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Epidemiological trends and burden of multiple myeloma mortality in South Asia: A retrospective analysis from 1990 to 2023 with advanced machine learning forecasting to 2050.

e19548 Background: Multiple myeloma (MM) is an increasingly important contributor to cancer-related mortality worldwide, yet long-term mortality trends in South Asia remain poorly defined. Understanding sex- and country-specific temporal patterns is essential. This study evaluated historical trends and projected future mortality burden of MM across South Asia from 1990 to 2050. Methods: We conducted a population-based retrospective analysis of age-standardized mortality rates (ASMRs) for multiple myeloma across South Asia from 1990 to 2023, using the Global Burden of Disease 2023 database, stratified by country and sex. Temporal trends were assessed using estimated annual percentage change (EAPC) with 95% confidence intervals (CIs). Advanced machine-learning–based time-series forecasting models were applied to project ASMRs through 2050, with uncertainty quantified using prediction intervals (PI). Results: Between 1990 and 2023, MM mortality increased significantly across South Asia (both sexes EAPC 1.23; 95% CI 1.06–1.40). The rise was more pronounced among females (EAPC 1.68; 95% CI 1.44–1.92) than males (EAPC 0.92; 95% CI 0.80–1.04), although absolute ASMRs remained consistently higher in males. At the country level, Pakistan demonstrated the steepest increase in MM mortality (both sexes EAPC 1.50), followed by India (1.25), Bangladesh (1.10), Nepal (0.58), and Bhutan (0.54). Female mortality increased substantially across all countries, particularly in Pakistan (EAPC 1.84), India (1.73), and Bangladesh (1.57). In contrast, male mortality trends were heterogeneous, with modest increases in most countries and a slight decline observed in Bhutan (EAPC −0.15; 95% CI −0.30 to −0.01). Forecasting analyses project a continued rise in MM mortality through 2050 across South Asia. Regional ASMRs are expected to nearly double, with sharper absolute increases among females and widening prediction intervals beyond 2035. Conclusions: Multiple myeloma mortality has increased steadily across South Asia over the past three decades, with disproportionately rapid rises among females and marked country-level heterogeneity. Forecasts indicate a sustained and growing mortality burden through 2050, underscoring the urgent need for improved early diagnosis, and treatment. Location Sex EAPC Lower 95%CI Upper 95%CI Bangladesh Both 1.10 0.88 1.31 Bangladesh Female 1.57 1.22 1.92 Bangladesh Male 0.83 0.71 0.95 Bhutan Both 0.54 0.42 0.67 Bhutan Female 1.34 1.23 1.45 Bhutan Male -0.15 -0.30 -0.01 India Both 1.25 1.08 1.43 India Female 1.73 1.48 1.97 India Male 0.93 0.79 1.07 Nepal Both 0.58 0.32 0.84 Nepal Female 1.10 0.81 1.40 Nepal Male 0.35 0.11 0.60 Pakistan Both 1.50 1.33 1.67 Pakistan Female 1.84 1.61 2.07 Pakistan Male 1.00 0.89 1.12 South Asia Both 1.23 1.06 1.40 South Asia Female 1.68 1.44 1.92 South Asia Male 0.92 0.80 1.04

Diagnostic efficiency in precision oncology: Quantifying time to treatment initiation for biomarker-positive vs biomarker-negative metastatic NSCLC.

e20760 Background: A primary concern in the integration of Next-Generation Sequencing (NGS) into first-line (1L) metastatic non-small cell lung cancer (mNSCLC) care is the potential for "diagnostic lag"—where the time required for molecular profiling delays treatment initiation. We sought to evaluate the operational efficiency of a large-scale community oncology molecular workflow by comparing the Time to Treatment (TTT) between patients receiving biomarker-driven targeted therapy and those receiving standard chemotherapy with or without checkpoint inhibitors. Methods: This retrospective study analyzed adults with stage IV mNSCLC (2024–2025) within a large community oncology network. Patients were segmented into two cohorts: the Targeted Cohort (Biomarker-positive [B+]; receiving guideline-concordant 1L targeted agents) and the Standard Cohort (Biomarker-negative [B-]; receiving 1L platinum-based chemotherapy and/or immune checkpoint inhibitors). TTT was defined as the interval from metastatic diagnosis to the first day of systemic therapy using a 14-day grace period for lab turn-around time. Comparative analysis focused on the kinetics of treatment initiation to determine if molecular testing requirements delayed therapy for the Targeted Cohort. Results: Among 1,552 patients (Targeted: n = 157; Standard: n = 1,395), the Targeted Cohort was younger (median 69 vs. 71 years) and had a higher proportion of females (67% vs. 50%). The median TTT for the Targeted Cohort was statistically shorter to the Standard Cohort [0.8 vs. 0.9 months (p = 0.003)], demonstrating that the requirement for NGS results did not extend the window to treatment. While clinical endpoints were captured, differences in median OS (Not Reached for Targeted vs. 11.5 months for Standard) and Median TTNT (11.9 vs. 6.1 months; p < 0.0001) were attributed to the inherent differences in underlying disease biology and the high efficacy of targeted agents, rather than the velocity of treatment initiation. Conclusions: These data demonstrate that modern, integrated molecular workflows in the community setting successfully mitigate diagnostic lag for B+ mNSCLC. The initiation of targeted therapy occurs with equal or greater efficiency compared to standard cytotoxic or immunotherapy regimens. These findings suggest that the perceived risk of treatment delay for NGS testing is not supported by real-world evidence, reinforcing that diagnostic precision can be achieved without compromising the speed of care delivery in the 1L setting.

Clinicopathological predictors of survival and disease progression in melanoma: A real-world cohort from the MENA region.

e21601 Background: Melanoma exhibits marked heterogeneity in clinical behavior, with survival outcomes strongly influenced by primary tumor biology. While established histopathological features are known to predict prognosis, real-world data from the Middle East and North Africa (MENA) region remain limited. Methods: We conducted a retrospective cohort study using electronic health record data from the American University of Beirut Medical Center, including adult patients diagnosed with melanoma between January 1, 2014 and August 1, 2024. The study aimed to identify clinicopathologic predictors of survival and disease progression in a real-world melanoma cohort. Overall survival (OS), progression-free survival (PFS), and recurrence-free survival (RFS) were estimated using Kaplan-Meier methods and compared using the log-rank test. Univariable and multivariable Cox proportional hazards models were used to identify independent predictors of mortality and disease progression. Results: The overall 5-year survival rate for the cohort was 82.8%, though outcomes were heavily influenced by primary tumor biology. Univariable Cox regression identified mitotic activity as the most potent predictor of mortality, where a count of ≥7 mitoses carried a hazard ratio (HR) of 4.11 (95% CI: 2.12-7.95, p < 0.001) compared to tumors with no mitoses. In the adjusted multivariable model, Breslow thickness category remained the sole independent predictor of death (adjusted HR 1.72 per category increase, 95% CI: 1.09-2.71, p = 0.020), confirming that the vertical depth of the primary lesion is the most reliable independent indicator of long-term mortality risk. PFS was significantly superior in early-stage patients compared to those with advanced disease (log-rank p = 0.020), with median PFS for the advanced group limited to 44.0 months. Multivariable analysis for PFS identified the Clark Level of invasion as a critical independent risk factor (adjusted HR 1.82, 95% CI: 1.07-3.08, p = 0.026), indicating that the anatomical layer of skin reached by the tumor significantly dictates the speed of disease advancement. Similarly, RFS was strongly influenced by stage, where advanced-stage patients faced a significantly higher risk of relapse (log-rank p = 0.003), driven primarily by the interrelated factors of tumor thickness and high mitotic counts. Conclusions: In this real-world cohort from the MENA region, primary tumor biology was the main determinant of long-term outcomes in melanoma. After multivariable adjustment, Breslow thickness remained the sole independent predictor of death, while measures of anatomic invasion independently predicted disease progression and recurrence. These findings highlight the continued prognostic value of classical histopathological features in routine clinical practice.

Perception and awareness of cancer immunotherapy among healthcare professionals and students at a tertiary referral center in the MENA region.

e23222 Background: Cancer immunotherapy has shaped the management of several malignancies; however, its safe and effective use requires adequate awareness among healthcare professionals. Data on perception and knowledge of cancer immunotherapy in low- and middle-income countries remain limited, highlighting the need for a systematic assessment of educational gaps. Methods: A cross-sectional survey of 335 healthcare professionals and students at the American University of Beirut Medical Center assessed perception and knowledge of cancer immunotherapy using a structured 21-item questionnaire. Participants included physicians, nurses, and medical and nursing students. Descriptive statistics were used to summarize participant characteristics and survey responses. Composite perception and knowledge scores were analyzed using Pearson correlations and multivariate linear regression to identify predictors of higher awareness. Results: Among 335 participants, 38.2% were students and 61.8% were healthcare professionals. Only 11% reported prior formal education in cancer immunotherapy, while 70.7% identified high cost as the main barrier to its use. Only 21.8% correctly identified skin as the most common affected organ, and only 31.6% correctly identified pneumonitis as a potentially life-threatening immune-related adverse event. Only 23.6% correctly identified the recommended initial corticosteroid dose for the management of immune-related adverse events, only 8.4% were aware of the Common Terminology Criteria for Adverse Events. Despite limited training, 78.5% considered immunotherapy awareness relevant to their field, and 65.7% expressed willingness to attend future educational activities. The mean (±SD) perception score was 3.80 (1.69) (range 0-6), and the mean knowledge score was 3.08 (3.41) (range 0-20). Perception and knowledge scores were moderately correlated (r = 0.43, p < 0.001). In multivariable linear regression, higher knowledge scores were independently associated with age > 40 years (β = 0.132, p = 0.042) and more than 5 years of clinical experience (β = 0.17, p = 0.006), while female sex (β = -0.121, p = 0.026) and no regular exposure to cancer patients (β = -0.114, p = 0.042) were associated with lower knowledge scores. Lower perception scores were independently associated with age 31-40 years (β = -0.128, p = 0.049) and no regular exposure to cancer patients (β = -0.153, p = 0.007). Conclusions: Awareness and knowledge of cancer immunotherapy were suboptimal among healthcare professionals and students at a tertiary referral center in Lebanon. Given the expanding use of immunotherapy and limited access to structured training across the MENA region, these findings highlight an urgent need for region-specific educational initiatives to improve safe delivery of immunotherapy in low- and middle-income settings.

Genomic determinants of radiation necrosis in diffuse glioma patients.

2053 Background: Diffuse gliomas are the most common primary brain tumors, requiring multimodal therapy. Radiotherapy (RT) represents a key pillar of treatment; however, radiation-induced brain toxicities remain a major challenge. Radiation necrosis (RN) is a delayed complication that can impair clinical outcomes and quality of life. Emerging evidence suggests that tumor biology, together with clinical factors, can influence radiation toxicity in a variety of cancer entities. However, in diffuse gliomas, tumor-intrinsic biomarkers predisposing to radiation toxicities remain poorly defined. We hypothesized that integrating clinical features with tumor genomic data could identify patients at increased risk of developing RN. Methods: We analyzed a cohort of 943 adult patients with diffuse gliomas treated between 2014 and 2024 at MD Anderson. All tumors were classified according to the WHO 2021 criteria into three diagnoses: GBM, astrocytoma (astro), and oligodendroglioma (OD). RN occurring at least 12 weeks after completion of RT was identified based on pathology and/or advanced brain tumor imaging (ABTI), which included conventional MRI, perfusion imaging and spectroscopy. A multivariate regression model was employed to identify clinical or genetic predictors for RN. Included covariates were demographics, diagnosis, and common genetic alterations. To address missing values, multiple imputation was utilized. Results: Sixty patients with RN were identified: 51 GBM (85%), 6 astro (10%), and, 3 OD (5%); compared with 883 controls: 682 GBM (77%), 140 astro (16%), and 61 OD (7%). Age, gender, and diagnoses were not associated with RN. We evaluated the top 22 altered genes and MGMT status. In the overall cohort, IDH1 (OR 0.15 [95% CI, 0.02–0.93]; p=0.042) and MDM2 (OR 0.11 [95% CI, 0.01–1.00]; p=0.050) alterations were associated with reduced RN risk, while ATR alterations were associated with increased RN risk (OR 6.05 [95% CI, 0.85–33.1]; p=0.049) on multivariable analysis. In the GBM subgroup, CDK4 (OR 3.32 [95% CI, 1.04–9.97]; p=0.042) and MSH6 alterations (OR 6.05 [95% CI, 1.12–33.1]; p=0.037) were associated with increased RN risk, whereas MDM2 alterations remained associated with reduced risk (OR 0.07 [95% CI, 0.01–0.69]; p=0.023). In the IDH -mutant diffuse glioma subgroup (RN n=9; controls n=201), ATRX alterations were associated with lower RN risk (OR 0.10 [95% CI, 0.01–0.73]; p=0.023). MGMT status was not associated with RN risk. Conclusions: In this cohort, RN risk was not associated with demographic factors, tumor diagnosis, or MGMT status, but was associated with specific tumor genomic alterations. The enrichment of DNA damage response–related genes among those associated with RN suggests a potential biological link between tumor genomics and RN toxicity. Prospective validation will be required to determine the utility of these findings for genome-based risk stratification.

Screening for intrinsic and acquired resistance mutations to anti-EGFR in real-world MSS colorectal cancer data.

3557 Background: Anti-EGFR (cetuximab, panitumumab) plus doublet chemotherapy is the first line standard of care for metastatic MSS left-sided RAS/RAF WT colorectal cancer (CRC). However, anti-EGFR clinical efficacy is limited by intrinsic and acquired resistance. Defining anti-EGFR intrinsic resistance mutations could improve patient selection for anti-EGFR treatment while defining anti-EGFR acquired resistance mutations could enable early detection of resistance via liquid biopsy. Methods: The intrinsic resistance cohort consisted of 163 metastatic MSS RAS/RAF WT colon adenocarcinoma patients treated in the first line with anti-EGFR with a DNA-seq sample collected before treatment (Tempus xT or xF). We screened mutations for anti-EGFR intrinsic resistance defined as HR > 2 for PFS via univariate CoxPH models. The anti-EGFR acquired resistance cohort consisted of 228 MSS CRC patients with a DNA-seq sample (xT or xF) within 12 months prior to and 0.5-24 months post treatment. We defined acquired resistance mutations as those significantly enriched post-treatment vs pre-treatment via McNemar test. An anti-VEGF acquired resistance cohort of 748 MSS CRC patients was used as a control. Enrichment of targetable gene fusions post-treatment was assessed via Wilcoxon test. FDR < 0.05 was considered significant. Results: The screen for intrinsic resistance mutations returned a single significant hit of PIK3CA non-exon 9 mutations (~3%, p < 0.01), while PTEN deletions (~2%), which are functionally similar, were also associated with shorter PFS but did not reach significance (p=0.08). PIK3CA non-exon 9 mutation or PTEN deletion were detected in ~5% of patients (n=9) and were associated with shorter PFS (HR = 3.6, 95% CI: 1.7-7.6, p < 0.001) and OS (HR = 2.6, 95% CI: 1.03-6.5, p < 0.05). Median PFS and OS were 6 and 14 months for patients with these resistance alterations, versus 11 and 29 months for non-altered patients. In a CoxPH model including age, sex, sidedness, and collection procedure, these alterations maintained a significant association with PFS (HR =5.2, 95% CI: 2.2-12.4, p < 0.01) but not OS (HR=2.7, 95% CI: 0.9-8.9, p=0.08). Analysis of acquired resistance to anti-EGFR treatment yielded significant mutation hits— KRAS, NRAS, EGFR , and MAP2K1— as well as significant enrichment of targetable fusions ( BRAF, FGFR, NTRK, ALK, ROS1, RET, NRG1 ). No mutations or fusions were observed to be associated with anti-VEGF acquired resistance. Conclusions: Patients harboring PIK3CA non-exon 9 mutation or PTEN deletion displayed intrinsic resistance to anti-EGFR therapy despite being RAS/RAF WT and may be offered anti-EGFR therapy per oncology guidelines. This small underrepresented subset of patients may not benefit from anti-EGFR therapy. Prospective clinical validation will be needed to determine if this subset of PI3K pathway alterations has utility in optimizing first line therapy selection.

PEMBROCABOSARC: A phase II trial combining pembrolizumab and cabozantinib in patients with advanced undifferentiated pleomorphic sarcoma.

11514 Background: There is a growing rationale for combining immunotherapy and VEGF inhibitors in sarcoma. We report results of an open-label multicentre phase 2 study assessing the anti-PD-1 antibody pembrolizumab (pembro) in combination with cabozantinib (cabo) in patients (pts) with advanced undifferenciated pleomorphic sarcoma (UPS). Methods: Pts aged > 18 years old, with advanced or metastatic UPS who received no more than three previous lines and no previous history of exposure to anti PD1/L1 or cabozantinib were included to receive cabo 40 mg daily and pembro 200 mg IV q21 days. The primary endpoint was 6-month non-progression (NP) per RECIST v1.1. This trial used a 2-stage optimal Simon’s design needing 8 NP at 6 months observed among 29 evaluable pts to be considered positive. Results: 33 pts were enrolled from December 27th, 2022 to September 25th, 2024, 32 were assessable for safety and 31 for efficacy. Overall, 13 (40.6%) pts had at least one dose reduction of cabo and 5 (15.6%) stopped treatment for a drug-related adverse event (3 related to cabo, 1 to pembro and 1 to both drugs). The most frequent adverse events related to treatment were asthenia, diarrhea, palmo-plantar syndrom and aminotransferase increase. There was no new emerging toxicity with the combination. One grade 5 pneumothorax was considered possibly related to cabozantinib by the investigator. At a median follow up of 13.8 months [95% CI: 12 – 17.2], 8 pts out of the first 29 evaluable pts were NP at 6 months (27.6% [95% CI: 12.7%-47.2%]). Among the efficacy population, 14 pts experienced tumor shrinkage resulting in a partial response (PR) in 8 (25.8%). Responses were long-lasting. The median overall survival was not reached. Conclusions: Combining VEGF and PD-1 inhibition showed favorable activity in unselected UPS compared to available evidence for each treatment in monotherapy. Correlative studies of immune biomarkers on paired tumor biopsies and plasma samples done at baseline and on-treatment are on-going to decipher biomarkers of response and resistance to treatment. Clinical trial information: NCT05182164 . Number of patients with at least one Grade 3 to 5 adverse event related to treatment. Adverse Event Grade 3 Grade 5 Diarrhea 2 (6.2%) 0 Palmo-plantar syndrom 2 (6.2%) 0 Aminotransferase increase 2 (6.2%) 0 Hypertension 1 (3.1%) 0 Headache 1 (3.1%) 0 Dysgeusia 1 (3.1%) 0 Skin rash 1 (3.1%) 0 Pyoderma 1 (3.1%) 0 Left ventricular dysfunction 1 (3.1%) 0 Pneumothorax 1 (3.1%) 1 (3.1%)

Exploring the role of a participatory live music practice on nurses experienced levels of compassion satisfaction and fatigue: A mixed method study

Objective To explore nurses’ compassion satisfaction and compassion fatigue in relation to a participatory live music practice, and to understand nurses’ own perspectives on this dynamic. Introduction A significant group of nurses experience compassion fatigue, the feelings of exhaustion and reduced capacity for empathy when caring for others, putting them at risk for work retention and turnover. Compassion satisfaction, the positive feelings derived from caregiving, may boost nurses’ well-being and resilience, and protects against compassion fatigue. Therefore, interventions enhancing compassion satisfaction provide dual benefits. This study examined to what extent an intervention based on participatory live music practice for nurses and their patients, by providing meaningful moments of compassion and bonding in the caring relationship, reduces nurses’ compassion fatigue and/or enhances their compassion satisfaction. Materials and methods A mixed-method explanatory design was applied. First, exploratory quantitative data in 30 nurses were obtained via surveys prior to and after a week of participatory live music practice. Compassion satisfaction and compassion fatigue were assessed using the 21-item Professional Quality of Life Scale (ProQoL). Secondly, sequential semi-structured interviews with 22 nurses were carried out in two phases. Quantitative data was analyzed using descriptive statistics and Wilcoxon Signed-Rank Test. Qualitative data underwent thematic analysis. Results Exploratory quantitative results suggested average levels of compassion satisfaction and fatigue, both before and after the week of participatory live music practice, with no significant changes over time. Qualitative results revealed two themes: (1) feelings of compassion satisfaction derived from observing patients’ response to the live music, leading to enhanced feelings of shared humanity and bonding, and a reconnection with nursing values; (2) perceived positive impact of the participatory live music on mood, work pleasure, and team dynamics. Conclusions While quantitative data showed no significant changes in levels of compassion fatigue and satisfaction in the period before and after the live music practice, qualitative data revealed that nurses perceive benefits and compassion satisfaction by engaging in a participatory live music practice in the hospital setting.

Emerging smart nanocarrier based drug delivery systems for cancer therapeutics

The Resolution–Throughput Conflict In Material Extrusion Additive Manufacturing (Adv. Mater. 36/2026)

A Bottom‐Up Zincophilic Gradient Design Enabling Long‐Cycle‐Life Zn Metal Anodes Under High Currents and Capacities

ABSTRACT Metal anodes are crucial for achieving high‐energy‐density electrochemical energy storage. However, their practical performance under high current densities and high areal capacities is hampered by sluggish ion‐transport kinetics. This leads to concentration polarization, which promotes surface‐localized deposition and results in dendritic “top‐growth”, ultimately causing cell failure. In this work, we design a bottom‐up zincophilic gradient nanofiber mat as a host structure that reverses the deposition pathway. By thermodynamically driving metal ion nucleation preferentially at the host base, this strategy enables uniform bottom‐up deposition. As a result, the Zn anode achieves an average Coulombic efficiency of 98.9% for 1972 cycles at a high current density of 20 mA cm −2 . Symmetric cells with this host exhibit exceptional stability, operating for 1095 h at an ultrahigh current density of 50 mA cm −2 and 1328 h under a high areal capacity of 10 mAh cm −2 , substantially outperforming existing approaches. This work establishes gradient engineering as an effective and widely applicable strategy for enabling long‐life metal anodes.

KANWhisper: leveraging learnable activation functions for interpretable and efficient arabic automatic speech recognition

Measurement of glycolysis with heavy water labeling

Comparative efficacy and safety of systemic therapies in high-risk hormone-sensitive prostate cancer: A network meta-analysis of 13 phase III randomized trials.

5081 Background: Treatment intensification improves survival in hormone-sensitive prostate cancer (HSPC). However, direct comparisons between triplet therapies consisting of androgen-deprivation therapy, docetaxel, and an androgen receptor pathway inhibitor (ADT+Docetaxel+ARPI) and ARPI doublets are limited. In addition, available evidence remains fragmented between high-risk non-metastatic (nmHSPC) and metastatic (mHSPC) disease states. We conducted a network meta-analysis (NMA) to rank treatment regimens and inform clinical decision-making. Methods: We analyzed 13 phase III RCTs including approximately 13,000 patients with high-risk HSPC, encompassing metastatic and high-risk non-metastatic disease. Treatment strategies included ADT alone, docetaxel (DOC), abiraterone (ABI), enzalutamide (ENZ), apalutamide (APA), darolutamide (DARO), and triplet combinations. A frequentist random-effects NMA was performed with overall survival (OS) as the primary endpoint. Secondary efficacy endpoints included progression-free survival (PFS) and time to castration resistance (TTCR). Safety was assessed using treatment-emergent grade ≥3 AEs, assuming network transitivity. Results: For the primary endpoint (OS), triplet therapies ranked highest, including ADT+DOC+DARO (HR 0.55 [95% CI 0.43–0.69]) and ADT+DOC+ABI (HR 0.60 [95% CI 0.45–0.81]) compared with ADT alone. ARPI doublets also demonstrated robust OS benefits, including ABI (HR 0.63 [0.58–0.69]), APA (HR 0.67 [0.51–0.89]) and ENZ (HR 0.69 [0.51–0.94]). No statistically significant OS difference was observed between triplets and ARPI doublets, although triplets numerically favored higher efficacy. For PFS (I² = 86.5%), triplet therapies remained superior, with ADT+DOC+DARO showing the greatest benefit (HR 0.24 [0.13–0.45]), followed by the ENZ doublet (HR 0.40 [0.27–0.60]). Secondary endpoints (TTCR, PSA-PFS) consistently favored ARPI-based regimens. Regarding safety, triplet therapies significantly increased the odds of Grade ≥3 AEs versus ADT (OR ~2.6–3.7), driven primarily by docetaxel-associated fatigue and ABI-related hypertension. Conversely, APA, ENZ, and DARO doublets demonstrated favorable safety profiles, with no significant increase in overall Grade ≥3 AEs compared with ADT alone (ORs 1.02–1.06). Benefits were consistent across nmHSPC and mHSPC subgroups (p for interaction = 0.66). Conclusions: Triplet therapy represents the efficacy standard for fit patients with high-volume mHSPC. However, ARPI doublets offer a compelling alternative with comparable survival benefits and a superior safety profile, making them the preferred choice for high-risk nmHSPC and patients prioritizing tolerability. Clinical selection should stratify based on disease volume and fitness for docetaxel-associated toxicity.

Necitumumab plus pembrolizumab and chemotherapy for untreated advanced squamous NSCLC: Phase I/II NEJ048A/NEXUS.

8528 Background: EGFR blockade enhances tumor antigen presentation and may potentiate PD-1 inhibition. This phase I/II study evaluated the safety and efficacy of adding necitumumab to pembrolizumab plus platinum-based chemotherapy in patients with previously untreated advanced squamous non–small cell lung cancer (NSCLC), a population with limited biomarker-driven treatment options. Methods: Patients received necitumumab (400–800 mg on days 1 and 8), pembrolizumab (200 mg on day 1), nab-paclitaxel (100 mg/m² on days 1, 8, and 15), and carboplatin (AUC 5 on day 1) every 3 weeks for four cycles, followed by necitumumab plus pembrolizumab maintenance. Phase I used a standard 3+3 dose-escalation design. Per protocol amendment, patients treated at the recommended dose (RD) in phase I (n = 6) and all phase II patients (n = 6) were pooled for efficacy analyses (n = 12). Tumor assessments were performed every 6 weeks per RECIST v1.1. Primary endpoints were safety and objective response rate (ORR). Data cutoff was September 14, 2025. Results: Twenty-one patients were enrolled, including 15 in phase I (400 mg, n = 6; 600 mg, n = 3; 800 mg, n = 6). One dose-limiting toxicity (DLT) occurred in the 800 mg cohort, which was determined as the RD and maximum tolerated dose (MTD). Among the 12 patients treated at the RD, the ORR was 75.0% (9/12; 95% CI, 42.8–94.5), with partial response in 9 patients, stable disease in 1 patient, and progressive disease in 2 patients. The disease control rate was 83.3%. The 24-week survival rate was 95.2%. Median progression-free survival and overall survival were not reached at the time of analysis. The most frequent adverse events (AEs) in 21 patients were hypomagnesemia (66.7%), acneiform dermatitis (66.7%), neutropenia (61.9%), decreased appetite (52.4%), anemia (52.4%), constipation (47.6%), stomatitis (42.9%), and leukopenia (42.9%). Grade 3 and 4 AEs occurred in 66.7% and 28.6% of patients, respectively, with no grade 5 events. Conclusions: The addition of necitumumab to pembrolizumab and platinum-based chemotherapy demonstrated manageable toxicity and resulted in a high ORR in patients with untreated squamous NSCLC. These findings support the potential activity of EGFR blockade–based immunochemotherapy and warrant further clinical investigation. Clinical trial information: 2031210387.

Chemotherapy-free neoadjuvant strategy in HR+/HER2− early breast cancer: Efficacy of CDK4/6 inhibitors plus endocrine therapy compared to chemotherapy-sequenced approach.

e12671 Background: In HR+/HER2- breast cancer (BC), neoadjuvant chemotherapy (NACT) remains a standard in many regions despite low pathological complete response (pCR) rates (7.5%–16.2%) and significant toxicity. The emergence of CDK4/6 inhibitors (CDK4/6i) has transformed management, with trials like CORALLEEN and WSG-ADAPT suggesting that neoadjuvant endocrine therapy (ET) plus CDK4/6i may offer comparable efficacy to NACT with improved tolerability. This study evaluates the feasibility of chemotherapy-sparing strategies by comparing the objective response rate (ORR) and safety of neoadjuvant ET+CDK4/6i versus NACT followed by ET+CDK4/6i in a real-world setting. Methods: We retrospectively analyzed 63 patients (aged 18–70 years) with HR+/HER2- BC across 11 tertiary hospitals in China. Patients were divided into two groups: those receiving neoadjuvant ET+CDK4/6i (n = 38; ribociclib, abemaciclib, dalpiciclib, or palbociclib) and those receiving NACT followed by ET+CDK4/6i (n = 25). ORR was defined by RECIST 1.1. Statistical analyses included Mann-Whitney U,X 2 , or Fisher’s exact tests, and logistic regression. Results: Baseline characteristics (age, Ki-67, T/N stage, and menopausal status) were well-balanced between groups ( P > 0.05). The overall ORR was 62%, with higher responses observed in patients with Ki-67≤20% (67%) compared to those with Ki-67 > 20% (58%). No significant difference in ORR was observed between the ET+CDK4/6i group (68%) and the chemo-sequenced group (52%) (OR: 0.41, 95% CI: 0.10–1.56; P = 0.200). In the Ki-67 > 20% subgroup, ET+CDK4/6i maintained a comparable ORR to the chemo-sequenced approach (63% vs. 53%, OR: 0.91, 95% CI: 0.64-1.29; P = 0.683). Among non-chemotherapy patients, ribociclib and abemaciclib showed similar efficacy (ORR 71% vs. 69%, OR: 1.07, 95% CI: 0.21-5.21; P = 0.936), while the dalpiciclib cohort achieved an ORR of 25% (n = 4, P = 0.121). Treatment was generally well-tolerated across cohorts. Conclusions: Neoadjuvant ET plus CDK4/6i achieves short-term ORR comparable to chemotherapy-sequenced regimens in HR+/HER2- early BC, even in patients with high Ki-67. These findings support the feasibility of chemotherapy-free neoadjuvant strategies for clinically selected patients, potentially mitigating toxicity without compromising initial treatment response.

20-year trends in socioeconomic disparities in breast cancer care for patients aged < 65 years old.

1559 Background: Socioeconomic disparities (SES) in cancer care have been well described, especially for younger patients with limited financial reserve and insurance vulnerability. It remains unclear, however, whether innovations in breast oncology have mitigated or exacerbated these gaps over time. We evaluated nearly 20-year trends across key breast cancer treatment and diagnostic modalities and sought to determine whether advances in care promote, or further undermine, health equity. Methods: Using the National Cancer Database, we identified working-aged individuals (18-64 yo) diagnosed with breast cancer from 2004–2022. As surrogates for improvements in breast cancer care, we examined: (i) Oncotype DX testing for stage I–II ER/PR-positive, HER2-negative disease; (ii) immediate breast reconstruction (IBR) after mastectomy; (iii) receipt of neoadjuvant chemotherapy (NACT) for stage II HER2-positive (HER2+) and triple-negative breast cancer (TNBC); and, (iv) immunotherapy by subtype and stage (2018–2022). We used multivariable logistic regression to generate adjusted predicted probabilities by median income quartile (MIQ) and year (or year group). Median Income Disparities (MID) were measured as the difference between the highest and lowest MIQ. Results: The final sample included 1,349,691 patients with mean age 51.8 (SD 8.64). Patient population included 7.7% Hispanic, 72.3% Non-Hispanic White, 13.2% Black, 5.9% Asian, and 0.9% unknown race/ethnicity. 76.7% of patients were privately insured, 10.8% Medicaid-covered, 6.2% Medicare-covered, 1.5% other, 1.8% unknown, and 3.1% uninsured. During the study period, overall adoption of treatment increased substantially over time, with SES disparities differing across modality. Oncotype DX testing demonstrated persistent income-related disparities across the study period (MID: 4.2–5.5%, p<0.05 for all). The largest and most durable inequities were seen in post-mastectomy IBR (17.60% in 2004-2008, narrowing to 11.70% in 2018-2022, p<0.05 for all). Receipt of NACT was associated with modest income-based differences that were greatest during years of rapid uptake for stage II HER2+ (4.9% in 2014–2017, p<0.05) and TNBC (4.8% in 2018–2022, p<0.05) breast cancer. Adoption of immunotherapy rose sharply from 2018–2022 across all incomes, with modest but narrowing gaps for stage III–IV disease (MID: 4.9% in 2019, p<0.05 to 1.1% in 2022,NS). Adjustment for insurance status did not significantly change socioeconomic gradients. Conclusions: Socioeconomic disparities in breast cancer care for women <65 years old vary markedly by treatment modality and adoption phase. Advancing equitable access to best-practice breast cancer care will require interventions at the health system, societal guidelines, and policy levels.

De-escalation of axillary surgery in clinically node-negative early-stage HR-positive, HER2-negative breast cancer.

e12624 Background: The role of axillary surgery in early-stage breast cancer continues to evolve. While sentinel lymph node biopsy (SLNB) remains the standard for axillary staging, its therapeutic value in biologically favorable, clinically node-negative disease has been increasingly questioned. Recent randomized trials, including SOUND and INSEMA, demonstrated that omission of SLNB in selected patients does not compromise oncologic outcomes. However, prospective real-world data on structured implementation of axillary surgery omission in older patients remain limited. This study evaluated the feasibility of omitting surgical axillary staging in patients aged > 59 years with early-stage hormone receptor–positive (HR+), HER2-negative (HER2−), clinically node-negative breast cancer (BC). Methods: This prospective study included 109 patients aged > 59 years with cT1–2N0M0 HR+HER2−BC treated between 2023 and 2025 at the N.N. Petrov National Medical Research Center of Oncology. The study protocol was approved by the local ethics committee, and all patients provided written informed consent. Clinically node-negative axillary status was confirmed by axillary ultrasound, mammography, and mammoscintigraphy/breast molecular imaging using 99mTc-MIBI. Surgical axillary staging was omitted in all patients. Preoperative sentinel lymph node localization using SPECT lymphoscintigraphy was performed for adjuvant radiotherapy planning. Results: Among 109 patients initially enrolled, two were excluded from the final analysis based on postoperative pathology (one HER2 3+ tumor and one positive surgical margin), leaving 107 patients for analysis. Median age was 66 years (range 59–86), and median tumor size was 15 mm (range 4–30). Most tumors were grade 1–2 (97.2%) and cT1 (78.0%). Invasive carcinoma of no special type was the predominant histology (89.0%). Lymphovascular invasion was present in 7.4%, and an associated ductal carcinoma in situ component in 27.8%. Estrogen receptor expression was ≥90% in 96.3%, progesterone receptor expression ≥60% in 74.1%, and Ki-67 ≤20% in 87.0%. All patients received adjuvant hypofractionated or ultra-hypofractionated radiotherapy and endocrine therapy (aromatase inhibitors 83.5%, tamoxifen 16.5%); none received chemotherapy. At a median follow-up of approximately 18 months no axillary, locoregional, or distant recurrences were observed. Conclusions: These findings support the careful implementation of omission of surgical axillary staging in selected postmenopausal patients with cT1–2N0, hormone receptor–positive (HR+), HER2-negative (HER2−) breast cancer and clinically negative axillary lymph nodes. At our institution, this approach has been implemented in patients aged > 59 years with ECOG performance status < 3, tumor grade 1–2, estrogen receptor expression > 20%, and a Ki-67 proliferation index < 30%.

Phase II study of mirogabalin for oxaliplatin-associated chemotherapy-induced peripheral neuropathy in gastrointestinal cancer: The SmiliNg trial.

12057 Background: Oxaliplatin is a key drug in the treatment of unresectable advanced or recurrent gastrointestinal (GI) cancers, however, chemotherapy-induced peripheral neuropathy (CIPN) often limits its use. Mirogabalin is an oral gabapentinoid that alleviates neuropathic pain by binding to the α2δ subunit of voltage-gated calcium channels, but evidence regarding the efficacy of mirogabalin for CIPN induced by oxaliplatin remains insufficient. SmiliNg trial evaluated the efficacy and safety of mirogabalin in patients with unresectable advanced or recurrent GI cancers who have oxaliplatin-associated CIPN. Methods: This single-center, single-arm exploratory phase II trial enrolled patients with unresectable or recurrent GI cancer who were receiving ongoing first-line oxaliplatin-based chemotherapy or continuing fluoropyrimidine-based therapy after discontinuation of oxaliplatin, and who had painful CIPN (including numbness/tingling) with a numerical rating scale (NRS) score of ≥ 4. Mirogabalin was administered orally twice daily and titrated weekly according to Cockcroft–Gault creatinine clearance. The primary endpoint was the change in 24-hour average pain NRS from baseline to week 6. Secondary endpoints included PRO-CTCAE-assessed improvement in numbness/tingling, adverse events (CTCAE v5.0), and attainment of maintenance dose. The planned sample size was 30 patients. Clinical trial information: UMIN000049555. Results: Between February 2023 and April 2025, 30 patients were enrolled. The median age was 64 years (range, 36–83), with female patients accounting for 33%. The primary cancer types included colorectal (n=17), small bowel (n=7), gastric (n=6), and esophageal (n=1) cancers. The Mean baseline 24-hour pain NRS was 5.80 (SD 1.97). The mean change from baseline at week 6 was −1.46 (SD 2.66) (p = 0.010; 90% CI −2.35 to −0.57) , thereby the prespecified primary endpoint was achieved. The proportions of ≥1 -point responders were 58%. On the PRO-CTCAE, the proportions of patients achieving a ≥1-category improvement in worst severity were 38% and 38% at weeks 3 and 6, respectively; the corresponding proportions for interference with daily activities were 34% and 27%. Maintenance-dose attainment rates at weeks 3 and 6 were 59% and 68%, respectively. The most common adverse events were somnolence (83%) and dizziness (38%). Grade ≥3 adverse events comprised AST/ALT increased, and pulmonary infection, each occurring in one patient; none were related to mirogabalin treatment. Conclusions: This study suggests that mirogabalin is effective and well-tolerated for the management of moderate-to-severe painful CIPN during oxaliplatin-based chemotherapy. These findings warrant further evaluation in a confirmatory trial. Clinical trial information: 000049555.

Cancer during pregnancy and child health perspectives: Evidence from real-world data.

11013 Background: Pregnancy-associated cancer (PAC), is rare but increasingly encountered, likely reflecting delayed childbearing and the rising incidence of early-onset cancers. However, real-world evidence on short- and long-term offspring outcomes following PAC remains limited, particularly with respect to childhood chronic and inflammatory conditions. Methods: We conducted a retrospective cohort study using electronic medical records from Clalit Health Services, Israel’s largest integrated healthcare system. Pregnancies among women aged 18–50 years between 2000 and 2024 were identified including PAC and non-PAC (controls). Annual incidence rates were calculated overall and by maternal age group. Short-term maternal, pregnancy, and neonatal outcomes were compared between PAC-exposed and cancer-free pregnancies using multivariable regression models. To assess long-term child outcomes, we included all identified PAC cases and their offspring and extended follow-up to capture chronic conditions (as documented diagnosis within electronic medical records) that typically manifest later in childhood. Results: The cohort included 3,561 PAC and 28,361 non-PAC participants. PAC incidence increased substantially over time, with highest incidence observed among women aged 35–45 years. Breast cancer was the most frequently diagnosed invasive malignancy during pregnancy. Gestational age at delivery was comparable between PAC and non-PAC pregnancies, although PAC-exposed offspring were slightly more likely to be born with low birth weight (HR 1.03; 95% CI 1.01–1.05; P = 0.01).In follow-up analyses, heterogeneous and outcome-specific differences in child health were observed. PAC exposure was associated with higher risks of inflammatory and immune-related conditions, including inflammatory bowel disease (HR 1.16; 95% CI 1.03–1.32; P = 0.013) and allergic conditions (HR 1.20; 95% CI 1.03–1.39; P = 0.017). Associations with asthma (HR 1.12; 95% CI 1.00–1.26; P = 0.056) and cardiovascular conditions (HR 1.16; 95% CI 1.00–1.26; P = 0.057) were also observed yet reached borderline statistical significance. All models were adjusted for maternal BMI, hypertension, diabetes, cardiovascular disease, age at delivery, socioeconomic status, depression, and child sex. Conclusions: The incidence of PAC has increased markedly over the past decade. Our findings suggest that cancer during pregnancy may be associated with increased risk of inflammatory/immune-related conditions in the born children. Ongoing analyses and preclinical models will further clarify the long-term clinical significance of these findings and their implications for maternal–child survivorship care.