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Interstitial lung disease as a predictor of inpatient outcomes among patients with breast cancer.
e12734 Background: Interstitial lung disease (ILD) is an important comorbidity among patients with breast cancer, influenced by prior thoracic radiation, autoimmune disease, and exposure to systemic therapies such as taxanes, CDK4/6 inhibitors, and immune checkpoint inhibitors. ILD may increase vulnerability to respiratory and systemic complications during hospitalization. Limited national-level data exist evaluating the impact of ILD on inpatient outcomes in this population. This study examines whether ILD independently predicts adverse in-hospital outcomes among hospitalized women with breast cancer. Methods: The National Inpatient Sample (2018–2022) was analyzed to identify hospitalized women ≥18 years with breast cancer using ICD-10 codes. Patients with missing data were excluded. ILD and clinical outcomes were identified using validated ICD-10 codes. Outcomes included in-hospital mortality, length of stay (LOS), and complications such as sepsis, acute kidney injury, acute myocardial infarction, acute pulmonary embolism (PE), and ARDS. Categorical variables were compared using Chi-square testing and continuous variables using Kruskal-Wallis testing. Multivariable logistic regression assessed the association between ILD and outcomes, adjusting for diabetes, COPD, chronic kidney disease, coronary artery disease, pulmonary hypertension, alcohol use, and smoking. Results: A total of 164,448 hospitalized women with breast cancer were identified. Mean age was 64.7 ± 14.2 years, and 66.7% were White. ILD was significantly associated with higher in-hospital mortality (OR 1.79; 95% CI 1.50–2.13; p < 0.01), ARDS (OR 3.71; 95% CI 2.11–6.53; p < 0.01), acute PE (OR 1.42; 95% CI 1.05–1.94; p = 0.024), and increased LOS (coef 1.13 days; 95% CI 0.81–1.46; p < 0.01). ILD was also associated with higher odds of sepsis (OR 1.14), cardiogenic shock (OR 1.18), and cardiac arrest (OR 1.44), though these did not reach statistical significance. Conclusions: ILD is an independent predictor of adverse in-patient outcomes among women hospitalized with breast cancer, including higher mortality, increased risk of ARDS and acute PE, and longer LOS. These findings highlight the need for heightened clinical vigilance and tailored inpatient management for this high-risk population.
Association of β-blocker selectivity with survival and immune-related outcomes in melanoma and lung cancer patients treated with immune checkpoint inhibitors.
11152 Background: Immune checkpoint inhibitors (ICIs) are standard of care for advanced melanoma and lung cancer. Retrospective studies suggest that non-selective β-blocker use correlates with improved overall survival, potentially through modulation of the tumor immune microenvironment. However, real-world evidence comparing the effect of selective versus non-selective beta-blockers remains limited. Methods: We conducted a multicenter retrospective study using the TriNetX Global Collaborative Network. Adult patients (≥18 years) with melanoma or lung cancer treated with immune checkpoint inhibitors (pembrolizumab, nivolumab, ipilimumab, atezolizumab, durvalumab, cemiplimab, or avelumab) were identified. Patients were categorized based on exposure to non-selective β-blockers (carvedilol, propranolol, nadolol, labetalol, timolol) or selective β-blockers (metoprolol, atenolol, bisoprolol, nebivolol, acebutolol) within two months before or at ICI initiation. The index date was first ICI exposure. One-to-one propensity score matching was performed using covariates selected based on baseline imbalance, including demographics, cardiovascular and cerebrovascular comorbidities, and prior procedures. The primary outcome was overall survival. Secondary outcomes included hospitalization and immune-related adverse events (irAEs), defined using a composite endpoint of organ-specific immune-mediated toxicities based on prior published methodology. Results: After matching, 3,720 patients with melanoma and 11,160 patients with lung cancer were included in the analysis. Among melanoma patients treated with ICIs, non-selective β-blocker use was associated with lower mortality (HR 0.799; 95% CI 0.652–0.980) and decreased hospitalization (HR 0.865; 95% CI 0.759–0.984) compared with selective β-blockers. Most immune-related adverse events did not differ between groups, except for higher hepatic toxicity with non-selective β-blockers (HR 1.382; 95% CI 1.064–1.796). In lung cancer patients, non-selective β-blocker use was associated with lower mortality (HR 0.847; 95% CI 0.797–0.900), reduced ICU admission (HR 0.87; 95% CI 0.800–0.946), and decreased hospitalization (HR 0.912; 95% CI 0.864–0.963). Additionally, fewer cardiovascular (RR 0.811; 95% CI 0.711–0.925) and respiratory (RR 0.842; 95% CI 0.772–0.918) immune-related adverse events compared with selective β-blockers. Conclusions: In this real-world, propensity-matched analysis, non-selective β-blocker use was associated with improved early survival and reduced healthcare utilization among melanoma and lung cancer patients treated with ICIs. These findings suggest that non-selective β-blockers represent a low-cost and available adjunct to immunotherapy and warrants prospective validation.
Localized (Z)- <i>n</i> -butylidenephthalide biodegradable wafer as surgical adjuvant in recurrent glioblastoma for extending survival and re-sensitizing chemotherapy: A compassionate use study.
e14089 Background: Surgical resection of recurrent glioblastoma is often limited by anatomical constraints and neurological deficit risks, particularly in multi-focal disease involving bilateral hemispheres, or spinal/deep structures. Surgery adjuncts, such as (Z)- n -butylidenephthalide ((Z)-BP) wafer, act as localized therapies designed to potentiate complete resection and re-sensitize residual tumors. We report outcomes of (Z)-BP wafer in heavily pretreated recurrent glioblastoma patients with disease ineligible for trials. Methods: This compassionate use program was approved by the Research Ethics Committee and the regulatory agency. Seven recurrent glioblastoma patients (bilateral [n=2], cervical spinal [n=1], thalamic [n=1], and supratentorial lesions [n=3] with exhausted standard treatments. Results: Safety profile aligned with prior Phase I results, supporting tolerability of up to six wafers (total 450 mg (Z)-BP). No seizures, brain edema, or wound issues were observed in this program. Treatment-emergent adverse events included surgery-related anemia (57.1%) and lymphocyte reduction (42.9%), and alanine aminotransferase increased (42.9%). Grade 3 events comprised decreased CD4 and total lymphocytes (28.6% each), attributable to surgery. Efficacy analysis demonstrated median overall survival of 14.5 (range 3.7-49.9) months. Response assessment revealed two partial response and five stable disease cases (100% control rate). Patients also maintained their performance status (Karnofsky and Modified Ashworth scores). Notably, resected tumor tissue analysis from one patient revealed a shift in O 6 -methylguanine-DNA methyltransferase promoter status from unmethylated to intermediate methylation. Conclusions: This study provides evidences that (Z)-BP wafer improves survival in heavily pretreated patients. The median survival of 14.5 months exceeding historical controls by 6-9 months, combined with favorable tolerability, epigenetic methylation changes, and preserved performance, supports further investigation. A randomized Phase IIb/III trial has been initiated to validate these findings with overall survival.
Iberdomide (Iber) maintenance following upfront autologous stem cell transplant (ASCT) in multiple myeloma (MM).
7528 Background: Lenalidomide (Len) maintenance after ASCT has been a standard of care for patients (pts) with MM. Historically, ~30% of pts discontinue Len within 1 year (yr) due to toxicity and there is a need for more effective and better tolerated maintenance strategies. Iber is a potent, oral cereblon E3 ligase modulator under evaluation in the relapsed/refractory and newly diagnosed settings. We report the results of the primary analysis of a Phase II trial of Iber maintenance following upfront ASCT. Methods: Pts ≥ 19 yrs of age with MM, within 1-yr of initiation of induction therapy and in a ≥ partial response (PR) at day 80-110 post-ASCT, were accrued. Iber was administered 1.0 mg orally days 1-21 of a 28-day cycle, continued until progressive disease (PD) or toxicity. Up to 2 dose reductions (0.75 mg/day then 0.6 mg/day) were allowed. Growth factor support was not permitted. Minimal residual disease (MRD) assessment by flow cytometry (10 -5 ) was performed at registration, post-cycle 12 and post-cycle 24. An optimal Simon two-stage design with type I and II errors of 0.1 was chosen to test whether the proportion of pts who are progression-free and on treatment at 1 yr is <60% against the alternative of ≥ 80%. If ≥ 27 out of 38 pts were progression-free (by 2016 IMWG criteria) and on treatment at 1 yr, Iber would be considered to have promising activity. Results: 38 pts (55% males, median age 61 yrs (range: 41-77)) received Iber. R-ISS at diagnosis was stage I (34%), II (39%), III (8%) and unknown (18%), with 34% having high-risk disease per 2025 IMS/IMWG criteria. All pts received triplet or quadruplet induction therapy, with 97% receiving Len and 84% receiving daratumumab. At day 80-110 post-ASCT, all pts had ≥ very good PR, with 22 (58%) ≥ complete response (CR) and 33 (87%) MRD-negative (neg). The median number of administered treatment cycles is 18 (range: 1-45), with 18 (47%) pts having ≥ 1 dose reduction, most commonly due to neutropenia (n=12). The most common grade (gr) 3/4 adverse event was neutropenia (gr 3 (n=19), gr 4 (n=5)). Within yr 1, 29% (11/38) discontinued Iber due to neutropenia (n=5), rash (n=1), infection (n=1), pt choice (n=1), or PD (n=3). After 1 yr, 6 pts discontinued due to neutropenia (n=4) and PD (n=2). While on Iber, 19 pts had deepening of response to stringent CR and 3 pts converted from MRD-positive to MRD-neg. The post-cycle 12 and 24 MRD-neg rates are 85% (23/27) and 100% (14/14), respectively. Conclusions: Iber demonstrated promising activity with dose reductions/discontinuations mainly due to neutropenia. Strategies including lower starting dose, growth factor support and more flexible management of neutropenia may enable more pts to remain on treatment. Longer follow-up will permit evaluation of sustained MRD-negativity and PFS, but overall, these results provide rationale for further exploration of Iber-based post-ASCT maintenance strategies. Clinical trial information: NCT05177536 .
Comparative incidence of infections and cytopenias in BCMA- vs GPRC5D-targeting bispecific antibodies for relapsed/refractory multiple myeloma: A systematic review and meta-analysis of proportions.
e19505 Background: Bispecific antibodies (BsAbs) targeting BCMA and GPRC5D have demonstrated substantial efficacy in relapsed/refractory multiple myeloma (RRMM). However, treatment is associated with significant infectious and hematologic toxicities. While individual trials report variable safety outcomes, a target-specific pooled analysis of these adverse events is lacking. Methods: We performed a systematic review and meta-analysis of proportions of phase 1/2 clinical trials evaluating BCMA-targeting (teclistamab, elranatamab, linvoseltamab) and GPRC5D-targeting (talquetamab) BsAbs administered at recommended phase 2 or approved doses in adults with RRMM. Primary outcomes were grade ≥3 infections and grade ≥3 neutropenia. Secondary outcomes included any-grade infections, any-grade and grade ≥3 anemia, any-grade and grade ≥3 neurotoxicity. Event proportions were pooled using random-effects models with variance-stabilizing transformation. Heterogeneity was assessed using I² and τ² statistics. Sensitivity analyses included leave-one-out diagnostics and alternative estimators. Results: Seven trial arms from phase 1/2 clinical trials, comprising 806 patients with RRMM, were included in the quantitative synthesis. Among BCMA-targeting BsAbs, the pooled incidence of grade ≥3 infections was 28.9% (95% CI 21.7–37.3) with substantial heterogeneity (I²=86%, P<0.01)). GPRC5D-targeting BsAbs demonstrated comparable pooled rates of grade ≥3 infections infections across dosing schedules, with overlapping confidence intervals and similarly high heterogeneity. Grade ≥3 neutropenia was common, with higher pooled rates observed among BCMA-targeting agents (45.5%, 95% CI 33.2–58.3; I²=92%, P < 0.01) compared with GPRC5D-targeting BsAbs. Any-grade infections occurred frequently across both targets (BCMA: 71.0%, 95% CI 66.1–75.4; I²=56%, P = 0.03). Hematologic toxicity was frequently observed across both targets. Among BCMA-targeting BsAbs, the pooled incidence of any-grade anemia was 41.6% (95% CI 35.4–48.0; I²=68%, P <0.01), while grade ≥3 anemia occurred in 31.5% of patients (95% CI 28.0–35.3; I²=25%, P=0.24). Any-grade neurotoxicity was infrequent, with a pooled incidence of 7.3% (95% CI 4.8–10.9; I²=59%, P=0.02), and grade ≥3 neurotoxicity was rare (0.49%, 95% CI 0.12–2.00; I²=0%, P=0.88). Sensitivity analyses confirmed the robustness of pooled estimates. Conclusions: Although pooled rates of grade ≥3 infections were comparable between BCMA- and GPRC5D-targeting BsAbs, BCMA-targeting agents demonstrated numerically higher rates of severe neutropenia. These findings support the need of prospective comparative safety studies, individualized risk stratification and proactive supportive-care strategies when selecting BsAbs therapy in patients with RRMM.
Global burden of lung cancer from 2000 to 2023 and projections to 2035: Implications for ctDNA-based molecular residual disease–guided care.
e22519 Background: Lung cancer remains a leading cause of cancer-related morbidity and mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of cases. Circulating tumor DNA (ctDNA)–based molecular residual disease (MRD) assays are increasingly studied in NSCLC to enable earlier detection of recurrence and guide perioperative and adjuvant treatment strategies. However, the relevance of MRD-guided approaches has not been contextualized within long-term global lung cancer burden trends. We evaluated temporal patterns in lung cancer burden from 2000–2023, projected trends through 2035, and explored implications for MRD implementation. Methods: Global Burden of Disease (GBD) 2000–2023 estimates were analyzed for tracheal, bronchus, and lung (TBL) cancer incidence, mortality, and disability-adjusted life years (DALYs). Age-standardized rates (ASRs) per 10,000 population were extracted overall and stratified by sex and sociodemographic index (SDI). Trend-based projection models were applied to observed ASRs to estimate burden through 2035. Analyses were descriptive, and implications for MRD-guided care were hypothesis-generating. Results: In 2023, global ASRs per 10,000 were 26.94 for incidence, 18.78 for mortality, and 568.80 for DALYs. Burden was higher in males than females for incidence (39.76 vs 16.06), mortality (36.53 vs 14.07), and DALYs (840.20 vs 327.39). High-SDI regions exhibited the highest incidence ASR (37.13) and DALYs ASR (755.10). Projections suggest persistent lung cancer burden through 2035, with the greatest burden in males and high-SDI settings. Conclusions: Global lung cancer burden remains substantial and is projected to persist through 2035, with marked disparities by sex and sociodemographic development. Although GBD does not distinguish histologic subtypes or capture treatment pathways, observed trends are likely driven predominantly by NSCLC. High-SDI regions—where perioperative systemic therapy and longitudinal surveillance are established—may represent priority settings to evaluate ctDNA-based MRD strategies. These findings provide a population-level framework to contextualize emerging molecularly guided approaches.
Effectiveness and safety of transarterial chemoembolization combined with apatinib in hepatocellular carcinoma: A systematic review and proportional meta-analysis.
e16199 Background: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and a leading cause of cancer-related mortality. Many patients present with advanced disease, limiting curative options. Transarterial chemoembolization (TACE) is a standard treatment for intermediate-stage HCC, and apatinib, a VEGFR-2 inhibitor, has shown antitumor activity in advanced disease. We evaluated the efficacy and safety of combining TACE with apatinib. Methods: A systematic review and proportional meta-analysis were conducted. Of 263 screened studies, 10 eligible randomized and retrospective studies were included. Primary outcomes were objective response rate (ORR), disease control rate (DCR), and progressive disease (PD). Safety outcomes included treatment-related adverse events. Pooled proportions were calculated using common- and random-effects models in R (version 4.4.3), with heterogeneity assessed using the χ² test. Results: TACE plus apatinib demonstrated meaningful clinical activity. Pooled ORR was 57% (common-effects; 95% CI, 0.53–0.61) and 56% (random-effects; 95% CI, 0.44–0.66), with a maximum reported ORR of 71% (95% CI, 0.62–0.79). Pooled DCR was 79% (common-effects; 95% CI, 0.75–0.82) and 82% (random-effects; 95% CI, 0.73–0.89), with a peak of 96% (95% CI, 0.85–0.99). PD rates were low at 16% (common-effects; 95% CI, 0.13–0.20) and 15% (random-effects; 95% CI, 0.10–0.23). These outcomes exceeded historical results reported for TACE monotherapy (ORR ~44%, DCR ~73%). Adverse events, including hand–foot syndrome, hypertension, fever, diarrhea, and proteinuria, were generally manageable. Conclusions: Combining TACE with apatinib improves tumor response and disease control compared with TACE alone in patients with HCC, with an acceptable safety profile. These findings support the combination as a promising treatment strategy and warrant further prospective evaluation.
Real-world outcomes of polatuzumab, rituximab, and lenalidomide in frail pts with diffuse large B-cell lymphoma.
e19055 Background: Patients (pts) with diffuse large B-cell lymphoma (DLBCL) who are elderly, frail, or have cardiac comorbidities are frequently ineligible for anthracycline-based chemotherapy and are underrepresented in clinical trials. Chemotherapy-sparing regimens incorporating antibody–drug conjugates and immunomodulatory agents may provide an alternative treatment strategy. Therefore, polatuzumab vedotin (Pola), rituximab, and lenalidomide (Pola-R 2 ) was evaluated in a real-world cohort of pts with aggressive DLBCL. Methods: A retrospective analysis of consecutive pts with DLBCL treated with Pola-R 2 at a single institution was performed. Pola at 1.8mg/kg and rituximab at 375mg/m 2 were administered on day 1 of each 21-day cycle with planned lenalidomide 10 mg on days 1–14. Interim response assessment was obtained after cycle 4 and end of treatment assessment after cycle 8. Response was assessed using 2014 Lugano criteria and Clonoseq MRD. The primary objective was feasibility and tolerability; secondary objective was early disease control. Kaplan Meir analysis was used for survival outcomes. Results: Twenty pts with median age of 81 yo (range 50–92) and median ECOG performance status of 3 (range 2–4) were included. Comorbidity burden was substantial, with 75% of pts having significant cardiac disease, 30% with renal disease and 30% with chronic pulmonary disease. 40% (n=8) received Pola-R 2 in the frontline setting and 60% in second line or beyond; 9 with anthracycline exposure. 85% of pts had stage IV disease and 70% had non germinal center B-cell. At a median follow-up of 7.7 months (range 2–13), median overall survival (OS) was not reached and median progression-free survival (PFS) was 8.6 months (95% CI 5.4- undefined). Estimated 6-month PFS and OS were 69% and 73%, respectively. Interim PET assessment after four cycles demonstrated CR in 50%, and PR in 25%. Of the 11 pts who completed treatment at time of submission, 90.1% achieved CR, of whom 81.8% had undetectable MRD. Improvement in performance status following treatment permitted consolidative treatment with stem cell transplant in 4 of these pts (1 autologous, 3 allogeneic). Overall, treatment was well tolerated, with only 2 discontinuations for quality of life. Neutropenia occurred in 80% of pts within the first 4 cycles leading to reduction of Lenalidomide to 7 days in 75% of pts. Only 1 hospitalization occurred while on treatment. Conclusions: In this elderly and frail population with high-risk DLBCL, Pola-R 2 was feasible with encouraging early disease control, including PET-defined complete responses and MRD negativity. While follow-up is shorter, these findings compare favorably with historical outcomes reported for attenuated chemoimmunotherapy regimens such as R-mini-CHOP. This supports further prospective evaluation of chemotherapy-sparing strategies for anthracycline-ineligible pts with aggressive lymphoma.
Standardizing communication during ICU transfers of oncology patients.
e23299 Background: Oncology patients have complex care plans. During transitions of care, precise communication of diagnostic, prognostic, and treatment information between medical teams is crucial. We recognized the lack of a standardized communication tool for floor-to-ICU (FTI) transfers of oncology patients. We aimed to increase the percentage of FTI transfers for oncology patients with sufficient written communication by developing a generalizable transfer template with an oncology-specific component to be implemented at the Hospital of the University of Pennsylvania. Methods: Key stakeholders were engaged across all Department of Medicine inpatient services. We conducted voice of the customer (VoC) interviews with the liquid oncology, solid oncology, and intensive care clinical teams. Incorporating this feedback, we developed a system-wide note template in the electronic medical record (EMR) called ICU-PASS. The template encourages users to summarize acute clinical events, interventions taken, outstanding results, and family communications. The tool was launched in 5/2025. Direct outreach to clinical teams and an educational campaign were conducted in the first 3 months post-launch, continuing until 8/2025. Usage data was collected through EMR tools. Retrospective review was conducted to evaluate changes to post-intervention documentation quality. Quantitative outcomes were analyzed with descriptive and inferential statistics. Results: The VoC interviews revealed disparate practices in FTI transfer documentation and a desire for more consistent, detailed descriptions of goals of care (GOC) conversations. An oncology-specific component was developed with three key elements: 1) name and notification of the outpatient oncologist; 2) a list of active chemotherapy with treatment intent; and 3) therapy-related GOC. One month before implementation, 46% (11/24) of oncology FTI transfers had complete documentation of critical events. The ICU-PASS had an oncology FTI usage during the initial 3 months of active intervention of 86.1% (62/72) (p < 0.01). In the subsequent 3 months of passive utilization, the ICU-PASS had a usage rate of 72.7% (99/136) (p = 0.01). The time needed to complete FTI transfer notes decreased from an average of 83 minutes (min) to 26 min. Complete documentation of GOC communication increased from 4.1% to 71.4% (p < 0.01). The percentage of these FTI transfers with an advanced care planning (ACP) note documented within 48 hours of transfer improved from 16.6% to 57.1% (p = 0.01). Conclusions: This study demonstrated an effective interdisciplinary approach to implementing an EMR-based standardized FTI communication tool, as well as the sustained impact of the tool on patient safety beyond a period of active intervention. Our tool significantly increased the transfer documentation rate, while also improving note efficiency and the ability of receiving teams to have timely GOC discussions.
TGF-β signaling alterations in bevacizumab-treated early-onset colorectal cancer: An artificial intelligence–enabled precision oncology study in diverse populations.
3649 Background: The transforming growth factor–β (TGF-β) signaling pathway plays a complex, context-dependent role in colorectal cancer (CRC), functioning in tumor suppression, immune modulation, and metastatic progression. Its interaction with anti-angiogenic therapy remains poorly defined, particularly across age and ancestry groups. Early-onset CRC (EOCRC) may exhibit distinct TGF-β pathway biology. We investigated ancestry-, age-, and treatment-associated patterns of TGF-β signaling alterations and their prognostic relevance in bevacizumab-treated CRC using an artificial intelligence–enabled precision oncology framework. Methods: We performed a retrospective analysis of 2,717 CRC patients from publicly available datasets with integrated genomic, clinical, and treatment annotations. Eligible cases included colorectal adenocarcinoma with sequencing data and documented bevacizumab exposure. Patients were stratified by age ( < 50 years [EOCRC] vs. ≥50 years [LOCRC]), ancestry (H/L vs. non-Hispanic White [NHW]), and treatment status. TGF-β pathway alterations, including mutations in core signaling components (e.g., TGFBR2), were analyzed as categorical variables. Differences in mutation frequencies were assessed using Fisher’s exact test. Overall survival (OS) was evaluated using Kaplan–Meier methods and Cox proportional hazards models. Conversational AI agents facilitated reproducible cohort construction and multi-dimensional querying. Analyses were exploratory. Results: Marked ancestry-, age-, and treatment-specific differences in TGF-β alterations were observed. Among bevacizumab-unexposed EOCRC, H/L tumors demonstrated substantially higher TGF-β alteration frequencies compared with NHW tumors (31.9% vs. 0.2%, p = 2 × 10⁻¹⁶). In NHW EOCRC, bevacizumab exposure was associated with increased TGF-β alterations relative to unexposed tumors (25% vs. 0.2%, p = 2 × 10⁻¹⁶). Similarly, bevacizumab-treated NHW LOCRC exhibited higher TGF-β alteration frequencies than unexposed counterparts (58% vs. 15.4%, p = 2.2 × 10⁻¹⁶). Among bevacizumab-unexposed LOCRC, H/L tumors showed higher TGF-β alterations than NHW tumors (34.2% vs. 18.0%, p = 2.41 × 10⁻⁵). In NHW LOCRC, bevacizumab-exposed tumors had a lower frequency of TGFBR2 alterations compared with unexposed tumors (1.3% vs. 7.1%, p = 0.03). Survival analyses suggested that TGF-β alterations were associated with improved OS in bevacizumab-unexposed NHW LOCRC, with borderline statistical significance (p = 0.08). Conclusions: The enrichment of TGF-β alterations in specific bevacizumab-exposed and ancestry-defined subgroups highlights potential interactions between angiogenic therapy and TGF-β pathway biology. These findings highlight the importance of incorporating ancestry-aware frameworks to advance precision oncology.
Operative and non-operative management of small bowel obstruction in colorectal cancer hospitalizations: A national inpatient sample analysis.
e15630 Background: Small Bowel Obstruction (SBO) is a common and serious complication among patients with Colorectal cancer (CRC). Admissions are usually clinically challenging. There is limited contemporary data on the outcomes of operative and non-operative treatments. Methods: We conducted a retrospective cross-sectional study using the National Inpatient Sample (NIS) database for the years 2018-2022. Adults aged 18 years with CRC and SBO who were hospitalized were identified. Management was classified as operative versus non-operative based on procedure coding. The primary outcome was in-hospital mortality; secondary outcomes were length of stay (LOS) and total hospital charges (TOTCHG). Baseline characteristics and outcomes were compared using survey-weighted tests. Survey-weighted multivariable logistic regression was used to estimate adjusted odds of mortality. Models adjusted for age, sex, race, payer, ZIP-income quartile, hospital region, teaching status, bed size, and comorbidities (CKD, CHF, DM, HTN, COPD, obesity). Results: The CRC+SBO cohort represented a weighted population of ~101,645 hospitalizations (unweighted n≈20,329). In-hospital mortality was lower with operative than with non-operative management (4.83% vs 8.09%, design-based p < 0.001). LOS distribution differed significantly by management (design-based p < 0.001): LOS 0–3 days (12.19% operative vs 45.56% non-operative), 4–7 days (30.10% vs 32.42%), 8–14 days (34.43% vs 16.05%), and ≥15 days (23.28% vs 5.98%). Mean charges were substantially higher with operative management ($148,487 [95% CI 145,345–151,629]) compared with non-operative ($53,589 [95% CI 51,742–55,436]). In adjusted analysis, operative management remained associated with lower in-hospital mortality (aOR 0.53, 95% CI 0.45–0.62; p < 0.001). Increasing age was associated with higher mortality (aOR 1.03 per year, p < 0.001). CHF (aOR 1.79, p < 0.001), CKD (aOR 1.35, p = 0.003), and COPD (aOR 1.35, p = 0.012) were associated with higher mortality. Female sex was associated with modestly lower mortality (aOR 0.85, p = 0.034). A higher ZIP income quartile (Q4 vs Q1) was associated with lower mortality (aOR 0.70, p = 0.003). Conclusions: In a national cohort of CRC hospitalizations complicated by SBO, operative management was associated with significantly lower adjusted in-hospital mortality, but substantially longer length of stay and higher hospital charges. These findings reinforce the need for risk-stratified decision-making based on patients who will gain the greatest benefit from surgery, and resource utilization to decrease length of stay and charges. There is a need for prospective studies to determine which CRC+SBO patients gain the greatest survival benefit.
Antigen-switch and BCR-axis–enriched multi-target CAR T re-infusion after prior CAR T failure in R/R B-cell NHL.
e19017 Background: Relapse after CAR T-cell therapy remains a critical unmet need in relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL), frequently associated with antigen escape and limited effective salvage options. We evaluated a non–single-antigen approach emphasizing antigen/construct switching beyond conventional CD19-only retreatment, incorporating targets across the B-cell antigen landscape, including the B-cell receptor (BCR) axis component CD79b, and enabling rapid sequential CAR-T administration in clinically aggressive disease. Methods: Patients with R/R B-NHL who had failed at least one prior CAR-T therapy received subsequent CAR-T infusion(s) targeting CD20, CD22, CD79b, CD19-BAFFR, CD19-NKG2D, or CD19/22 constructs. The primary objectives were safety and efficacy (overall response rate, ORR). Responses were assessed per standard lymphoma response criteria (best overall response). Safety was graded using ASTCT criteria for CRS/ICANS and CTCAE for hematologic toxicity. Results: Thirteen post–CAR-T-exposed patients were analyzed (DLBCL spectrum predominating; including primary CNS lymphoma). The strategy achieved an ORR of 84.6% (11/13) with a complete response (CR) rate of 69.2% (9/13); progressive disease occurred in 23.1% (3/13). Responses were observed across multiple non-CD19 targets, including CD20-, CD22-, and CD79b-directed products, supporting clinical activity of antigen-switch strategies after CAR-T failure. In several patients, CAR-T products were administered in close temporal sequence (approximately within 48 hours in the recorded treatment course), demonstrating feasibility of rapid multi-target deployment. No unexpected safety signals were observed; inflammatory toxicities were manageable, with no high-grade CRS/ICANS reported in this cohort (per available dataset), supporting the tolerability of multi-target and rapid sequential approaches. Conclusions: In this real-world/IIIT cohort of R/R B-NHL patients previously failing CAR-T therapy, multi-target CAR-T re-infusion enriched for non-CD19 and BCR-axis targets produced a high ORR and CR rate with feasible rapid sequential administration and manageable toxicity. These findings support prospective, protocolized evaluation of antigen-switch and BCR-axis–informed multi-target CAR-T strategies to address post–CAR-T relapse. These data align with the current ASCO focus on overcoming post–CAR-T antigen escape by rational antigen switching and multi-target sequencing, including BCR-axis targeting, to improve depth of response in ultra-refractory B-NHL. Clinical trial information: ChiCTR1900025419.
Health-related quality of life following tumor-infiltrating lymphocyte (TIL) therapy with commercial lifileucel in metastatic melanoma: Real-world longitudinal patient-reported outcomes.
9547 Background: Although the efficacy of lifileucel has been demonstrated in metastatic melanoma, real-world longitudinal patient-reported outcomes remain limited. We evaluated health-related quality of life (HRQoL) among patients treated with commercial lifileucel at Moffitt Cancer Center using the Functional Assessment of Cancer Therapy–Melanoma (FACT-M) instrument. Methods: FACT-M surveys were administered at Baseline, Day +7, Month +6, and End of Treatment (April–December 2025). Scores were calculated using validated procedures. Clinical benefit was defined as complete response/ no evidence of disease or partial response as the best response per RECIST v1.1. Minimally important differences (MID) were defined as 4–7 points for the FACT-G total score and 4–6 points for the FACT-M combined scores. Comparisons used Wilcoxon rank-sum tests. Results: Thirty-two patients were enrolled, with 97 surveys completed out of 105 requested (92% completion rate). Median age was 66 years (range 29–78); 56% were male (n=18) and 44% female (n=14). ECOG performance status was 0–1 in 93%. Patients received a median of 5 IL-2 doses (range 1–6), and 53% experienced clinical benefit (n=17). Baseline, Day +7, and Month +6 FACT-M subscale and total scores are presented in Table 1. Among all patients, FACT-M and FACT-G scores remained stable from baseline to Day +7 and demonstrated clinically meaningful improvement exceeding the minimally clinically important difference at Month +6. While baseline HRQoL scores did not differ by treatment outcome (median FACT-G, 87 in both groups; median FACT-M, 108 in patients without clinical benefit and 109 in those with benefit), scores were significantly higher across follow-up assessments among patients with clinical benefit compared with those without. Median FACT-G scores were 102 vs. 76 (p=0.012), and median FACT-M scores were 125 vs. 94 (p=0.017), respectively. Conclusions: HRQoL, as measured by FACT-G and FACT-M, was maintained following commercial lifileucel in a real-world metastatic melanoma cohort, supporting the tolerability of TIL therapy. HRQoL outcomes varied according to clinical benefit. Larger studies with extended follow-up are warranted to confirm these findings. Median baseline, day+7, and month +6 FACT-M subscale and total scores. Characteristic BaselineN = 17 1 Day +7N = 11 1 Month +6N = 13 1 Baseline to Month+6 difference Physical well Being (PWB) 25 20 26 +1 Social well Being (SWB) 25.67 25.20 26.00 +0.33 Emotional well Being (EWB) 22.2 22.2 23.3 +1.1 Functional well Being (FWB) 21 20 23 +2 Melanoma (MS) 22.3 20.6 24.5 +2.2 Melanoma Surgery (MSS) 24.5 24.5 27.1 +2.6 FACT-G (sum of PWB, SWB, EWB, + FWB) 90 89 97 +7 FACT-M (sum of FACT-G + MS) 111 111 124 +13 1 Median.
Safety and efficacy of B7H3/IL13Rα2 bispecific armored CAR-T for treatment of recurrent/refractory glioblastoma.
e14062 Background: Recurrent/refractory glioblastoma (GBM) carries an extremely poor prognosis with limited therapeutic options. CAR-T therapy represents an innovative strategy for GBM, yet monospecific, single-infusion CAR-T is hindered by tumor antigen escape and inadequate efficacy durability. To address these two key challenges, we developed a fully human bispecific armored CAR-T targeting B7H3/IL13Rα2 and adopted a pharmacokinetic (PK)-guided precision multiple-infusion regimen to enhance efficacy and durability. Methods: This investigator-initiated first-in-human study adopted a 3+3 dose-escalation design, with four dose levels: 2.5, 5.0, 10, and 20 million cells. Eligible patients were 18-75 years old with recurrent/refractory GBM, confirmed by immunohistochemistry (IHC) to have ≥30% expression of both B7H3 and IL13Rα2. Administration was via intracavity/intraventricular Ommaya catheter, with serial cerebrospinal fluid (CSF) and peripheral blood CAR-T PK monitoring (CAR-T qPCR levels, flow cytometry subsets, and cytokines) guiding personalized dosing frequency. The primary objective was safety, and secondary objective was preliminary tumor response assessed by RANO2.0 criteria. Results: Two patients with IDH-wildtype, MGMT-unmethylated recurrent GBM completed low-dose (2.5 million cells) CAR-T infusions: the first received 4 doses, and the second 2 doses. No dose-limiting toxicities (DLT) occurred; adverse events (AEs) mainly included fatigue, thrombocytopenia, abnormal liver function, and hypoalbuminemia, all manageable with supportive care without ICU admission. Cytokine release syndrome (CRS) was grade 1 at maximum, resolving spontaneously within 3-5 days. Abundant central memory T cells were detected in CSF, and high CAR-T copy numbers persisted for ≥3 weeks post-infusion, demonstrating favorable durability. Best overall response: the first patient achieved ≥30% tumor reduction determined by RANO2.0 criteria with no progression during 3-month follow-up; the second maintained stable disease (SD). Conclusions: B7H3/IL13Rα2 bispecific CAR-T exhibits favorable safety in recurrent/refractory GBM: Low-dose, PK-guided multiple infusions avoided DLT, with all AEs reversible via standard interventions. It also demonstrates robust in vivo expansion and persistence, supporting subsequent dose-escalation trials. Clinical trial information: NCT07193628 .
Experiences of a cancer survivorship elective in a US medical school: The first 10 years.
9025 Background: Cancer survivorship care is an increasingly important competency in medical education, but early introduction in medical school curriculum is uncommon, and longitudinal evaluation of survivorship curricula is limited. We report here our 10 years’ experience of a dedicated UME cancer survivorship course. Methods: A 15-week elective was offered to pre-clerkship Y2 students (5-14 participants /y) annually from 2016-25, including one fully remote class in 2020. Attendees had a year of prior longitudinal clinical experience. Key topics of the curriculum were developed from ASCO and NCCN Survivorship Guidelines. Sessions were facilitated by a clinical oncologist (MCF) and co-hosted by rotating guests with clinical experience in cancer care. These included a primary care physician, survivors, caregivers, a medical geneticist, a palliative care nurse, social workers, a nutritionist, and a PT/OT specialist. The final assessment was a proposed individualized survivorship care plan (SCP), based on a one-to-one interview with a survivor. Students completed pre- and post-course surveys, assessing satisfaction with course structure, change in confidence dealing with topics covered, and the course’s influence on specialty choice. Likert scale responses (1-4) were analyzed using paired t-tests and Cohen’s d for confidence changes. Descriptive statistics summarized satisfaction and career impact. Results: Of 102 students participating over 10 years, 90 returned pre/post surveys (88%). Students overall reported a high level of satisfaction with the course (mean 3.60/4, SD 0.49), particularly valuing guest sessions with survivors (3.84/4), caregivers (3.86/4), and social work (3.91/4). They felt the course was adequately rigorous for the M2 level (3.59/4), provided useful skills for future interprofessional collaboration (3.60/4), and was effectively tested by the final assignment (3.47/4). Multimedia assignments were the most valuable to students (3.47/4). Confidence in speaking to and caring for cancer survivors increased very significantly post-course (mean change +0.75, t = 7.81, p < 0.001, d = 1.02), and students felt that the skills they learned were relevant to their future careers (3.53/4). Over half of students (56%) indicated the course strengthened their interest in pursuing an oncology-focused field while another f26% indicated an interest in remaining committed to cancer-related issues in some capacity. Conclusions: A dedicated undergraduate cancer survivorship curriculum is novel, feasible, sustainable, and highly valued by medical students. The course produced significant gains in confidence, increased interest in oncology, and highlighted the educational value of interprofessional, survivor-centered learning. Early integration of survivorship education may improve future physician comfort with holistic cancer care and enhance career interest in the field.
An exploratory study of the potential clinical impact of ethnicity in patients with retroperitoneal sarcoma.
e23533 Background: Surgery is the mainstay of treatment for localized retroperitoneal sarcoma (RPS), but emerging data and interest support multimodality therapy, especially in the neoadjuvant setting. We studied the association of ethnicity with RPS outcomes and potential biases in non-surgical therapy utilization at an academic sarcoma referral center in a major U.S. city. Methods: Data were reviewed for all RPS patients under the care of a single sarcoma-trained surgical oncologist between July 2022 and December 2025. Inclusion criteria were: non-metastatic, primary disease; the most common RPS histologic types (liposarcoma, leiomyosarcoma, undifferentiated pleomorphic sarcoma, malignant peripheral nerve sheath tumor, solitary fibrous tumor); and curative-intent, complete resection (R0/R1). For study patients, clinicopathologic data were summarized. Development of local recurrence (LR) or distant metastasis (DM) was used to determine disease-free interval (DFI). Results: Among 112 patients during the study period, 35 met inclusion criteria. By histologic type, 23 patients had liposarcoma (66%), 9 leiomyosarcoma (26%) and 3 other (8.6%). Study patients were categorized by ethnicity: Caucasian (Group A, n = 12, 34%), Hispanic (B, n = 13, 37%), Asian/Middle Eastern (C, n = 10, 29%). A balanced distribution of histologic types was seen within each ethnic group. In Group A, neoadjuvant therapy (systemic or radiation) was given in only 1 patient in Group A (8.3%) versus 4 in B (30%) and 2 in C (20%) (Fisher’s exact test p = 0.44). No patient received adjuvant therapy in Groups A or B, while this was given in 2 additional patients in C (40% total). Disease progression (defined as either LR or DM) occurred in 4 out of 9 patients in A (44%), 2 out of 11 in B (18%) and 4 out of 8 in C (50%). Average DFI was 6 months in A, 5 in B and 8 in C. Conclusions: With the limitation as a single center study, our cohort was representative of the histologic types seen in RPS and all patients underwent a uniform approach to management. Potential differences in outcome after surgery were observed that may segregate by ethnic group. Although based on a small sample size, a trend of higher utilization of neoadjuvant therapy and a lower frequency of disease progression after surgery was noted in Hispanic versus non-Hispanic patients. The current study highlights the need for further investigation into the impact of ethnicity in RPS management.
Effect of nanobody-STING agonists on the tumor microenvironment and adoptive cell therapy for solid tumors.
e14601 Background: Adoptive cell therapies (ACT), including TCR- and CAR-engineered T cells, have demonstrated durable clinical benefit in hematologic malignancies but have shown limited efficacy in solid tumors due to poor T cell infiltration, functional suppression, and early exhaustion within the tumor microenvironment (TME). Strategies to remodel the TME and support T cell function are therefore a major clinical priority. Activation of the stimulator of interferon genes (STING) pathway can induce antitumor inflammation and innate immune activation; however, clinical translation of STING agonists has been limited by poor tumor accumulation and dose-limiting systemic toxicity, often requiring intratumoral administration. We hypothesized that systemic, yet tumor-enriched STING activation could safely reprogram the TME and enhance the therapeutic efficacy of ACT in solid tumors. Methods: We developed an albumin-hitchhiking nanobody–STING agonist (AHNSA) platform designed to exert significantly more effects in the TME. AHNSA was evaluated as an adjuvant to ACT in a TCR-transgenic OT-I T cell transfer model using MC38-OVA tumors. Antitumor efficacy and survival were assessed by tumor volume measurements and Kaplan-Meier survival analyses. Tumor-infiltrating immune populations and transferred T cells were analyzed by flow cytometry and immunohistochemistry to evaluate innate immune activation, T cell infiltration, proliferation, functional state, and expression of exhaustion-associated markers, as well as global changes in TME composition. Results: Systemic administration of AHNSA following ACT resulted in significantly improved tumor control and survival compared with ACT alone. AHNSA treatment increased intratumoral accumulation of dendritic cells and inflammatory macrophages, consistent with STING-mediated innate immune activation, and significantly enhanced infiltration of adoptively transferred T cells. Transferred T cells exhibited increased activation and proliferation with reduced expression of exhaustion markers (PD1, LAG3), indicating improved functional persistence. Immune profiling revealed a coordinated shift toward a pro-inflammatory TME, including enrichment of CD8⁺ T cells and antigen-presenting cells and depletion of immunosuppressive populations such as myeloid-derived suppressor cells, M2 macrophages, and regulatory T cells. Conclusions: Targeted systemic STING agonism using an albumin-hitchhiking nanobody platform overcomes key delivery and toxicity barriers associated with STING activation and potently enhances adoptive T cell therapy by reprogramming the solid tumor microenvironment. These findings support a clinically relevant combination strategy to improve the efficacy of cellular immunotherapies in solid tumors and provide a strong rationale for translational development.
Multi-center prospective study evaluating an AI-enabled clinical decision support tool to improve biomarker testing in early-stage NSCLC.
8044 Background: Non-adherence to guideline-concordant biomarker testing in non-small cell lung cancer (NSCLC) can limit access to targeted therapies and adversely impact survival. We evaluated an AI-enabled clinical decision support (AI-CDSS) program comprising: (1) education around baseline testing rates; (2) continuous monitoring to generate real-time alerts for eligible patients with missing biomarker testing; and (3) longitudinal feedback via dashboards. Here, we report the effectiveness of this program in identifying and closing biomarker testing gaps for patients with early-stage NSCLC. Methods: In this descriptive study, we analyzed patients with confirmed NSCLC across 6 geographically and socioeconomically diverse US community health systems. The AI-CDSS identified early-stage patients eligible for biomarker testing (eNSCLC as AJCC 8th edition Stg IB-IIIB (T3, N2) with planned curative intent treatment). Biomarker testing included EGFR, ALK, and PD-L1. We compared testing adherence between a baseline period (BL: 24 months through 3 months prior to the health system-specific roll-out) and a post-launch period (PL: roll-out through Oct 2025). The AI-CDSS was implemented on a rolling basis across health systems (BL from Feb 2022 - Dec 2024 and PL from Feb 2024 - Oct 2025). Testing rates were calculated as the proportion (%) of patients with testing completed within 90 days of pathologic diagnosis in each period. The improvement in test rates (absolute lift) is calculated as the difference in PL - BL testing percentages in the two periods. Results: A total of 662 patients with eNSCLC (270 BL and 392 PL) were included in the analysis. Patients were predominately white (85%), had a history of smoking (88%), with a median age of 70 years at diagnosis. The stage distribution was as follows: Stage III (34%), Stage II (37%), Stage IB (25%), and Stage IB or IIA [indeterminate] (5%). The absolute lift in biomarker testing within 90 days of pathologic diagnosis before vs after intervention was 18% for EGFR, 24% for ALK, and 13% for PDL1 biomarkers. Among patients with molecular testing who received adjuvant treatment, 89% were on guideline-concordant adjuvant treatment. Conclusions: Implementation of an AI-CDSS was associated with clinically meaningful improvements in rates of biomarker testing for eNSCLC and resulted in high concordance with guideline-directed adjuvant therapy. Appropriate and timely biomarker testing is essential for perioperative treatment planning. This study provides preliminary evidence that AI can use complex electronic health records to provide real-time interventions that can promote guideline-concordant care. Testing gap results. Biomarker Baseline N Baseline Test Rate Post Launch N Post Launch Test Rate Absolute Lift EGFR 264 49% 392 67% 18% ALK 270 43% 389 67% 24% PD-L1 270 59% 389 72% 13%
Phase 2 study of metronomic cyclophosphamide with pembrolizumab in checkpoint inhibitor–refractory melanoma.
TPS9599 Background: Immune checkpoint inhibitors (ICI) are standard of care treatment in advanced, metastatic melanoma as well as adjuvant treatment of resected high-risk disease. However, approximately 50% of patients do not respond to primary anti-programmed death ligand-1 (anti-PD1) treatment (primary resistance) or progress after initial response (secondary resistance). Second line treatments in this setting include addition of the anti-cytotoxic T-lymphocyte associated protein 4 (anti-CTLA-4) drug ipilimumab or targeted treatment in BRAF mutant melanomas. However, CTLA-4 blockade can confer significant immune-mediated toxicity in a low performance status (PS) population, and not all patients are eligible for BRAF/MEK inhibition. There remains an unmet clinical need to optimize ICI efficacy and overcome resistance. It is hypothesized that suppressive regulatory T-cells (T reg )may inhibit the anti-tumor effect of ICI. Cyclophosphamide (CTX) is an alkylating anticancer agent. Prior studies in patients with recurrent ovarian cancer and soft tissue sarcoma have demonstrated that the combination of anti-PD1 agents with metronomic, or low dose, frequent, CTX was effective with no new safety signals. Methods: This phase 2, single-center, single-arm study explores the efficacy of adding oral metronomic CTX to intravenous pembrolizumab in patients with ICI-refractory locally advanced or metastatic melanoma. Key inclusion criteria are measurable disease by RECIST v.1.1 and receipt of investigational treatment within 9 weeks of last ICI treatment. Patients may have previously received single agent pembrolizumab or dual ICI with anti-LAG3 and anti-PD1 (relatlimab/nivolumab). Key exclusion criteria are symptomatic, untreated brain metastases, BRAF V600 mutation without prior receipt of BRAF/MEK inhibition, or prior grade 3 or greater immune-related adverse event (irAE). The primary endpoint is objective response rate (RR) as defined by complete response (CR) + partial response (PR) by RECIST v 1.1. A Simon's minimax two-stage design will be used, with the null hypothesis that the true response rate is .05 and the alternative hypothesis that true response rate is 0.3. In Stage I, a total number of 7 patients will be accrued. If there are 0 responses among 7 patients, the study will be stopped; otherwise, an additional 7 patients will be accrued to Stage II. 3 of 14 planned patients have been enrolled. This trial was approved by the UC Irvine Institutional Review Board; approval number is 6168. Trial registration NCT06771544. Clinical trial information: NCT06771544 .
Doctor, am I cured? Characteristics of long-term survivors with advanced melanoma treated with immunotherapy.
e21502 Background: Immune checkpoint inhibitors (ICIs) have transformed the prognosis of advanced melanoma, enabling a subset of patients to achieve prolonged survival. The concept of long-term survivors (LTS) raises the question of whether some metastatic patients who respond to immunotherapy may never relapse and could be considered potentially cured. Characterizing this population is relevant to identify predictors of durable benefit. Methods: A total of 244 patients with unresectable stage III or stage IV melanoma treated at Instituto Roffo, University of Buenos Aires, were included. Among them, 156 had a minimum clinical follow-up of 3 years. LTS were defined as patients with an overall survival (OS) ≥36 months. Demographic characteristics, histologic subtype, mutational status, treatment received, objective response, and adverse events were analyzed. Results: Data from 72 patients (46.1% of the 156 with follow-up ≥3 years) were analyzed. Median age was 58 years, and 65% were male. Melanoma subtypes were cutaneous (62%), mucosal (13%), and acral (10%). BRAF mutation was detected in 37 patients (51%). Most patients received immunotherapy as first-line treatment (79%). The most frequently used regimens were anti–PD-1 agents (pembrolizumab or nivolumab) and the combination of ipilimumab plus nivolumab. Best responses included stable disease in 30% (n=11), partial response in 11% (n=24), and complete response in 51% (n=37), with a median treatment duration of 724 days. The most frequent adverse events were vitiligo (n=22), rash (n=9), pruritus (n=11), thyroiditis (n=22), asthenia (n=20), and transaminitis (n=10), mostly grade 1. Eight grade 3 and two grade 4 events (myocarditis and myositis) were reported. The main reasons for treatment discontinuation were toxicity (41%) and planned completion (31%). Median OS and progression-free survival (PFS) in the LTS cohort were 75.6 and 58.9 months, respectively. Conclusions: Nearly half of patients with a follow-up ≥3 years achieved prolonged OS (≥3 years) with immunotherapy, and two thirds remain progression-free. These findings suggest that beyond extending survival, a subset of patients may never relapse and could be considered potentially cured, representing a paradigm shift in the management of advanced melanoma.