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Real-world outcomes of nasopharyngeal carcinoma in a 20-year retrospective cohort from a lower-middle income country.
e18093 Background: Nasopharyngeal carcinoma (NPC) is frequently diagnosed at advanced stages in low- and middle-income countries (LMICs), where real-world treatment delivery challenges may further impact outcomes. Long-term outcome data from LMIC settings remain limited. We evaluated clinicopathologic characteristics, treatment patterns, and survival outcomes of NPC patients treated at a tertiary care center over two decades. Methods: This retrospective observational cohort included patients with histologically confirmed NPC diagnosed between January 2006 and December 2025. Demographics, stage, histology, treatment modality, and outcomes were abstracted from institutional records. Treatments included radiotherapy alone, concurrent chemoradiotherapy (CCRT), and systemic therapy, according to disease stage and clinical status. Overall survival (OS) was estimated using Kaplan-Meier methodology, with exploratory analyses by stage and treatment factors. Results: Eighty four patients were included; median age was 45 years, with male predominance (76%). Most patients presented with advanced disease, with 87% diagnosed at stage III–IV, including approximately 18% with metastatic disease at presentation. The predominant histologic subtype was non-keratinizing/undifferentiated carcinoma (>90%). Among non-metastatic patients, CCRT was the primary treatment in nearly 80%, reflecting guideline-concordant care. Median OS for the entire cohort was 23.5 months, with a clear stage-dependent survival gradient. Patients presenting with metastatic disease had poor outcomes despite systemic therapy. Among initially non-metastatic patients, recurrence occurred in approximately one-quarter, with failures predominantly distant rather than local, suggesting effective locoregional control but ongoing risk of systemic relapse. Treatment interruptions and delays, reflective of real-world practice constraints, were frequently observed and were associated with inferior survival. Conclusions: In this large real-world LMIC cohort, most NPC patients presented with advanced disease, and distant metastasis remained the dominant pattern of failure despite effective locoregional therapy. Outcomes were further compromised by treatment delays and interruptions. These findings highlight the need for earlier diagnosis, improved systemic strategies, and strengthened multidisciplinary treatment delivery to improve survival in resource-limited settings.
A multicenter phase II trial of encorafenib, binimetinib, and cetuximab for early relapsed stage II/III <i>BRAF</i> <sup>V600E</sup> -mutated colorectal cancer: TRESBIEN trial (OGSG 2101).
3567 Background: Patients with BRAF V600E -mutated colorectal cancer (CRC) who experience early recurrence during or shortly after adjuvant therapy show an extremely poor prognosis. The efficacy of BRAF-targeted triplet therapy for early relapse remains unclear. Methods: We conducted a prospective, open-label, multicenter, phase II trial evaluating the efficacy and safety of encorafenib, binimetinib and cetuximab in BRAF V600E -mutated CRC patients who relapsed during or within 6 months after completing adjuvant chemotherapy. Patients received encorafenib 300 mg once daily and binimetinib 45 mg twice daily in 28-day cycles, plus intravenous cetuximab 400 mg/m 2 once on day 1 of cycle 1, then 250 mg/m 2 once weekly until disease progression or occurrence of unacceptable adverse events. The primary endpoint was objective response rate (ORR) by blinded independent central review. Secondary endpoints were overall survival (OS), progression-free survival (PFS), disease control rate (DCR), and safety. Sample size was determined based on a threshold ORR of 6.0% and an expected ORR of 26.0% (one-sided α = 0.05, power = 0.90). Results: Between January 2022 and April 2025, 25 patients were enrolled across 14 institutions. Baseline characteristics included: median age 68 years (range, 28–81); female, n = 18 (72.0%); right-sided, n = 18 (72.0%); pStage II/III, n = 2 (8.0%)/23 (92.0%); MSI-H, n = 5 (20.0%); and prior oxaliplatin-based adjuvant chemotherapy, n = 22 (88.0%). Twenty-four patients were evaluable for efficacy. The ORR was 62.5% (95% CI, 40.6–81.2, one-sided P < 0.001), and DCR was 87.5% (95% CI, 67.6–97.3). With median follow-up time of 18.0 months, the median PFS was 7.4 months (95% CI, 4.7–10.6), and the median OS was 33.9 months (95% CI, 11.0–NE). No Grade ≥3 adverse events (≥10%) and treatment-related deaths were observed. Conclusions: The combination of encorafenib, binimetinib, and cetuximab demonstrated favorable efficacy and a manageable safety profile in patients with BRAF V600E -mutated CRC who relapsed early recurrence during or shortly after adjuvant chemotherapy. This triplet regimen can be a promising treatment strategy for this poor prognostic population. Clinical trial information: jRCTs051210152.
Cetuximab in combination with immunotherapy and chemotherapy as preoperative induction therapy for locally advanced HNSCC: A retrospective study.
e18027 Background: The survival of head and neck squamous cell carcinoma (HNSCC) patients has improved with the use of anti-epidermal growth factor receptor (EGFR) therapy and immunotherapy. However, the benefits and safety of preoperative induction therapy with the combination therapy for locally advanced HNSCC (LA-HNSCC) remain unclear. Methods: This is a retrospective analysis of the efficacy and safety of preoperative cetuximab combined with immunotherapy and chemotherapy in patients with LA-HNSCC treated during March 2023 to March 2025. Patients who had no previous drug treatment, received cetuximab + immunotherapy + chemotherapy before surgery were eligible. The primary endpoint was major pathological response (MPR) rate. Secondary endpoints included R0 resection rate, downstage migration rate, disease-free survival rate and safety. Results: 12 patients were included in the analysis (including 3 p16-negative oropharyngeal cancer, and 7 hypopharyngeal cancer). Most patients had stage IVA (3) or stage IVB (7) disease. Ten patients were treatment-naive, and 2 had recurrent disease after prior surgery. The combination drug regimen was cetuximab + PD-1 monoclonal antibody + chemotherapy (mainly taxanes + platinum-based drugs). Drug treatment was administered for 2-5 cycles, with a median of 3 cycles.Efficacy evaluation was performed after the completion of preoperative induction therapy. ORR (overall response rate) was 41.67%, and DCR (disease control rate) was 100%. 11 (91.67%) patients achieved R0 resection. The interval time between the last drug treatment and surgery was 3 to 5 weeks, with a median of 4 weeks. No surgical complications occurred. 1 patient achieved pCR (pathological complete response), and the MPR (major pathological response) rate was 41.67%. 11 patients (91.67%) achieved postoperative downstaging of T and/or N stage.Follow-up continued until December 2025, with a median follow-up duration of 18 months. 4 patients developed disease progression, including 3 local recurrence and 1 distant metastasis. One patient who did not achieve downstaging experienced local recurrence more than a month after surgery and died eight months post-operation;The 6-month DFS (disease-free survival) rate was 91.67%. The incidence of grade ≥3 adverse events (AE) was 58.33%, The most frequent grade≥3 AE was leukopenia，neutropenia and lymphocytes decreased. AEs led to a reduction in the dosage of chemotherapy drugs for one patient and a delay in the treatment time for one patient. There was no treatment discontinuation and deaths due to AEs. Conclusions: In this retrospective study, cetuximab combined with immunotherapy and chemotherapy can achieve a surgical downstaging effect without increasing surgical complications, and show encouraging efficacy and tolerability in the preoperative induction therapy of LA-HNSCC.
Outcomes after unrelated donor allogeneic hematopoietic cell transplantation in age ≥65 using post-transplant cyclophosphamide.
6560 Background: The use of allogeneic hematopoietic cell transplantation (allo-HCT) in older adults has increased with reduced-intensity conditioning and post-transplant cyclophosphamide (PTCy) based GVHD prophylaxis. While PTCy has demonstrated excellent GVHD control across multiple disease types, age-related toxicities and non-relapse mortality remain significant challenges in older patients with acute leukemia and myelodysplastic syndrome (MDS). Understanding age-associated risks in contemporary unrelated donor (URD) HCT platforms may help guide patient selection, counseling, and future refinements in transplant practice. Methods: We analyzed adults undergoing first URD allo-HCT (8/8 or 7/8 HLA-matched) with PTCy-based GVHD prophylaxis for acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome reported to CIBMTR, 2017–2021, using the P-5891 dataset. Patients were grouped into <65 and ≥65 years. Outcomes included overall survival (OS), non-relapse mortality (NRM), relapse, acute GVHD, and chronic GVHD. Univariable and multivariable Cox proportional hazards or Fine-Gray competing risks models were used as appropriate. Variables with p < 0.2 in univariable analysis and clinically relevant factors were included in multivariable models. Results: Of 2,271 patients, 849 (37%) were ≥65 years. Older patients were more frequently treated with reduced-intensity or non-myeloablative conditioning, had a Hematopoietic Cell Transplantation–Comorbidity Index (HCT-CI) ≥3, and had a Karnofsky Performance Status (KPS) <90. On multivariable analysis, age ≥65 was associated with significantly inferior OS (HR 1.20, 95% CI 1.02-1.40, p=0.029), with 3-year OS of 52.1% vs 63.4% (log-rank p<0.001). Other independent predictors of worse OS included reduced-intensity conditioning, higher disease risk index, KPS <90, and HCT-CI ≥3; graft source was not significant. Competing-risk analyses showed significantly higher NRM in ≥65 years (3-year cumulative incidence 22.7% vs 13.6%; HR 1.56, 95% CI 1.21–2.01, p<0.001), which was the primary driver of inferior survival. Importantly, relapse incidence was similar (HR 0.90, p=0.249), and no differences were found in GVHD rates: grade II–IV acute GVHD (HR 0.98, 95% CI 0.81–1.17, p=0.785), grade III-IV acute GVHD (HR 0.91, 95% CI 0.64-1.30, p=0.600), or moderate-to-severe chronic GVHD (HR 0.90, 95% CI 0.68-1.20, p=0.467). Conclusions: In patients undergoing unrelated donor HCT with PTCy-based GVHD prophylaxis for acute leukemia or MDS, those aged ≥65 years had significantly lower overall survival and higher non-relapse mortality compared to younger patients, with similar relapse and GVHD rates. These findings suggest the need to optimize the PTCy-based prophylaxis platform, such as reduced PTCy dosing with the addition of novel agents, in patients with advanced age.
The influence of advanced age on outcomes in patients with diffuse large B-cell lymphoma treated with CAR-T therapy.
7034 Background: Chimeric antigen receptor T-Cell (CAR-T) has emerged as a potentially curative treatment for diffuse large B-Cell lymphoma (DLBCL). The median age at DLBCL diagnosis is 66 years with nearly 30% of patients diagnosed at ≥75 years. Studies have examined outcomes of CAR-T therapy in DLBCL, with elderly patients (≥ 65 years) included in analyses; however, clinical trial populations have underrepresented the true age distribution of the disease. This study evaluates the impact of advanced age on survival and toxicity outcomes in patients with DLBCL treated with CAR-T therapy. Methods: A multicenter retrospective cohort study was conducted using TriNetX, a federated database of over 159 million de-identified electronic health record and claims data. Patients aged ≥75 years with DLBCL treated with CD19-directed CAR-T therapy were compared with a 1:1 propensity score–matched cohort of patients aged 18–65. Propensity score matching was performed based on demographics, comorbidities, and baseline laboratory values. Primary outcomes included 1-year and 3-year overall survival (OS), as well as the development of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and infection within 100 days following CAR-T infusion. Outcomes were assessed using Kaplan–Meier survival analyses, hazard ratios (HR), risk ratios (RR), and 95% confidence intervals (CI). Results: Prior to PSM, there were 326 patients ≥ 75 years and 816 patients aged 18-65 years who were treated with CD-19 directed CAR-T for DLBCL. After PSM, there were 241 patients in each cohort. There was no statistically significant difference in one-year or three-year overall survival between patients ≥ 75 years vs. 18-65 years (1-year HR: 0.89, 95% CI [0.63-1.26]; 3-year HR: 1.00, 95% CI [0.74-1.36]). Interestingly, patients ≥ 75 years were at a lower risk for the development of CRS compared younger patients (RR: 0.84, 95% CI [0.72, 0.98]). There was no statistically significant difference in the risk for development of ICANS (RR: 0.98, 95% CI [0.70–1.38]). Risk of infection at 100 days post-CAR-T infusion was lower in patients ≥ 75 years (RR: 0.75, 95% CI [0.58–0.95]). Conclusions: In this large multicenter real-world analysis, patients aged ≥75 years experienced comparable overall survival and no increased toxicity following CAR-T therapy for DLBCL. These findings suggest that advanced age alone should not preclude CAR-T eligibility and support broader consideration of CAR-T therapy in appropriately selected older adults. Outcome Age ≥75 (n=241) Age 18-65 (n=241) HR/RR [95% CI] 1-year OS 71.6% 68.6% 0.89 [0.63-1.26] 3-year OS 47.3% 53.7% 1.00 [0.74-1.36] CRS 52.3% 62.2% 0.84 [0.72–0.98] ICANS 21.6% 22.0% 0.98 [0.70–1.38] Infection (≤100 days) 30.3% 40.7% 0.75 [0.58–0.95]
ELECTRA: An open-label, multicenter, phase 1b/2 study of elacestrant in combination with abemaciclib in patients with brain metastasis from ER+/HER2− breast cancer.
TPS1155 Background: Endocrine therapy (ET) + cyclin dependent kinase 4/6 inhibitor (CDK4/6i) is the mainstay for the management of ER+/HER2- mBC as 1 st -line therapy. However, tumors eventually develop resistance to ET, leading to disease progression. In the EMERALD phase 3 trial, single-agent elacestrant demonstrated a significantly prolonged progression-free survival (PFS) vs SOC ET ( ESR1 m tumors HR 0.55; 95% CI 0.39-0.77; all pts HR 0.70; 95% CI 0.55-0.88) with a manageable safety profile (Bidard 2022), leading to the first oral SERD approved. In a subgroup analysis in patients with ESR1m tumors who had received prior ET+CDK4/6i ≥12 months, the median PFS for elacestrant was of 8.6 months vs 1.9 months with SOC ET (HR=0.41; 95% CI, 0.26-0.63) [Bardia CCR 2024]. Currently, there are no approved systemic treatments for patients with ER+/HER2- breast cancer who have brain metastasis. ELECTRA (NCT05386108) is an open-label phase 1b/2, multicenter study evaluating elacestrant in combination with abemaciclib. The phase 1b portion of ELECTRA evaluated the combination of elacestrant with abemaciclib in patients with ER+/HER2- mBC regardless of metastatic site and ESR1 status. The recommended phase 2 dose (RP2D) of the combination was determined to be elacestrant 345 mg QD with abemaciclib 150 mg BID (Ibrahim ASCO 2024). The phase 2 portion of ELECTRA is ongoing to further characterize efficacy and safety of this combination in patients with brain metastases from ER+/HER2- breast cancer, as both compounds cross the blood-brain barrier (Conlan, 2020; Tolaney, 2020). Methods: Phase 2 eligibility includes patients with ER+/HER2- locally advanced or metastatic breast cancer and measurable brain metastasis (≥ 1 active and measurable brain metastasis per RECIST v1.1). Patients must have received prior therapy in the metastatic setting, including ≥ 1 endocrine therapy, ≤ 2 chemotherapy regimens, and 0-2 prior CDK4/6i (excluding abemaciclib). The phase 2 primary objective is ORR per RECIST v1.1; secondary objectives include intracranial response rate, DoR, CBR, PFS, OS, PK, and quality of life. The phase 2 portion of ELECTRA is actively recruiting patients worldwide. Clinical trial information: NCT05386108 .
Clonal hematopoiesis-related outcomes associated with radioligand therapy in prostate cancer: A “real-world” analysis.
5045 Background: Radioligand therapy with radium-223 (Rad) and lutetium-177 (Plu) demonstrates notable hematologic toxicities in patients (pts) with prostate cancer (PC), including myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Delivery of ionizing radiation to the bone microenvironment is a known risk factor for accelerating clonal hematopoiesis, although the incidence of clonal cytopenias with these agents is not well characterized. We hypothesized that pts treated with Rad and/or Plu would have higher risk of clonal cytopenia of undetermined significance (CCUS) vs matched controls in the “real-world”. Methods: We performed a retrospective study using de-identified aggregate data from the TriNetX US Research Collaborative Network from January 2010 to December 2025. Adult males with PC who received ≥1 administration of Plu and/or Rad were included; pts with prior myeloid malignancy were excluded. Primary outcomes were incidence of CCUS and MDS. Propensity score matching (PSM) was performed based on age, race, prior diagnosis of leukopenia, anemia, thrombocytopenia, or pancytopenia. Risk ratios (RR) with 95% confidence intervals (CI) were calculated. Results: We identified 2,569 pts treated with Plu alone and 2,007 treated with Rad alone and compared them with pts with advanced PC without exposure to either agent (unexposed control) (Table 1). After PSM, the incident risk of CCUS was greater in Rad-exposed pts (RR 2.62, 95% CI 1.45 – 4.73, p < 0.001) while Plu was not associated with a significant increase in CCUS or MDS. Direct comparison after PSM (n=1,433) demonstrated lower risk of pancytopenia (RR 0.46, 95% CI 0.37 – 0.56, p <0.001) and CCUS (RR 0.41, 95% CI 0.20 – 0.81, p =0.008) in Plu vs Rad. In unadjusted analysis, pts receiving both Plu and Rad had increased incidence of CCUS vs Plu alone (RR= 3.64, 95% CI 1.87 - 7.07, p <0.001) and higher risk of MDS vs either agent alone. Conclusions: This “real-world” analysis demonstrates that compared with unexposed controls, Rad – but not Plu – is associated with an increased risk of CCUS. Treatment with Plu and Rad portends a higher risk of CCUS than Plu alone, as well higher risk of MDS than either drug alone. Study limitations include its retrospective nature, missing/ unknown data (e.g. bone marrow and mutation analysis), and potential selection and confounding biases. As treatment sequencing evolves for pts with metastatic PC, further evaluation of clonal hematopoiesis, MDS/AML with adequate sample size and follow up in this population is warranted. ¹⁷⁷Lu-PSMA-617 Exposed(n = 2,569) Unexposed(n =2,569 ) Risk Ratio (95% CI) p -value CCUS 1.03% (26) 0.67% (17) 1.54 (0.84 – 2.82) 0.16 MDS 0.94% (24) 0.55% (14) 1.72 (0.89 – 3.32) 0.10 Radium-223 Exposed(n = 2,007) Unexposed(n = 2,007) Risk Ratio (95% CI) p -value CCUS 1.97% (39) 0.75 (15) 2.62 (1.45 – 4.73) <0.001 MDS 0.85% (17) 0.75% (15) 1.13 (0.57 – 2.26) 0.72
New-onset inflammatory bowel disease associated with immune checkpoint inhibitor therapy: A real-world multicenter analysis.
11141 Background: Immune checkpoint inhibitors (ICIs) are increasingly used across a broad range of malignancies and are known to cause immune-mediated gastrointestinal toxicity. While acute colitis is a recognized adverse effect, the potential for ICIs to trigger de novo inflammatory bowel disease (IBD), a chronic immune-mediated condition with long-term treatment implications, has not been well studied, as ICIs enhance immune activation in ways that may also affect normal intestinal immune balance. With the expanding use of ICIs across cancer types and earlier lines of therapy, we examined the association between ICI exposure and the risk of developing incident IBD compared with chemotherapy. Methods: We conducted a retrospective cohort study using the TriNetX global federated research network, including adults (≥18 years) diagnosed with malignancy between 2020 and 2024. Patients with pre-existing Crohn’s disease, ulcerative colitis, or prior IBD-directed biologic or targeted therapy were excluded. Two cohorts were defined: patients treated with PD-1/PD-L1 or CTLA-4 inhibitors and patients treated with chemotherapy without ICI exposure. Propensity score matching (1:1) was performed to balance demographics, cancer type, and comorbidities, yielding 63,190 patients per cohort. Outcomes assessed within 365 days included incident IBD diagnoses, initiation of first-line IBD therapies, and escalation to biologic or targeted IBD agents. Risk estimates, hazard ratios (HRs), and Kaplan–Meier analyses were performed. Results: After propensity score matching, baseline characteristics were well balanced between cohorts. The risk of developing incident IBD was significantly higher among ICI-treated patients compared with chemotherapy-treated patients (risk ratio [RR] 2.96, 95% CI 1.86–4.70). Time-to-event analysis demonstrated a significantly increased hazard of IBD following ICI exposure (HR 3.37, 95% CI 2.12–5.35; log-rank p < 0.001). Escalation to biologic or targeted IBD therapies was also more common in the ICI cohort (RR, 3.04; 95% CI, 1.90–4.87; HR, 3.46; 95% CI, 2.16–5.55). In contrast, initiation of first-line therapies (mesalamine or budesonide) did not differ significantly between groups (RR 0.97, 95% CI 0.93–1.01). Conclusions: Among cancer patients without pre-existing IBD, immune checkpoint inhibitor therapy was associated with a significantly increased risk of de novo IBD and a greater likelihood of requiring advanced IBD therapies compared with chemotherapy alone. These findings suggest that, in a subset of patients, immune checkpoint inhibition may be associated with the development of chronic intestinal immune disease, highlighting the need for increased awareness and longitudinal gastrointestinal monitoring as ICI use continues to expand.
Chronic condition cost burden among older Medicare cancer patients.
e23164 Background: With the rising comorbidity burden among cancer patients of older age, understanding the prevalence and added costs of chronic conditions within Medicare’s oncology population is required for value-based care management. Methods: We examined episode costs across seven cancer types using deidentified baseline episode files from Medicare’s Enhanced Oncology Model (EOM) (2016-2020). We first analyzed the prevalence of four common chronic conditions: morbid obesity, hypertension, endocrine disorders, and heart disease based on Hierarchical Condition Category for each cancer. Then we calculated trended winsorized standardized mean patient cost per episode for patients with these chronic conditions and compared with those without any of the four comorbidities as a reference group. Results: Hypertension has the highest prevalence of ~60%, followed by endocrine disorders (> 40%), heart disease (> 28%), and morbid obesity (~5%). Across all cancer types, patients with morbid obesity demonstrated the highest cost burden. Specifically the incremental costs ranged from $3,640 for small intestine/colorectal cancer to $8,194 for lymphoma, increasing 10–15% above the reference group. Heart disease is associated with a $4,600 increase in average cost for chronic leukemia, with a smaller increase seen in myeloma, but no meaningful impact in the other cancers. Prostate cancer patients with any of the four conditions had appreciably higher costs than their reference counterparts. Conclusions: Multiple chronic conditions in cancer patients increase the cost and complexity of oncology care. Specifically, addressing morbid obesity through prevention and tailored management may help reduce costs. Weight management and proactive management of comorbidities, along with integrated care models, may be essential to control costs and enhance outcomes in oncology. Prevalence (%) and patient trended winsorized standardized mean cost by cancer type. Referencegroup Hypertension Heart Disease Endocrine disorder Morbid Obesity Breast Cancer $48,355 (27.5) $47,068 (55.0) $49,358 (28.6) $48,142 (45.6) $54,590 (6.1) Chronic Leukemia $57,853 (18.2) $57,846 (62.3) $62,496 (43.1) $58,865 (49.9) $63,963 (5.6) Lung Cancer $64,667 (20.4) $64,932 (64.0) $64,363 (45.0) $65,353 (48.2) $69,926 (3.9) Lymphoma $55,386 (19.6) $55,337 (60.7) $56,929 (40.4) $56,204 (51.6) $63,580 (4.5) Multiple Myeloma $89,861 (19.4) $86,964 (61.9) $88,560 (40.8) $87,147 (49.5) $95,460 (4.9) Prostate Cancer $46,357 (19.5) $49,019 (65.9) $52,084 (42.7) $50,132 (42.4) $52,794 (4.3) Small Intestine / Colorectal Cancer $38,952 (27.6) $38,330 (59.2) $39,060 (33.6) $38,695 (42.0) $42,592 (5.5)
Hematologic and cardiovascular outcomes of SGLT2 inhibitors in patients with chronic lymphocytic leukemia and type 2 diabetes: A real-world TriNetX analysis.
7050 Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) exhibit biologically plausible metabolic and immunomodulatory effects beyond glycemic control that may be relevant in chronic lymphocytic leukemia (CLL), by reducing insulin resistance, activating AMPK signaling, suppressing downstream PI3K/AKT/mTOR activity, and improving cellular metabolic homeostasis. SGLT2i also decrease systemic and adipose-derived inflammation by inhibiting the NLRP3 inflammasome, reducing IL-6 and TNF-α levels, and mitigating oxidative stress. Improved mitochondrial efficiency and modulation of HIF-1α signaling may influence leukemic cell survival and immune exhaustion, suggesting a plausible role for SGLT2i in reducing infection risk, cardiovascular events, and survival outcomes in patients with CLL. However, real-world clinical evidence remains limited. Methods: We conducted a retrospective cohort study using the TriNetX Analytics Network to evaluate outcomes associated with SGLT-2i use in adults with CLL and type 2 diabetes mellitus. SGLT-2-exposed and non-exposed cohorts were compared for infectious complications, hematological outcomes like cytopenias, cardiovascular (CV), and all-cause mortality. Propensity score matching minimized confounding due to contemporary CLL therapies, baseline demographics, comorbidities, and treatment-related outcomes. Time-to-event outcomes were analyzed using Kaplan-Meier and Cox models. Results: After propensity score matching, with comparable mean short and long term follow durations (60-821 days), SGLT2 inhibitor use was associated with a significantly lower risk of pneumonia (5.4% vs 8.0%; HR 0.70, 95% CI 0.56-0.89) and CV mortality (13.9%, vs 21.9%) with improved survival on KM analysis (p<0.001; HR-0.70, 95% CI 0.59-0.83). A modest reduction in sepsis was observed in SGLT2i users (4.7% vs 6.0%), but did not reach statistical significance (HR 0.82, 95% CI 0.65-1.05). All-cause mortality was numerically lower in the SGLT2 cohort (7.4% vs 8.5%), but no significant difference in survival was observed (HR 0.91, 95% CI 0.76-1.10). The SGLT2i group showed lower thrombocytopenia risk and a similar rare risk of AIHA between the two cohorts, with no significant difference in time-to-event analysis, suggesting that SGLT2 inhibitors may preferentially reduce selective infectious complications and CV mortality without significant improvement in overall mortality. Conclusions: SGLTI might have biologically plausible cardioprotective, metabolic, and immunomodulatory effects that may improve outcomes related to inflammation and infection, and reduce CV mortality in CLL, without a demonstrable short-term overall mortality benefit. Longer follow-up and prospective studies are needed to define the durability of these effects and their impact on survival.
PD-1 inhibition with camrelizumab in cervical cancer: A systematic review and meta-analysis.
e17515 Background: Cervical cancer is the fourth leading cause of cancer mortality in women worldwide. PD-L1 is expressed in 34.4-96% of cervical cancers. Camrelizumab is a high-affinity humanized anti-PD-1 IgG4 antibody with anti-tumour activity. This study systematically evaluates the pooled efficacy and safety of Camrelizumab in cervical cancer. Methods: A literature search was performed across PubMed, Embase, Web of Science, the Cochrane Library, Ovid MEDLINE, and Scopus. Randomized controlled trials, single-arm trials, prospective or retrospective cohort studies, and case-control studies with pathologically confirmed cervical cancer patients treated with Camrelizumab as monotherapy or in combination with chemotherapy or VEGFR-TKIs (Apatinib or Famitinib) were included. Statistical analyses were performed using R (version 4.4.1) with pooled proportions and corresponding 95% confidence intervals (CI) calculated for each outcome. Statistical heterogeneity was assessed using the I² statistic. A sensitivity analysis was conducted using a leave-one-out approach and combined results were presented using forest and funnel plots. Results: The meta-analysis included nine studies comprising 427 patients evaluating the efficacy of Camrelizumab either used as monotherapy, with chemotherapy, or with VEGFR-TKIs (Apatinib or Famitinib) in cervical cancer. Given the predominance of single-arm studies and high heterogeneity among them, random-effects models were applied throughout. 52 patients achieved complete response (CR) with a pooled CR rate of 0.14 (95% CI 0.09-0.22). Disease control rate (DCR) was assessed in eight studies including 342 patients with a proportion of 0.81 (95% CI 0.64-0.91). The proportion of objective response rate (ORR) was 0.60 (95% CI 0.36-0.80). Progressive disease (PD) outcomes were reported in a cohort of 342 patients corresponding to a proportion of 0.16 (95% CI 0.07-0.31). The pooled partial response (PR) rate was 0.46 (95% CI 0.32-0.60). 103 of 342 patients achieved stable disease (SD), resulting in a proportion of 0.30 (95% CI 0.21-0.41). 7 studies reported grade ≥3 adverse events and 2 reported treatment-related deaths. Commonly reported adverse events included neutropenia, anaemia, leukopenia, hypertension, lymphopenia, and myelosuppression. Conclusions: This systematic review and meta-analysis indicates that PD-1 inhibition with Camrelizumab demonstrates clinically meaningful antitumor activity in cervical cancer, both as monotherapy and in combination regimens, addressing a disease with limited effective therapeutic options. The consistency of efficacy signals across diverse study designs supports Camrelizumab as an active immunotherapeutic approach in this setting.
Is the investment in metastatic breast cancer research sufficient and aligned with patient priorities?
e13099 Background: To inform strategic investment in metastatic breast cancer (MBC) research, it is essential to understand how funding is distributed across key scientific and patient-identified priority areas and to identify gaps where additional investment is needed. The MBC Alliance has shown that funding of research specifically devoted to metastasis (mets) has grown from 7-13% of all BC funding from 2014-2020. Here, we evaluate trends in the number of funded projects and total funding dollars supporting topics prioritized by people living with MBC. Methods: A collaborative effort between funders and patient advocates was undertaken to analyze topics in MBC research projects funded from 2014-2020. Individuals living with MBC were surveyed to prioritize topics of interest. Grant data were aggregated from the International Cancer Research Partnership database, the Health Research Alliance database, and MBCA member organizations, representing awards from 83 government and nonprofit funders worldwide. Relevant projects were identified from the database of 7,251 total projects either by research domains or by a predetermined set of keywords; then reviewed and confirmed manually. Results: Topics of highest priority included tumor microenvironment, quality of life (QOL), brain and leptomeningeal mets, treatment of rare MBC types (including triple-negative, inflammatory, and lobular), and pregnancy. Analysis of projects funded indicate variation in both the number of projects and total funding across priority topics. Tumor microenvironment comprised 33% of MBC projects. There were statistically significant increases in preclinical research in the topic areas of detection, diagnosis and prognosis, and in both development and clinical testing of systemic therapies. Brain and leptomeningeal mets comprised 6.8% of all MBC projects, and treatment of rare subtypes comprised 2.5%. QOL comprised 1.5% of all projects with 72% of those related to investigating the physical effects of diagnosis and treatment. Pregnancy was the smallest topic investigated, comprising only 0.25% of all projects, and these were mostly related to investigating the underlying biology (14/18). Conclusions: Of the total number of research projects related to MBC, 44% were in areas of greatest interest to people living with the disease. Continued collaboration between funders and scientists engaging with patient advocates is critical for translating these insights into targeted investment strategies. Despite recent growth in MBC research funding, the proportion of BC research dollars dedicated to MBC is still insufficient. Given the potential impact of disruptions to research funding, we remain concerned about the future of MBC research specifically, and the stability of the broader cancer research landscape.
Neoadjuvant treatment of QL1706 in patients with resectable microsatellite instability-high/mismatch repair-deficient colon cancer: Results from a phase 1b trial.
3620 Background: Immune checkpoint inhibitors in neoadjuvant setting have brought clinical benefits for patients with various tumors. This study aimed to evaluate the efficacy and safety of iparomlimab and tuvonralimab (QL1706), a bifunctional antibody targeting both PD-1 and CTLA-4, as neoadjuvant treatment in patients with microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) colon cancer. Methods: In this single-arm phase 1b trial, previously untreated patients with resectable stage IIb-III MSI-H/dMMR colon cancer were recruited. Patients were administered neoadjuvant treatment of QL1706 at 5 mg/kg via intravenous infusion every three weeks for four cycles. Radical resection was scheduled between 4 and 6 weeks after last dose of neoadjuvant treatment. The primary endpoint was pathological complete response (pCR) rate. The efficacy analysis set included patients who were confirmed dMMR/MSI-H, received at least one dose of treatment, and had post-surgery pathological results. The safety analysis set included patients who received at least one dose of treatment. Results: As of data cut-off date on Oct 15, 2025, 43 patients were enrolled (median age: 56.0 years; males: 58.1%; ECOG PS 1: 55.8%; Lynch syndrome: 34.9%). Scheduled radical resection were performed in 34 patients. A total of 34 patients were included in the efficacy analysis set. The pCR rate was 88.2% (30/34, 95% confidence interval [CI]: 72.5%-96.7%). The major pathologic response rate was 91.2% (31/34, 95% CI: 76.3%-98.1%). In high-risk patients (T4 or N2), the pCR rate was 86.4% (19/22, 95% CI: 65.1%-97.1%). All patients (100%) received surgery had R0 resection. Median treatment exposure was 2.1 months (range, 0.0-3.9). Treatment-emergent adverse events (TEAEs) of grade ≥3 occurred in 12 patients (27.9%); two (4.7%) patients were treatment-related. Immune-related adverse events grade ≥3 occurred in two (4.7%) patients, including one grade 3 acute kidney injury and one grade 4 hypersensitivity, both of which recovered finally. Treatment-related serious adverse events occurred in three (7.0%) patients. No patient cancelled or delayed the surgery due to TEAE. No TEAE leading to death occurred. The incidence of grade ≥3 TEAE during the surgery phase was 11.8% (4/34). Conclusions: Neoadjuvant treatment of QL1706 showed promising pCR rate and manageable safety in patients with MSI-H/dMMR colon cancer. A phase 3 trial is ongoing to further confirm the efficacy and safety of QL1706 as neoadjuvant treatment in patients with resectable MSI-H/dMMR colon cancer. Clinical trial information: NCT06686576 .
The efficacy and safety of postoperative adjuvant donafenib therapy for patients with high-risk recurrence hepatocellular carcinoma after radical resection: A multicenter retrospective study in China.
e16274 Background: Hepatectomy is a crucial treatment for long-term survival in patients with HCC; however, the high recurrence rate impacts prognosis. Currently, there is no standard adjuvant therapy for this patient population. This study investigates efficacy and safety of Donafenib as postoperative adjuvant therapy for patients with a high risk of recurrence after radical resection of HCC. Methods: We analyzed clinicopathological data of HCC patients with a high risk of recurrence after radical resection, recruited from 7 medical centers between January 2021 and October 2024. High risk was defined by tumor diameter > 5 cm; multiple lesions; microvascular invasion (MVI) grade 1 or 2; lesions complicated by tumor thrombus (TT); and alpha-fetoprotein (AFP)≥200 μg/L. Patients with Donafenib Group received Donafenib monotherapy (D) or combination regimens (D+TACE-DT, D+ICI-DI) as adjuvant therapy, and Control Group underwent observation. We examined recurrence-free survival (RFS), overall survival (OS), and safety according to CTCAE 5.0. Results: 394 HCC patients were included, with a median age of 59 years at the data cut-off in August 2025. The median follow-up time is 22.9 months (IQR 14.3 -32.6) in Donafenib Group and 39.1 months (IQR 24.0-45.8) in Control Group. The Donafenib Group contains 219 patients (101 D, 85 DT and 33 DI) and Control Group 175 patients. The general cohort comprised 82.0% males, 77.9% with HBV infection, 91.6% with Child-Pugh A, 86.2% with ECOG PS 0. 50.5% had multiple high-risk factors, 47.7% had tumors > 5 cm, 26.6% multiple lesions, 58.4% MVI grade 1 or 2, 7.4% TT, and 36.0% AFP≥200 μg/L. The median RFS was prolonged in Donafenib Group compared with Control Group (38.6 months vs. 20.4 months; HR, 0.592; 95% CI: 0.442–0.792; p = 0.0004). The RFS rates at 2 and 3 years were 62.0% (54.4–68.7) and 56.9% (47.8–65.0) in Donafenib Group, 46.7% (39.1–53.9) and 36.8% (29.6–44.1) in Control Group. The OS was improved in Donafenib Group (HR, 0.531; 0.324–0.870; p = 0.0108). The OS rates at 2 and 3 years were 89.0% (83.4–92.8) and 88.1% (82.1–92.2) in Donafenib Group, 79.3% (72.4–84.7) and 71.7% (64.1–77.9) in Control Group, respectively. Multivariate analysis identified MVI and China liver cancer stage IIIA as independent risk factors for RFS. Postoperative adjuvant Donafenib was an independent protective factor for RFS (HR, 0.513; p < 0.0001) and OS (HR, 0.523; p = 0.0113). 91 patients (41.6%) experienced treatment-related adverse events (TRAE) of any grade, grade 3 TRAE 4.6% concluding with rash (3.2%), hand-foot syndrome (0.9%) and thrombocytopenia (0.5%); no patients experienced grade 4 or 5 TRAE. Conclusions: Postoperative adjuvant Donafenib was associated with prolonged RFS and OS in HCC patients with high risk of recurrence following radical resection, with a manageable safety profile.
First-in-human phase I study of HSK41959, an MTA-cooperative PRMT5 inhibitor, in patients with <i>MTAP</i> -deleted advanced solid tumors.
e15097 Background: PRMT5 is an essential epigenetic regulator that drives cell proliferation. MTAP deletion, occurring in 10–15% of solid tumors, causes methylthioadenosine (MTA) accumulation and creates a synthetic-lethal vulnerability to PRMT5 inhibition. HSK41959 is an oral, MTA-cooperative PRMT5 inhibitor that can selectively inhibit the growth of MTAP-deleted tumor cells while preserving PRMT5 function in normal cells. Here, we report preliminary results from a phase I study of HSK41959 in patients with MTAP-deleted advanced solid tumors. Methods: This multicenter, open-label, two-part study enrolled adult patients with MTAP-deleted advanced solid tumors. In the dose-escalation (Part 1), HSK41959 was administered orally once daily at doses ranging from 50 to 800 mg in 21-day cycles. Part 2 was cohort expansion. The primary objectives were to determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of HSK41959. Secondary objectives included safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary antitumor activity. Results: As of December 26, 2025, 19 patients had received HSK41959 at five dose levels (50, 100, 200, 400, 800 mg/day). No dose-limiting toxicities were observed. Treatment-related adverse events (TRAEs) occurred in 72.2% of patients; the most common were anemia (27.8%), nausea (22.2%) and diarrhea (22.2%). The majority of TRAEs were grade 1. No treatment-related serious adverse events, discontinuations, or deaths were observed. Among 11 efficacy evaluable patients, the objective response rate was 27.3%, and the disease control rate was 81.8%. Three patients with non-small cell lung cancer achieved partial responses and two had stable disease with tumor shrinkage. This trial is ongoing. Conclusions: HSK41959 is well tolerated without unexpected safety issues. Preliminary efficacy data demonstrate favorable activity of HSK41959 in patients with MTAP-deleted solid tumors. Clinical trial information: NCT06968572 .
Early inpatient radiation for central nervous system (CNS) tumors: Timing, predictors, and in-hospital outcomes.
e14036 Background: Initiating radiation therapy (RT) early during acute CNS tumor admissions may mitigate complications. We examined whether RT within 48 hours of admission is associated with different in-hospital outcomes than later RT, and explored patient and hospital factors linked to early RT. Methods: Using the Nationwide Inpatient Sample (2016–2020), we identified 332,100 CNS tumor hospitalizations and classified encounters by RT timing: ≤48 hours (n=3,495; 1.1%) versus >48 hours (n=328,605; 98.9%). Categorical outcomes were compared with Pearson chi square tests; continuous measures with t-tests. A multivariable logistic regression modeled predictors of receiving early RT, reporting adjusted odds ratios (OR) with 95% confidence intervals (CI). Results: Compared with the later group, early RT was associated with lower in-hospital mortality (1.7% vs 3.5%, p<0.001), lower need for mechanical ventilation (1.4% vs 5.3%, p<0.001) vasopressors (0.3% vs 0.8%, p=0.001), and lower rates of acute kidney injury (4.7% vs 6.3%, p<0.001), sepsis (2.3% vs 5.4%, p<0.001), hemorrhage (6.0% vs 9.3%, p<0.001), organ failure (15.0% vs 23.9%, p<0.001), and major adverse cardiac events (4.3% vs 7.3%, p<0.001). Palliative care consultation (5.2% vs 11.1%, p<0.001) and DNR orders (8.6% vs 13.5%, p<0.001) were less common with early RT. Seizures (20.7% vs 24.4%, p<0.001) and acute hydrocephalus (3.4% vs 5.2%, p<0.001) were less common with early RT. Patients receiving early RT were younger (49.81±23.10 vs 50.63±23.68 years, p=0.041), had similar comorbidity burden (Charlson Comorbidity Index 4.801±2.645 vs 4.790±2.578, p=0.796), longer length of stay (7.37±13.32 vs 6.84±9.39 days, p=0.018), and higher total charges ($143,869±281,692 vs $100,646±143,754, p<0.001). In multivariable modeling of predictors of receiving early RT, early RT had lower odds of ventilation (OR 0.287, 0.203–0.406, p<0.001), vasopressor use (OR 0.387, 0.209–0.719, p=0.003), sepsis (OR 0.455, 0.349–0.594, p<0.001), hemorrhage (OR 0.722, 0.613–0.850, p<0.001), organ failure (OR 0.663, 0.569–0.772, p<0.001), MACE (OR 0.746, 0.611–0.911, p=0.004), acute hydrocephalus (OR 0.565, 0.456–0.699, p<0.001), seizures (OR 0.843, 0.754–0.944, p=0.004), and brain surgery (OR 0.812, 0.740–0.891, p<0.001). In contrast, frailty/malnutrition/sarcopenia emerged as a significant positive predictor of early RT (OR 1.306, 1.156–1.477, p<0.001), indicating that patients flagged as frail were more likely to receive radiation within the first 48 hours despite overall markers of acuity tending to delay treatment. Conclusions: Early RT patients experienced significantly lower mortality and markedly reduced rates of critical complications. These findings indicate that delivering RT within 48 hours confers a substantial protective effect and supports efforts to expedite radiation initiation for hospitalized CNS tumor patients.
Correlates of patient enrollment in a population-based randomized controlled trial of cascade genetic testing in families with hereditary cancer susceptibility.
10528 Background: Clinical trials that enroll patients through virtual approaches are growing but there is little information about the impact on access. The Genetic Information and Family Testing (GIFT) study was a population-based cluster RCT that evaluated an online platform that delivered cancer genetic education and home germline testing to families with hereditary cancer susceptibility. We examined correlates of patient enrollment to address potential barriers to trial access. Methods: We identified a random sample of adult patients with any cancer type diagnosed in Georgia or California in 2018-19 who linked to a pathogenic variant (PV) in a cancer susceptibility gene through a SEER-based data infrastructure. We initiated a mailed survey four years after diagnosis. We invited all respondents who recalled a PV on testing to enroll online in GIFT. Enrolled patients could invite their first- and second-degree relatives to enroll through the online platform. The primary endpoint was the proportion of relatives who received testing through the platform. We examined clinical and sociodemographic correlates of patient enrollment. Results: 4,300 patients were selected and 2,285 completed the survey (53.1%); 2,006 of 2,285 respondents were eligible and invited to GIFT (87.8) and 412 enrolled (20.5). The Table shows clinical and sociodemographic correlates of patient enrollment for the 1,994 with complete data. There were no substantial differences in enrollment by PV grouping, cancer type, sex, or race/ethnic groups. Enrollment was lower in older patients, those with lower education levels, and those living in census tracts with higher poverty levels. Conclusions: GIFT successfully enrolled a diverse patient population through a virtual approach. Moderate sociodemographic gradients observed in GIFT motivate strategies to ensure access to clinical trials that use virtual approaches to patient enrollment. Trial Registration: NCT05552664 at clinicaltrials.gov. Patients Enrolled n % p Gene Type with PV 0.601 BRCA1/2 or other breast cancer-related 1,650 22 Lynch Syndrome or other gastrointestinal (GI)-related 225 23 Cancer type 0.702 GI 145 20 Ovary/uterine 86 23 Female breast 1,234 22 Prostate 72 24 Other 407 19 Sex 0.594 Male 222 20 Female 1,722 22 Age <.001 <45 501 27 45-64 1,025 22 65+ 414 15 Education <.001 HS or less 311 12 Some college 531 22 College graduate 527 25 Graduate degree 499 26 Race/Ethnicity 0.379 Non-Hispanic White 1,270 22 Black 180 25 Asian 164 19 Hispanic 345 19 Census Tract Poverty 0.204 >19% 145 19 10-19% 401 19 <10% 1,398 23
A phase Ib/IIa study of BAT8010+BAT1006, an anti-HER2 monoclonal antibody-exatecan conjugate combined with an ADCC-enhanced HER2 mAb in patients with advanced solid tumors: Results from the 1L HER2-positive breast cancer cohort.
1046 Background: BAT8010 is an ADC targeting HER2, while BAT1006 is a humanized monoclonal antibody targeting another epitope of HER2, with ADCC enhancement activity via completely devoid of fucose. Expansion cohort of 1st-line HER2-positive breast cancer (BC) patients enrolled, treated with BAT8010 + BAT1006. Methods: Patients in this open-label, multicenter clinical trial received BAT8010 + BAT1006 on day 1 of a 21-day cycle until intolerable or disease progression occurred. The study objectives included assessing tolerability, safety, pharmacokinetic characteristics, immunogenicity, and preliminary efficacy. Results: As of January 9, 2026, 46 HER2-positive BC patients were enrolled, and received BAT8010 2.4 mg/kg in combination with BAT1006 15 mg/kg. Favorable efficacy was observed with a manageable and predictable safety profile; dose optimization is ongoing in the BAT8010 2.1 mg/kg in combination with BAT1006 15 mg/kg dose cohort. Safety: Among the 46 patients who received at least one dose of BAT8010 in combination with BAT1006, at least one treatment-emergent adverse event (TEAE) was reported in 41/46 (89.1%) patients. The most common TEAEs (≥30%) were neutropenia, leukopenia, anemia, infusion-related reaction (IRR), thrombocytopenia, elevated alanine aminotransferase and diarrhea. Most TEAEs were Grade 1/2; however, Grade 3 or higher AEs were reported in 67.4% of patients, including neutropenia (27/46, 58.3%), leukopenia (16/46, 34.8%), and anemia (7/46, 15.2%). No cases of interstitial lung disease (ILD)/pneumonitis were reported. Efficacy: Among 46 patients with at least one tumor assessment, 1 patient achieved CR, 34 PR, and 11 SD, yielding an ORR of 76% (35/46) and a DCR of 100% (46/46); mPFS: not yet mature. Conclusions: BAT8010 in combination with BAT1006 is well-tolerated with manageable toxicity, and demonstrates promising preliminary antitumor activity in HER2-positive BC. Dose expansion studies in this patient population are ongoing, and further confirmatory clinical trials are planned to initiate for the additional validation of its safety and efficacy. Clinical trial information: NCT06376136 .
Real-world treatment patterns and outcomes among patients with high-risk and very high-risk non-metastatic prostate cancer.
e17120 Background: Patients with high-risk (HiR) and very high-risk (VHiR) non-metastatic prostate cancer (nmPC) are at increased risk of biochemical recurrence (BCR), distant metastasis, and death. Real-world (rw) data on treatment patterns, including androgen receptor pathway inhibitors (ARPI) use, and long-term outcomes of patients with nmPC remain limited. We assessed treatment patterns and outcomes among patients with HiR and VHiR nmPC. Methods: This retrospective cohort study included patients from the EHR-derived, deidentified Flatiron Health Research Database, which included 384,351 patients with PC. Patients diagnosed with nmPC between January 1, 2011, and November 30, 2025, were classified as HiR if they met ≥1 criterion: Gleason score (GS) ≥8, grade group (GG) 4-5, prostate-specific antigen (PSA) ≥20 ng/mL, or clinical (c)T3-T4 or VHiR if they met ≥2 criteria: GS ≥8, GG 4-5, PSA ≥40 ng/mL, or cT3-T4. Patients with cN1 or distant metastasis within 90 days of diagnosis were excluded. rw time to BCR (rwTTBCR), rw metastasis-free survival (rwMFS), and rw overall survival (rwOS) were estimated using Kaplan-Meier and Cox proportional hazards models adjusted for age and race. Results: A total of 63,045 patients met criteria (median [IQR] age, 70 [64-75] years). 89.5% were HiR and 10.5% were VHiR. Baseline demographic characteristics and ADT use were similar across risk groups. However, radiation therapy (RT) use was higher in the VHiR group (78.4% v 67.6%), while surgery was more common in HiR (41.5% v 27.6%). Within 6 months of radical prostatectomy (RP) or RT initiation, 2.6% of patients received an ARPI (VHiR, 6.2%; HiR, 2.2%). Overall, 23.6% of patients developed BCR, with similar rates across risk groups (VHiR, 23.4%; HiR, 23.6%). Among patients with BCR, 51.8% received an ARPI after BCR and prior to distant metastasis (VHiR, 64.2%; HiR, 50.4%). Outcomes for the overall cohort and by risk group are presented below (Table). In adjusted Cox models, VHiR disease was associated with shorter rwTTBCR (HR, 1.28; 95% CI, 1.22-1.34; P < .001), shorter rwMFS (HR, 1.32; 95% CI, 1.27-1.37; P < .001), and worse survival (HR, 1.35; 95% CI, 1.29-1.42; P < .001). Conclusions: This large rw cohort observed worse clinical outcomes in patients with VHiR compared with HiR. ARPI use in the localized setting remains low, with increasing use post-BCR, particularly in patients with VHiR disease. As ARPIs continue to be approved in the nmPC setting, future research should examine rw outcomes among patients receiving ARPI to improve treatment strategies for patients with nmPC at highest risk of progression. rw Outcomes overall and by risk group Overall VHiR HiR rwTTBCR, mo (95% CI) 79.0 (77.7-80.4) 64.8 (61.3-67.5) 80.7 (79.4-82.5) rwMFS, mo (95% CI) 74.8 (73.9-75.8) 60.9 (59.1-62.8) 76.5 (75.6-77.5) rwOS, mo (95% CI) 124.0 (122.5-125.6) 105.4 (101.7-109.9) 126.1 (124.1-127.9)
Temporal trends and disparities in liver cancer incidence in the United States, 1999–2022: A Joinpoint regression analysis.
e16307 Background: Liver cancer incidence has changed substantially in the United States over the past two decades, with notable variation across demographic subgroups. A detailed evaluation of long-term trends and population disparities is essential to characterize the evolving burden of disease. Methods: Liver cancer incidence data from 1999 to 2022 were obtained from the CDC WONDER database. Age-adjusted incidence rates were calculated per 100,000 population using the 2000 U.S. standard population. Analyses were stratified by sex, age group (< 40, 40–74, > 70 years race and ethnicity (Non-Hispanic White, NH Black's, NH Asian or Pacific Islander, NH American Indian or Alaska Native, and Hispanic). Joinpoint regression was used to estimate annual percent change (APC) and average annual percent change (AAPC) with 95% confidence intervals (CIs). Results: A total of 545,380 incident liver cancer cases were identified in the United States and Puerto Rico. Incidence increased from 4.06 in 1999 to 6.39 in 2022. Two joinpoints were identified, with incidence rising from 1999–2008 (APC 4.94%, 95% CI 4.35%–6.25%), increasing more modestly from 2008–2015 (APC 2.64%, 95% CI 1.39%–3.42%), and declining from 2015–2022 (APC −2.05%, 95% CI −2.88% to −1.39%). Overall, the AAPC was 2.07% (95% CI 1.88%–2.31%). Incidence remained higher in males than females. Among females, rates increased from 2.23 to 3.26 (AAPC 1.81%, 95% CI 1.61%–2.03%), while among males, rates rose from 6.30 to 9.96 (AAPC 1.97%, 95% CI 1.77%–2.19%). Incidence changed minimally among individuals < 40 years (AAPC 0.83%, 95% CI 0.44%–1.24%), increased most steeply among those aged 40–74 years (AAPC 3.22%, 95% CI 3.02%–3.47%), and was highest among adults > 70 years (AAPC 2.11%, 95% CI 1.79%–2.52%). Incidence increased among American Indian or Alaska Native, White, Black, and Hispanic populations, while declining among Asian or Pacific Islander individuals (AAPC −2.03%, 95% CI −2.32% to −1.68%). Conclusions: Liver cancer incidence in the United States increased substantially from 1999 through the mid-2010s, followed by a recent decline. The steepest increases occurred among adults aged 40–74 years, while Asian or Pacific Islander populations experienced sustained reductions. Persistent sex-, age-, race-, and ethnicity-based disparities highlight the need for targeted prevention, early detection, and risk-factor mitigation strategies.