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A 3D tumorwide multi-omic atlas of intratumoral heterogeneity in <i>IDH</i> -mutant glioma.
2067 Background: Isocitrate dehydrogenase mutant (IDHmut) glioma affects over 20,000 adults per year. Treatment failure often results from intratumoral heterogeneity, in which genomic subclones undergo selection for treatment-resistant populations. Understanding this heterogeneity is critical to selecting therapeutic combinations that are efficacious across the entire tumor, but few genomic studies go beyond analyzing a single tumor sample per patient. Methods: 3D whole tumor sampling was used to obtain 324 spatially mapped samples from 32 IDHmut gliomas. Whole exome (n=323), RNA (318), ATAC sequencing (92), and Hi-C (14) were performed. PyClone reconstructed clonal evolution, weighted gene/peak correlation network analyses derived co-expression (RNA) and gene regulatory (ATAC) programs, and comparison of tumor Hi-C results to normal brain identified tumor-specific chromatin loops. Results: Regional tumor content (purity) inversely correlated with distance from tumor centroid ( R = -0.32, p = 2.8×10 -8 ) and inter-sample distance was associated with subclonal ( R = 0.24, p = 8.1x10 -15 ) and transcriptional ( R = 0.12, p = 1.0x10 -5 ) similarity. Beyond IDH1 in the combined 17 astrocytomas and 15 oligodendrogliomas, tumor-wide alterations were recurrently observed in TP53 (altered in 64%; tumor-wide in 58%), ATRX (55%; 39%), TERT promoter (45%; 45%) and FUBP1 (18%; 6%). Despite high cohort prevalence, glioma-associated drivers CIC (altered in 42%), PIK3CA (36%), and ARID1A (18%) were tumor-wide in only one patient each, while MUC4 (33%), NOTCH1 (27%), SETD2 (24%), and PIK3R1 (15%) were never observed in the tumor founding clone. Tumors with CIC alterations harbored a median of 5 unique mutations with a median combined tumor-wide cancer cell fraction of 45%. Hi-C identified 5,579 tumor-specific promoter-enhancer interactions across 4,144 loops. The genes associated with these promoters enriched for tumor-specific RNA programs associated with OPC signature ( p adj = 3x10 -14 ), NPC signature ( p adj = 3.87x10 -14 ), and neuronal mimicry (1.2×10 -13 ). We discovered adversely prognostic gene expression programs in astrocytoma independently validated in chromatin regulatory programs. Conclusions: Tumor-wide sampling of IDHmut glioma revealed evidence of radial tumor growth and 3D patterns of cellular organization, in sharp contrast to intermixed patterns in IDH wildtype glioma. Most inter-patient heterogeneity in driver alterations was subclonal. Our data also revealed regulatory loops that explain tumor cell-specific expression signatures. A significant, adverse prognostic marker in astrocytoma was discovered and cross-validated.
Neoadjuvant antibody–drug conjugate regimens without concurrent chemotherapy versus standard chemotherapy in early HER2-positive breast cancer: A systematic review and meta-analysis of randomized trials.
e12644 Background: Standard neoadjuvant therapy for HER2-positive early breast cancer combines multi-agent chemotherapy with HER2-targeted antibodies and is associated with substantial toxicity. HER2-directed antibody–drug conjugates (ADCs) may enable de-escalation. We compared efficacy and toxicity of neoadjuvant ADC-based regimens given without concurrent chemotherapy versus standard chemotherapy-based regimens, including by platinum use in the control arm. Methods: We searched PubMed, Embase, Cochrane CENTRAL, Scopus, and Web of Science through December 18, 2024 for randomized controlled trials in early/locally advanced HER2-positive breast cancer. Eligible trials compared neoadjuvant ADC-based regimens without concurrent chemotherapy versus standard chemotherapy-based regimens. Outcomes were pathologic complete response (pCR; per trial definition), grade ≥3 adverse events (AEs), and treatment discontinuation. Odds ratios (ORs) were pooled and heterogeneity was summarized with I². Results: Nine randomized trials (n = 2,021; mean age 50.7±13.7) were included. There was no significant difference in pCR between groups (OR 0.93, 95% CI 0.62–1.40; I² = 59.8%). ADC-based regimens were associated with fewer grade ≥3 AEs (OR 0.30, 95% CI 0.11–0.84; I² = 91.5%). Treatment discontinuation did not differ (OR 1.10, 95% CI 0.39–3.12; I² = 85.8%). Findings were consistent when stratified by platinum use in the control regimen. Conclusions: In HER2-positive early breast cancer, neoadjuvant ADC-based regimens without concurrent chemotherapy achieve pCR comparable to standard chemotherapy while substantially reducing severe toxicity without increasing discontinuation, independent of platinum use. Confirmation in phase III trials with mature survival endpoints is needed.
An open-label, single-center phase II trial of mitoxantrone hydrochloride liposome combined with programmed death-1 (PD-1) inhibitors for pretreated recurrent or metastatic nasopharyngeal carcinoma.
6047 Background: Liposomal mitoxantrone (Lipo-MIT) in combination with programmed death-1 (PD-1) inhibitors exhibits potential synergistic antitumor effects. This study aimed to evaluate the efficacy and safety of this regimen in patients with pretreated recurrent/metastatic nasopharyngeal carcinoma (R/M NPC). Methods: This was a single-arm, Simon two-stage clinical study enrolling patients with R/M NPC who were refractory to platinum-based chemotherapy and PD-1 inhibitors. Patients received intravenous infusion of Lipo-MIT (20 mg/m²) combined with a PD-1 inhibitor on Day 1 of each 21-day treatment cycle, for a maximum of 6 cycles. Subsequent maintenance therapy with PD-1 inhibitors alone was administered until disease progression, occurrence of intolerable toxicity, or completion of 2-year treatment. The primary endpoint was objective response rate (ORR). Key secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety profile. Results: A total of 32 patients were enrolled between February 3, 2024, and July 21, 2025, all of whom were included in the efficacy and safety analysis sets. The ORR was 40.6% (95% confidence interval [CI], 24.2–59.2), and the DCR was 78.1% (95% CI, 59.6–90.1). With a median follow-up duration of 8.1 months (range, 4.7–17.2 months), the median OS was not reached and the median PFS was 7.4 months (95% CI, 6.0–not reached [NR]). Grade 3 or higher treatment-related adverse events (TRAEs) were observed in 18 patients (56.3%), and the most common TRAEs were leukopenia (25.0%), anemia (21.9%), neutropenia (18.8%), pneumonia (15.6%), and thrombocytopenia (12.5%). No treatment-related deaths were observed. Conclusions: Lipo-MIT combined with PD-1 inhibitors demonstrates promising antitumor activity with manageable toxicities in patients with pretreated R/M NPC. Long-term survival data are pending as follow-up is still ongoing. Clinical trial information: NCT06472713 .
Evaluation of a taxane mRNA-based profile in neoadjuvant therapy across I-SPY2 investigational arms.
597 Background: Neoadjuvant chemotherapy is standard in early-stage breast cancer (eBC), enabling tumor downstaging and treatment tailoring. Taxanes are a core component of standard neoadjuvant regimens across breast cancer subtypes, and biomarkers of taxane response may inform treatment strategies. In I-SPY2, high-risk eBC patients (pts) were randomized to standard taxane-anthracycline-cyclophosphamide (T-AC) or investigational regimens (IRs). A 113-gene model has been validated in multiple cohorts and in the I-SPY2 T-AC arm. Here, we extend these analyses to nine I-SPY2 IRs, which all include a T-AC backbone. Methods: Agilent gene expression data from 987 high-risk eBC pre-treatment tumors (GSE194040) were analyzed from pts treated with T-AC ± nine IRs. Pts were scored on a scale from 0-100 and association of score (per 50-point increase) with pCR was assessed using logistic regression. For benchmarking, the raw score was Z-scaled, and OR was calculated per 1 standard deviation increase (OR/1SD) to enable comparison with published I-SPY2 biomarkers. Results: In a pooled multivariable logistic model including all treatment arms (N = 987), a 50-point increase in score was strongly associated with higher odds of pCR after adjusting for treatment arm, hormone receptor (HR) and HER2 (OR = 2.99, p = 7.93e-13). Allowing for treatment-specific score effects did not reveal statistically significant interactions. The score was benchmarked against 27 I-SPY2 qualifying biomarkers using OR/1SD increase. In the full cohort (N = 987), it ranked among biomarkers with the largest effect sizes for pCR. When analyses were stratified by treatment arm, the score was the top-ranked biomarker by effect size in the T-AC arm (N = 210) and trebananib arm (N = 134), while effect estimates in other arms were directionally consistent but not uniformly statistically significant. Furthermore, the score provided independent predictive information beyond I-SPY2 Response Predictive Subtypes (RPS). In multivariable models adjusting for RPS, the score remained significantly associated with pCR in the full cohort and the T-AC arm. As an illustrative example, using score quartiles defined in the full cohort, pCR rates among HR+/HER2− pts (N = 379) increased from 6.0% (8/134) in the lower quartile to 43.1% (28/65) in the upper quartile. Similarly, among TN pts (N = 363), pCR rates increased from 16.7% (5/30) in the lower quartile to 48.7% (77/158) in the upper quartile. Conclusions: A taxane-specific gene expression score was strongly associated with pCR across all taxane-containing I-SPY2 regimens and provided information beyond established response predictive subtypes. These findings suggest that taxane sensitivity contributes substantially to treatment response across I-SPY2 therapies and highlights the potential value of incorporating additional drug-specific biomarkers to further refine response prediction.
Neoadjuvant chemo-immunotherapy and surgical resection in locally advanced non-small cell lung cancer with N3 lymph node involvement (NEO-SURG).
TPS8127 Background: The emergence of neoadjuvant and peri-operative chemoimmunotherapy in locally-advanced non-small cell lung cancer (NSCLC) has revolutionized the treatment of resectable NSCLC. Importantly, in multiple phase III trials, patients with multi-station N2 disease derive profound benefit from neoadjuvant chemoimmunotherapy. NSCLC with N3 involvement has been excluded from neoadjuvant/perioperative studies, as these cancers have historically been considered unresectable and treated with definitive chemoradiotherapy (CRT) followed by durvalumab. However, CRT is associated with high rates of treatment-related adverse events and most patients experience disease relapse within 2 years. Whether patients with select N3 lymph node-positive NSCLC may benefit from neoadjuvant chemo-immunotherapy followed by surgery is an important unaddressed question. This phase II trial seeks to evaluate the feasibility and clinical utility of neoadjuvant chemoimmunotherapy followed by surgery in patients with locally-advanced stage III B/C NSCLC with select N3 involvement. Methods: This phase II, multi-center, single-arm study is evaluating neoadjuvant chemoimmunotherapy in patients with stage III B/C NSCLC with contralateral mediastinal or ipsilateral supraclavicular (N3) lymph node involvement. Select eligibility criteria include: ECOG performance status 0-1, pathologically-confirmed contralateral mediastinal or ipsilateral supraclavicular N3 disease, ≤2 involved lymph node stations, primary tumor appropriate for resection per multi-disciplinary review (any T stage), physical fitness for resection, wild-type EGFR/ALK . Patients will receive neoadjuvant cemiplimab 350mg IV plus histology-specific chemotherapy every 3 weeks for 4 cycles prior to planned surgical resection followed by adjuvant radiotherapy (optional) and 1 year of adjuvant cemiplimab. The primary endpoint is pCR rate defined by IASLC consensus guidelines. Secondary endpoints include objective response rate (per RECIST v1.1), R0 resection rate, major pathologic response (≤10% viable tumor) rate, disease-free survival and overall survival. A total of 21 patients will be enrolled. A Simon-2 stage design will be used such that 12 patients will be enrolled initially and, if at least one pCR is observed, the trial will proceed to the second stage with enrollment of an additional 9 patients. This design yields a type I error rate of 5% and power of 80% when the true pCR rate is 20%. In addition, a Pocock stopping rule at 5% type I error will be deployed to assess feasibility of surgical resection. The study will be halted for futility if 8 of the first 12 patients do not proceed with surgical resection. The study is open for accrual at Georgetown University, University of Virginia, and Washington University. Clinical trial information: NCT06449313 .
Camrelizumab combined with concurrent chemoradiotherapy versus chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: A retrospective cohort study in central China.
e18083 Background: Immune checkpoint inhibitors have demonstrated efficacy in recurrent or metastatic nasopharyngeal carcinoma (NPC). Additionally, adjuvant PD-1 blockade with camrelizumab has improved survival in locoregionally advanced NPC from endemic regions. However, its role in concurrent chemoradiotherapy (CCRT) for locoregionally advanced NPC remains unclear, particularly in non-endemic areas where evidence is scarce. This study assessed the efficacy and safety of camrelizumab plus CCRT in patients with locoregionally advanced NPC from Central China, a non-endemic region. Methods: In this retrospective cohort study, patients with stage III-IVa NPC from Central China were included. The camrelizumab group received two to three cycles of induction chemotherapy (docetaxel 75 mg/m² and cisplatin 75 mg/m²), followed by CCRT with intensity-modulated radiotherapy, concurrent cisplatin (40 mg/m² weekly for five to seven cycles), and two cycles of camrelizumab (200 mg). Maintenance camrelizumab was administered for 6-12 cycles post-CCRT. The control group received identical treatment without camrelizumab. The primary endpoint was the 3-year disease-free survival (DFS) rate. Results: Between January 2019 and October 2022, 103 patients were enrolled (48 in the camrelizumab group and 55 in the control group). With a median follow-up of 37 months, the 3-year DFS rate was 81.3% (39/48) in the camrelizumab group versus 69.1% (38/55) in the control group. Corresponding 3-year rates for locoregional recurrence-free survival, distant metastasis-free survival, and overall survival were 89.6% (43/48), 85.4% (41/48), and 83.3% (40/48) in the camrelizumab group, compared with 87.3% (48/55), 76.4% (42/55), and 72.7% (40/55) in the control group. Grade 3 or 4 treatment-related adverse events occurred in 14.6% (7/48) of patients in the camrelizumab group and 3.6% (2/55) in the control group. Reactive capillary endothelial proliferation, a camrelizumab-specific event, affected 83.3% (40/48) of patients (mostly grade 1-2; 4.2% [2/48] grade 3-4). Common grade 3-4 events included leukopenia, neutropenia, and weight loss. Conclusions: Camrelizumab combined with CCRT demonstrated promising antitumor activity and a manageable safety profile in locoregionally advanced NPC from non-endemic areas. These findings warrant validation in prospective randomized trials. Limitations include the retrospective design and small sample size.
Neurotoxicity in immune checkpoint inhibitor-associated myositis with elevated soluble IL-2 receptor levels: Novel therapeutic strategies.
e14536 Background: Immune checkpoint inhibitors (ICIs) are used to treat a variety of cancer types, including melanoma, lung cancer, and breast cancer. Approximately 1-5% of patients receiving ICIs develop neurotoxicity (N-TOX). N-TOX is driven by a loss of immune tolerance, leading to aberrant activation of T-cells, astrocytes, and microglia. There is a need to better understand the pro-inflammatory milieu in N-TOX to facilitate novel treatment strategies for treatment. Therefore, we performed a retrospective review in a single institution in patients who developed N-TOX to better understand this patient population. Methods: We conducted a retrospective study of cytokine samples (CSF and/or serum) from 33 patients who developed N-TOX after ICI therapy at Moffitt Cancer Center between 2023 and 2025. Cytokine-13 panels (ARUP Laboratories, Utah) were obtained in serum only (N = 15), CSF only (N = 13), or both serum and CSF (N = 5). Results: Primary cancer types were melanoma (N = 9), lung (N = 5), renal (N = 3), head/neck (N = 3), thyroid (N = 2), urothelial, cervical, endometrial (N = 1), Merkel cell, penile, appendiceal, breast, sarcoma, liver, esophageal, and gastric (all N = 1). N-TOX syndromes included myositis (N = 17), encephalitis (N = 9), neuropathy (N = 8), myasthenia gravis (N = 2), meningitis (N = 1), and demyelinating disease (N = 1). In our cohort group, serum cytokine analysis demonstrated elevated IL-10 (10.7 +/- 5.6 pg/ml, reference < 2.8 pg/ml, p = 0.003) without significant changes in other serum cytokines. Of note, 80% of serum cytokines were collected after initiation of steroids. CSF cytokine analysis did not demonstrate any significant elevation in cytokine levels. Subgroup analysis of N-TOX myositis patients showed a significant elevation in serum sIL2R (1203 +/- 307 pg/ml, reference 175-858 pg/ml, p = 0.024) without elevation in serum interferon gamma. Subgroup analysis of N-TOX neuropathy and N-TOX encephalitis patients did not show any significant elevation in serum or CSF cytokine levels, respectively. Conclusions: Serum sIL2R was elevated in selected N-TOX patients with myositis, which suggests that therapeutic strategies to influence this cytokine or its downstream substrates may be effective. We are currently undertaking a prospective cohort with muscle biopsies to better understand this association. The serum IL-10 elevation is an anti-inflammatory response likely confounded by treatment effect.
Mosunetuzumab plus polatuzumab vedotin (Mosun-Pola) versus rituximab, gemcitabine and oxaliplatin (R-GemOx) in patients with relapsed/refractory large B-cell lymphoma (R/R LBCL): Updated efficacy and safety from the phase 3 SUNMO study including in second-line (2L) versus third-line plus (3L+) patient subgroups.
7007 Background: At the primary analysis, Mosun-Pola demonstrated superior efficacy versus R-GemOx, with infrequent cytokine release syndrome (CRS) events and manageable safety in patients (pts) with R/R LBCL in the Phase 3 SUNMO trial (NCT05171647; Budde et al. 2025). We report updated efficacy and safety, including in the 2L setting. Methods: Pts with R/R LBCL ineligible for autologous stem-cell transplant (ASCT) were randomized 2:1 to Mosun (subcutaneous)-Pola or R-GemOx. Dual primary endpoints were IRC-assessed progression-free survival (PFS) and objective response rate (ORR); secondary endpoints included complete response (CR) rate, duration of response (DOR), duration of CR (DOCR), and safety. Overall survival (OS) was not assessed as the data cut-off was prior to the pre-defined final OS analysis. Results: At data cut-off (August 8, 2025), 138 and 70 pts were assigned to Mosun-Pola or R-GemOx, respectively. Overall, 91 pts had 1 prior line of therapy (LOT; 2L; Mosun-Pola, n=61; R-GemOx, n=30) and 117 had ≥2 prior LOT (3L+; Mosun-Pola, n=77; R-GemOx, n=40). With a median follow-up of 28.3 months (mos), Mosun-Pola continued to demonstrate superior PFS benefits over R-GemOx (HR, 0.41; 95% CI: 0.28–0.60; Table). ORRs with Mosun-Pola were 70.3% vs 40.0% with R-GemOx. The observed PFS benefit of Mosun-Pola over R-GemOx was similar in 2L (HR, 0.38; 95% CI: 0.22–0.67) and 3L+ (HR, 0.48; 95% CI: 0.29–0.81) subgroups. With Mosun-Pola vs R-GemOx in 2L, the 2-year PFS rates were 40.3% vs 20.1%, and the 2-year DOCR estimates were 60.8% vs 37.5%, respectively. Median DOCR was not reached with Mosun-Pola in 2L and 3L+ subgroups. ORRs with Mosun-Pola vs R-GemOx were 75.4% vs 36.7% in 2L pts, and 66.2% vs 42.5% in 3L+ pts, respectively. The safety profile was unchanged since the primary analysis. Grade (Gr) ≥2 CRS occurred in 4% of Mosun-Pola-treated pts and no ICANS events occurred. The safety profile was consistent in 2L pts: Gr 2 CRS occurred in 3% of Mosun-Pola-treated pts, with no Gr ≥3 CRS events. Conclusions: Mosun-Pola continues to show notable efficacy with manageable safety in pts with ASCT-ineligible R/R LBCL, particularly in the 2L setting. Clinical trial information: NCT05171647 . Mos (95% CI), unless stated Mosun-Pola (n=138) R-GemOx (n=70) 2L Mosun-Pola (n=61) 2L R-GemOx (n=30) 3L+ Mosun-Pola (n=77) 3L+ R-GemOx (n=40) Median PFS 11.6 (5.6–17.6) 3.8 (2.9–4.1) 17.6 (5.6–NE) 3.6 (2.1–5.3) 8.6 (4.0–16.2) 3.9 (2.1–5.6) Median DOR 18.8 (11.5–NE) 6.0 (3.7–23.9) 18.8 (11.3–NE) 6.0 (3.9–NE) 21.5 (9.5–NE) 5.4 (2.3–18.3) CR, % (95% CI) 51.4 (42.8–60.0) 24.3 (14.8–36.0) 60.7 (47.3–72.9) 20.0 (7.7–38.6) 44.2 (32.8–55.9) 27.5 (14.6–43.9) Median DOCR NE 18.3 (3.9–NE) NE (15.6–NE) 21.4 (3.9–NE) NE (21.5–NE) 7.5 (2.3–NE) NE, not estimable.
Efficacy and safety of anlotinib plus docetaxel versus docetaxel monotherapy in advanced non–small cell lung cancer: A systematic review and meta-analysis.
e20734 Background: Docetaxel monotherapy remains a standard second-line treatment for patients with advanced non–small cell lung cancer (NSCLC) who experience disease progression following first-line chemoimmunotherapy. However, its clinical benefit is limited by modest efficacy and the development of treatment resistance. Given the paucity of robust evidence evaluating combination strategies, we conducted this meta-analysis to assess whether anlotinib plus docetaxel provides superior therapeutic efficacy with an acceptable safety profile compared with docetaxel alone. Methods: We systematically searched PubMed, the Cochrane Central Register of Controlled Trials, Scopus, and Web of Science for randomized controlled trials (RCTs) and retrospective studies. Continuous outcomes were pooled as mean differences, and dichotomous outcomes as risk ratios, using a random-effects model. Results: Six studies comprising 609 patients were included, with a mean age of 55 years. Anlotinib plus docetaxel significantly improved progression-free survival (PFS; p < 0.00001), objective response rate (ORR; p = 0.001), and disease control rate (DCR; p < 0.00001), with median overall survival ranging from 12.0 to 16.82 months in the combination group compared with 9.2 to 10.9 months in the docetaxel monotherapy group. Combination therapy was associated with higher rates of hand–foot syndrome (p < 0.0001), hypertension (p < 0.0001), hypertriglyceridemia (p = 0.05), and fatigue (p = 0.05). No significant differences were observed in thrombocytopenia (p = 0.72), proteinuria (p = 0.37), abnormal liver function (p = 0.07), oral mucositis (p = 0.23), or diarrhea (p = 0.25). Conclusions: In this systematic review and meta-analysis, anlotinib combined with docetaxel demonstrated significantly improved therapeutic efficacy and survival outcomes compared with docetaxel monotherapy in patients with advanced NSCLC who progressed after prior treatment. These benefits were achieved without a meaningful increase in hematologic toxicities. Although combination therapy was associated with higher rates of hand–foot syndrome and hypertension, these adverse events were largely manageable with standard supportive measures. Collectively, these findings suggest that anlotinib plus docetaxel represents a promising, clinically meaningful second-line treatment option for advanced NSCLC, with improved efficacy and manageable toxicity, and warrants prospective randomized validation.
Impact of <i>BRCA</i> pathogenic variants and novel targeted agents on ovarian reserve measured by anti-Müllerian hormone levels in young women with early breast cancer: A biomarker analysis of the PREFER study.
526 Background: The impact of germline BRCA (g BRCA ) pathogenic variants (PVs) and of novel targeted agents (anti-HER2 therapy, CDK4/6 inhibitors, or immunotherapy) on ovarian reserve in young women treated with chemotherapy (CT) for early breast cancer (BC) remains limited. This biomarker analysis of the PREFER study prospectively evaluated ovarian reserve using anti-Müllerian hormone (AMH) according to main patient and treatment characteristics. Methods: We included premenopausal women enrolled in the prospective PREFER study (NCT02895165) and candidates to (neo)adjuvant CT at the coordinating centre, the IRCCS San Martino Policlinic Hospital, Genoa, Italy. Serial serum AMH measurements were performed at baseline (prior to any CT initiation), during, and after systemic treatment. Longitudinal changes in centrally measured AMH were analysed using mixed-effects models on log-transformed values. Analyses explored the impact of patient (including age and gBRCA status) and treatment (CT alone or with anti-HER2 therapy, CDK4/6 inhibitors, or immunotherapy) characteristics on AMH levels over time. Results: Between 2012 and 2025, 309 premenopausal patients were enrolled at the coordinating centre, of whom 194 were included in the present analysis. Median age at diagnosis was 37 (IQR 33-40) years, with 146 patients (75.3%) aged ≤40 years and 48 (24.7%) 41-45 years. Overall, 85 patients (43.8%) had hormone receptor-positive/HER2-negative, 62 (32.0%) HER2-positive, and 47 (24.2%) triple-negative BC. In the entire cohort, AMH levels showed a marked decline during CT, followed by partial recovery during follow-up (p<0.001), irrespective of patient and treatment characteristics. Younger women showed higher baseline values (2.31 vs 1.11 µg/L for ≤40 years and 41-45 years) and greater post-treatment recovery (p<0.001). Among patients with known gBRCA status (n=147), patients harbouring gBRCA PVs (n=29, 19.7%) showed lower baseline levels (1.60 vs 2.18 µg/L for gBRCA carriers vs non-carriers) and a lower post-treatment recovery compared to non-carriers (n=118, 80.3%) (p=0.01). Regarding treatment exposure, 106 patients (54.6%) received CT alone, 62 (32.0%) CT plus anti-HER2 agents, 10 (5.2%) CT plus immunotherapy, and 16 (8.2%) CT followed by CDK4/6 inhibitors. No significant differences over time were observed according to treatment exposure (p=0.41); however, numerically lower mean AMH values after end of CT were observed among patients treated with CDK4/6 inhibitors and immunotherapy. Conclusions: In this PREFER biomarker analysis, older age and gBRCA PVs were associated with reduced ovarian recovery after treatment. Limited sample size precludes definitive conclusions on the gonadal impact of immunotherapy or CDK4/6 inhibitors; further analyses are urgently needed in this field.
Demographic and clinicopathological factors impacting survival in malignant carcinoid tumors: A SEER database analysis.
e16319 Background: Malignant carcinoid tumors are indolent neuroendocrine neoplasms with generally favorable survival. While prior studies have described outcomes, a comprehensive, contemporary analysis of demographic, socioeconomic, and geographic factors and their impact on survival across all major carcinoid subtypes remains a significant gap in current epidemiological literature. Methods: A population-based cohort study was conducted using the Surveillance, Epidemiology, and End Results (SEER) database (2000-2022). Patients were identified using ICD-O-3 codes for malignant carcinoid tumors: 8240/3, 8243/3, 8245/3, and 8249/3. Overall survival was analyzed using Cox proportional hazard regression performed with GraphPad Prism software, adjusting for key clinicopathological variables. Results: Among 94,867 identified patients (median follow-up 59 months; 27,503 deaths), significant demographic predictors of higher mortality included: older age (≥65 years; HR 1.9, 95%CI 1.3-2.7, p = 0.0003), male sex (HR 1.4, 95%CI 1.3-1.4, p < 0.0001), Black race (HR 1.1, 95%CI 1.1-1.2, p < 0.0001), lower household income ( < $80,000; HR 1.1, 95%CI 1.1-1.2, p < 0.0001), and rural county of residence (HR 1.1, 95%CI 1.0-1.1, p = 0.0013). Predictors of lower mortality included: Asian/Pacific Islander race (HR 0.77, 95%CI 0.71-0.83, p < 0.0001), Hispanic ethnicity (HR 0.91, 95%CI 0.86-0.96, p = 0.0002), and being married or partnered (HR 0.71, 95%CI 0.68-0.73, p < 0.0001). Significant disease/treatment factors for worse mortality included: adenocarcinoid histology (worst outcome; HR 1.9, 95%CI 1.6-2.2), followed by goblet cell carcinoid (HR 1.6, 95%CI 1.5-1.7) and atypical carcinoid (HR 1.4, 95%CI 1.3-1.5), all versus typical carcinoid (p < 0.0001). Distant stage (HR 2.5, 95%CI 2.4-2.6) and regional stage (HR 1.4, 95%CI 1.3-1.4) predicted worse survival versus localized disease (p < 0.0001). Receipt of chemotherapy (HR 1.7, 95%CI 1.6-1.8) or radiotherapy (HR 1.3, 95%CI 1.2-1.3) was associated with higher mortality (p < 0.0001), likely reflecting advanced disease. Surgery had a strong association with better overall survival (HR 0.46, 95%CI 0.44-0.47, p < 0.0001). Conclusions: This large-scale analysis confirms the indolent nature of carcinoid tumors but identifies significant and multifaceted demographic disparities in survival, independent of disease factors. Age, sex, race, socioeconomic status, and geography are significant prognostic variables. Histologic subtype and stage remain powerful determinants. The association of systemic therapy with higher mortality underscores its use in advanced cases, while surgery is strongly associated with improved outcomes. These findings highlight populations at risk and can inform strategies to mitigate survival disparities.
Demographic and molecular landscape of biliary tract cancers in and near Bronx, NY.
e16161 Background: Biliary tract cancers (BTCs), including gallbladder cancer (GBC) and intrahepatic (iCCA), perihilar (pCCA) and distal (dCCA) cholangiocarcinoma, are a rare diverese group of malignancies that have been linked to different demographic and environmental factors. Moreover, they are driven by both distinct and shared molecular mechanisms. We noticed an unfortunately high incidence of BTCs in our patient population – a population that is enriched in minority groups, immigrants, and socioeconomic barriers. Here we describe the landscape of our BTC cases to elucidate anthropologic and molecular drivers of BTC in our community. Methods: We reviewed the charts of BTC patients who were diagnosed between 2021-2022 who had a touchpoint with our healthcare system. We collected demographic information such as gender, date of birth, and self-reported race and ethnicity, and recorded diagnosis-specific details, such as BTC subtype, pathological date of diagnosis, and stage at diagnosis (n = 138). Molecular tumor characteristics obtained through tissue immunohistochemistry or NextGen Sequencing (NGS) at presentation were aggregated when available (n = 86). Results: GBC patients were more likely to be female than male (63% vs 37%) with median age of diagnosis of 63.5 (vs 70.5 in males). Among female BTC patients, there was near equal prevalence of GBC and iCCA (~40%). All CCA subtypes had male predominance and earlier median age of diagnosis with a notably early median age of diagnosis of 57 in the pCCA group. Among different race and ethnicity groups, iCCA and dCCA patients were primarily White non-Hispanic (WNH) (39% and 32%) with most remaining cases being Hispanic (29% and 26%) or Black non-Hispanic (BNH) (22% and 21%). Conversely, Hispanic and BNH patients each made up 27% of pCCA cases and WNH only 18%. Both Hispanic and BNH patients each had a 30-40% prevalence of GBC and iCCA per cancer, while iCCA was the most common BTC among WNH (61%). NGS studies show enrichment of TP53 mutations, especially in GBC and iCCA (75% vs 52%), which also showed frequent RAS-RAF-MAPK and RB1 pathways alterations and TERT promoter mutations. All but one IDH1 mutations were in iCCA. KRAS mutations, especially G12V, were frequent in pCCA and dCCA (18% and 30%). Uniquely, pCCA mutations were mainly related to DNA repair (MLH1, BRCA2), chromatin regulation (ARID1A, PBRM1), and RNA splicing (SF3B1, RBM10). Three cases each of GBC and iCCA were PDL1-positive; fewer had high TMB. Conclusions: The unique BTC patient population in our community recapitulates known trends in gender and race-ethnicity prevalence. Molecular alterations we detected also align with known BTC alterations in cell cycle, survival, epigenetic and metabolic signaling. Importantly, differences in the distribution of molecular signatures are emerging. We aim for our expanding database to serve as a hypothesis-generating tool to ultimately improve the care of all BTC patients.
Combining immune checkpoint inhibition and dendritic cell vaccination in advanced pleural and peritoneal mesothelioma: The phase 1b MESOVAX trial.
2548 Background: Mesothelioma (M) remains a rare malignancy with limited therapeutic options. While immunotherapy combinations have recently become the standard of care for non-epithelioid subtypes, further strategies are required to enhance clinical outcomes. Dendritic cell vaccines (DCvax) have demonstrated preliminary activity and a favorable safety profile in M. Preclinical data suggest that DCvax induces PD-L1 expression on tumor cells; therefore, combining DCvax with Pembrolizumab (P) may sensitize patients (pts) to PD-1 blockade. Methods: MESOVAX is a proof-of-concept, Phase Ib, study evaluating the safety of P 200 mg combined with an autologous anti-tumor DCvax administered every 3 weeks (Q3W) for 6 cycles, followed by P monotherapy until disease progression or up to 2 years. Subcutaneous IL-2 (3 MU) was administered for 5 days following each vaccination. The primary endpoint was safety. Secondary endpoints included: changes in PD-L1 expression evaluated in pre- and post-therapy tumor samples by immunohistochemistry (IHC); immunological efficacy evaluated in vivo by DTH test and ex vivo measuring the immune response against selected tumor antigens (i.e MESOTHELIN, WT1, 5T4, TWIST-1, KRT-18, THBS2) by Interferon gamma (IFNγ) Enzyme-Linked Immunosorbent Spot (ELISpot) Assay; and treatment activity (objective response rate [ORR], duration of response [DOR], progression-free survival [PFS], and overall survival [OS]). Results: As of 28/11/2025, 9 pts (median follow-up: 32.5 months (mths)) were evaluable for safety and efficacy. Median age was 62 years; 89% (n = 8) were male, and all had epithelioid histology. Treatment-related adverse events (TRAEs) of any grade occurred in all 9 pts, with the most frequent being injection site reactions, asthenia, and fever. No grade 3–4 TRAEs were reported. Regarding treatment exposure, 4 pts received 6 cycles of P+DC, 6 pts received maintenance P, and one pt completed the maintenance phase. Best overall responses included 1 partial response (PR), 4 stable diseases (SD), and 4 progressive diseases (PD), with a median PFS of 5.3 mths (95% CI 1.8–17.3). Notably, one pt with prolonged SD (duration 9 mths) exhibited a PD-L1 conversion in the tumor tissue (from negative to positive) following treatment. Regarding the immunological activity, 4 pts experienced a positive DTH test during treatment, and interestingly for 3 of them we were able to measure a concomitant increase of the ex vivo antitumoral immune response against the tested antigens. Conclusions: The combination of DCvax and P is safe and demonstrates encouraging clinical activity in pretreated epithelioid M. The observed PD-L1 induction at the tumor site supports the synergistic potential of this combinatorial immunotherapeutic strategy. This trial is supported in part by a research grant from Investigator-Initiated Studies Program of MSD Italia S.r.l. Clinical trial information: NCT03546426 .
A pathology-based model for postoperative recurrence or metastasis prediction and adjuvant immunotherapy implications of clear-cell renal cell carcinoma: A multi-center, retrospective study.
e16539 Background: Approximately 30% of patients with clear cell renal cell carcinoma experience recurrence after surgery, making it crucial to improve the prognosis for these patients. Stratification of patients with non-metastatic clear cell renal cell carcinoma (ccRCC) based on the risk of postoperative recurrence helps guide adjuvant immunotherapy after surgery. Methods: We enrolled 2,154 patients from two centers. Only patients without postoperative adjuvant therapy were used to analyze risk factors and constructing models. A multivariable model was constructed to predict disease-free survival (DFS) and stratify patients. The log-rank test was used to examine the effects of immune checkpoint inhibitors (ICIs) and targeted therapy on DFS across different strata. Results: We identified seven independent risk factors including: sex, microvascular invasion (MVI), T stage, pathological grade, sarcomatoid differentiation, necrosis and capsular involvement. Using these seven characteristics, a prognostic model (MISNCST model) for non-metastatic clear cell renal cell carcinoma was constructed. Using the constructed model, we stratified the patients and validated the stratification efficacy with DFS, overall survival (OS), and cancer-specific survival (CSS) as endpoints (all p < 0.001). With our model, we stratified patients who either received or did not receive postoperative adjuvant therapy and found that ICIs significantly improved DFS in the high-risk group patients. Compared to the current medication criteria in clinical trials for ICIs, our model demonstrated superior overall performance. Conclusions: We identified 7 crucial prognostic features influencing the prognosis of non-metastatic ccRCC, and developed a prognostic model using these features. Based on our model, we stratified patients and discovered that high-risk patients could benefit from treatment with ICIs. Comparison of stratification approaches between the MISNCST model and other cohorts in terms of the five-year recurrence risk. Training Set (N=1605) Sensitivity Specificity Youden's Index MISNCST model 0.550 0.944 0.494 KEYNOTE-564 0.275 0.972 0.247 PROSPER RCC 0.438 0.932 0.370 CheckMate 914 0.388 0.951 0.339 IMmotion010 0.250 0.984 0.234
Clinical outcomes with <i>ERBB2</i> gene amplification and activating mutations in muscle-invasive bladder cancer patients treated with neoadjuvant chemotherapy.
4595 Background: Activating ERBB2 mutations (mut) are associated with improved pathologic response (pCR) to neoadjuvant chemotherapy (NAC) in patients with muscle-invasive bladder cancer (MIBC). However, the impact of ERBB2 gene amplification (amp) on pCR and of aggregate ERBB2 gene variants (amp and mut) on relapse and survival is unknown. We previously reported that high tumor mutational burden (TMB) is associated with improved pCR and relapse-free survival (RFS) in a cohort of MIBC patients treated with cisplatin-based NAC followed by cystectomy (Burgess et al. GU ASCO ‘26). In the current analysis, we assessed the impact of ERBB2 gene variants on clinical outcomes in the previously reported cohort. Methods: 91 patients with MIBC who received cisplatin-based NAC followed by radical cystectomy underwent genomic analysis of diagnostic transurethral resection of bladder tumor specimens with the Tempus xT platform. Sample size was prespecified by statistical design. Correlation of ERBB2 gene variants with TMB and clinical outcomes was performed using logistic regression, Cox proportional hazards models, and Kaplan-Meier techniques. Results: Median follow for the cohort was 63.6 months. pCR was achieved in 31.9%. Thirty-eight (41.8%) patients relapsed. Only 4 (4.4%) received adjuvant immune checkpoint inhibition (ICI). ERBB2 mut and amp were exclusively found in 4 (4.4%) and 13 (14.3%) patients, respectively. All ERBB2 mut were p.S310F. pCR occurred in 3 (75%) patients with mut and 6 (46.2%) patients with amp. In those with amp and no pCR (7), 4 were ypTaN0 or ypT1N0. In aggregate, the presence of ERBB2 gene variants (mut + amp, n = 17) was associated with an improved pCR rate compared to no ERBB2 gene variant (OR = 3.038, p = 0.048). ERBB2 variants (mut + amp) were not clearly associated with a TMB > 10 Mut/Mb (OR = 2.217, p = 0.178). Five patients with ERBB2 gene variants relapsed (29.4%, OR = 0.518, p = 0.288). Three (75%) mut and ten (76.9%) amp patients remain alive. The median RFS for patients with and without ERBB2 gene variants in aggregate is 124.1 and 54.7 months (HR = 0.460, p=0.094). The median overall survival (OS) for patients with and without ERBB2 gene variants is Not Reached and 107.6 months (HR = 0.381, p=0.098). Conclusions: The impact of ERBB2 gene variants (mut + amp) on survival in MIBC-patients treated with NAC has not been previously reported. In this cohort collected before widespread use of peri-operative ICI, the presence of ERBB2 gene variants was associated with improved pCR rates and showed strong trends for improved RFS and OS but not clearly associated with high TMB. These findings establish a prognostic role for ERBB2 amp in addition to previously reported ERBB2 mut in patients with MIBC. Whether peri-operative use of ICI or ERBB2-targeted agents may influence these findings warrants further investigation.
Sintilimab (PD-1 antibody) plus gemcitabine and docetaxel (GT) as first-line or later-line therapy in patients with advanced epithelioid sarcoma: A prospective, multicenter, single-arm, phase II clinical study.
11574 Background: Advanced epithelioid sarcoma (ES) responds poorly to conventional chemotherapy, with an objective response rate (ORR) of 15-27% and a median progression-free survival (mPFS) of only 4-6 months, highlighting the urgent need for new therapeutic strategies. This study aims to evaluate the efficacy and safety of Sintilimab (An approved PD-1 antibody) plus the gemcitabine and docetaxel (GT) in patients with advanced ES that has not been treated by chemotherapy. Methods: This is a single-arm, prospective phase II study conducted in China (ChiCTR2500095527). Patients received Sintilimab (200mg, d1, q3w) combined with gemcitabine (1000mg/m², d1,8, q3w) and docetaxel (70mg/m², d8, q3w) for up to 6 cycles, followed by Sintilimab maintenance for up to 2 years or until disease progression, intolerable adverse reactions or death. The primary endpoint was ORR, and secondary endpoints included PFS, overall survival (OS), and safety. Additionally, tumor tissue and/or blood samples were collected from patients before treatment and at the time of progression for exploratory biomarker analysis. Results: Between October 2024 and January 2026, Of the 19 planned patients, 16 eligible patients were enrolled. The median age was 36 years (range: 22-61), with 5 males and 11 females. All patients had metastatic or unresectable locally advanced disease (ECOG performance status 0: 12.5%; stage IV: 75.0%). With the cutoff date of January 15, 2026, 14 patients were evaluated, the median follow-up time was 8.6 months (range, 2.9 to 14.6 months), the objective response rate (ORR) was 35.71% (5/14), all of them were partial responses (PR), and the disease control rate (DCR) was 100% (14/14). The median PFS and OS were not reached. Treatment-related adverse events (TRAEs) occurred in all patients, with grade ≥3 TRAEs observed in 4 (28.57%) patients, included two case of neutropenia, and one case each of thrombocytopenia and transaminase elevation. Conclusions: The combination of Sintilimab and GT demonstrated promising efficacy in chemotherapy-naïve patients with advanced ES, achieving an ORR of 35.71% and a remarkably high DCR. Despite limited follow-up, the preliminary PFS data suggest a potential benefit from PD-1 immunotherapy. The combination showed a manageable safety profile with no new safety signals identified. Clinical trial information: ChiCTR2500095527.
Clinical activity and safety of RNK08954 in advanced non–small cell lung cancer (NSCLC) patients with <i>KRAS</i> G12D mutation (NCT06667544).
3006 Background: KRAS G12D is the most prevalent subtype of KRAS mutations across solid tumors. RNK08954 is a potent and selective KRAS G12D small molecule oral inhibitor. It inhibited proliferation of KRAS G12D-mutant cells and demonstrated significant tumor regressions in mouse xenograft models. Here we report the results of RNK08954 from Phase 1 first-in-human study. Methods: This ongoing multicenter open-label trial of RNK08954, comprises of: Phase 1a dose-escalation (U-BOIN design, 5 dose levels: 200, 400, 800, 1000 and 1200 mg RNK08954 single agent QD) and Phase 1b dose optimization and expansion cohorts (NSCLC, Pancreatic, and other tumor types). Key endpoints were determining the recommended doses for expansion (RDE), safety, tolerability, antitumor activity (objective response rate (ORR), disease control rate (DCR), duration of response (DoR), progression free survival (PFS)), pharmacokinetics and pharmacodynamics. Patients (pts) enrolled into the study had solid tumors not amenable to standard therapy; 0 or 1 ECOG PS; and KRAS G12D mutation. Results: At data cutoff (Jan 20, 2026), 106 pts were enrolled, with 47 pts presenting with NSCLC. The median age was 65 years, and 91.5% of pts had ECOG 1. Prior lines of therapy ranged between 1 and 3, with a median of 14 mo since NSCLC diagnosis. The ORR was 38.5% (15/39; 95% CI: 23.4, 55.4), DCR was 94.9% (37/39; 95% CI: 82.7%, 99.4%), median DoR was not reached (NR) at the time of analysis (Q1, Q3: 4.8, NR) and median PFS will be reported with mature data. ctDNA analysis demonstrated correlation with clinical benefits. RNK08954 demonstrated a near-dose dependent exposure across dose levels. Both 1000 and 1200 mg were chosen for RDE, and the recommended Phase 2 is considered as 1200 mg QD. Overall, treatment was tolerated, with diarrhea (78.7%), nausea (61.7%) and vomiting (55.3%) being the most frequent treatment related events (TRAEs) and were mainly Grade 1. Grade 3 TRAEs occurred in 23.4%, with diarrhea most frequent TRAEs (10.6%). No Grade 3 or higher transaminase elevation (ALT/AST) was observed, only one patient experienced Grade 3 neutropenia.There were no fatal events. Further updated results will be presented at the meeting. Conclusions: RNK08954 was well tolerated and displayed promising antitumor activity in pts with KRAS G12D-mutant NSCLC. The study supports further evaluation either as monotherapy or in combination with standard of care and/or novel agents. Clinical trial information: NCT06667544 .
Correlation of CT changes, PET response, and histopathologic tumor regression in treated advanced <i>EGFR</i> -mutant NSCLC before disease progression.
8655 Background: Previous studies have examined the correlation between radiologic and pathologic responses using PET, CT, and histopathologic regression in patients receiving chemotherapy or immunotherapy. However, data on the relationship among these modalities after EGFR-TKI treatment remain limited, particularly in the context of emerging induction EGFR-TKI strategies. Methods: We conducted a two-arm, phase II clinical trial (PTR-1) enrolling patients with advanced EGFR-mutant NSCLC. After 12 weeks of EGFR-TKI therapy, participants were randomized (1:1) to either continue TKI treatment or undergo primary tumor resection. Surgery aimed to achieve locoregional control with negative margins, and lymph node dissection was not mandatory. All resected specimens were evaluated for pathologic response according to IASLC recommendations. Radiologic response was assessed by RECIST 1.1, and major pathologic response (MPR) and PET metabolic response were evaluated. Results: A total of 91 patients were enrolled, with 72 randomized into two treatment arms; 2 patients declined surgery. The median interval from treatment initiation to surgery was 3.7 months, and 18% of patients underwent resection beyond 4.5 months. Among the 34 resected cases, MPR was achieved in 29.4% (10/34) and pathologic complete response (pCR) in 5.9% (2/34). Patients harboring EGFR exon 19 deletions demonstrated higher rates of pathologic response than those with L858R mutations. The correlation between CT-based tumor regression and histopathologic response was weak (r = 0.30). Pathologic response rates were 24.5% in patients with partial response (PR) and 43.8% in those with stable disease (SD) by RECIST. The correlation coefficients between PR or SD status of the primary tumor and pathologic response were 0.15 and −0.29, respectively. Complete metabolic resolution on FDG-PET corresponded to MPR in 66% of cases. A preoperative SUVmax < 2.5 was associated with a mean pathology residual viable tumor of 20.7% and a 42.8% MPR rate, while patients with ≥90% regression in PET signal achieved MPR in 66.6% of cases. Conclusions: CT-based tumor regression modestly reflects histopathologic response after EGFR-TKI induction but with poor correlation, particularly in radiologic SD cases. This represents the first trial-based dataset analyzing imaging–pathology correspondence in advanced EGFR-mutant NSCLC prior to disease progression. PET metabolic response demonstrated relatively better discrimination of major pathologic responders, though its predictive accuracy remains limited. These findings underscore the need for refined imaging biomarkers or other NGS data to identify optimal candidates for local consolidation therapy in late stage and future neoadjuvant setting in early stage strategies in EGFR-mutant NSCLC. Clinical trial information: NCT05215548 .
Adjuvant DC-CIK plus high-dose interferon-α versus high-dose interferon-α alone in resected stage IIB–IIID melanoma: A propensity score–matched real-world study with long-term follow-up.
e21536 Background: High-dose interferon-α (HD-IFN) has historically served as a standard adjuvant therapy for resected stage IIB–IIID melanoma, yet relapse remains common. While dendritic cell-cytokine induced killer (DC-CIK) cell therapy has demonstrated antitumor activity across various malignancies, its specific efficacy in the adjuvant setting for melanoma remains unclear. We compared outcomes of DC-CIK plus HD-IFN versus HD-IFN alone in a real-world cohort. Methods: We retrospectively analyzed 903 patients with completely resected stage IIB–IIID melanoma between 2012 and 2016. Patients received either HD-IFN alone (20 MIU for 4 weeks, followed by 10 MIU for 11 months) or HD-IFN plus DC-CIK immunotherapy (at least 3 cycles). For DC-CIK preparation, an HLA-guided antigen loading strategy was employed. Autologous DCs were pulsed with peptides (MART-1/S-100) for HLA-A02/A24+ patients or tumor lysates for others and subsequently co-cultured with CIK cells to generate the effector product. Propensity score matching (1:1) was performed. Endpoints were recurrence-free survival (RFS), overall survival (OS), and toxicities. Results: After propensity score matching, a total of 586 patients were included in the final analysis, with 293 patients in each group. Baseline characteristics were well balanced between the two groups. The cohort comprised 209 patients with stage IIB-IIC disease (35.7%) and 377 patients with stage III disease (64.3%). With a median follow-up of 101.9 months, combination therapy significantly improved RFS compared with HD-IFN alone (median, 23.9 vs. 13.4 months; Hazard Ratio [HR], 0.67; 95% CI, 0.56–0.80; P<0.05). Although no significant difference in OS was observed in the overall population (median, 63.5 vs. 48.2 months; HR, 0.89; 95% CI, 0.72–1.10; P = 0.279), subgroup analysis revealed a significant OS benefit for stage III patients receiving combination therapy (median, 51.5 vs. 35.4 months; P = 0.033). Similarly, the combination group demonstrated superior median RFS in stage III disease (18.7 vs. 9.1 months; P < 0.01) and across specific subtypes, including acral (23.6 vs. 13.8 months; P < 0.01) and cutaneous melanoma (21.4 vs. 12.9 months; P < 0.05). Grade ≥3 adverse events occurred in 15.0% of the combination group and 12.5% of the monotherapy group, with no treatment-related deaths. Conclusions: DC-CIK combined with HD-IFN regimen was associated with significantly prolonged RFS compared with HD-IFN alone in resected stage IIB–IIID melanoma. Notably, this combination therapy demonstrated a significant OS benefit in patients with stage III disease, highlighting a high-risk subgroup that may derive the greatest survival advantage from this strategy. Prospective studies are warranted to confirm these findings and better define the role of DC-CIK–based adjuvant strategies.
Dietary changes in head and neck cancer patients pre- and post-chemotherapy and/or radiation therapy.
e24126 Background: Head and neck squamous cancer (HNSCC) patients often face challenges with adequate nutritional intake due to the location of their disease and treatment-related adverse effects. As many as 60% of HNSCC patients present with malnutrition at diagnosis due to tumor location and burden. Currently, there are no specific nutrient guidelines for HNC patients. This study aimed to examine changes in nutrient intake and diet quality in patients with HNSCC before and after completion of radiation therapy (RT) or chemoradiation (CRT). Methods: This study used data from an ongoing longitudinal observational study that included newly diagnosed HNSCC patients receiving RT or CRT at Emory Winship Cancer Institute and MD Anderson Cancer Center. Adults aged ≥ 21 years with non-recurrent, non-metastatic HNSCC were enrolled. Dietary intake was assessed using the Automated Self-Administered 24-Hour Dietary Assessment Tool (ASA24) before treatment initiation and one-month post-treatment. Two dietary interviews were completed at each time point and averaged to estimate nutrient intake using the USDA Food and Nutrient Database and diet quality using Healthy Eating Index-2020 (HEI) scores. Macronutrients were expressed as % of kcal, and other nutrients were energy-adjusted per 1000 kcal. Linear mixed models assessed pre- to post-treatment changes, adjusting for age, BMI, sex, HPV status, treatment, and time, with false discovery rate (FDR) correction for multiple testing. Results: Among the 103 patients analyzed, 83.3% were male, with a mean age of 59.2 yrs (SD = 10.5 yrs). 76.5% were HPV positive, and 66.7% received CRT. Pre-treatment, the mean BMI was 29.4 kg/m 2 (SD = 6.43 kg/m 2 ); the mean total energy intake was 2010 kcal/day (SD = 752 kcal/day), and the mean HEI total score was 48.0 (SD = 48.5). Overall, total energy intake did not change significantly pre- and post-treatment (FDR = 0.198). However, there was a decrease in % kcal from total fat (FDR < 0.01), solid fats (FDR = 0.0144), saturated fat (FDR < 0.01), and monounsaturated fat (FDR = 0.0154). Additionally, % kcal from carbohydrates increased (FDR < 0.01). For micronutrients, iron, Vitamin B1, Vitamin B2, Vitamin B6, Vitamin B9, Vitamin B12, Vitamin D, magnesium, and calcium intake all significantly increased (all FDR < 0.05). Total HEI score did not significantly change (FDR = 0.813), but whole fruit (FDR = 0.013) and total fruit (FDR < 0.01) intake significantly decreased. Conclusions: Despite stable energy intake and diet quality, treatment was associated with decreased fat and fruit intake and increased carbohydrate and certain micronutrient intake. These changes in diet could be attributed to treatment side effects, which can alter food preferences. Further research is warranted to examine the association between treatment side effects and nutritional intake. The findings may inform the development of clinical nutrition guidelines for HNSCC patients.