institutional prospective study in Japan. A total of 172 chemotherapy-naïve adult pts with advanced solid tumors (GI, Lung, Breast, GYN, Melanoma) and ECOG performance status of 0-1 were registered. This follow-up study was planned for 3 years after the final patient enrollment. The primary endpoint was overall survival (OS). Secondary endpoints were the proportion of pts receiving MBRT, overall response rate, progression-free survival (PFS), and PFS ratio (PFS on MBRT/PFS on prior therapy). Results: Median follow-up period was 25.0 months (0.5–45.2). Forty-six pts (26.7%) received MBRT. The number of pts treated with MBRT was 21 in the 1st-line, 22 in the 2nd-line, 6 in the 3rd-line, and 6 in the 4th-line or later setting. Median OS was significantly longer in pts treated with MBRT (not reached) than in those who did not receive MBRT (26.2 months, HR 0.62 [95% CI: 0.39–0.99], log-rank p=0.047). PFS and response rates were shown in Table. Among pts who received 2nd-line MBRT (N=15), the median PFS ratio (PFS on MBRT in 2nd-line/PFS on 1st-line therapy), was 1.2 (range: 0.4–14.6), and 7 pts (47%) achieved a PFS ratio of >1.3, indicating a clinically meaningful benefit of the first-line CGP based MBRT. In an exploratory analysis, propensity score matching (age, sex, cancer type) was performed between pts registered in this study and concurrent real-world pts who did not undergo the first-line CGP, resulting in 67 pts per group. Median OS was significantly longer in the FIRST-Dx group than in the real-world group (23.5 months vs 13.4 months, HR 0.61 [95% CI: 0.40–0.94], log-rank p=0.02). Conclusions: MBRT identified by CGP in the first-line setting improved access to targeted therapies and was associated with superior survival outcomes than SoC in advanced solid tumors. Our data suggest that CGP in Japan should be available prior to SoC initiation. Clinical trial information: jRCT1050220041. Median progression-free survival and response rate. MBRT SoC p-value Median PFS (months) 1st-line 13.7 11.3 0.04 2nd-line 11.0 5.6 <0.01 Response Rate (%) 1st-line 52.4 37.8 0.24 2nd-line 45.5 13.2 <0.01
Institutional disparities in actionable mutation detection in pancreatic ductal adenocarcinoma: An AACR Project GENIE analysis.
e16378 Background: The identification of actionable mutations in pancreatic ductal adenocarcinoma (PDAC) informs eligibility for precision therapies. However, institutional disparities in the implementation of comprehensive genomic profiling (CGP) are not well characterized. Notably, more than half of cancer patients in the United States receive care in community oncology settings. Methods: A total of 9,273 PDAC samples from the AACR Project GENIE (v18.0) were analyzed to compare academic medical centers and community practices. Actionable mutations assessed included homologous recombination deficiency (HRD) genes (BRCA1, BRCA2, PALB2, ATM), oncogenic drivers (KRAS, BRAF), and fusion targets (NTRK1/2/3). Statistical significance was determined using Chi-square and Fisher exact tests. Results: The academic centers accounted for 88.1% of the samples (8,167/9,273) compared to 11.9% (1,106/9,273) from the community practices. The community panels had a smaller median size (82 vs 328 genes, p < 0.001), however, 93% of the community samples were from one network using comprehensive panels (613 genes), resulting in an average of 543 genes per patient compared to 690 genes per patient in the academic setting. Despite this slight difference in testing comprehensiveness, mutation detection varied significantly across all categories (all p < 0.001) (Table). Based on academic detection rates, a significant proportion of community patients may have missed eligibility for targeted therapy: HRD 107 (91% of expected) including 61 BRCA1/2 (92%), BRAF 23 (92%), and NTRK 40 (98%). An additional 831 patients with KRAS-mutations (87%) were undetected, missing clinical trial access for emerging KRAS inhibitors. Conclusions: Community PDAC patients face considerable inequities in actionable mutation detection, with 7- to 13-fold lower detection rates for common alterations, and up to 41-fold for rare fusions, despite only 1.3-fold difference in average genes tested per patient. These disparities likely stem from variations in gene panel content, testing algorithms, or variant interpretation rather than sequencing capacity alone. Standardized CGP with quality assurance across all practice settings and academic-community partnerships is urgently needed to ensure equitable access to precision oncology. Actionable mutation detection rates. Category Genes Community n (%) Academic n (%) Fold Diff HRD (Individual) BRCA1/2 5 (0.45) 487 (5.96) 13x PALB2 1 (0.09) 105 (1.29) 14x ATM 6 (0.54) 399 (4.89) 9x HRD Combined All 4 genes* 11 (0.99) 875 (10.71) 11x Oncogenic Drivers KRAS 128 (11.57) 7084 (86.74) 7.5x BRAF 2 (0.18) 183 (2.24) 12x Fusion Targets NTRK1/2/3 1 (0.09) 301 (3.69) 41x *BRCA1+BRCA2+PALB2+ATM. All comparisons p<0.001.
Response to neoadjuvant chemoimmunotherapy in EGFR- or ALK-mutated non-small cell lung cancer.
8054 Background: The role of immunotherapy in non-metastatic EGFR-and ALK-mutated lung cancer is limited, in part because of a lack of efficacy, and partly because of the high response rates to mutation-targeting therapies. However, a subset of immunotherapy-responsive lung cancers may be cured, but only if immunotherapy is included in the treatment strategy. Therefore, a blanket exclusion of all EGFR-and ALK-mutated patients from immunotherapy may restrict a small subset of patients from a potentially curative option. Our objective was to determine the rate of highly immunotherapy-responsive tumors harboring EGFR and ALK mutations. Methods: Adult patients in the NCDB with clinical stage I-III NSCLC diagnosed between 2021 and 2023 and treated with neoadjuvant chemoimmunotherapy followed by definitive surgery (wedge resection, segmentectomy, lobectomy, or pneumonectomy) were included. Outcomes were pathologic complete response (pCR, defined as pathologic T0N0 after definitive resection) and nodal downstaging (pathologic N lower than clinical N stage). Covariates of interest for univariate analyses and multivariable logistic regression were year of diagnosis, region, age, sex, race/ethnicity, insurance, Charlson-Deyo score, clinical stage, and receipt of neoadjuvant immunotherapy. Results: Of 3,107 eligible patients, 1,133 (36.4%) were tested for EGFR and/or ALK mutations. Overall, 132 (11.7%) patients were found to have mutation(s) in EFGR (99 patients), ALK (27 patients) or both (6 patients). Among those with cN1-3 tumors, nodal downstaging was observed in 57.4% of patients with EGFR/ALK mutations and 74.2% of wild-type patients (p<0.001). The rate of pCR was 16.7% in EGFR-/ALK-mutated patients, and 30.9% in wild-type patients (p<0.001). Higher tumor grade was associated with significantly higher odds of pCR in EGFR/ALK wild-type patients (OR 2.448, 95% CI 1.58-3.89, p<0.001), but not in EGFR-/ALK-mutated patients (OR 2.63, 95% CI 0.37-18.74, p=0.33). Conclusions: While a less common practice, neoadjuvant chemoimmunotherapy in patients with EGFR-/ALK-mutated NSCLC demonstrated a pCR rate of 17% in this large real-world NCDB cohort. Further study on the role of neoadjuvant chemoimmunotherapy for this population is indicated given the potential for curative response, particularly in patients with mutations lacking effective targeted therapy. Mutation Type EGFR/ALKwild-type (n=1152) EGFR-/ALK- mutated (n=132) p EGFR (n=105) Exon 18, 19, 20, and/or 21 54 (51.4%) Other exon 11 (10.5%) ALK (n=33) EML4-ALK, KIF5B-ALK, TFG-ALK, and/or KLC1-ALK 13 (39.4%) Other rearrangement 10 (30.3%) Response Outcomes Nodal Downstaging (pN < cN), cN1-3 patients only 482/650 (74.2%) 50/87 (57.4%) <0.001 Complete Pathologic Response (ypT0N0) 356 (94.2%) 22 (16.7%) <0.001
Efficacy and safety of tislelizumab as neoadjuvant therapy combined with MRD monitoring in locally advanced dMMR/MSI-H colon cancer: A prospective pilot study.
3651 Background: PD-1 blockade has demonstrated high efficacy in metastatic and neoadjuvant settings for dMMR/MSI-H colorectal cancer. This study aimed to evaluate the efficacy and safety profile of neoadjuvant tislelizumab monotherapy in locally advanced dMMR/MSI-H colon cancer patients, with integrated minimal residual disease (MRD) monitoring. Methods: Histologically confirmed locally advanced dMMR/MSI-H colon adenocarcinoma are eligible for enrollment. Participants received 4 cycles of neoadjuvant tislelizumab (200 mg IV Q3W) followed by clinical response assessment. Patients continued receiving 4 additional cycles or underwent radical surgery based on the multidisciplinary team (MDT) decision. Non-operative management (NOM) was a choice of cCR patients after 8 cycles of treatment. MRD status was assessed by a tumor-informed, bespoke ctDNA assay (HuaJianwei) at baseline, during and post-treatment. The primary endpoint was pCR rate. Secondary endpoints included cCR rate, MPR rate, DFS, NOM rate, biomarker exploration, and safety. Results: Forty patients were enrolled between November 2022 and May 2025 (median follow-up: 13.58 months) and one requested to withdraw from the study. Twenty-eight (71.8%) underwent surgery, including 8 patients who received less than 6 cycles of neoadjuvant therapy, 18 patients who completed 8 cycles, and 2 patients who received more than 8 cycles based on MDT decision. Of resected patients, 22 (78.6%) achieved pCR and 26 (92.9%) achieved MPR. Nine patients opted for NOM due to cCR, with an overall CR rate of 79.5%. Grade 3 irAEs occurred in 4 patients (10.3%), including pneumonitis (n=2), renal insufficiency (n=1), and stroke (n=1). No treatment-related deaths occurred. Baseline MRD testing was completed in 29 patients, 28 (96.6%) of whom were positive. Rapid clearance of MRD was observed in 48.3% (14/29) of patients after 1 cycle and 75.9% (22/29) of patients after 2 cycles. Only one patient (1/10) remained MRD-positive post-treatment due to pneumonitis-related therapy discontinuation. Conclusions: Neoadjuvant tislelizumab monotherapy confers favorable efficacy and a manageable safety profile in locally advanced dMMR/MSI-H colon cancer with high pCR rates and feasible NOM for cCR patients. MRD monitoring provides valuable, real-time assessment of treatment response to guide surgical and surveillance decisions. Longer follow-up is needed to confirm response durability, particularly in NOM patients. Clinical trial information: NCT06262581 .
Factors contributing to non-initiation of planned systemic therapy among inpatients evaluated for a phase II randomized controlled oncology trial.
e23353 Background: The Spine Patient Optimal Radiosurgery Treatment for Symptomatic MEtastatic Neoplasms (SPORTSMEN) multicenter phase II randomized controlled trial (clinicaltrials.gov ID NCT05617716) evaluates radiation therapy (RT) for symptomatic spinal metastases with the primary endpoint of pain relief at 3 months post-treatment. Among inpatients, a validated Inpatient Metastatic Spine Score (IMSS) (PMID 40025847) identifies patients with sufficient anticipated survival to meet the SPORTSMEN primary endpoint. Because receipt of systemic therapy strongly contributes to survival in metastatic disease, patient eligibility to receive systemic therapy is a component of the IMSS. Understanding why intended systemic treatment does not occur may refine identification of patients most likely to benefit from RT. Methods: Inpatients at a National Cancer Institute-designated cancer center evaluated for SPORTSMEN initially planned for but ultimately not receiving systemic therapy were retrospectively evaluated. Clinical characteristics, trial enrollment status, radiation treatment, functional status, hospitalization events, IMSS (based on initial documented intent for systemic therapy), and treatment decisions were abstracted from the electronic medical record. Review of medical oncology documentation and goals of care discussions identified changes in treatment planning. Results: Three patients were identified. All patients met SPORTSMEN eligibility criteria (including documented IMSS prognosticating life expectancy > 3 months) and had documented Medical Oncology plans for systemic therapy at the time of trial enrollment consideration. Baseline ECOG performance status ranged from 1 to 3. Documented decline in performance status following evaluation (occurring over a median of 5 days) and changes in goals of care primarily drove treatment non-initiation. Changes from initial support of systemic therapy to documented non-initiation occurred over a median of 6 days. Two patients transitioned to hospice shortly after evaluation, and one transitioned to palliative-intent care. The median time from SPORTSMEN evaluation to transition in care goals was 10 days. Two of these three patients would not have qualified for SPORTSMEN enrollment by IMSS had the decision to withhold systemic therapy been initially communicated. Conclusions: Among inpatients evaluated for the SPORTSMEN trial where initial Medical Oncology documented intent for systemic therapy was withdrawn, reversal occurred over a period of six days. This timeframe should be considered for inpatients being considered for trial enrollment with regard to overall prognosis. Integration of longitudinal functional assessments and early goals of care discussions alongside validated prognostic tools may improve identification of patients most likely to benefit from RT.
Retrospective evaluation of immune checkpoint inhibitors in soft tissue sarcoma.
e23570 Background: Soft tissue sarcomas (STS) are rare, and metastatic disease confers a poor prognosis. There are limited treatment options for systemic disease, and standard chemotherapy is the first line for many subtypes. Given the success of ICI (immune checkpoint inhibitors) in many solid tumors, ICI has been investigated in STS as well. This retrospective observational study aimed to investigate the efficacy of ICI in STS. Methods: We queried the Global Collaborative Network, comprising 170 HealthCare Organizations, using the TriNetX research platform, a federated network of de-identified electronic medical records, for identifying patients with soft tissue sarcoma (STS) using ICD10CM as well as ICD-O codes. Population was divided into two cohorts based on receipt of ICI. Propensity score matching (1:1 greedy nearest-neighbor, caliper 0.1) was performed for age, race, gender, and comorbidities. Kaplan–Meier survival analysis and comparative statistics were performed. Using the Cox proportional hazards model, we explored the effect of covariates including sex, age at index, race, marital status, obesity, nicotine dependence, alcohol use. Results: 14,623 STS cases were identified, of which 363 received ICI. Patients who received ICI were older (61.2 ± 16.4 vs 56.1 ± 19.2 years, p< 0.001), predominantly whites (75% vs 50%, p < 0.001); no significant difference in gender (males: 54% vs 49%, p = 0.0785). Prior to PSM, median follow up period was 358.5 days in ICI group and 846 days in non-ICI group. Survival probability at the end of time window was lower in ICI group (10.57% vs 22.56%, p < 0.001). After PSM, the group which received ICI had lower survival probability (11.26% vs 29.31%, p < 0.001), with median OS of 520 days in ICI group compared to 3161 days in non-ICI group. On reviewing the cox proportional hazard models, it was seen that nicotine dependance (HR 1.266 (1.096, 1.462), p = 0.0013), being male (HR 2.977 (2.589, 3.423), p < 0.001), or older age at index (HR 1.148 (1.076, 1.224), p < 0.001) increased the risk of death, while being married (HR 0.877 (0.815, 0.945), p = 0.0005)) decreased the risk of death. Conclusions: Our study aids in providing real-world data regarding the use of ICI in STS. In literature, we have seen no significant difference between ICI and SOC with OS ranging from 6.1 - 17 months with ICI. Even though our study did not show any survival benefit compared to non-ICI cohort, the median OS of ~17 months in ICI group is equivalent to current literature. STS are heterogenous disease, and further studies are required to determine which histologic subtype would benefit most from ICI.