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The mediating roles of psychological resilience and social support in the relationship between phubbing and psychological distress in adolescents

Scientific Reports Mehmet Sıddık Vangölü Jun 01, 2026 DOI: 10.1038/s41598-026-55006-w

Preferences among women for home-based self-sampling over clinic-based provider-collection for cervical cancer screening in the US.

Journal of Clinical Oncology Joel Fokom Domgue, Monalisa Chandra, Olajumoke Oladoyin et al. Jun 01, 2026 DOI: 10.1200/jco.2026.44.16_suppl.e22572

e22572 Background: Self-sampling for human papillomavirus testing is an evidence-based strategy that can improve cervical cancer screening access and increase screening uptake among under-screened populations. However, preference for and drivers of home-based self-sampling over clinic-based testing (the current standard of care) have not yet been fully studied among screening-eligible women in the US. Methods: Using the 2024 US Health Interview National Trends Survey (HINTS 7) data, we conducted a cross-sectional analysis of women eligible for cervical cancer screening to assess their perspectives about at-home self-sampling for cervical cancer screening and factors associated with preferring this sampling method. We also examined reasons for considering home-based self-sampling for cervical cancer screening. Results: Among the 2,300 women (mean age: 45.5 years, SD: 29.2) included in this study, most were non-Hispanic Whites (60.3%), married/living as married (58.2%), insured (91.9%), and educated up to post-high school or some college (61.6%). Of these, 20.4% preferred at-home self-sampling, 60.8% preferred clinic-based testing, and 18.8% were uncertain about their choice. Non-Hispanic Black women (aOR: 0.45 [95% CI: 0.21–0.96]) had lower odds of preferring at-home self-sampling over clinic-based testing compared to Non-Hispanic Whites. Women who had experienced prejudice or discrimination when getting medical care had higher odds (1.94 [1.16–3.22]) of preferring at-home self-sampling. The most commonly reported reasons for preferring at-home self-sampling were: privacy (54.9%), time constraints (35.1%), and avoiding embarrassment (33.4%). Conclusions: A small proportion of cervical cancer screening-eligible women in the US prefer at-home self-sampling over clinic-based testing. To address cervical cancer inequities and increase screening uptake among under-screened populations, US guidelines should incorporate this innovative screening strategy, and targeted interventions to promote home-based self-sampling are needed.

Longitudinal assessment of circulating tumor cells (CTCs) in the peripheral blood of patients with metastatic breast cancer (MBC) on treatment with CDK4/6 inhibitors.

Journal of Clinical Oncology Sofia Agelaki, Sofia Chatziavraam, Anna Stylianou et al. Jun 01, 2026 DOI: 10.1200/jco.2026.44.16_suppl.e13064

e13064 Background: The detection and enumeration of circulating tumor cells (CTCs) in the peripheral blood is an independent poor prognostic factor for patients (pts) with metastatic breast cancer (MBC), while longitudinal CTC assessment holds promising role also as a real-time biomarker for monitoring treatment efficacy and disease progression. CDK4/6 inhibitors represent a key treatment option for hormone receptor-positive (HR+) MBC. We herein aimed to assess the clinical value of CTCs and their kinetics for HR+ MBC pts treated with CDK4/6 inhibitors. Methods: Peripheral blood (PB) was obtained from pts with HR+ MBC: a) at baseline before the start of CDK4/6 inhibitors plus endocrine treatment (N = 39), and b) at the first evaluation of treatment response (N = 24/39 pts; paired samples). CTCs were in parallel isolated using Ficoll density gradient centrifugation, and the automated size-based Parsortix system (ANGLE plc). CTC detection and enumeration was performed by immunofluorescence staining for cytokeratins (CKs)/CD45/dapi and observation via fluorescence microscopy. Results: CTCs (CK+/CD45- cells) were detected by any assay in 15/39 (38.5%) of pts at baseline and in 5/24 (20.8%) at the first evaluation, with a total of 71 and 25 CTCs identified, respectively (mean CTC No per patient: n = 1.82 and 1.04). Overall 12 pts (50%) were CTC-positive at any time point, whereas 12 pts (50%) were consistently CTC-negative at both time points. A significant overall reduction in CTCs counts was observed from baseline to first evaluation (Sum of Ranks: 65 vs 13, p = 0.038, Wilcoxon t test). No associations were found between CTC detection or their kinetics, with clinicopathological features or treatment response. However, Kaplan Meier analysis revealed significantly reduced overall survival (OS) rates among pts with ≥ 5 CTCs at baseline (median OS: 18.0 versus 48.4 months; p = 0.010), at first evaluation (median OS: 18.0 versus 47.2 months; p = 0.000), or at any time point (median OS: 18.0 versus 47.2 months; p = 0.013). Conclusions: CTCs numbers significantly decreased during treatment in HR+ MBC pts receiving CDK4/6 inhibitors. The presence of ≥5 CTCs at any time point was strongly associated with significantly reduced overall survival, supporting their role as a negative prognostic biomarker in HR+ MBC.

Conditional survival in advanced melanoma treated with immune checkpoint inhibitors.

Journal of Clinical Oncology Chloe Lim, Thi Phuong Le Nghiem, Arkhjamil Angeles et al. Jun 01, 2026 DOI: 10.1200/jco.2026.44.16_suppl.12108

12108 Background: Immune checkpoint inhibitors (ICI) have improved survival in advanced melanoma, with some patients achieving durable remissions. Traditional survival estimates at diagnosis do not reflect how prognosis changes over time. Conditional survival (CS) provides a framework for time-dependent prognostication in long-term responders. Methods: We conducted a population-based retrospective cohort study of patients with unresectable/metastatic cutaneous melanoma treated with ≥1 dose of PD1-inhibitor based therapy in British Columbia (2012 -2022). Progression-free survival (PFS), overall survival (OS), and melanoma-specific survival (MSS) were estimated using Kaplan–Meier methods. Median follow-up was estimated using reverse Kaplan-Meier methods. Conditional PFS was calculated from ICI initiation and stratified by baseline characteristics and treatment response. Results: Among 897 patients, median age was 65 years (range 19-99); 48% (n=436) were M1c-d and 32% (n=290) received dual ICI. Median follow-up was 6.0 years (95% CI 5.7-6.3) and median OS was 3.2 years (95% CI 2.8-3.8); 5- and 10-year OS rates were 41% and 27%, respectively, while MSS rates were 49% and 38%, respectively. 5- and 10-year PFS rates were 31% and 22%, respectively. Conditional PFS analyses showed a decreasing risk of progression over time, most pronounced in patients achieving a complete response (Table 1). At 3-years post ICI initiation, patients in a complete response had a 5-year conditional PFS rate of 91% (95% CI 85-95%). Further analysis will assess whether their mortality normalizes relative to age- and sex-matched population controls to contextualize long-term survivorship. Conclusions: CS demonstrates dynamic improvement in prognosis among advanced melanoma patients who remain progression-free after ICI and provides clinically meaningful, time-updated prognostic information to guide patient counseling and follow-up strategies. Five-year conditional PFS rate at ICI initiation (year 0) and subsequent PFS timepoints. Strata (%; 95% CI) Year 0 Year 1 Year 2 Year 3 Year 4 All patients 31% (28-34%) 53% (48-57%) 67% (62-72%) 80% (75-84%) 90% (85-93%) ECOG 0 or 1 34% (31-38%) 55% (50-59%) 68% (63-73%) 81% (76-85%) 90% (85-94%) ECOG >=2 17% (11-24%) 42% (28-55%) 60% (40-75%) 72% (48-86%) 86% (55-96%) M0/M1a/M1b 33% (29-38%) 52% (46-58%) 67% (60-73%) 81% (73-86%) 90% (83-94%) M1c/M1d 29% (25-33%) 54% (47-60%) 67% (59-74%) 79% (71-85%) 90% (82-94%) Complete response 77% (71-82%) 82% (76-87%) 88% (82-92%) 91% (85-95%) 95% (90-98%) Partial response 27% (21-33%) 36% (28-43%) 50% (41-59%) 68% (57-78%) 88% (76-94%) PD1-inhibitor only 28% (24-32%) 47% (42-52%) 62% (56-68%) 77% (70-82%) 89% (83-93%) PD1 with CTLA4 38% (32-44%) 66% (57-73%) 78% (69-85%) 87% (77-93%) 92% (82-96%)

A phase 2 study of darolutamide plus leuprolide acetate in hormone therapy–naïve recurrent and/or metastatic androgen receptor (AR)–positive salivary gland cancer (ETCTN 10553).

Journal of Clinical Oncology Alan Loh Ho, Varinder Kaur, Shetal Arvind Patel et al. Jun 01, 2026 DOI: 10.1200/jco.2026.44.16_suppl.6012

6012 Background: A subset of salivary gland cancers (SGCs) express the androgen receptor (AR). A prior AR+ SGC trial with the anti-androgen enzalutamide alone failed to meet its primary endpoint. This is a multicenter, phase II study evaluating the efficacy and safety of the anti-androgen darolutamide (Bayer) in combination with androgen-deprivation therapy (ADT; leuprolide acetate) in hormone-therapy naïve patients with AR+ SGCs. Methods: Patients with locally advanced/unresectable or recurrent/metastatic AR+ SGCs were enrolled. AR status was determined locally by immunohistochemistry (IHC). Prior AR-targeted therapy was not allowed, unless administered in the neoadjuvant and/or adjuvant setting >6 months before disease recurrence. Darolutamide 600 mg orally twice daily was given with leuprolide acetate intramuscular injections (1 cycle= 28 days). The primary endpoint was best overall response (BOR) rate according to RECIST v1.1 within 1 year of initiating treatment. Secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity. Exploratory endpoints were evaluating biomarkers in serially obtained research biopsies and exploring efficacy among patients who had not received prior systemic therapy. A two-stage minimax design was used to detect a 50% BOR rate (vs. 25%) (alpha = 9%; beta = 83%). ≥3 responses in the first 9 patients would trigger accrual to 20; ≥8 responses would be considered promising. Results: Study accrual of 20 patients (pts) with AR+ SGCs was completed on 10/30/25. 15 males, 5 females with a median age of 70.5 years were enrolled. Among the 9 pts in the first stage, 6 confirmed partial responses (PRs) were observed, allowing for full study accrual. With a data cutoff of 1/21/26, the best RECIST v1.1 responses among 20 pts were 8 (40% [19.1% 63.9%]) PRs (7 confirmed, 1 unconfirmed with pt still on treatment), 10 (50% [27.2%, 72.8%]) stable disease (SD), 1 (5% [1%, 24.9%]) progression of disease; 1 pt on treatment has not had radiographic assessments yet. 6 (30% [11.9%, 54.3%]) pts came off trial for disease progression, 1 (5% [1%, 24.9%]) withdrew consent after 6 cycles, and 13 (65%, [40.8%, 84.6%]) remain on treatment. Among 5 female pts, best responses were 1 (5% [1%, 24.9%]) PR, 3 (15% [3.2%, 37.9%]) SD, 1 (5% [1%, 24.9%]) PD. With additional follow-up, PFS, OS, and biomarker data (AR IHC %, HER2 status) will be presented. Conclusions: In this molecularly selected cohort of patients with SGC, darolutamide plus ADT possesses significant clinical activity, validating AR as a relevant therapeutic target in a subset of SGCs. Analysis of serial research biopsies will be performed to identify biomarker and/or drug combination strategies to enhance the efficacy of AR-targeting. Clinical trial information: NCT05669664 .

Treatment response and clinical outcomes of patients with triple negative invasive apocrine breast carcinoma.

Journal of Clinical Oncology Courtnie Brown, Paige Brown, Alexis Ann LeVee et al. Jun 01, 2026 DOI: 10.1200/jco.2026.44.16_suppl.e12727

e12727 Background: Invasive apocrine carcinoma (IAC) is a rare subtype of breast cancer that is classically triple negative (TN) and associated with lower grade and proliferation rates compared to ductal triple negative breast cancer. Despite these pathologic features that suggest a lack of response to cytotoxic chemotherapy, apocrine and non-apocrine breast cancers are commonly managed with similar systemic treatment approaches. We investigated the treatment courses and outcomes of patients with TN-IAC. Methods: We conducted a retrospective cohort study using electronic medical record review of patients diagnosed with early-stage IAC treated at a single academic institution to determine treatment courses and outcomes. We identified patients in which “apocrine” was used as a descriptor of pathology. Given inconsistent pathologic definitions, patients were classified into two groups. Classical apocrine (c-IAC) tumors were defined as TN disease with pathology specifically designated as “IAC” or invasive ductal carcinoma with apocrine features with low grade (grade 1–2) and Ki-67 ≤ 20%. The “Other Apocrine” group consisted of those patients with high grade disease with apocrine features, Ki-67 > 20%, and/or HER2 or hormone receptor positivity. Patients with de novo metastatic disease and those without invasive disease were excluded. Data collected included clinicopathologic characteristics and type of local/regional and systemic therapies received. Our primary outcome was recurrence free interval (RFI) defined as the absence of recurrence from the time of diagnosis to the last documented follow up date. Results: We identified 69 cases with apocrine used as a descriptor of pathology. Of those 69, we identified 18 c-IAC cases and 41 Other Apocrine cases. c-IAC patients were more likely to have chemotherapy omitted (39% vs 5%, p value of .024). In the c-IAC group there were 0 recurrences over the median follow up of 52.7 months. Among the Other Apocrine patients there were 13 recurrences over the median follow up of 104.5 months. Conclusions: Patients with TN c-IAC had no documented recurrences and were less likely to receive chemotherapy than patients with other types of apocrine-related carcinoma of the breast. Classical apocrine carcinoma of the breast represents an identifiable subtype of breast cancer which may allow for chemotherapy de-escalation. Cohort characteristics. Category c-IAC (n=18) Other Apocrine (n=41) Age (median, range) 67.5 (44-89) 62 (30-87) ER+ (>10%) (%) 0 (0) 16 (39) HER2+ (%) 0 (0) 15 (37) Elevated Ki67 ≥ 20% (%) 3 (17) 22 (54) Tumor Size in cm (median, range) 1.7 (0.8-4.1) 2.0 (0.3-11.0) Node positive (%) 3 (17) 16 (39) Receipt of chemotherapy (%) 11 (61) 39 (95) Median Follow Up (months) 52.7 (3.7-171.8) 104.5 (<0.1-292.6) Recurrence, n (%) 0 (0) 13 (32%)

Impact of being aged 80 years and older on treatment decision-making: Discrepancies in cancer care and associated outcomes.

Journal of Clinical Oncology Lisa Liu, Mustafa Shehadeh, Alvaro Zevallos Barboza et al. Jun 01, 2026 DOI: 10.1200/jco.2026.44.16_suppl.e13770

e13770 Background: Patients aged ≥80 years old (yo) account for ~14% of lung cancer (LC) diagnoses, yet are often underrepresented in clinical trials. We characterized the demographics, clinical features, treatment (tx) patterns, and outcomes of Veterans aged ≥80 with LC treated in a single-center VA cohort. Methods: Utilizing the VA Informatics and Computing Infrastructure (VINCI) database, we performed a retrospective study looking at patients ≥80 with a diagnosis of LC between 01 Jan 2014 and 01 Mar 2025 at a single VA medical center. Overall survival (OS) was estimated using the Kaplan–Meier (KM) method and differences were assessed using the log-rank test in R (Ver 4.5.1). Results: We included 184 patients (98.4% male), with a median age of 84. Race was 53.3% Black, 37.0% White, and 9.8% other/unknown. Most had a smoking history (94.4%). Histology was 81.0% non–small cell LC, 9.2% neuroendocrine carcinoma, and 9.8% unknown. Stage distribution was 47.8% I, 8.2% II, 9.3% III, 25.3% IV, and 9.4% unknown. Among stage I–II (n = 102), 61.8% underwent surgery (SG), 25.5% received non-surgical tx (radiation (RT)/chemotherapy (CT)/immunotherapy (IO)), and 12.6% received no tx. Among stage IV (n = 46), 34.8% received CT, 28.3% received other tx (RT/SG/IO), and 37.0% received no tx. Married patients were more likely to receive tx than unmarried (86.3% vs 64.7%). Palliative care consultation occurred in 19.2% of patients. NGS was performed in 24 patients, yielding 22 results; TP53 was most common (73%), followed by CDKN3A (13.6%) and KRAS (13.6%). Median and 5-year OS are illustrated in Table 1. Conclusions: In Veterans aged ≥80 years with LC, OS was strongly associated with functional status, stage, and tx intensity. These data suggest that advanced age alone should not preclude curative-intent management and support individualized, geriatric-informed tx selection for this population. n (%) a Median Age (IQR) (yo) Median OS (95% CI) (months) p-value 5-Year OS (95% CI) (%) p-value Race Black 98 (59.0) 84.0 (82.0 - 88.0) 48.2 (29.4 - 78.4) 0.85 46.0 (36.7 - 57.6) 0.79 White 68 (41.0) 84.0 (81.8 - 87.0) 49.2 (40.9 - 94.9) 44.2 (33.2 - 58.8) ECOG 0-1 52 (55.9) 84.0 (82.0 - 86.3) 61.3 (47.9 - 127.2) <0.001 57.1 (44.3 - 73.6) <0.001 ≥2 41 (44.1) 84.0 (82.0 - 88.0) 7.8 (4.8 - 27.6) 12.9 (5.7 - 29.1) Stage I-II 102 (62.2) 83.5 (81.0 - 86.0) 78.4 (60.3 - 102.0) <0.001 59.7 (50.3 - 71.0) <0.001 III-IV 62 (37.8) 85.0 (83.0 - 88.0) 6.6 (4.4 - 20.7) 18.4 (10.8 - 31.3) Treatment Local Only (SG, RT) 92 (68.1) 83.5 (81.0 - 86.0) 81.7 (54.2 - 110.5) 0.02 58.7 (48.8 - 70.5) 0.002 Systemic Only (CT, IO) 22 (16.3) 84.5 (83.0 - 86.8) 20.7 (15.3 - 70.6) 24.2 (11.3 - 51.8) Both local and systemic 21 (15.6) 83 (82.0 - 85.0) 85.5 (30.2 - n/a b ) 59.2 (40.7 - 86.2) a Analyses performed using available data. Patients with missing data/small subgroups excluded. Thus, totals may not sum up to the full cohort (n = 184). b Upper confidence limit not reached due to insufficient events.

Oncogenic EGFR amplification in EGFR-mutated NSCLC: EGFR subtype–dependent association with benefit from first-line osimertinib.

Journal of Clinical Oncology Saori Murata, Tatsuya Yoshida, Takashi Ooe et al. Jun 01, 2026 DOI: 10.1200/jco.2026.44.16_suppl.e20534

e20534 Background: De novo oncogenic amplification, including EGFR and MET represents a biologically relevant layer of genomic heterogeneity in EGFR -mutated non–small cell lung cancer (NSCLC) and may influence the clinical efficacy of first line (1L) osimertinib. However, the clinical significance of baseline de novo oncogenic amplification at treatment initiation remains incompletely understood. Methods: We retrospectively identified patients with advanced EGFR -mutated NSCLC who underwent The Oncomine Dx Target Test (DxTT) at National Cancer Center Hospital, Japan (Jan 2020–Aug 2025) and received 1L osimertinib. We reanalyzed the DxTT-generated BAM files using Ion Reporter Software v5.18 (NCCH Oncomine Focus v1.2 workflow). Copy number variants (CNV) amplification such as EGFR and MET was defined as a 5th-percentile estimated copy number ≥4 (≥2 copies above diploid) . PFS was assessed using the Kaplan–Meier method and the Cox proportional hazards model. Data cutoff: January 11, 2026. Results: A total of 109 patients were included in the study. The median age (range) was 66 years (30-86); 76 patients (69.7%) were female and 64 (58.7%) were never smokers. The primary EGFR mutation was ex19 del in 51 (46.8%) and L858R in 50 (45.9%). EGFR amplification was the most frequent (26/109, 23.9%), whereas other potentially actionable amplifications were uncommon, including FGFR1 (3/109, 2.8%), MET (2/109, 1.8%), and ERBB2 (2/109, 1.8%). Overall, PFS did not differ significantly by EGFR amplification status (median PFS [ EGFR amp+ vs. amp-]: 18.4 vs. 15.6 months; p=0.63). In subtype stratified analyses, EGFR amplification was associated with longer PFS in the ex19del subgroup but shorter PFS in the L858R subgroup. An adjusted Cox model showed a significant EGFR amplification-by-subtype interaction (p=0.031). The effect of EGFR amplification (amp+ vs. amp−) differed by subtype: ex19del HR 0.41 (95% CI, 0.16-1.04; p=0.061) versus L858R HR 1.72 (95% CI, 0.66-4.45; p=0.266). Among EGFR amplification positive patients, EGFR copy numbers (CN) were widely distributed (median 11.1; IQR 7.8-22.8; max 106.9), with CN 4-<10 in 42.3%, CN 10-<20 in 26.9%, and CN ≥20 in 30.8%. No clear difference in PFS was observed according to EGFR CN high vs. low as the cutoff 11.1 (HR, 0.75; 95% CI, 0.26–2.19; p = 0.60). In this EGFR amplification subgroup, 8 (30.8%) harbored co-occurring gene amplifications ( MYC [n=3]), and PFS did not differ significantly between EGFR amplification only and EGFR amplification plus other amplifications (median PFS, 13.1 months [95% CI, 8.8-NR] vs. 32.2 months [95% CI, 4.4-NR]; p=0.48). Conclusions: The prognostic association of de novo EGFR amplification with 1L osimertinib benefit appears to be dependent on EGFR subtype, which supports an interpretation and molecular stratification that integrates EGFR subtype and amplification status, beyond EGFR mutation status alone.

Shared and distinct molecular signatures of resistance to different endocrine therapies (Alliance A011106).

Journal of Clinical Oncology Meenakshi Anurag, Yongchao Dou, Jeremy Hoog et al. Jun 01, 2026 DOI: 10.1200/jco.2026.44.16_suppl.566

566 Background: Endocrine therapy (ET) resistance (ETR) remains a primary challenge in ER+ breast cancer. Analyzing pretreatment tumor transcriptomes across trials with early response endpoints can reveal shared and specific ETR signatures. This study utilizes baseline RNA data from the Phase III ALTERNATE trial (Alliance A011106, NCT01953588; Anastrozole [A], Fulvestrant [F], or AF) and the ACOSOG Z1031B trial (NCT00824941) to identify predictors of early Ki67 response in postmenopausal ER+/HER2– patients. Methods: ETR was defined as week-4 on-treatment Ki67 >10%. Baseline gene expression from ALTERNATE was analyzed to identify differentially expressed (DE) genes (Wilcoxon test, P<0.05) and Hallmark pathways associated with ETR, both across and within individual treatment arms. Feature selection was performed using mixOmics. A Pan-Endocrine Therapy Signature (PETS) was developed by uniting DE genes identified across all three ALTERNATE arms and Z1031B. All statistical analyses were conducted in R (P<0.05). Results: Overall ETR rate in the ALTERNATE RNA-seq cohort (n=733) was 26%. ETR was associated with high Risk of Recurrence (ROR), Oncotype RS, and Mammaprint scores (calculated from RNA-seq data in research setting). In luminal tumors (n=649), ETR was linked to chr 3q13.33, 8q24.13, and 20q13.12 cytoband upregulation and 17q21, 18q23, 3p21.1, and 10q24.32 cytoband downregulation. ETR tumors showed T-cell, E2F target, and interferon-γ enrichment; sensitive tumors favored early estrogen response and muscle differentiation. At individual gene level, high MYBL2 , PIF1 , TROAP and with low HJURP predicted ETR across all samples (AUC>0.70). A deep learning model using all protein-coding genes achieved AUC 0.82 (training) and 0.79 (test) in predicting ETR. Cross-trial integration identified ETR-associated PETS, enriched for genomic instability. PETS performed comparably to established signatures and strongly correlated with MYBL2 signature (r=0.93). Top ETR predictors were MYBL2 , AURKB , and EME1 for Arm A and IL4I1 , TNFAIP6 , and ANLN for Arm AF. AF-resistant tumors were enriched for systemic lupus and RIG-I–like receptor signaling; sensitive tumors favored PI3K–AKT, EGFR TKI resistance, AMPK, and insulin signaling. Conclusions: Baseline transcriptomics identify shared and therapy-specific ETR markers. The 15-gene PETS defines a convergent resistance signature, performing similar to established signatures in predicting ETR and correlating with MYBL2. Enrichment of cell-cycle and immune pathways in resistant tumors may suggest patient stratification approach for alternative or combinatorial strategies to overcome early ETR in ER+ breast cancer. Acknowledgement: https://acknowledgments.alliancefound.org. Support: U10CA180821, U10CA180882, U24CA1. Clinical trial information: NCT01953588 .

A systematic review and meta-analysis of cardioprotective effects of SGLT2 inhibitors compared to non-SGLT2 inhibitors in patients receiving cardiotoxic chemotherapy.

Journal of Clinical Oncology Venkata Sai Abhilash Meda, Anjani Mahesh Kumar Cherukuri, Anirudh Bapatla et al. Jun 01, 2026 DOI: 10.1200/jco.2026.44.16_suppl.e24037

e24037 Background: As anticancer therapies advanced over the past decades, cancer-related mortality has decreased, but the risk of cancer therapy-related cardiotoxicity has become an emerging concern in cancer survivors. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have shown protective effects against anthracycline (AC)-induced cardiotoxicity and exhibit partial anticancer effects in animal models. However, clinical evidence for this is scarce. We planned to study the cardioprotective effects of SGLT2 inhibitors in patients undergoing therapy with Cardiotoxic Chemotherapeutic agents. Methods: We conducted a systematic search of PubMed, Embase, and the Cochrane Library and identified Randomized Controlled Trials and observational studies comparing sodium-glucose cotransporter-2 inhibitors (SGLT2i) with non-SGLT2i therapy among cancer patients receiving Cardiotoxic chemotherapy. Outcomes included all-cause mortality, new-onset HF, heart failure (HF) exacerbation, HF hospitalization, myocardial infarction (MI), and arrhythmias. Dichotomous outcomes were pooled using a random-effects model in RevMan Version 5.4 to estimate risk ratios (RRs) with 95% confidence intervals (CIs). Heterogeneity was assessed using the I² statistic. Subgroup analyses were performed for anthracycline-based versus other potentially cardiotoxic chemotherapy regimens. Results: Six studies comprising 30,858 patients were included. SGLT2i therapy was associated with a significant reduction in all-cause mortality overall (RR = 0.54; 95% CI 0.41–0.70; P < 0.00001), with similar benefits in anthracycline-treated patients (RR = 0.48; 95% CI 0.28–0.83; P = 0.008) and in those receiving other cardiotoxic chemotherapy regimens (RR = 0.54; 95% CI 0.33–0.90; P = 0.02). HF hospitalization was significantly reduced with SGLT2i (RR = 0.31; 95% CI 0.18–0.55; P < 0.0001), as was the incidence of new-onset HF (RR = 0.28; 95% CI 0.10–0.82; P = 0.02), whereas HF exacerbation showed a nonsignificant trend toward reduction (RR = 0.60; 95% CI 0.28–1.29; P = 0.19). Arrhythmias were reduced by approximately 48% with SGLT2i therapy (RR = 0.52; 95% CI 0.32–0.85; P = 0.009), with no significant difference observed for MI (RR = 1.44; 95% CI 0.83–2.50; P = 0.20). Conclusions: This study shows a statistically significant reduction in all-cause mortality, heart failure incidence, hospitalizations, and cardiac supraventricular arrhythmias (Atrial fibrillation/flutter) in patients who received SGLT2 inhibitor therapy. Our analysis did not show any significant change in the incidence of Myocardial Infarction or frequency of heart failure exacerbations. This study also provides a foundation for future pharmacodynamic studies aimed at exploring the mechanisms underlying cardio-protection.

Structured oncologist appraisal of AI-generated clinical literature summaries.

Journal of Clinical Oncology Kamal Menghrajani, James DeRosa, Mona Ascha et al. Jun 01, 2026 DOI: 10.1200/jco.2026.44.16_suppl.e23296

e23296 Background: In alignment with the American Society of Clinical Oncology’s guiding principles for responsible use of AI in oncology, particularly accountability, transparency, and oversight, there is a need to understand how AI-generated clinical literature summaries perform under real-world physician review. Although AI tools are increasingly used to synthesize medical literature at the point of care, oncology poses unique challenges due to rapidly evolving evidence, complex guidelines, and comorbid conditions. The frequency and nature of AI-generated errors, and the role of physician oversight in identifying clinically ready outputs, remain incompletely characterized. Methods: We conducted an observational evaluation of AI-generated clinical literature summaries produced within an AI-assisted clinical reference platform (DoxGPT). Physicians performed structured clinical appraisal (PeerCheck), classifying summaries as acceptable for clinical application or rejected, with reasons documented for rejection. Time from outreach to review completion was assessed, as was review consistency among multiple reviewers. Data collection is ongoing, and descriptive statistics are presented. Results: To date, more than 30,000 physician appraisals have been completed across 416,829 AI-generated summaries. For summaries deemed clinically acceptable, the median number of reviewers was 2 (range, 1 to 26). Median time to review was 4 hours from email request. The largest specialty categories were Oncology (n = 39,326, 9.4%), Obstetrics and Gynecology (n = 22,816, 5.5%), and Cardiology (n = 17,511, 4.2%). Overall, 86% of summaries were accepted as ready for clinical application (n = 25,950). Rejection rates varied by specialty (1.8% to 31%), with higher rejection observed in medical genetics (31.3%, n = 96) and lower rejection observed in oncology and interventional radiology (1.8%, n = 59), noting limited sample sizes in some specialties. Among 4,216 rejected summaries, common reasons included missing data (38.8%, n = 1,635), factual errors (28.2%, n = 1,188), oversimplification (13.1%, n = 551), outdated information (8.4%, n = 353), citation errors (6.8%, n = 287), and misunderstanding the clinical question (1.7%, n = 70). Additional oncology-specific analyses will be presented. Conclusions: AI-based clinical reference tools can produce clinically useful outputs but remain prone to identifiable error types. Structured physician oversight is essential to ensure accuracy, completeness, and clinical applicability. In this evaluation, most AI-generated summaries were considered ready for clinical use, and physician review was completed rapidly, supporting the feasibility of timely human oversight. Missing clinically relevant information was the most common cause of rejection, underscoring the value of physician review in strengthening AI-assisted clinical information synthesis.

Phase II study of izalontamab (SI-B001) in combination with paclitaxel or docetaxel in patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).

Journal of Clinical Oncology Ye Guo, Liqiong Xue, Bihui Li et al. Jun 01, 2026 DOI: 10.1200/jco.2026.44.16_suppl.6019

6019 Background: Izalontamab is a bispecific antibody targeting EGFR and HER3. Here we present safety and efficacy results from a phase II study on izalontamab in combination with paclitaxel/docetaxel in patients with R/M HNSCC. Methods: Patients with R/M HNSCC who had progressed on prior anti-PD-(L)1 therapy, with or without platinum-based chemotherapy, and received no more than two prior lines of treatment were enrolled. Izalontamab was administered at 12mg/kg QW in combination with paclitaxel (80mg/m 2 IV QW) (for patients without prior exposure to paclitaxel) or docetaxel (35mg/m 2 IV D1D8D15 Q4W) (for patients with prior exposure to paclitaxel). Primary endpoint was investigator-assessed ORR. Secondary endpoints included PFS, OS, DCR, and DoR. Results: As of Nov 7, 2025, a total of 45 patients (44 HNSCC and 1 sinnonasal) were enrolled, of whom 35 (77.8%) received one prior line of therapy and 10 (22.2%) received two prior lines of therapy. HNSCC patients who received at least one dose of study drug were included in the analysis. Median follow-up was 15.0 months. Overall, ORR was 43.2%, confirmed ORR was 31.8%, median PFS was 4.0 months, and median OS was 10.0 months. In patients treated with izalontamab combo with paclitaxel (n = 34), ORR was 52.9%, confirmed ORR was 41.2%, median PFS was 5.4 months, and median OS was 11.2 months. Grade≥3 TRAEs occurred in 57.8% of patients. The most common grade≥3 TRAE was leukopenia (20.0%), followed by neutropenia (15.6%), rash (13.3%), and anemia (8.9%). One (2.1%) patient discontinued study treatment due to TRAE. No treatment-related death was observed. Conclusions: Izalontamab in combination with paclitaxel showed encouraging antitumor activity and a manageable safety profile in patients with R/M HNSCC who were previously treated with anti-PD-(L)1 therapy. Clinical trial information: NCT05054439 . Izalontamab+Paclitaxel(N=34) Izalontamab+ Docetaxel(N=10) Total(N=44) ORR, % (95% CI) 52.9 (35.1, 70.2) 10.0 (0.3, 44.5) 43.2 (28.3, 59.0) cORR, % (95% CI) 41.2 (24.6, 59.3) 0 31.8 (18.6, 47.6) DCR, % (95% CI) 73.5 (55.6, 87.1) 30.0 (6.7, 65.2) 63.6 (47.8, 77.6) Median DOR (mo) (95% CI) 5.0 (3.7, 11.0) NR (NR, NR) 5.0 (3.7, 11.0) Median PFS (mo) (95% CI) 5.4 (3.9, 6.6) 1.5 (0.4, 3.6) 4.0 (2.8, 5.5) Median OS (mo) (95% CI) 11.2 (6.6, 19.3) 6.6 (0.4, 13.8) 10.0 (6.6, 13.8)

Integrating tumor mutation profiles, preoperative circulating tumor DNA (ctDNA), and clinical features to a predicting model for early peritoneal recurrence in stage II-III gastric cancer following curative gastrectomy.

Journal of Clinical Oncology Quang Thong Dang, Viet Hai Nguyen, Dat Quang Tran et al. Jun 01, 2026 DOI: 10.1200/jco.2026.44.16_suppl.3056

3056 Background: Peritoneal recurrence is the common failure pattern after curative gastrectomy and is most consequential within the first 2 years. Early risk identification can alter treatment strategy. Conventional clinicopathologic models are inadequate for individualized early detection. Tumor-informed circulating tumor DNA (ctDNA) enables detection of minimal residual disease (MRD) and may help refine risk stratification. Methods: We conducted a prospective cohort study of 134 patients with stage II–III gastric adenocarcinoma undergoing curative-intent gastrectomy (MRD cohort). Clinicopathologic variables, tumor mutation profiles, and ctDNA metrics were integrated to train and internally validate machine-learning models using logistic regression, random forest, and XGBoost for the primary endpoint of peritoneal recurrence within 12 months and 24 months after surgery. External validation was performed using the Yang et al. dataset. Results: Among 134 MRD patients with complete molecular and clinical data, 19 (14.2%) and 35 (26.1%) developed peritoneal recurrence within 12 months and 24 months, respectively. ctDNA positivity and higher max variant allele frequency (max VAF) were strong predictors of early peritoneal relapse, with additional contributions from pathologic stage and preoperative CEA, PI3K–AKT or EMT pathway genes. Across algorithms, ctDNA-integrated models consistently outperformed clinical-only baselines, with XGBoost showing the best overall discrimination on cross-validation. Findings generalized on external validation with the Yang et al. dataset, supporting model transportability. Conclusions: Integrating tumor-informed ctDNA with clinical and genomic features enables actionable prediction of early peritoneal recurrence after curative gastrectomy. This tool can trigger strategy modification of either stricter follow-up, adjuvant therapy intensification, or consideration of neoadjuvant approaches, in selected high-risk patients. Multicenter validation and prospective utility studies are warranted. Clinical trial information: NCT05029869 .

Concurrent chemoradiotherapy plus cytokine-induced killer cells therapy or observation in patients with locoregionally advanced nasopharyngeal carcinoma: A ten-year follow-up of a randomized, phase II study.

Journal of Clinical Oncology Xiuyu Cai, Song-Bin Guo, Jiang Li et al. Jun 01, 2026 DOI: 10.1200/jco.2026.44.16_suppl.2558

2558 Background: Concurrent chemoradiotherapy (CCRT) is the standard of care for patients with locoregionally advanced nasopharyngeal carcinoma (NPC). We aimed to evaluate the efficacy and safety of Cytokine-Induced Killer cells (CIK) consolidation therapy in combination with CCRT in these patients. Methods: Patients with locoregionally advanced NPC were randomized in a 1:1 ratio to receive concurrent chemoradiotherapy therapy plus CIK consolidation therapy or concurrent chemoradiotherapy alone in this single-center, randomized, phase II study. The primary endpoints were disease-free survival (i.e., survival period free from disease recurrence [distant metastasis and/or locoregional recurrence] or death from any cause) and overall survival in the intention-to-treat population. Safety was a secondary endpoint. Results: 58 patients were enrolled in this study (29 in the CIK therapy group and 29 in the control group). The median follow-up time was 144.70 months. In the CIK therapy group, the 10-year disease-free survival rate was significantly higher than that in the control group (82.5% versus 61.3%; hazard ratio for recurrence or death, 0.258; 95% confidence interval [CI], 0.094-0.712; P=0.005). The 10-year overall survival rate was 86.2% and 67.5%, respectively; (hazard ratio for death, 0.377; 95% CI, 0.131-1.087; P=0.06). The main adverse effects of CIK was fever which resolved after symptomatic treatment. In the CIK therapy group, 23.1% of patients experienced acute adverse events of grade 3 or 4 versus 17.2% in the control group during CCRT. The most frequent adverse events of grade 3 are mucositis, followed by decreased appetite, marrow suppression. Conclusions: CIK consolidation therapy plus CCRT significantly improved disease-free survival in patients with locoregionally advanced NPC. (This trial is registered with Chinese CilnicalTrial.gov, number ChiCTR-TRC-08000262). Clinical trial information: ChiCTR-TRC-08000262 .

Clinical diagnostic utility of cerebrospinal fluid ctDNA in central nervous system lymphoma: A systematic review and meta-analysis.

Journal of Clinical Oncology Bryan Everth Rudas Sulca, Ivan Alegre-Cordero, Freddy Fabricio Arcos et al. Jun 01, 2026 DOI: 10.1200/jco.2026.44.16_suppl.e15067

e15067 Background: Diagnosis of central nervous system lymphoma (CNSL), including primary (PCNSL) and secondary (SCNSL) forms, is challenging due to the limited sensitivity of conventional cerebrospinal fluid (CSF) studies. Cerebrospinal fluid circulating tumor DNA (ctDNA) analysis has emerged as a minimally invasive liquid biopsy that may complement standard diagnostic approaches. We performed a systematic review and meta-analysis to evaluate the diagnostic performance of CSF ctDNA in CNS lymphoma. Methods: PubMed, EMBASE, Scopus, and Web of Science were systematically searched for studies evaluating ctDNA detection in CSF from patients with suspected or confirmed CNS lymphoma. Random-effects meta-analyses of proportions were conducted, with prespecified subgroup analyses for PCNSL and SCNSL. Comparative analyses of CSF versus plasma ctDNA detection were performed when available. Risk of bias was assessed using QUADAS-2. Results: Fourteen studies including 370 CSF samples were analyzed. The pooled ctDNA detection rate in CNS lymphoma was 0.70 (95% CI 0.63–0.75; I² = 1.8%). Detection rates were similar in PCNSL (0.68, 95% CI 0.55–0.79; I² = 31.2%) and SCNSL (0.71, 95% CI 0.55–0.83; I² = 0%). CSF ctDNA showed significantly higher detection compared with plasma-based testing (OR 12.54, 95% CI 1.02–154.41; I² = 72.3%). Most studies showed moderate risk of bias, mainly related to patient selection, while index test domains demonstrated low risk. Conclusions: CSF ctDNA analysis shows consistently high diagnostic performance in CNS lymphoma but should not be interpreted as a standalone diagnostic test. When integrated with conventional modalities, it represents a valuable adjunctive tool, particularly in clinically challenging cases. Prospective studies with standardized diagnostic frameworks are needed to define its optimal clinical role.

A real-world analysis on the management of post-mastectomy lymphedema in breast cancer patients: The therapeutic promise of glucagon-like peptide-1 receptor agonist.

Journal of Clinical Oncology Muluken Megiso, Dawit Yesho, Chidebube Zeleke Ugwu et al. Jun 01, 2026 DOI: 10.1200/jco.2026.44.16_suppl.e12695

e12695 Background: Post mastectomy lymphedema syndrome (PMLS) is an established complication of mastectomy, and the risk is further exacerbated by obesity and insulin resistance. Glucagon-like-peptide 1 receptor agonists (GLP-1RAs) are known to reduce body mass index (BMI) and inflammation while improving insulin sensitivity. However, data on the management of PMLS with GLP-1RA in breast cancer (BC) patients is limited to case reports and clinical observations. To address this evidence gap, we conducted the first retrospective multicenter, real-world analysis to assess the efficacy and safety of GLP-1RA for the management of PMLS in BC patients. Methods: All BC patients aged 18-90 years with a diagnosis of PMLS between January 1, 2000, and January 1, 2025, were identified in the TriNet X database (150 million patients across 108 healthcare organizations). BC patients on GLP-1RA therapy of ≥ 2 months (cohort A) were matched to non-users (cohort B) using propensity score matching (1:1). The primary endpoint was the incidence of lymphedema-associated complications (lymphangitis, cellulitis, skin ulcer/breakdown, upper limb pain). Secondary endpoints included utilization of diagnostics (lymphoscintigraphy), procedures (manual lymphatic drainage), and pain medication utilization. Patients with outcomes before the study window were excluded. Cox proportional hazards and multivariate logistic regression analysis were performed to assess if there was a significant reduction in the primary and secondary endpoints. Subgroup analysis was performed. Results: Among 4,580 matched BC patients, 2,290 were assigned to each cohort (demographics were similar: mean age of 61 vs 61 years, White 69% vs 71%, Black 21% vs 20%; however, mean BMI was higher in the GLP-1RA cohort: 36 vs 31). GLP-1RA use was associated with a 59% reduction in lymphangitis [HR: 0.41 (0.22–0.76)], a 53% reduction in manual lymphatic drainage [HR: 0.47 (0.39–0.56)], and a 61% reduction in lymphoscintigraphy utilization [HR: 0.38 (0.23–0.64)]. No significant reductions were observed in cellulitis, skin breakdown, or pain medication utilization. Notably, subgroup analyses of non-diabetic patients and those with BMI < 29 demonstrated consistent therapeutic benefits. Conclusions: GLP-1RA use was associated with a significant reduction in lymphangitis and healthcare utilization for PMLS. This protective signal remained consistent across non-obese and non-diabetic subgroups, suggesting a disease-modifying effect potentially driven by improved lymphatic flow and reduced inflammation. These findings warrant prospective validation as they have important implications for clinical practice.

Next-generation sequencing in non-small cell lung cancer management in Lebanon: Clinical practices and barriers to implementation.

Journal of Clinical Oncology Mahmoud Hammad, Hasan Numan, Arafat H. Tfayli et al. Jun 01, 2026 DOI: 10.1200/jco.2026.44.16_suppl.e20692

e20692 Background: Next-generation sequencing (NGS) is a cornerstone of precision oncology; it enables comprehensive genomic profiling and allows for the identification of actionable mutations to guide treatment. International guidelines recommend NGS before initiating therapy in advanced non-small cell lung cancer (NSCLC). However, real-world NGS implementation remains inconsistent, particularly in low and middle-income countries. In Lebanon, data on NGS utilization and barriers to integration in lung cancer are limited. Methods: We conducted a cross-sectional descriptive study in Lebanon using a 25-item, self-administered online questionnaire distributed to licensed pulmonologists, radiation oncologists, and hematologist-oncologists through national professional societies. Data were analyzed using IBM SPSS statistics. Results: 33 clinicians responded, of whom 67% were males. Most respondents were medical oncologists (58%), followed by pulmonologists (12%) and radiation oncologists (9%), with 49% having > 20 years of clinical practice. 45% of the participants worked in academic hospitals, while 55% practiced in community settings, and most managed 10 lung cancer patients per month (67%). Overall, 84% reported familiarity with NGS testing. NGS use was reported by 65.2% of clinicians for nonsquamous metastatic NSCLC (mNSCLC) (95% CI: 44.2-86.3%) and 36.4% for squamous mNSCLC (95% CI: 14.5-58.2%). NGS was most frequently ordered at initial diagnosis (60%), followed by after first-line therapy failure (24%). Tissue-based NGS was used by 76% of clinicians, while 38% of academic clinicians reported routinely ordering both tissue and liquid biopsy; no respondents used liquid biopsy alone. Tumor molecular profiling was most performed through third-party laboratories (64%), with fewer clinicians reporting access to both in-house and external testing (20%). The reported turnaround time was most frequently between 1-2 weeks (33%) or 2-3 weeks (38%), while 21% reported turnaround times exceeding 3 weeks. Among clinicians who did not routinely order NGS for nonsquamous mNSCLC, single gene testing was common, with testing for EGFR mutations (100%), ALK rearrangement (91%), ROS1 rearrangement (73%), and less frequently BRAF, KRAS, and MET. The reported benefits of NGS included identification of actionable mutations (68%) and personalized treatment options (86%), while cost or lack of insurance coverage (91%) and tissue sample inadequacy (41%) were the predominant barriers. Conclusions: This study addresses a critical regional knowledge gap by estimating real-world NGS use in mNSCLC care in Lebanon, revealing variable adoption despite high perceived clinical value. Financial and tissue-related barriers remain key limitations, underscoring the need for policy and institutional support to advance precision oncology in the region.

Comparative outcomes of prophylactic anticoagulation in patients with multiple myeloma receiving immunomodulatory therapy.

Journal of Clinical Oncology Ana Chachua, Alankrita Taneja Jun 01, 2026 DOI: 10.1200/jco.2026.44.16_suppl.e19542

e19542 Background: Patients with multiple myeloma have a substantially increased risk of venous thromboembolism (VTE), further amplified among those receiving immunomodulatory drug-based (IMiD) therapy, particularly early in treatment and with other prothrombotic agents. Direct oral anticoagulants (DOACs) and low–molecular-weight heparin (LMWH) are commonly used for thromboprophylaxis, but comparative real-world outcome data remain limited. Methods: We conducted a retrospective cohort study using the TriNetX Research Network of adults with multiple myeloma initiating IMiD therapy who received prophylactic anticoagulation with a DOAC (apixaban, rivaroxaban, edoxaban, or dabigatran) or LMWH (dalteparin or enoxaparin) within one month of diagnosis and IMiD initiation. Patients with prior VTE were excluded. Cohorts were matched 1:1 using propensity scores. Outcomes included VTE, all-cause mortality, and major bleeding at 1 year. A lenalidomide-restricted sensitivity analysis was performed. Results: After propensity score matching, 699 patients per group were included. At 1 year, all-cause mortality occurred in 74 patients (10.6%) receiving DOACs and 117 patients (16.8%) receiving LMWH (HR 0.59, 95% CI 0.44–0.79; p=0.005). There were no significant differences in VTE or major bleeding. In a lenalidomide-restricted sensitivity analysis, DOAC use remained associated with lower 1-year mortality compared with LMWH (7.7% vs 17.0%; HR 0.42, 95% CI 0.29–0.61; p<0.001), among 533 patients per cohort. Conclusions: In this real-world cohort of patients with multiple myeloma receiving IMiD-based therapy, DOAC prophylaxis was associated with lower 1-year all-cause mortality compared with LMWH, with no significant differences in VTE or major bleeding. These findings support further prospective studies to define optimal thromboprophylaxis strategies in this population. Outcomes at 1 year after propensity score matching (n = 699 per cohort). Outcome (1-year) DOAC (n=699) LMWH (n=699) HR (95% CI) P value All-cause mortality 10.6% 16.8% 0.59 (0.44–0.79) 0.005 Venous thromboembolism (PE or DVT) 7.5% 7.1% 1.02 (0.68–1.55) 0.55 Pulmonary embolism 3.4% 3.2% 1.01 (0.56–1.82) 0.051 Deep venous thrombosis 4.8% 5.1% 0.90 (0.57–1.51) 0.24 Major bleeding (ICH or GI bleed) 2.6% 2.5% 1.00 (0.52–1.94) 0.70 After propensity score matching incorporating age, sex, race, metastatic disease, proteasome inhibitor and systemic corticosteroid therapy, underlying comorbidities, and history of critical illness or intensive care unit admission.

Prospective comparison of patient-derived organoid drug screening with standard guideline recommendations for colorectal cancer liver metastasis.

Journal of Clinical Oncology Dan Sha, Ziwei Yu, Xiaoya Xu et al. Jun 01, 2026 DOI: 10.1200/jco.2026.44.16_suppl.e15609

e15609 Background: Treatment options for colorectal cancer liver metastasis (CRLM) are limited, and resistance to standard regimens remains a major challenge. Patient-derived tumor organoids (PDTOs)-based drug sensitivity testing offers a promising strategy to guide personalized therapy. This prospective study aimed to evaluate the accuracy of PDTOs drug sensitivity in predicting clinical response to guideline-recommended treatments in CRLM. Methods: In this prospective observational cohort study, patients with CRLM underwent tumor biopsy for PDTOs generation. Established PDTOs underwent drug sensitivity screening against a panel of clinically relevant agents, including chemotherapies (e.g., oxaliplatin, irinotecan, 5-FU) and targeted therapies (e.g., cetuximab, regorafenib, fruquintinib). Patients concurrently received standard guideline-based treatments. The primary endpoint was the concordance between PDTOs sensitivity (in vitro) and the patient’s objective clinical response (in vivo). Results: From March 2023 to October 2025, 30 patients with CRLM who successfully established 39 organoids were enrolled in this study (median age 57.9 years). The patients were categorized by their prior treatment history: treatment-naive (n = 14), and those with failure of first-line (n = 5), second-line (n = 4), third-line (n = 4), fourth-line (n = 2), or fifth-line (n = 1) therapy. Fresh tumor biopsies were obtained from colon (n = 10), rectum (n = 4), liver (n = 21), lung (n = 2), ascites (n = 1), and bone (n = 1). A total of 39 organoids were used for drug sensitivity screening, which performed at a median PDTOs age of 48 days (range 41-58). Of note, organoids were successfully established from both primary colorectal cancers and their paired liver metastases in 9 patients. The organoids faithfully recapitulated the key characteristics, including pathological morphology, immunohistochemical markers, and mutational profiles, of their original tumors. Overall, PDTOs-based prediction of clinical outcome was more accurate for combination regimens (FOLFOX/FOLFIRI) than for monotherapy, which was partly due to the antagonistic (28.2%, 11/39) treatment interactions in combined treatments. For combinations versus monotherapy, the predictive metrics were as follows: accuracy, 79.5% vs 64.1%; sensitivity, 92.3% vs 61.5%; specificity, 73.1% vs 65.4%; positive predictive value (PPV), 63.2% vs 47.1%; and negative predictive value (NPV), 95.0% vs 77.3%. Conclusions: This study confirms the clinical feasibility of biopsy-derived PDTOs and highlights their clinical utility: they not only predict response to combination regimens more accurately than to monotherapy but also provide a high NPV, thereby preventing ineffective treatments and unnecessary toxicity, and guiding precision therapy selection. Clinical trial information: ChiCTR2300068842.

Survival outcomes and prognostic factors in luminal A (LumA) early breast cancer (EBC): Real-world evidence from a public cancer center in Peru.

Journal of Clinical Oncology Guillermo Valencia, Yandira Espinoza, Patricia Rioja et al. Jun 01, 2026 DOI: 10.1200/jco.2026.44.16_suppl.e23406

e23406 Background: Luminal A (LumA) early breast cancer (EBC) generally has excellent prognosis (5-year survival ≥ 95%) due to favorable biology and high response to endocrine therapy (ET). However, prognosis is strongly associated with anatomic burden (T/N and stage). In resource-limited settings lacking genomic assays, adjuvant decisions rely on clinicopathological factors and may affect real-world outcomes. We described outcomes and prognostic factors in Peruvian LumA EBC. Methods: Retrospective cohort of LumA (defined as ER/PgR-positive, HER2-negative, and ki-67≤20% by immunohistochemistry) EBC pts treated at a public cancer center in Peru (2018-2022). RFS and OS were estimated by Kaplan-Meier. Cox models evaluated factors associated with recurrence and death (two-sided p < 0.05). Results: A total of 151 pts were included; median age was 55 years (48-61) and 61% were postmenopausal. Most tumors had ductal histology (89%) and grade 2 (39%). T2 disease was most frequent (40.5%). Nodal status: N0 28.5%, N1 69%, N3 2.5%. Stage distribution was predominantly IIA (59%) and I (24%). Breast-conserving surgery was performed in 55%. Adjuvant ET was administered in 87%, (anastrozole, 43%); adjuvant chemotherapy and radiotherapy were given in 52% and 66.5%, respectively; among stages I and IIA, 32% and 62% received adjuvant chemotherapy (gene expression assays were not available). After a median follow-up of 42 months (3-79), 42 recurrences occurred; 1-, 3- and 5-year RFS were 96%, 84% and 69% (median RFS not reached). Node-positive involvement was associated with higher risk vs. node-negative (HR: 2.12, 95% CI, 1.01-4.45; p = 0.044). In stage IIA, chemotherapy followed by ET was associated with higher recurrence risk compared with ET alone (HR 3.45, 95% CI, 1.42-8.37; p = 0.006), likely reflecting confounding by indication. After a median follow-up of 54 months, 19 deaths occurred; 1-, 3- and 5-year OS were 100%, 93% and 89% (median OS not reached). Stages IIB-III were associated with inferior OS vs. stages I-IIA (HR 3.14, 95% CI, 1.27-7.74, p = 0.013). Conclusions: In this real-world Peruvian cohort of LumA EBC, nodal involvement and higher stage were stronger prognostic factors. Lower 5-year RFS/OS than typically reported may reflect higher baseline anatomic risk and tertiary-center case mix. In stage IIA, the association between chemotherapy use and recurrence reflects treatment selection based on clinicopathological risk and chemotherapy prioritization for high-risk lacking genomic stratification. These outcomes highlight the need to optimize risk stratification when genomic assays are unavailable.