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Updated results of benmelstobart combined with anlotinib and chemotherapy as neoadjuvant therapy for locally advanced head and neck squamous cell carcinoma: A single-arm, open-label phase II clinical trial.

6045 Background: Locally advanced head and neck squamous cell carcinoma (HNSCC) is characterized by high risks of local recurrence and distant metastasis, resulting in poor prognosis. Neoadjuvant therapy has the potential to improve survival outcomes in these patients. This study aimed to evaluate the safety and efficacy of benmelstobart in combination with anlotinib and chemotherapy as neoadjuvant therapy for resectable locally advanced HNSCC. Preliminary results were presented at the 2025 ESMO Congress (Abstract 1454eP), and updated consecutive results are reported herein. Methods: This single-center, phase II clinical trial enrolled patients with stage III/IVA HNSCC who met predefined eligibility criteria. Patients underwent neoadjuvant therapy with benmelstobart (1200mg), anlotinib (10mg), cisplatin (60mg/m²), and nab-paclitaxel (125mg/m², d1, d8) for three 21-day cycles. Surgical resection was performed within two weeks after neoadjuvant therapy completion, with tumor specimens collected for pathological evaluation. The primary endpoint was major pathological response (MPR) rate. Postoperative adjuvant therapy was administered based on risk assessment. Secondary endpoints included objective response rate (ORR), pathological complete response (pCR) rate, 2-year disease-free survival (DFS), 2-year locoregional recurrence-free survival (LRFS), 2-year distant metastasis-free survival (DMFS), 2-year overall survival (OS), and safety assessment. Results: As of Jan 9, 2026, a total of 36 patients who met the inclusion and exclusion criteria were enrolled. The median age was 61 years (range: 38-77), with males accounted for 91.7%. ECOG performance status 0 was observed in 80.5% of patients, and hypopharyngeal carcinoma was the most common primary tumor site (50.0%). Stage III and IVA disease accounted for 25.0% and 75.0% of patients, respectively. At the data cut-off date, 32 patients completed neoadjuvant therapy, achieving an ORR of 96.9% and a disease control rate (DCR) of 100%. Among them, 27 patients underwent surgery and completed histopathological assessment. MPR was achieved in 23 cases (including 20 with pCR), resulting in an MPR rate of 85.2% (95%CI: 66.3%-95.8%). The incidence of all grade treatment-emergent adverse events (TEAEs) was 86.1% (31/36). The incidence of grade≥3 TEAEs was 8.3% (3/36), most commonly myelosuppression (5.6%) and renal impairment (2.8%). Conclusions: The combination of benmelstobart, anlotinib, and chemotherapy demonstrated promising efficacy as neoadjuvant therapy for resectable HNSCC, with high ORR and MPR rates, along with an acceptable safety profile. These updated results support further evaluation of this combination in randomized controlled trials. Clinical trial information: NCT0669949 .

A multicenter randomized phase II trial of topical betamethasone ointment for preventing severe chemoradiotherapy-induced oral mucositis in head and neck cancer.

12015 Background: Severe oral mucositis (OM) is a major unmet clinical problem during cisplatin-based chemoradiotherapy (CRT) for head and neck cancer, with no established preventive strategy. Although topical dexamethasone has shown benefit during radiotherapy alone, its efficacy during CRT is limited. This study represents the first randomized trial evaluating a potent topical corticosteroid, betamethasone ointment, for preventing severe OM during cisplatin-based CRT. Methods: Patients with head and neck cancer receiving CRT with the oral cavity included in the radiation field were enrolled at six institutions in Japan. Upon development of grade 1 OM (CTCAE v5.0), patients were randomized to standard oral care alone (control) or standard oral care plus topical betamethasone ointment applied three times daily (intervention). Treatment continued until completion of radiotherapy or onset of grade 3 OM. The primary endpoint was time to grade 3 OM, analyzed using multivariable Cox proportional hazards models. Secondary endpoints included time to grade 2/3 OM and incidence of oral candidiasis. Results: A total of 68 patients were analyzed (intervention n=35; control n=33). The cumulative incidence of grade 3 OM was significantly lower in the intervention group (14.3%) than in the control group (48.5%). Topical betamethasone significantly reduced the risk of grade 3 OM (HR 0.246, 95% CI 0.081–0.749). Betamethasone also delayed the onset of grade 2/3 OM. Non-use of a spacer was independently associated with grade 2 OM. Betamethasone did not increase oral candidiasis, whereas denture use was a significant risk factor. Conclusions: Topical betamethasone ointment substantially reduced the incidence of severe OM during cisplatin-based CRT without increasing oral candidiasis. This simple, low-cost, and widely accessible intervention could be rapidly implemented in routine clinical practice to mitigate CRT-induced toxicity. To our knowledge, this is the first randomized trial demonstrating the efficacy of a potent topical corticosteroid for preventing severe OM during cisplatin-based CRT. Clinical trial information: jRCTs071200013.

Evaluation of a large language model–generated after-visit summary from outpatient hematology/oncology progress notes.

e13692 Background: Oncology progress notes are technical and may be difficult for patients to interpret. We evaluated readability, patient-education quality, and clinician-rated completeness, accuracy, and safety of a large language model (LLM)-generated after-visit summary (AVS) derived from outpatient hematology/oncology progress notes. Methods: Single-center retrospective study of 150 de-identified progress notes from adult outpatient hematology/oncology encounters (IRB #PRO00041351; waiver of consent granted for retrospective de-identified review). AVS were generated in a HIPAA-compliant environment using Google AI Studio Gemini 3 Pro Preview (temperature = 1; no post-processing) and were not used for clinical care. Flesch Reading Ease (FRE) and PEMAT understandability/actionability (0-100) were computed for each note and AI AVS; paired comparisons used Wilcoxon signed-rank tests. One independent oncology clinician reviewed each AI AVS versus its source note using a 15-item Oncology AI-AVS Completeness & Accuracy Survey (completeness = % items present; mean item accuracy 0-2) and assigned safety risk (low/moderate/high). Results: Patients had median age 64.5 years (IQR 54.2-72.0); 66.0% female; 64.7% stage IV. AI AVS had higher FRE than progress notes (mean 64.9 vs 41.3; mean paired diff +23.6, 95% CI 22.6-24.6; p < 0.001). PEMAT understandability (85.7 vs 32.2; diff +53.5; p < 0.001) and actionability (60.8 vs 16.9; diff +43.9; p < 0.001) were higher; understandability improved in 150/150 pairs and actionability in 149/150. Clinician review: completeness mean 95.4% (SD 4.4) and mean item accuracy 1.93/2 (SD 0.07). Safety risk was low in 135 (90.0%) and moderate in 15 (10.0%); none high. Conclusions: An LLM-generated AVS derived from outpatient oncology progress notes was associated with improved readability and PEMAT scores while maintaining high clinician-rated completeness and accuracy; a minority were rated moderate risk, supporting continued clinician oversight and prospective evaluation. Outcomes (N=150). Metric Note AI AVS Diff/P FRE mean (SD) 41.3 (8.3) 64.9 (6.5) +23.6; < 0.001 PEMAT understandability % mean (SD) 32.2 (12.1) 85.7 (10.2) +53.5; < 0.001 PEMAT actionability % mean (SD) 16.9 (8.9) 60.8 (16.0) +43.9; < .0001 Completeness % mean (SD) -- 95.4 (4.4) -- Accuracy (0-2) mean (SD) -- 1.93 (0.07) -- Safety risk n (%) -- Low 135 (90); Moderate 15 (10); High 0 --

Are patient-reported outcome measures valid across diverse cancer populations?: A review of psychometric evidence.

e23260 Background: Patient-reported outcome (PRO) assessments improve cancer care and health outcomes, including quality of life, patient satisfaction, and survival, and often provide a more accurate reflection of patients’ health status than clinician-reported assessments. Despite increasing use of PROs in oncology research and practice, the extent to which PRO instruments have been systematically evaluated for psychometric performance among underserved populations, such as racial and ethnic minorities, individuals of low socioeconomic status, and rural residents, remains unclear. This systematic review examines existing evidence on the psychometric evaluation of PRO instruments in cancer care among underserved populations. Methods: We examined peer-reviewed studies published in English and conducted in the United States. Three academic databases (i.e., PubMed, Scopus, and Web of Science) were searched for studies assessing PRO instruments among underserved cancer patients. Titles and abstracts were screened, followed by full-text review. Data were systematically extracted on PRO instruments used, study populations, and psychometric evaluations, including comprehension, usability, validity, reliability, and differential item functioning (DIF). Results: A total of 12 studies met inclusion criteria. Findings were generally supportive of widely used instruments, particularly PROMIS measures. Several studies conducted DIF analyses across diverse sociodemographic groups, identifying DIF for select items and domains. While aggregate-level DIF was often small, individual-level DIF by race/ethnicity, education, and language preference was observed, highlighting items that may warrant further evaluation. Studies examining comprehension and usability indicated that literacy was associated with understanding PRO items, whereas age and race were not consistently associated. Few studies examined whether individuals from different racial and ethnic groups interpret PRO items similarly, and limited evidence was found on psychometric evaluation of PRO measures translated into languages other than Spanish. Conclusions: PRO instruments used in cancer care demonstrate overall psychometric support in underserved populations. DIF findings underscore the importance of understanding why items may function differently across groups, including the role of lived experience and cultural context. Additional studies that intentionally evaluate psychometric performance and item comprehension in underserved populations are needed to support equitable interpretation and implementation of PROs in cancer care.

Effect of first-line treatment of CLL/SLL with the all-oral combination of sonrotoclax (sonro) and zanubrutinib (zanu) on minimal residual disease (uMRD) rates, including in patients with del(17p)/TP53.

7043 Background: Oral, fixed-duration BTKi-BCL2i combinations are effective and convenient options for first-line treatment of CLL. However, all current regimens, including those using second-generation BTKi, are limited by low uMRD rates of 29-47%. We hypothesize that upgrading the BCL2i component of BTKi-BCL2i with sonro, a next generation BCL2i with ~14x pharmacological potency compared with venetoclax, may lead to improved uMRD rates. Here, we report updated safety and efficacy results in patients with treatment-naive CLL/SLL treated with zanu+sonro (320 mg cohort) in a phase 1/1b study (NCT04277637), with a median follow-up of 30.9 months (range, 3.1-41.9 months). Methods: Study treatment consisted of lead-in zanu 320 mg QD for 8-12 weeks, after which sonro was added with a ramp-up to the target dose of 320 mg QD. Patients were treated until progression, unacceptable toxicity, or protocol-defined elective discontinuation after 96 weeks of combination treatment at target dose. Primary endpoint was safety per NCI-CTCAE v5.0. Secondary endpoints included overall response rate (ORR). Exploratory endpoints included uMRD4 rates in peripheral blood per flow cytometry and next generation-sequencing (NGS). Results: Of the 86 patients enrolled in the sonro 320 mg cohort, 45 (52%) remained on treatment at data cut-off, and 40 (47%) discontinued sonro, most due to protocol-defined elective discontinuation (85%; n=34). The most common (≥30%) any-grade treatment-emergent adverse events (TEAEs) were neutropenia (38%), contusion (38%), COVID-19 (33%), and upper respiratory tract infection (30%). Neutropenia was the most common grade ≥3 TEAE (29%). No TLS occurred, and no AEs led to death. In 84 efficacy-evaluable patients, the ORR was 100%, with 46 (55%) achieving complete response. Median time to response was 2.6 months (range, 1.5-9.1 months). No patients in the 320 mg cohort experienced progression with an estimated 30-month PFS of 100%. The best uMRD4 rate assessed by flow cytometry was 99% (83/84) and 100% (10/10) in patients with TP53 /del(17p) mutations. Median time from reaching sonro target dose to uMRD was 3.0 months (range, 2.3-27.4 months), and the best uMRD4 rates by weeks 24, 48 and 96 were 81% (69/85), 91% (63/69) and 98% (55/56), respectively. No patient with uMRD4 reverted to MRD4+. In the NGS evaluable set, best uMRD5 (<10 -5 ) was 86% (66/77). Updated results will be presented. Conclusions: Sonro+zanu was well tolerated and achieved uMRD rates of >90%, including in patients with high-risk cytogenetics. The depth and kinetics of uMRD achieved with sonro+zanu highlights the improved potency and differentiated profile of this combination vs available combination therapies in first-line CLL. Sonro+zanu is being evaluated in two phase 3 clinical trials (NCT06073821, NCT07277231). Clinical trial information: NCT04277637 .

Leptomeningeal carcinomatosis in pancreatic cancer: Clinical presentation, management, and outcomes—A systematic review.

e16431 Background: Leptomeningeal carcinomatosis (LMC) is a rare and devastating complication of advanced malignancies, occurring in fewer than 1% of patients with pancreatic cancer. Owing to its rarity, the clinical presentation, diagnostic approaches, management strategies, and outcomes remain poorly defined. We conducted a systematic review to characterize the clinical features, diagnostic modalities, treatments, and survival outcomes of pancreatic cancer–associated LMC. Methods: We conducted a systematic search of PubMed, Embase, Web of Science, and conference proceedings from January 2001 through December 2025 to identify reported cases of pancreatic cancer complicated by leptomeningeal carcinomatosis (LMC). Eligible cases included histologically confirmed pancreatic adenocarcinoma, neuroendocrine tumor, or mucinous neoplasm with leptomeningeal involvement confirmed by neuroimaging, cerebrospinal fluid analysis, or autopsy, and sufficient clinical detail. Data extracted included demographics, tumor characteristics, diagnostic modalities, treatments, and outcomes. Results: Twenty-five cases of pancreatic cancer–associated leptomeningeal carcinomatosis (LMC) were identified. Median age at pancreatic cancer diagnosis was 57 years (IQR, 45–72), and 60% were male. Histology was predominantly pancreatic ductal adenocarcinoma (84%). LMC developed a median of 11 months after cancer diagnosis. Common neurologic presentations included headache (80%), cranial nerve deficits (40%), confusion or encephalopathy (36%), seizures (32%), and gait ataxia (28%). Diagnosis relied primarily on contrast-enhanced brain MRI (92%), while CSF cytology was positive in only 40% of cases despite abnormal findings. Management was largely palliative, including whole-brain radiotherapy (44%), intrathecal chemotherapy (20%), systemic therapy continuation (32%), and supportive care alone (28%). Median survival following LMC diagnosis was 14 days. Conclusions: Leptomeningeal carcinomatosis in pancreatic cancer is a terminal complication with severe neurologic morbidity and poor survival. Early recognition and prompt MRI evaluation are critical in symptomatic patients. Current therapies offer limited benefit, emphasizing the need for improved diagnostics and CNS-penetrant treatments to advance patient-centered care. Baseline characteristics of patients with pancreatic cancer–associated leptomeningeal carcinomatosis (N = 25). Characteristic Value Sex (M/F) 60% / 40% Age PC dx, yrs 57 (45–72) Age LMC dx, yrs 57 (45–80) Tumor site Head 36%, Tail 28%, Body 24% Histology PDAC 84%, Mucinous 8%, NET 4% Stage IV 36% CA 19-9, U/mL 533 (1–22,700) Smoking known 20% Pathogenic mutation 20% Values are N (%) or median (IQR/range). PC = pancreatic cancer; LMC = leptomeningeal carcinomatosis; PDAC = pancreatic ductal adenocarcinoma; NET = neuroendocrine tumor.

Updated 5-year survival outcomes of short-course radiation followed by mFOLFOX-6 plus avelumab in locally advanced microsatellite-stable rectal adenocarcinoma: The Averectal phase II study.

3643 Background: Total neoadjuvant therapy (TNT) for microsatellite-stable (MSS) locally advanced rectal cancer consists of induction or consolidation chemotherapy combined with either long-course chemoradiation (LCCRT) or short-course radiation therapy (SCRT). While TNT has yielded variable outcomes across studies, it has consistently improved pathologic complete response (pCR) rates and paved the way for non-operative management strategies. However, the use of SCRT within TNT has been associated with higher rates of local recurrence. The integration of immunotherapy into total neoadjuvant therapy (TNT) improves outcomes in LARC, particularly pathologic complete response (pCR), which may translate into improvements in disease-free survival (DFS) and overall survival (OS), in addition to improvement in local recurrence rate (LRR) especially when used with SCRT, potentially through synergistic effects with radiotherapy. Methods: The Averectal trial is an investigator-initiated, open-label, single-arm, multicenter, phase II study including 44 patients. 40 patients with LARC completed treatment with SCRT (5 Gy x5 fractions) followed by 6 cycles of mFOLFOX-6 plus avelumab every 2 weeks, followed by TME. The primary outcome was pCR vs. historical control. Secondary outcomes were 3-year DFS, LRR and the association of the ImmunoScore (IS) with outcomes including pCR. Results: 15/40 (37.5 %) patients achieved pCR compared to 16 % in the historical control group with statistically significant p = 0.025, and 27/40 (67.5 %) had a major pathologic response. Patients who achieved pCR had a higher mean IS compared with those who did not (68 vs. 52, p = 0.049). With a median follow up of 72.8 months (range 15.4-97.1), the median OS and DFS were not reached. The mean OS and DFS were 85.3 months and 79 months respectively, and the 5-year OS and DFS were 81.9% and 74.6%. Only 2/40 patients had local recurrence, accounting for a LRR of 5%. In patients with high versus low IS, median OS was not reached in either group (p = 0.9), with mean OS of 79.3 months versus 84.7 months, respectively. Similarly, median DFS was not reached, although there was a trend towards improved DFS in the high IS group (p = 0.175), with mean DFS of 77.6 months versus 70.7 months for high and low IS, respectively. Conclusions: The addition of avelumab to TNT in patients with MSS LARC resulted in a statistically significant increase in pCR, notably among those with high IS, and was associated with continued improvement in survival outcomes at 5 years. Clinical trial information: NCT03503630 .

Response to neoadjuvant chemotherapy in both the breast and lymph nodes in patients with inflammatory breast cancer.

614 Background: Optimal outcomes in Inflammatory Breast Cancer (IBC) are achieved with trimodal therapy. We sought to evaluate how differences in response to neoadjuvant chemotherapy (NAC) in the breast and axilla impact locoregional recurrence-free, distant recurrence-free and overall survival in patients with IBC. Methods: A retrospective analysis was performed on patients with IBC enrolled in a prospective registry from 2007-2025. All patients underwent NAC followed by modified radical mastectomy. Comparisons between three pathologic response groups—(A) pCR, no residual disease in breast or lymph nodes, (B) complete response in breast but not axillary nodes, and (C) complete response in axillary nodes, but not breast—were performed using Kaplan-Meier and pairwise Cox proportional hazards models. Results: 545 patients were included; median age was 50 (IQR:41-58). pCR was identified in 150 (28%) patients, while 34 (6%) were in group B, and 55 (10%) were in group C. Of patients with pCR, 6 (4%) had locoregional recurrence (LRR), compared to 6 (17%) of patients in group B, 5 (9%) of patients in group C, and 79 (25%) in patients without pCR. There was decreased risk of LRR in patients with pCR compared to no pCR, or group B (HR:0.118 CI 0.05-0.27 P<0.001; HR:0.18 CI 0.06-0.55 P=0.017). A similar decreased risk of LRR was observed in patients with group C compared to no pCR (HR:0.297 CI 0.12-0.73 P=0.01). Of patients with pCR, 31 (20%) had distant recurrence, compared to 14 (41%) of patients in group B, 23 (41%) of patients in group C, and 183 (60%) in patients who did not have pCR. There was decreased risk of distant recurrence in patients with pCR compared to no pCR, or patients in group C (HR0.25 CI 0.17-0.37 P<0.0001; HR0.43 CI0.25-0.74 P=0.007). There was also a decreased risk of distant recurrence in patients with group C compared to no pCR (HR0.59 CI 0.38-0.91 P=0.027). Mean OS was longer in patients with pCR compared to partial response or no pCR (12.4 vs 7.95 years). The risk of death was lower in patients with pCR compared to partial or no pCR, as well as those with group C compared to no pCR. Conclusions: In patients with IBC, the lowest risk for recurrence was achieved with pCR. However, even with pCR, there was still a 20% chance of distant recurrence. Partial response through clearance of the lymph node disease provided some reduction in risk of recurrence compared to no pCR.

Expression of Concern: An Integrated SNP Mining and Utilization (ISMU) Pipeline for Next Generation Sequencing Data

Eco-friendly fabrication and characterization of polyherbal silver nanoparticle-loaded shampoo with enhanced antibacterial efficacy for the topical management of scalp and hair folliculitis

Mixed‐Isomers Strategy for Thermally Stable and High‐Performance Thick‐Film All‐Small‐Molecule Organic Solar Cells

ABSTRACT All‐small‐molecule organic solar cells (all‐SMOSCs) have emerged as promising candidates for next‐generation photovoltaic technologies due to their advantages in chemical tunability, purification ease, and batch‐to‐batch consistency. Despite significant progress, their power conversion efficiencies (PCEs) still trail those of polymer‐based solar cells (PSCs), primarily due to suboptimal charge management and morphology control. By introducing two structurally similar yet functionally complementary isomers, BTP‐Br‐γ and BTP‐Br‐δ, into a high‐performing host system (MPhS‐C2:BTP‐eC9), herein we construct quaternary blends that exhibit superior morphological robustness, efficient charge transport, and suppressed energy loss. The optimized quaternary device delivers a record PCE of 19.06% (certified at 18.7%), representing the highest value reported for all‐SMOSCs to date. Further investigations reveal that the quaternary devices also exhibit high thickness tolerance to device efficiency and thermal stability, owing to fast exciton dissociation, long carrier diffusion length, low recombination loss, and rapid charge extraction. The work offers a promising strategy to bridge the performance gap between all‐SMOSCs and PSCs, paving the way for their practical deployment in high‐efficiency organic photovoltaics.

Salt‐Templated Crystallization Yields Oriented Interconnected Macroporous Polymer Gels for Ultrafast and High‐Capacity Atmospheric Water Harvesting

ABSTRACT Sorption‐based atmospheric water harvesting (SAWH) is a promising strategy for freshwater production. While salt‐based composites are widely employed as SAWH sorbents, they are often constrained by limited water yield from low sorption capacity and slow sorption/desorption kinetics due to diffusion barriers. Here, a new strategy is proposed to enhance moisture transport and storage space by fabricating oriented interconnected macroporous polymer gels via salt‐templated crystallization‐induced confined polymerization. Benefiting from this optimized interconnected hierarchical structure and the synergistic effect between PAMPS and LiCl, the salt‐templated crystallization gel (STC/TiN‐gel@LiCl) exhibits a record‐breaking moisture uptake of 7.19 g g − 1 , ultrafast sorption kinetics of 1.96 g g − 1  h − 1 , and rapid desorption rate of 96.8% per hour under 1.0 sun illumination. After 20 cycles under high‐humidity conditions (25°C, 90% RH), the gel retains over 90.4% of its initial water uptake capacity without leakage, confirming its long‐term durability. Moreover, it delivers an outstanding water production rate of 3.29 kg kg − 1  day − 1 even under low‐temperature and moderate humidity conditions (14.5°C, 55.6% RH). This work pioneers an oriented interconnected macroporous architecture engineering strategy to concurrently unlock rapid transport and high‐capacity storage in hygroscopic gels, establishing a new paradigm for atmospheric water harvesting.

Clinical outcomes of regenerative endodontic treatment with injectable platelet-rich fibrin in mature necrotic teeth in a retrospective cohort study

Receptor-substrate competition for the TonB homolog FusB suggests a model for ferredoxin import

Effect of a financial navigation intervention on financial toxicity among patients with breast cancer: A randomized controlled trial in China.

1520 Background: Financial toxicity (FT) is a common and burdensome consequence of breast cancer treatment, adversely affecting patients’ psychological well-being, treatment adherence, and quality of life. Financial navigation (FN) has been proposed as an effective strategy to mitigate FT; however, high-quality randomized evidence evaluating its impact on patient-centered outcomes remains limited. Methods: This assessor-blinded, parallel-group randomized controlled trial enrolled adult female patients with breast cancer who had undergone surgery and were receiving or scheduled for adjuvant therapy. Participants were randomized to an FN intervention or usual care (n = 41 per group). The FN intervention included individualized needs assessment, cost-related health education, referral to financial and social resources, and personalized counseling. Outcomes were assessed at baseline (T0), 1 month (T1), and 3 months (T2) post-discharge. Primary outcome was FT, with secondary outcomes including cost-related health literacy (CRHL), shared decision-making (SDM) ability, and perceived stress. Intention-to-treat analysis using generalized estimating equations was applied. Results: Of 311 patients screened, 82 were enrolled. Compared with controls, the FN group demonstrated significantly lower subjective FT at T1 (mean difference = 4.76, 95% CI 0.75–8.76, P = 0.020) and T2 (mean difference = 4.66, 95% CI 0.94–8.37, P = 0.014). CRHL significantly improved at T1 (mean difference = 3.15, 95% CI 0.91–5.38, P = 0.006) and further increased at T2 (mean difference = 5.56, 95% CI 3.53–7.59, P < 0.001). SDM ability was also higher in the FN group at T2 (mean difference = 3.24, 95% CI 0.47–6.00, P = 0.022). No significant effects were observed in material or behavioral FT domains. Perceived stress was higher in the FN group at T2 ( P = 0.032). Conclusions: This randomized controlled trial demonstrates that financial navigation is an effective intervention for alleviating subjective financial toxicity and improving cost-related health literacy and shared decision-making among patients with breast cancer. By providing rigorous randomized evidence, this study advances the field beyond descriptive and observational research and offers high-level evidence supporting financial navigation as a clinically actionable strategy to address cancer-related financial toxicity. These findings contribute to the global effort to mitigate financial toxicity and support the integration of structured financial navigation programs into survivorship care models across diverse healthcare settings. Clinical trial information: NCT06484140 .

Genomic and clinical correlates of belzutifan treatment in renal cell carcinoma (RCC): A retrospective analysis of 150 RCC patients.

4541 Background: Belzutifan is a hypoxia-inducible factor-2α (HIF-2α) inhibitor approved for RCC that targets a central driver in RCC pathogenesis; however, predictive biomarkers of response remain poorly defined. Methods: Comprehensive DNA (592-gene panel or whole exome) and RNA (whole transcriptome) sequencing were performed by Caris Life Sciences on RCC samples. Clear cell RCC and RCC-NOS with VHL mutations were included. Belzutifan time on treatment (ToT) was derived from insurance claims, and patients were classified as responders or non-responders using the median ToT. Results: A total of 150 belzutifan-treated RCC tumors were included in the analysis, of which 29% were primary kidney tumors and the remainder were from metastatic sites. The study population was classified as responders (n=57) or non-responders (n=93) using a median time on treatment of 85 days (95% CI: 71–114). Baseline characteristics were similar, except responders were younger (median age 57 vs 64 years, p=0.007). Transcriptomic analysis showed similar HIF-2α (median 7.78 vs 7.61) and CA9 (4.82 vs 4.54) expression between responders and non-responders without statistical significance. Responders showed enrichment of PTEN (15.8% vs. 3.3%, p=0.03) and PIK3R1 alterations (7.0% vs. 0.0%, p=0.04). Responders demonstrated numerically higher frequencies of PBRM1 (54.4% vs. 44.3%, p=0.46) and PIK3CA mutations (8.8% vs. 3.3%, p=0.24). Alterations in DNA damage response genes were also numerically more common among responders, including TP53 (14.0% vs. 4.9%, p=0.11) and ATM (3.5% vs. 1.6%, p=0.56), although none of these differences reached statistical significance. In contrast, non-responders exhibited numerically higher frequencies of BAP1 (18.0% vs. 8.8%, p=0.10), SETD2 (26.2% vs. 19.3%, p=0.27), and ARID1A (5.1% vs. 1.8%, p=0.30), all of which were also not statistically significant. Conclusions: HIF2-α RNA expression alone does not predict belzutifan response in RCC. Responders demonstrated alterations in PBRM1, PI3K/AKT/mTOR, and DNA damage response genes, while non-responders showed numerically higher frequencies of chromatin remodeling mutations including BAP1 and SETD2. Study limitation included small sample size and short follow-up. Larger datasets are required to validate these findings.

Interpretable machine learning for prognostic survival prediction in mycosis fungoides: Model development and external validation.

e22612 Background: Mycosis fungoides (MF) has heterogeneous outcomes and persistent disparities, yet lacks widely adopted, validated prognostic tools. We developed and externally validated machine learning (ML) survival models using registry variables to identify independent predictive indicators and generate individualized survival predictions. Methods: MF (ICD-O-3 9700/3) diagnosed 2000–2021 was identified in SEER-22 database. Overall survival (OS) was from diagnosis to death (any cause) or last follow-up. Independent predictors were evaluated with a fully adjusted multivariable Cox model including race, age, sex, Summary Stage, and county-level household income quartiles (2021 USD). To develop a transportable prediction tool using routinely captured registry variables, ML models were trained in a complete-case SEER-22 cohort using age, sex, race group, stage, income group, rural–urban residence, and diagnosis period (≤2010 vs 2011+). We trained LASSO-penalized Cox (LASSO-Cox), random survival forest (RSF), and gradient-boosted Cox (XGBoost-Cox) models using a temporal split by year of diagnosis (training ≤2016; test > 2016) with cross-validated tuning. Performance was assessed by Harrell’s C-index, Uno time-dependent AUC (12/24/36/48 months), and Brier scores. External validation applied the locked SEER-22 models to an independent SEER-8 MF cohort with harmonized covariates at 12–60 months. Results: In the fully adjusted Cox model, Black vs White race was associated with worse OS (HR 1.76, 95% CI 1.60–1.93) and Asian/Pacific Islander vs White with improved OS (HR 0.81, 95% CI 0.66–0.98). Age and advanced stage were strong predictors of death, and male sex was modestly but significantly associated with poorer survival. A socioeconomic gradient was observed: lower-income counties ( < $50k) had higher hazards than the highest-income quartile (≥$95k), with stepwise decreases across higher income levels. ML modeling included 13,447 patients (train 9,849; test 3,598). Internal test discrimination was high (C-index: LASSO-Cox 0.835; RSF 0.818; XGBoost-Cox 0.824), with LASSO-Cox AUC 83.9–84.9% across 12–48 months. External validation (SEER-8, n = 4,753) showed good transportability for LASSO-Cox (C-index 0.757; AUC 76.6–78.2% across 12–60 months) and RSF (C-index 0.765), while XGBoost-Cox performed poorly (C-index 0.562; AUC 54.9–57.6%). Conclusions: Parsimonious ML survival models using routinely available demographic, clinical stage, and socioeconomic surrogates provide robust MF prognostication, with LASSO-Cox and RSF demonstrating strong external generalizability.

Nab-paclitaxel plus S-1 induction chemotherapy for patients with locally advanced pancreatic cancer: A multicenter, open-label phase 2 study.

4225 Background: The prognosis of locally advanced pancreatic cancer is dismal. The objective of the present study was to evaluate safety and efficacy of nab-paclitaxel plus S-1 in previously untreated locally advanced pancreatic cancer. Methods: This multicenter, single-arm phase 2 study was conducted at 4 centers in China. Patients with Eastern Cooperative Oncology Group performance status of 0-1 received up to 8 cycles of nab-paclitaxel 120 mg/m² (day 1,8) plus 80-120mg/d S-1 (day 1-14 each 21-day cycle). After induction, patients without disease progression or unacceptable adverse events were eligible to receive continued therapy according to investigators’ evaluation, including: continued chemotherapy, chemoradiation, or surgery. The primary endpoint was 6-month progress-free survival rate. The secondary endpoints were progress-free survival, overall survival, objective response rate, R0/R1 rate and safety. The reported efficacy outcomes were analyzed in the intention-to-treat population, and safety outcomes were analyzed in the treated population. This trial is registered with ClinicalTrials.gov, NCT03885219. Results: Between April 25, 2019, and March 29, 2023, 60 patients were enrolled in the study. 31 (51.7%) of 60 enrolled patients discontinued induction therapy, with reasons including disease progression (13 [21.7%] patients), adverse events (12 [20.0%] patients), alteration in treatment (4 [6.7%] patients), and withdrawal from study (2 [3.3%] patients). 29 (48.3%) of 60 enrolled patients completed induction treatment, 22 (36.7%) patients finished all 8 cycles of treatment, and 11 (18.3%) patients underwent surgery (10 achieved R0/R1 resection status). The 6-month progression-free survival rate was 71.0% (95%CI: 57.6%-80.9%); 12-month progression-free survival rate was 45.0% (95%CI: 32.0%-57.2%) and 12-month overall survival could reach up to 83.3% (95%CI: 70.3%-90.9%). The median progression-free survival was 11.1months (95% CI: 8.1-14.2); median overall survival was 20.2 months (95% CI: 11.2-29.2). During induction, 54 patients achieved disease control and the disease control rate was 90.0% (95% CI: 79.5%-96.2%). 16 patients had a best response of partial response; the objective response rate was 26.7% (95% CI: 16.1%-39.7%). Grade 3 or higher treatment-related adverse events (TRAEs) occurred in 32 (53.3%) patients. The most common grade 3 or higher TRAEs were neutropenia (23 [38.3%] of 60 patients), followed by leukopenia (13 [21.7%]) and fatigue (4 [6.7%]). No treatment-related deaths were reported. Conclusions: The data from this trial supports the favorable and efficacy of nab-paclitaxel plus S-1 for locally advanced pancreatic cancer, as well as the possibility of converting unresectable disease into surgically resectable disease. Clinical trial information: NCT03885219 .

Clinical and radiographic responses to trastuzumab deruxtecan in molecularly defined ependymomas.

e14097 Background: Ependymomas are rare central nervous system (CNS) tumors lacking approved targeted therapies, and recurrent disease remains difficult to treat. Recent systematic profiling has identified HER2 protein expression in a subset of ependymomas, suggesting a potential role for HER2-directed antibody–drug conjugates (ADCs). Trastuzumab deruxtecan (T-DXd), a next-generation HER2-targeted ADC with documented CNS activity in breast cancer, has not been systematically evaluated in primary CNS tumors. Methods: Two patients with recurrent, molecularly defined ependymoma who had progressed after standard therapies were treated off-label with trastuzumab deruxtecan (T-DXd). The cohort included one patient with MYCN-amplified spinal ependymoma with intracranial dissemination and another with supratentorial ZFTA-RELA–fused ependymoma. Clinical, radiographic, and metabolic responses were assessed using serial MRI and 18 F-FDOPA PET imaging. In the MYCN-amplified case, high-dimensional spatial profiling with multiplexed immunofluorescence (CyCIF) was performed to characterize tumor-cell intrinsic programs related to lineage state, proliferation, and signaling. Results: Both tumors demonstrated membranous HER2 expression by immunohistochemistry (estimated 2+–3+). In the MYCN-amplified case, HER2 expression was widespread across tumor compartments, while spatial profiling identified EGFR/MAPK-linked proliferative niches enriched for cycling and dedifferentiated tumor cell states. Treatment with T-DXd induced marked radiographic responses, with reductions of 84% and 54% in intracranial measurable lesions. The ZFTA-RELA–fused tumor demonstrated durable clinical stability on T-DXd over ~10 months, with a 27% reduction in enhancing tumor burden and a 46% decrease in metabolic tumor volume on serial 18 F-FDOPA PET imaging, meeting PET-RANO criteria for metabolic partial response. Treatment was generally well tolerated, with expected low-grade adverse effects. Conclusions: This study provides early clinical evidence that HER2-directed ADC therapy may benefit select patients with ependymoma across distinct molecular subtypes. Integration of molecular pathology with spatial tumor profiling revealed features that may inform patient selection and rational combination strategies. Together, these results support further prospective evaluation of HER2-targeted ADCs in molecularly selected ependymoma cohorts and highlight the value of protein-level and spatial profiling in identifying actionable vulnerabilities in rare CNS tumors.

Local and state paid sick leave policies and timeliness of treatment initiation among working-age patients with early-stage breast cancer.

11064 Background: Local and state paid sick leave (PSL) mandates have been associated with increased use of preventive services, including cancer screening, and reduced emergency care utilization. Little research has examined PSL policies and cancer after diagnosis. This study evaluates associations of PSL policies and timely treatment initiation among women with early-stage breast cancer. Methods: We identified patients aged 18-64 years newly diagnosed with stages 0-II breast cancer from the National Cancer Database in 2004-2023 and linked then to area-level policy implementation, measured as the month and year the state, county, or city required PSL. Primary outcomes were receipt of definitive surgery or neoadjuvant therapy within 30, 60, and 90 days of diagnosis. We compared changes in treatment initiation between patients residing in areas with and without PSL policies during and after the month and year of diagnosis. We used a staggered difference-in-differences design to account for differential timing of implementation, adjusting for patient demographics, clinical, and area-level characteristics. Random errors were clustered at the state level. Supplemental analyses stratified by county-level unemployment rates and individual insurance coverage. Results: The study included 1,891,411 patients, of whom 249,313 (13.2%) resided in an area with PSL policies at diagnosis. Patients in areas with PSL policies were more likely to have Medicaid, reside in higher-income and metropolitan areas. PSL policy implementation was significantly associated with a 3.4 percentage point (PPT) increase in the probability of treatment ≤30 days (95% CI: 1.1-5.7), 3.0 PPT increase ≤60 days (95% CI: 1.6-4.3), 1.3 PPT increase ≤90 days (95% CI: 0.5-2.1) (Table). Improvements in timely treatment were concentrated in low-unemployment areas; no significant improvements were observed in high-unemployment areas. The magnitude of associations between PSL policies and treatment initiation was stronger among patients without private insurance than with private insurance. Conclusions: Local and state PSL mandates were associated with earlier treatment initiation among working-age patients with early-stage breast cancer, especially in areas with low female unemployment rate. Findings suggest that PSL policies play an important role in timely cancer treatment for employed women who may not have PSL through their jobs. Association of paid sick leave policies and breast cancer treatment initiation. Time from diagnosis to surgery/neoadjuvant therapy (days) DID PPT Lower 95% CI Upper 95% CI P-value Overall ≤30 3.4 1.1 5.7 0.004 ≤60 3.0 1.6 4.3 0.000 ≤90 1.3 0.5 2.1 0.001 Low female unemployment ≤30 2.2 -0.7 5.0 0.136 ≤60 3.8 1.8 5.8 0.000 ≤90 1.2 0.3 2.2 0.012 High female unemployment ≤30 1.8 -0.6 4.2 0.145 ≤60 -1.2 -4.5 2.0 0.459 ≤90 -1.4 -3.7 0.9 0.232