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Conditional survival by primary extranodal site in diffuse large B-cell lymphoma: A population-based landmark analysis.

7071 Background: Diffuse large B-cell lymphoma (DLBCL) frequently presents with extranodal involvement. Prior population-based studies report site-specific survival differences from diagnosis, but these estimates are influenced by early mortality and may not reflect prognosis among longer-term survivors. We therefore evaluated conditional survival by primary site using landmark analyses. Methods: Adolescents and adults (≥15 years) with primary extranodal DLBCL diagnosed in the Surveillance, Epidemiology, and End Results (SEER) database (2002–2022) were identified. Overall survival was assessed using multivariable Cox models adjusted for age, sex, race/ethnicity, and era. Landmark Cox models at 12 and 24 months estimated survival among patients alive at each timepoint. Gastrointestinal (GI) tract served as the reference site. Results: Among 30,963 patients, survival differed significantly by primary site (p<0.001). From diagnosis, CNS/brain involvement was associated with markedly worse survival compared with GI disease (HR 2.09, 95% CI 2.00–2.19), while several sites appeared favorable at diagnosis. Among 12-month survivors (n=20,497), excess risk for CNS persisted (HR 2.46). In contrast, early advantages for bone/bone marrow and head/neck diminished, and breast, skin/soft tissue, and testis were associated with higher subsequent hazards (HR ~1.2 each). At 24 months (n=17,614), increased risk remained for CNS (HR 2.47), lung/pleura (HR 1.41), breast (HR 1.35), skin/soft tissue (HR 1.23), and testis (HR 1.26), while most other differences were small or no longer significant. Conclusions: Prognostic differences by primary site change after conditioning on early survival. CNS involvement remains high risk, while several sites that appear favorable at diagnosis lose this advantage over time. Landmark analyses provide more meaningful risk estimates for survivors but cannot account for site-specific treatment differences in SEER. Adjusted hazard ratios for overall survival by primary extranodal site among 12- and 24-month survivors. Site (ref: GI) 12m HR (95% CI) 24m HR (95% CI) Site (ref: GI) 12m HR (95% CI) 24m HR (95% CI) Bone/Bone marrow 1.01 (0.93–1.11) 0.96 (0.87–1.07) Breast 1.24 (1.09–1.42) 1.35 (1.17–1.55) CNS/Brain 2.46 (2.29–2.65) 2.47 (2.27–2.68) Head/Neck 1.03 (0.96–1.11) 1.08 (1.00–1.17) Hepatobiliary/Pancreas 1.18 (1.04–1.34) 1.12 (0.97–1.29) Kidney/Adrenal 1.26 (1.07–1.48) 1.07 (0.88–1.29) Lung/Pleura 1.39 (1.26–1.54) 1.41 (1.26–1.58) Skin/Soft tissue 1.23 (1.14–1.33) 1.23 (1.13–1.34) Spleen 0.91 (0.80–1.04) 0.92 (0.80–1.06) Testis 1.23 (1.11–1.37) 1.26 (1.12–1.41) Adjusted for age, sex, race/ethnicity, and diagnosis era. Landmark Cox models among patients alive at 12 and 24 months.

Comparative analysis of subcutaneous Isa VRd (ISASOCUT) and intravenous Isa VRd (IMROZ) in transplant-ineligible newly diagnosed multiple myeloma across age groups.

7561 Background: Intravenous (IV) isatuximab (Isa) plus bortezomib, lenalidomide, and dexamethasone (VRd) significantly improved PFS in patients (pts) with transplant-ineligible newly diagnosed multiple myeloma (Ti NDMM) in the IMROZ randomized Phase (Ph) 3 study (NCT03319667). Efficacy and safety of subcutaneous (SC) Isa VRd, using an innovative on-body injector (OBI), has been demonstrated previously, including in Ti NDMM pts in the ISASOCUT Ph2 study (NCT05889221). Bortezomib was administered twice weekly (BIW) in IMROZ vs weekly in ISASOCUT. Here, safety and efficacy of Isa OBI VRd (ISASOCUT) and Isa IV VRd (IMROZ) are evaluated at 8 months (mos) follow-up. Methods: This analysis included 74 pts from ISASOCUT (Isa OBI VRd) and 265 from IMROZ (Isa IV VRd). Isa OBI VRd pts received Isa 1400 mg (weekly cycle [C]1, then every 2 weeks [Q2W] up to C12, and Q4W thereafter); each cycle lasted 28 days. SC bortezomib (1.3 mg/m 2 ) was given BIW in C1 and weekly thereafter. Isa IV VRd pts received Isa 10 mg/kg weekly in C1, then Q2W, followed by Q4W from C18 onwards. SC bortezomib (1.3 mg/m 2 ) was given BIW from C1-4. C1-4 lasted 42 days, with the remainder lasting 28 days each. This comparative analysis evaluated safety and efficacy at 8 mos follow-up by baseline age group (<75 yrs, ≥75 yrs). Results: Baseline demographic and disease characteristics were similar between Isa OBI VRd and Isa IV VRd pts. Incidence of serious TEAEs were similar between groups (35.1% and 42.2% for Isa OBI VRd and Isa IV VRd, respectively) and across age groups. The rate of systemic infusion reaction was lower with Isa OBI VRd vs Isa IV VRd (4 [5%] vs 60 [22.8%]). Grade (G) ≥3 neutropenic complications occurred in 2.7% Isa SC OBI pts and 3.8% Isa IV pts and were similar across age groups (<75 yrs, 2% vs 4.1%; ≥75 yrs, 4% vs 2.9%). Study discontinuation due to TEAEs occurred in 2.7% Isa SC OBI pts and 8.7% Isa IV pts, with lower rates in Isa SC OBI (<75 yrs, 0% vs 8.2%; ≥75 yrs, 8% vs 10.3%). Across both age groups, a lower incidence of G2 peripheral neuropathy (PN) was observed with Isa OBI VRd (weekly V) vs Isa IV VRd (BIW V) (<75 yrs, 20.4% vs 28.7%; ≥75 yrs, 20% vs 35.3%) as well as G≥3 PN (<75 yrs, 2% vs 9.2%; ≥75 yrs, 0% vs 7.4%). Isa OBI VRd (weekly V) was associated with less bortezomib dose reduction due to nervous system disorders (Isa OBI VRd [weekly V] vs Isa IV VRd [BIW V]: <75 yrs, 14.3% vs 37.4%; ≥75 yrs, 28.0% vs 35.3%). ≥VGPR rates for Isa OBI VRd and Isa IV VRd were 87.8% and 83.2%, respectively (RR: 1.055; 95% CI: 0.934-1.192), in pts aged <75 yrs and 80.0% and 82.6%, respectively (RR: 0.968; 95% CI: 0.774-1.211), in pts aged ≥75 yrs. Conclusions: In this comparative analysis, Isa OBI VRd with weekly bortezomib (ISASOCUT) is more tolerable for pts regarding PN than the BIW schedule (IMROZ). Both groups maintained similar ≥VGPR rates across age groups. These findings support the efficacy and safety of the Isa SC OBI with weekly bortezomib. Clinical trial information: NCT05889221 and NCT03319667 .

Clinicopathologic features and survival outcomes of stage IE pulmonary marginal zone lymphoma: A National Cancer Database (NCDB) analysis.

e19076 Background: Pulmonary marginal zone lymphoma (PMZL) is a rare, indolent B-cell neoplasm and the most common form of primary pulmonary lymphoma. Its heterogeneous clinical presentation and lack of standardized tx guidelines make diagnosis and management challenging. Existing studies are limited by small sample sizes and single-institution experiences, leaving gaps in understanding its clinical features, natural history, and long-term outcomes. This study aims to comprehensively define clinicopathologic characteristics, contemporary tx patterns, and survival outcomes to inform clinical practice and guide decision-making. Methods: The NCDB Participant User File (PUF) for non-Hodgkin lymphoma was used to identify adult pts (≥18 yrs) with stage IE PMZL diagnosed between 2004–2022 using ICD-O-3 histology code 9699/3 and primary site codes C34.0–C34.9. AJCC analytic stage was used as a surrogate for early-stage disease, as Ann Arbor stage is not reliably captured. The database was used to examine clinicopathologic features and tx characteristics. Survival analysis was performed using Kaplan–Meier methods, and Cox proportional hazards models evaluated independent prognostic variables. Results: A total of 3,941 pts were included. Median age was 68 yrs (range 19–90, SD 11.9). Most pts were female (61.3%) and White (86.6%). The majority were treated at academic/research facilities (59.9%) vs community programs (38.1%). Tumors most commonly arose in lobar lung parenchyma (79.3%), with 0.9% involving the main bronchus. Charlson–Deyo score (CDS) was 0 in 67.9% and ≥1 in 32.1%. Regarding tx, 46.2% underwent surgical resection, while 53.3% had no surgery. RT was administered in 14.7%, systemic chemo in 14.6%, and immunotherapy in 14.4%. Overall, 63.0% received active tx, 18.0% were managed with active surveillance, and 17.8% were coded as unspecified tx. Median OS for the cohort was 165.4 mos (95% CI 156.0–174.8); mean OS was 153.8 mos (95% CI 148.6–159.0). Pts receiving active tx had median OS of 158.6 mos vs 122.6 mos with surveillance. Median OS was 178.5 mos for CDS=0 vs 128.8 mos for CDS ≥1. On multivariable analysis, increasing age was associated with higher mortality (HR 1.081/yr, p<0.001). Tx at academic/research programs was associated with lower mortality (HR 0.27–0.33, p=0.002–0.011). Female sex was associated with improved survival (HR 0.75, p<0.001), while CDS ≥1 increased mortality risk (HR 1.65, p<0.001). Main bronchus involvement was associated with worse outcomes (p=0.004). Surgical tx improved survival (HR 0.74, p=0.001), and immunotherapy showed a modest survival benefit (HR 1.29, p=0.036). Conclusions: Adults with stage IE PMZL exhibit indolent disease, excellent long-term survival, and favorable outcomes across tx approaches, with age, comorbidity burden, and tx facility type significantly impacting OS.

The use of circulating tumor DNA to stratify the risk of recurrence after surgical debulking in epithelial ovarian cancer.

5604 Background: Accurate risk stratification after debulking surgery in ovarian cancer remains challenging. Although surgical debulking status (SDS) and CA125 are standard prognostic markers, patients remain at high risk of recurrence despite optimal debulking and normalization of CA125. Circulating tumor DNA (ctDNA) has emerged as a sensitive biomarker for detecting molecular residual disease (MRD). We evaluated the prognostic value of post-surgical ctDNA compared with SDS and post-surgical CA125 in predicting recurrence. Methods: In a prospectively collected cohort of ovarian cancer patients undergoing standard-of-care treatment, we evaluated 37 patients with a reportable post-surgical MRD before initiation of adjuvant chemotherapy. Tumor-informed, patient-specific panels created from whole genome sequencing of matched tumors and normal samples were used to assess MRD (Precise MRD, Myriad Genetics). Postoperative CA-125 was stratified using a standard clinical cutoff of 35 U/mL. Median follow-up was 30 months (IQR 21.9). Results: Post-operative ctDNA was detected in 75.7% (28/37) of patients with 24.3% (9/37) detected at ultra-low levels ≤100 PPM. Among ctDNA-positive patients, 85.7% (24/28) recurred, compared with no recurrences among ctDNA-negative group (median PFS: 7.6 [3.0-23.2] months vs. not reached; p<0.001). Post-operative CA125 showed a similar trend with elevated-CA125 patients having a shorter median PFS (7.5 [2.8-21.1] vs. 25.1 [9.7-58.0]; p<0.05). Optimal SDS showed a trend toward longer median PFS (Optimal: 22.0 [4.1-58.0] vs. suboptimal: 10.8 [2.8-19.9], p=0.075). Notably, all patients with suboptimal SDS and detectable ctDNA experienced recurrence (4/4). Among patients achieving no gross residual disease (NGR; n=25), ctDNA strongly stratified outcomes: 82.4% (14/17) of ctDNA-positive patients recurred, whereas there we no recurrences in ctDNA-negative patients (median PFS: 4.6 [2.9-38.9] vs. not reached; p<0.001). The median tumor fraction (TF) within this cohort for positive cases was 432.0 PPM (IQR: 49.4–2510.0), where 29.4% (5/17) were detected below 100 PPM. Similarly, within the NGR group, normal-CA125 patients demonstrated a trend toward improved PFS (38.9 [6.9-58.0] vs. 4.6 [2.7-23.2]; p=0.11). Importantly, among patients with normal-CA125 (n=15), ctDNA further discriminated risk: 90% (9/10) of ctDNA-positive patients recurred with a median PFS of 20.3 (4.1-38.9) months, while no recurrences occurred in ctDNA-negative patients (p<0.05). Within this subgroup, the median TF was 235.0 PPM (IQR: 71.4–2640.0), where 26.7% (4/15) were below 100 PPM. Conclusions: Postoperative ctDNA after surgical debulking predicts early recurrence in ovarian cancer, including patients with NGR, supporting its role as a biomarker of MRD and postoperative risk stratification along with CA125.

Projected burden of lung cancer and pneumonia among older adults in the United States: A CDC WONDER forecasting analysis, 1999–2035.

e23066 Background: Lung cancer and pneumonia commonly coexist and contribute substantially to mortality in older adults. Evaluating long-term mortality trends for both conditions is essential to assess the impact and limitations of health interventions. This study examined mortality trends due to lung cancer and pneumonia among U.S. adults aged ≥65 years by demographic and geographic factors. Methods: We retrospectively analyzed CDC WONDER mortality data from 1999–2024 for individuals aged ≥65 years. Lung cancer and pneumonia deaths were identified using ICD-10 codes C34 and J18. Age-adjusted mortality rates (AAMRs) per 100,000 were calculated. Temporal trends were assessed using Joinpoint regression to estimate annual percent changes with 95% confidence intervals, and future mortality was projected using an optimized ARIMA model. Results: From 1999–2024, 161,596 deaths were attributed to lung cancer and pneumonia. AAMRs were highest in Kentucky (19.4) and lowest in Utah (4.7). Overall AAMRs declined from 22.2 in 1999 to 10.3 in 2024, with projected reductions from 9.82 in 2025 to 5.06 in 2035 (AAPC −3.09; 95% CI −3.58 to −2.61; p<0.001). Mortality declined in both sexes but remained higher in males. In 2024, AAMRs were highest among non-Hispanic Black individuals and in the South, followed by the Midwest. Nonmetropolitan areas had higher AAMRs than metropolitan regions. Conclusions: Although mortality declined overall, disparities persist, particularly among males, non-Hispanic Black populations, rural residents, and those in the South and Midwest. Targeted strategies addressing healthcare access and comorbidity burden remain essential. Characteristic Number of Deaths (N) Age-Adjusted Mortality Rate (per 100,000):1999 Age-Adjusted Mortality Rate (per 100,000):2024 Average Annual Percent Change (AAPC) (1999–2024) with 95% CI Overall 161,596 22.2 10.3 -3.02 (-3.64 to -2.40) Sex Female 64,290 13.4 8.1 -1.85 (-2.67 to -1.01) Male 97,306 35.8 13.4 -3.76 (-4.79 to -2.71) Race and Ethnicity White 138,440 22 10.9 -2.65 (-3.53 to -1.77) Black or African American 15,634 23.9 11 -3.14 (-4.76 to -1.49) Hispanic or Latino 6,182 13.9 6.6 -2.71 (-3.63 to -1.78) Census Region West 31,065 22.8 8.5 -3.50 (-4.76 to -2.22) South 62,970 23.2 11.6 -2.74 (-4.00 to -1.46) Northeast 30,673 20.5 10 -2.72 (-3.50 to -1.93) Midwest 36,888 21.7 10.5 -2.89 (-3.98 to -1.79) Urbanization (1999–2020) Age-Adjusted Mortality Rate (per 100,000): 1999 Age-Adjusted Mortality Rate (per 100,000): 2020 Metropolitan 107,681 21.5 10.5 -3.66 (-4.55 to -2.77) Non-metropolitan 29,876 25.1 12.8 -3.37 (-4.22 to -2.51) Age Group Crude Mortality Rates per 100,000: 1999 Crude Mortality Rates per 100,000: 2024 65–74 years 69,679 17.9 7.8 -3.40 (-4.66 to -2.12) 75–84 years 66,721 27.3 13 -2.71 (-3.96 to -1.45) 85+ years 25,196 25.5 13.5 -2.63 (-3.50 to -1.75)

Evaluation of baseline circulating eMDSCs in patients with advanced non–small cell lung cancer treated with first-line immunotherapy-based treatment.

e20616 Background: Early myeloid-derived suppressor cells (eMDSCs) are implicated in tumor-driven immune dysregulation, but their prognostic role in patients with advanced non-small cell lung cancer (NSCLC) treated with immunotherapy-based regimens remains unclear. Methods: Patients with advanced-stage NSCLC eligible for immunotherapy (IO)-based treatment according to programmed death-ligand 1 (PD-L1) expression were prospectively enrolled within the APOLLO11 trial at the Istituto Nazionale dei Tumori of Milan. Clinical and pathological characteristics were collected through the REDCap platform. Baseline circulating eMDSCs were quantified by flow cytometry and defined as CD11b⁺CD33⁺CD15⁻ cells within the Lin⁻HLA-DR⁻ peripheral blood mononuclear cells. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Optimal cut-offs for eMDSC levels were defined using both objective response rate (ORR)-based and survival-optimized (MaxStat) approaches. Cox proportional hazards models were used to assess the prognostic impact of eMDSCs and to test interactions with treatment type. Results: Among 84 patients, 31 (36.9%) were female, and the mean age of the overall cohort was 70.1 years. Most patients were current or former smokers (95.2%) and had adenocarcinoma histology (75.0%). First-line chemo-IO was administered in 70 patients (83.3%), while 14 (16.7%) received IO alone. Median follow-up was 20.5 months (95% CI 18.3–24.4), median OS was 13.5 months (95% CI 9.9–not reached), and median PFS was 5.0 months (95% CI 4.5–6.4). Baseline eMDSC levels were low and right-skewed (median 0.38%, IQR 0.12–1.33). Using a MaxStat-derived cut-off (0,42%), median PFS differed according to eMDSC levels (5.2 vs 2.7 months), with a higher risk of progression observed in patients with low eMDSC levels (HR 1.9, p < 0.05). Similar results (PFS 5.2 vs 2.8 months) were observed using an ORR-derived cut-off (0,044%). Low eMDSC levels remained associated with shorter PFS after adjustment for treatment (p = 0.023) and histology (p = 0.024), while the association was attenuated (p = 0.14) after adjustment for performance status (PS). PS showed a strong independent prognostic impact (p < 0.001). Conclusions: Low baseline circulating eMDSC levels were associated with shorter PFS in patients with advanced NSCLC treated with immunotherapy-based regimens; this association was independent of treatment type and histology but attenuated after adjustment for PS. These findings support a prognostic role for eMDSCs and highlight the complexity of myeloid immune regulation beyond peripheral blood measurements.

Distinguishing hemoglobin nadir from clinically significant anemia events during curative treatment for early breast cancer: Mapping hemoglobin trajectories.

e23389 Background: Anemia is a frequent complication during treatment for early breast cancer (EBC), yet the temporal relationship between hemoglobin (Hb) decline, Hb nadir & clinically significant anemia events (CSAE) remain poorly defined. Characterization of anemia trajectories & event timing may inform risk stratification & supportive care planning. Methods: We conducted a retrospective cohort study of consecutive patients with EBC undergoing curative surgery between Jan'24 to Aug'25 at a tertiary cancer center. Hb values were captured at baseline, at surgery & at nadir. The primary endpoint was time to CSAE, defined as any of the following: Hb < 8.5 g/dL, ≥2 g/dL decline from baseline, or red blood cell transfusion. Time to CSAE was analyzed independently of time to Hb nadir & both were calculated for those receiving neoadjuvant (NACT) or adjuvant (ACT) chemotherapy. Those without CSAE were censored at the end of predefined risk period. Prespecified covariates evaluated for time-to-event associations included age, menopausal status, baseline anemia status, tumor grade, nodal status, tumor-subtype, therapy setting (NACT or ACT) & chemotherapy intensity (dose-dense and/or platinum-based). Results: Among 1,228 patients (median age 53 yrs; SD 11.2), 71.1% were postmenopausal. Baseline anemia was present in 45.8% (mild 23.5%, moderate 20.0%, severe 2.3%). Mean baseline Hb was 11.91 g/dL (SD 1.62), declining to 10.75 g/dL (SD 1.32) at surgery among NACT recipients, with a nadir of 9.73 g/dL (SD 1.49) during perioperative therapy. CSAE occurred in 67.4%, with a median time to event of 21 wks (95% CI 19.5–22.4), occurring independently of Hb nadir timing (median 17 wks). On univariate analysis, absence of baseline anemia, age > 50 yrs, postmenopausal status, & receipt of NACT were each associated with earlier CSAE. On multivariable cox analysis, receipt of NACT (HR 1.93, 95% CI 1.31–2.83; p = 0.001), absence of baseline anemia (HR 1.52, 95% CI 1.23–1.85; p < 0.001), & postmenopausal status (HR 1.41, 95% CI 1.06–1.87; p = 0.018) remained independently associated with higher CSAE risk. Conclusions: In this real-world EBC cohort, CSAE were common & independent of Hb nadir timing. Notably, patients without baseline anemia experienced earlier CSAE. Postmenopausal status & receiving NACT further increased CSAE risk. These findings support proactive anemia risk assessment across all patients, including those with normal baseline Hb, to inform anticipatory supportive care strategies. Univariate estimates and multivariable predictors of clinically significant anemia events. Variable Category Time to CSAE (wk) 95% CI Multivariable HR (95% CI) NACT Yes 20.0 18.6–21.3 1.93 (1.31–2.83) No 26.0 21.6–30.3 Baseline anemia Absent 19.0 17.3–20.6 1.52 (1.23–1.85) Present 26.0 20.7–31.2 Menopause Post 20.0 18.4–21.5 1.41 (1.06–1.87) Pre 30.0 18.4–41.6

Propensity score–matched analysis of trifluridine-tipiracil plus bevacizumab (FTD/TPI+Bev) vs anti-EGFR re-treatment in pretreated metastatic colorectal cancer (mCRC).

3581 Background: The SUNLIGHT trial established FTD/TPI+Bev as a preferred 3rd-line option for unselected mCRC patients (pts). Recently, the phase II randomized PARERE trial reported high response rates and favorable progression-free survival (PFS) with anti-EGFR re-treatment in RAS/BRAF wild-type (wt) mCRC pts selected by liquid biopsy versus regorafenib. In the absence of head-to-head comparisons between these two strategies, we performed an indirect analysis, using propensity score matching (PSM) to minimize baseline imbalances. Methods: Two cohorts of pretreated (≥2 previous lines) mCRC pts were compared: pts with RAS/BRAF wt tumors receiving FTD/TPI+Bev enrolled in the Italian real-world FLOWER trial, and RAS/BRAF wt pts at the liquid biopsy enrolled in Arm A (panitumumab (Pan) re-treatment followed by regorafenib) of the PARERE trial. PSM was applied adjusting for age, sex, ECOG performance status, number (N) of metastatic sites, N of prior treatment lines, tumor sidedness, and presence of liver and peritoneal metastases. Results: Overall, 75 pts treated with FTD/TPI+Bev and 103 pts treated with Pan were included. In the unmatched populations, median PFS was 6.0 months with FTD/TPI+Bev vs 4.1 months with Pan (p<0.001). Median OS was 13.6 months and 11.6 months, respectively (p=0.756). ORR was 9.3% with FTD/TPI+Bev and 16.5% with Pan (p=0.172). After PSM, 68 pts per cohort were analyzed. Median PFS was 5.0 months with FTD/TPI+Bev vs 3.9 months with Pan [HR 1.65 (95% CI, 1.14-2.38), p=0.007]. Median OS was 13.1 months vs 11.6 months, respectively [HR: 0.89 (95% CI: 0.59-1.34); p=0.569]. ORR remained numerically higher in the Pan group, although not statistically significant (p=0.34). Results were consistent regardless of N of anti-EGFR-free lines [1 vs ≥2; HR for PFS: 0.85 (95% CI: 0.58-1.23), p=0.379; HR for OS 0.85 (95% CI: 0.56-1.29), p=0.446], type of prior anti-EGFR therapy [Pan vs Cetuximab; HR for PFS: 0.80 (95% CI: 0.58-1.10), p=0.163; HR for OS 0.87 (95% CI: 0.61-1.24), p=0.435], and response to previous anti-EGFR treatment [HR for PFS: 0.87 (95% CI: 0.59-1.28), p=0.485; HR for OS 0.80 (95% CI: 0.59-1.28), p=0.279]. Toxicity profiles differed between treatments: neutropenia (any grade (G) 52% vs 3%; G3-4: 37% vs 1%), anemia (39% vs 15%; G3-4: 5% vs 1%), nausea (25% vs 10%; G3-4: 4% vs 0%), thrombocytopenia (24% vs 7%; G3-4: 4% vs 0%) and hypertension (21% vs 1%; 4% vs 0%) were more frequent with FTD/TPI+Bev, whereas rash occurred exclusively in the Pan group (81%; G3-4: 19%). Conclusions: Although underpowered, this indirect comparison suggests that FTD/TPI+Bev may achieve longer PFS than Pan re-treatment in pretreated mCRC pts, while anti-EGFR rechallenge may be associated with numerically higher response rate, with no OS difference. Prospective randomized trials are warranted to confirm these findings.

Longitudinal physical activity patterns and patient-reported cognitive function among patients with lymphoma receiving chemotherapy in a nationwide prospective cohort.

12111 Background: Up to 70% of patients with cancer experience cancer-related cognitive impairment and physical activity (PA) may prevent or mitigate this concerning symptom. However, longitudinal data on PA before and during therapy for lymphoma and their associations with cognitive function across the treatment continuum are limited. This study examined PA patterns before, during, and after chemotherapy in patients with lymphoma compared with controls, and associations between pre-chemotherapy PA and cognitive changes over time in patients only. Methods: Cognitive function was assessed via the patient-reported Functional Assessment of Cancer Therapy-Cognitive Function perceived cognitive impairment subscale, and PA via the Aerobics Center Longitudinal Study questionnaire at pre-chemotherapy (T1), 1 month post-chemotherapy (T2), and 6 months following T2 (T3) in patients with lymphoma and age- and sex-matched non-cancer controls recruited from 19 NCORP sites across the US. MET-hours per week (MET-hrs/wk) were calculated, and meeting PA guidelines was defined as ≥150 minutes/week of moderate intensity or ≥75 minutes/week of vigorous intensity PA, or an equivalent combination. Linear mixed-effects models (LMMs) examined longitudinal PA changes between patients and controls and pre-chemotherapy PA’s association with cognitive changes in patients only, adjusting for age, sex, race, education, cognitive reserve, BMI, anxiety, and depression at T1. Results: Participants included 242 patients with lymphoma (74.4% non-Hodgkin) and 209 controls (mean age [SD], 55.3 [14.8] vs 53.7 [14.9] years; male, 62.8% vs 58.9%). In patients, 36.8% met PA guidelines at T1, decreasing to 23.3% at T2 and rising to 40.8% at T3, whereas about half of controls met guidelines across T1-T3 ( p < 0.05 at T1 and T2). Compared to controls, patients had lower PA (MET-hrs/wk) at T1 ( β[95% CI] -4.81[-9.64, 0.02]; p =0.051), which declined to T2, resulting in significantly lower PA at T2 ( β[95% CI] -7.48[-11.93, -3.03]; p =0.001); from T2 to T3, PA increased more in patients vs controls ( β[95% CI] 6.38[2.31, 10.45]; p =0.002), reaching comparable levels at T3. Cognition declined from T1 to T2 in patients meeting ( β[95% CI] -11.42[-15.19, -7.66]; p <0.001) and not meeting ( β[95% CI] -9.29[-12.09, -6.49]; p <0.001) PA guidelines at T1; however, only those meeting guidelines showed cognitive recovery from T2 to T3 ( β [ 95% CI] 3.64[0.28, 7.00]; p =0.034). Conclusions: In patients with lymphoma, PA significantly declined during chemotherapy; despite recovery to pre-treatment levels by 6 months post-chemotherapy, most remained insufficiently active. Further, active patients before treatment showed cognitive recovery after chemotherapy, suggesting that pre-chemotherapy PA may support post-treatment cognitive resilience, warranting further investigation.

Microwave assisted green synthesis of copper nanoparticles for enhanced photocatalytic, photothermal, and antibacterial applications

Integrating <i>Vibrio natriegens</i> for Photon Manipulation in Living Lighting Devices

ABSTRACT Photon manipulation with bacteria is an emerging field in photonics (lasers, bio‐imaging, and cell‐sensing) and optoelectronics (bacterial‐hybrid light‐emitting diodes (BaHLEDs) and photovoltaics). In BaHLEDs, living photon down‐conversion filters based on the direct use of bacteria in optically desirable hydrophobic and/or waterless coatings have not been realized yet. Herein, we put forward a simple concept: the engineering of fluorescent Vibrio natriegens ( V. natriegens ) that enable easy‐to‐prepare, untreated bacteria‐silicone filters for the first red‐emitting BaHLEDs. More specifically, we have rationalized genetic and material engineering tools to optimize i) the protein production time with a 1.7‐fold enhanced volumetric productivity compared to E. coli with the same spectroscopic quality for the fluorescent protein (FP) DsRed, ii) the straightforward fabrication of highly emissive and stable V. natriegens ‐silicones, and iii) device reproducibility and performance to reach competitive devices with stabilities ranging from a few days up to weeks depending on device working conditions and architectures. Overall, this work sets in bacterial photon down‐conversion using V. natriegens directly as a viable and more straightforward concept toward further advances in living lighting applications.

A randomized phase III trial of chemo-immunotherapy vs immunotherapy alone for the vulnerable older adult with advanced non–small cell lung cancer: The ACHIEVE study—ECOG-ACRIN EA5221.

TPS8674 Background: Lung cancer disproportionately affects older adults, with 70% of cases diagnosed in patients ≥65 years old, though older adults are often underrepresented in clinical trials. 1,2 KEYNOTE-189 3 and KEYNOTE-407 4 studies established superiority of chemotherapy-immunotherapy (chemo-IO) compared to chemotherapy irrespective of PD-L1 tumor proportion score (TPS) in patients with ECOG PS 0-1. Single-agent pembrolizumab was also shown to be superior to chemotherapy based on KEYNOTE-024 5 and KEYNOTE-042 6 studies. KEYNOTE-189 3 /407 4 studies highlighted synergistic benefit from chemo-IO across TPS subsets while single-agent IO benefit is mostly in the TPS ≥50% population. It is unknown if single-agent IO versus chemo-IO is superior for patients with PD-L1 TPS 1-49%, especially in older adults. There is increased risk for toxicity for adults with co-morbidities and impaired function that is enriched along the age continuum. Use of single-agent IO may limit benefit from synergy. Alternatively, chemo may increase toxicity and adversely impact quality of life (QOL) and survival in older adults. The goal of this study is to evaluate overall survival (OS) in older adults with metastatic NSCLC, PD-L1 TPS 1-49% treated with first-line single-agent IO versus chemo-IO. Methods: This phase 3 study randomizes (1:1) patients age ≥70 years old with metastatic NSCLC, PD-L1 TPS 1-49% to treatment with pembrolizumab versus pembrolizumab plus chemotherapy with primary endpoint of OS. Patients undergo an abbreviated baseline geriatric assessment (GA) of function, nutrition, cognition, and QOL with opportunity for modification of chemotherapy regimen and dosing based on results. Patients are treated with 4 cycles of induction pembrolizumab 200 mg IV every 3 weeks (Arm A) or 4 cycles of induction pembrolizumab 200 mg IV every 3 weeks in combination with chemotherapy (Arm B). Chemotherapy is investigator-selected from platinum doublet (carboplatin/pemetrexed, carboplatin/paclitaxel, carboplatin/ nab -paclitaxel) or single-agent options (pemetrexed, paclitaxel, nab -paclitaxel) with dose attenuation per investigator discretion. Induction is followed by up to two years of maintenance pembrolizumab (200 mg IV every 3 weeks or 400 mg IV every 6 weeks) with option for continuing maintenance pemetrexed. Modified GA is repeated at specified time points. Optional stool studies are collected at baseline and after four cycles of therapy. Secondary endpoints include progression-free survival, objective response rate, tolerability and QOL. Exploratory aims evaluate GA metrics as predictors of clinical outcomes and relate gut microbe diversity and abundance to treatment outcomes. Efficacy analyses are conducted on an intention-to-treat basis. Enrollment is ongoing, and current accrual (as of January 6, 2026) is 22 of 304. Clinical trial information: NCT06096844 .

Daratumumab plus bortezomib, lenalidomide, and dexamethasone (DVRd) in patients (pts) with newly diagnosed multiple myeloma (NDMM): Final analysis of transplant-ineligible (TIE) pts in the phase 3 CEPHEUS study.

7513 Background: The phase 3 CEPHEUS study established that DVRd improved overall minimal residual disease (MRD)-negativity (neg) rates and progression-free survival (PFS) vs VRd in pts with TIE or transplant-deferred (TD) NDMM. The first analysis of the DVRd TIE subpopulation at a median follow-up of 58.7 months (mo) showed a complete response or better (≥CR) rate of 80.6% and overall MRD neg rate of 60.4%, with ~70% of pts alive and progression free. This final analysis of the CEPHEUS TIE subpopulation describes a longer median follow-up of 76.0 mo. Methods: The primary endpoint of overall MRD neg rate (10 -5 and ≥CR), and secondary endpoints, including investigator-assessed PFS and ≥CR rate, and sustained MRD neg (confirmed MRD neg ≥12 months +/- 1 mo apart without MRD positivity in between and ≥CR) were assessed in the TIE population. The study was closed at the final analysis and pts were able to continue their study treatment via post-study access. Results: Of 395 pts enrolled, 289 pts with TIE NDMM received either DVRd (n=144) or VRd (n=145). The overall MRD neg rate at 10 -5 was 61.1% for DVRd and 40.0% for VRd (odds ratio [OR] 2.35; 95% CI 1.47–3.77; P =0.0004) and at 10 -6 was 46.5% for DVRd vs 27.6% for VRd (OR 2.27; 95% CI 1.39–3.71; P =0.0010). Sustained MRD neg rate at 10 -5 was 49.3% for DVRd and 29.0% for VRd (OR 2.40; 95% CI 1.47–3.91; P =0.0005) and at 10 -6 was 37.5% for DVRd and 16.6% for VRd (OR 3.01; 95% CI 1.73–5.24; P &lt;0.0001). Overall ≥CR rate was 80.6% for DVRd and 61.4% for VRd (OR 2.64; 95% CI 1.54–4.51; P =0.0003). Median investigator-assessed PFS was not estimable (NE; 95% CI 74.81–NE) for DVRd and was 50.20 mo (95% CI 41.95–62.95) for VRd (HR 0.55; 95% CI 0.39–0.78; P =0.0007), with 59.3% for DVRd vs 38.3% for VRd alive and progression free at 72 mo. OS favored DVRd over VRd (HR 0.84; 95% CI 0.57–1.24), particularly when censoring for COVID-19, which significantly impacted this study (HR 0.74; 95% CI 0.49–1.12). The treatment effect was consistent across most subgroups (Table). Conclusions: After median follow-up of over 6 years, the final analysis of the CEPHEUS trial demonstrated that TIE pts treated with DVRd continue to have deep and durable responses compared with those on VRd, which is crucial for patients for whom transplant is not an option. These data continue to reinforce DVRd as a standard of care in the TIE NDMM population. Clinical trial information: NCT03652064 . MRD neg (10 -5 ) rate, % Median PFS, mo BL characteristic DVRd VRd OR 95% CI DVRd VRd HR 95% CI ISS stage I 66.0 41.7 2.72 1.30–7.11 NE 60.5 0.52 0.28–0.97 II 59.3 45.6 1.73 0.82–3.68 NE 49.4 0.50 0.28–0.88 III 57.5 30.0 3.16 1.26–7.94 66.4 43.8 0.66 0.35–1.24 Cytogenetic risk High 50.0 50.0 1.00 0.28–3.57 58.0 31.7 0.82 0.36–1.87 Standard 63.8 39.6 2.68 1.55–4.66 NE 61.6 0.58 0.38–0.89 ECOG PS 0 57.7 45.6 1.63 0.76–3.47 NE 59.9 0.33 0.17–0.64 ≥1 63.0 36.4 2.99 1.63–5.48 74.8 47.2 0.70 0.46–1.06

Development of an oncology generative AI foundation model trained on more than a million longitudinal patient journeys across the United States.

10558 Background: Incidence of cancer diagnoses continues to increase, while the average cost of cancer screening, such as mammogram or colonoscopy, remains high, ranging from hundreds to over a thousand dollars. This study explores the potential of building an oncology foundation model based on Generative Pre-trained Transformers (GPT) to predict future outcomes for patients. We assess the prediction accuracy and feasibility of leveraging the foundation model to inform when screening should be prioritized, thereby reducing the associated burden of unnecessary procedures. Methods: The advancement of generative AI offers the opportunity to model the progression of human disease over time. In this study, we extended the GPT architecture and pre-trained it with a subset of Truveta Data containing the electronic health record (EHR) from the journeys of 1.4 million de-identified patients diagnosed with 4 types of cancer (lung, breast, colorectal, prostate). Each sequence of the patient journey—including demographics (age, gender), conditions, lab results (represented by SNOMED-CT and LOINC codes), and the corresponding event time—was tokenized before passing through the GPT model for training. For validation, 1000 patients were randomly sampled from our test data, in which each type of cancer diagnosis constituted 19%-30% of the samples. We used the model to generate synthetic future patient journeys for the selected patients and compared the predicted outcomes with the actual cancer diagnoses within one year. Results: The model achieved sensitivities above 78%, with positive predictive values (PPV) between 66% and 90%. More importantly, it demonstrated high specificities above 91%, with corresponding negative predictive values (NPV) above 90%. Conclusions: The high specificities and NPV indicate the feasibility of applying generative foundation model pre-trained with EHR data to predict negative cancer outcomes with high accuracy. Since the percentage of screening tests leading to positive cancer diagnosis is relatively low, the projected negative predictive outcomes offer valuable signals for clinicians, which they can use to complement their expert assessment to avoid unnecessary screening and subsequently reduce the burden of screening costs. Performance of the foundation model on cancer outcome prediction. Lung Breast Colorectal Prostate Positive predictive value (PPV) 72.77% 90.11% 65.78% 88.88% Sensitivity 80.28% 79.00% 78.13% 78.26% Negative predictive value (NPV) 91.87% 96.29% 90.35% 96.27% Specificity 94.50% 91.45% 94.56% 92.07%

Comparative efficacy of belantamab mafodotin plus bortezomib and dexamethasone (BVd) vs standard of care in patients with relapsed/refractory multiple myeloma (RRMM).

7568 Background: BVd is approved in the United States as a third-line or later (3L+) option for patients with RRMM based on the DREAMM-7 study of BVd vs daratumumab (D) plus bortezomib (V) and dexamethasone (d; DVd). This study aimed to compare the relative efficacy of BVd vs pomalidomide (P) plus Vd (PVd), elotuzumab plus Pd (EPd), isatuximab plus Pd (IsaPd), and idecabtagene vicleucel (ide-cel) in adults with 3L+ RRMM who received a proteasome inhibitor and an immunomodulatory drug. In the absence of head-to-head trials, indirect treatment comparisons (ITCs) can inform on the relative efficacy of regimens. Methods: ITCs of progression-free survival (PFS) and overall survival (OS) were conducted using the eligible study populations (only patients with ≥2 prior lines of therapy [LOT]) from the DREAMM-7 (BVd), DREAMM-8 (PVd), ELOQUENT-3 (EPd), ICARIA-MM (IsaPd), and KarMMA-3 (ide-cel) trials. Individual pt data (IPD) were available for patients treated with BVd and PVd, while only published summary data were available for patients treated with EPd, IsaPd, and ide-cel. In base-case analyses, study populations were weighted (using inverse probability of treatment weighting to compare to PVd and matching adjusted indirect comparison for the other treatments) to match in terms of age, prior exposure to bortezomib, prior exposure to lenalidomide, refractoriness to lenalidomide, number of prior LOT, and cytogenetic risk. Weighting was done separately for each comparator treatment. Weighted Cox regression was then performed to compare outcomes of patients treated with BVd to each respective comparator treatment. Results: In the base-case models, weighting yielded very good balance for all matched covariates (standardized mean difference &lt;0.25 for each covariate across each comparison, and &lt;0.10 in all cases except for age, prior bortezomib, and &gt;4 prior LOT in the PVd comparison). Hazard ratios for BVd vs EPd, IsaPd, and ide-cel for PFS and OS significantly favored BVd (Table). For BVd vs PVd, PFS significantly favored BVd and OS numerically favored BVd. Conclusions: In DREAMM-7, direct comparison of BVd vs DVd showed PFS and OS improvements with BVd. This indirect comparison of patients in the 3L+ setting further showed that BVd improved PFS and OS vs PVd, EPd, IsaPd, and ide-cel. Comparison (sample size/effective sample size value) BVd vs PVd (86 and 68/35) BVd vs EPd(103/42 and 60) BVd vs IsaPd(85/52 and 154) BVd vs Ide-cel(96/50 and 254) Outcome PFS OS PFS OS PFS OS PFS OS Hazard ratio 0.517 0.604 0.337 0.405 0.538 0.348 0.468 0.509 95% confidence interval 0.275, 0.972 0.331, 1.103 0.173, 0.654 0.209, 0.787 0.346, 0.836 0.195, 0.623 0.287, 0.762 0.274, 0.945 p-value 0.041 0.101 0.001 0.008 0.006 &lt;0.001 0.002 0.033

Sharing geriatric and functional status assessment data with older adults who have cancer: Patients’ preferences and utility.

e13761 Background: Geriatric assessments (GA) improve clinical outcomes for older adults undergoing cancer treatment, but their preferences regarding the use and sharing of GA results are unknown. As part of a cancer care delivery trial, we collected data on the utility of sharing GA results with patients, sharing preferences, and potential for unintended consequences. We report these descriptive outcomes in an interim analysis after 20% enrollment. Methods: Eligible patients were age ≥ 65 and starting a new chemotherapy-based treatment. Participants completed a GA, wore a FitBit for 3 days (to determine Objective Functional Status, OFS), and then completed the preferences questionnaire. GA assessed domains were: functional, social, psychological, cognition, co-morbidity, nutrition, toxicity risk, and financial hardship. Responses were summarized with descriptive statistics. The study was IRB approved and registered (NCT06652347). Results: For this analysis, 52 patients were approached and 20 (38%) enrolled. 1 withdrew prior to questionnaire completion. Mean (SD) age was 71.7 (6.6). 55% were male, 20% non-White race, and 20% lived alone. Most participants wanted assessment results shared with them: 84% for the GA and 79% for the OFS. Participants preferred to know results before deciding on a cancer treatment (68% GA and 58% OFS). They agreed/strongly agreed that results were useful (74% GA and 68% OFS) and easy to understand (79% GA and 84% OFS). 68% (GA) and 79% (OFS) would recommend them to others making treatment decisions. The GA identified more abnormalities than participants’ expected in 21% and fewer in 16%. OFS activity level was lower than expected for 11% and higher for 26%. The GA and OFS helped participants understand their cancer care and health, interact with their care team, and feel in control of their care and empowered to take an active role (Table). Few felt worried by their results (Table). Conclusions: Patients wanted to know their GA and OFS results before deciding on a cancer treatment. They found results easy to understand, empowering, and believed knowing helped them understand and participate in their cancer care. Sharing results with patients may promote optimal individualized shared decision-making around cancer treatment for older adults. Clinical trial information: NCT06652347 . Knowing my results will… GAn (%)*Agree/Strongly Agree OFSn (%)* Agree/Strongly Agree Help me better understand my cancer care 11 (58%) 7 (37%) Help me better understand my overall health 15 (79%) 10 (53%) Help me discuss my treatment with my cancer care team 11 (58%) 8 (42%) Help me prepare for visits with my cancer care team 9 (47%) 9 (47%) Help me take a more active role in my cancer care 10 (53%) 7 (37%) Help me feel in control of my cancer care 8 (42%) 9 (47%) Make me worry about treatment side effects 2 (11%) 1 (5.3%) Make me worry about my cancer 0 (0%) 0 (0%) Make me worry about my overall health 0 (0%) 0 (0%) *(N=19 after 1 withdrawal).

Large-scale assessment of ChatGPT performance in medical oncology clinical decision-making.

e13664 Background: Large Language Models (LLMs) hold significant promise as a support tool in oncology decision-making. However, large-scale studies measuring LLMs’ performance in this area are still lacking. Methods: At an Italian annual review course in medical oncology ( www.grandangolo.org ), a digital audience-response system was used to let the attendees vote on multiple-choice questions on challenging clinical cases covering 8 major cancers. Each cancer-specific session was chaired by an internationally recognized faculty of experts. Four independent reviewers captured the faculty’s discussion to generate the reference database of answers, which was later used to compare responses originating from the audience and from ChatGPT (OpenAI, GPT-5.2 Thinking, Jan 2026). ChatGPT was zero-shot prompted to generate the most appropriate answer, rank the correct ones, if more than one were acceptable, and identify the wrong answers, if any. The faculty’s and ChatGPT’s preferred 1st, 2nd, other acceptable choices, and wrong answers, were identified by the reviewers. Results: Among the 550 attendees, the median number of oncologists who voted was 158 (range 86-258). A total of 51 out of 53 consecutively-presented, multiple-choice clinical cases, comprising 210 answer options, were fully addressed and voted on by the audience. Across cases, the median % of oncologists whose selected answer matched the faculty’s 1st or 1st/2nd choices was 60% (range 6-97%) and 82% (range 7-99%), respectively. ChatGPT’s responses matched the faculty’s 1st or 1st/2nd choices in 57% (29/51) and 75% (38/51) of cases, respectively. The median % of oncologists selecting the wrong answer was 7% (range 0-93%), while ChatGPT selected the wrong answer in 16% (8/51) of the cases. These 8 cases were among those most frequently missed by the audience (wrong response rate, range 25-93%), attributed by reviewers to unclear case descriptions or drug reimbursement issues. Given the multiple acceptable answers to most cases, the agreement between the audience’s votes and the output of ChatGPT was explored. The preferred choice by ChatGPT matched the top-2 most-voted answers by the audience in 90% (46/51) of cases. Conclusions: These results indicate high agreement between ChatGPT’s answers to a large number of challenging cases in medical oncology and those provided by the faculty of internationally recognized experts.

Time of day of liver transplant reperfusion as a predictor of disease-free and overall survival in patients with advanced hepatocellular carcinoma.

e16282 Background: Circadian rhythms moderate cancer biology by regulating cell cycle progression, DNA activity, immune surveillance, and metastatic potential. We aim to assess the relevance of circadian rhythms for the prognosis of patients (pts) undergoing liver transplantation (LT) for hepatocellular carcinoma (HCC). Methods: This retrospective study included pts with curative-intent liver transplantation for HCC. The time of day (ToD) of each graft reperfusion was recorded, and its impact on disease-free survival (DFS) and overall survival (OS) was analysed using time-slot stratification and restricted cubic spline Cox modelling. Baseline characteristics were compared to assess group comparability. Results: From 2015 to 2020, 200 consecutive patients, including 79% males with a median age of 61.4 ± 7.1 yrs underwent liver transplant for HCC at a single centre. Mean (±SD) of waiting time on list, MELD score, and alpha-fetoprotein level (AFP) were 267 ± 293 days, 14.7 ± 7.5 UI and 18.9 ± 59.1 ng/mL, respectively. Pts were allocated to four 6-hour time slots according to graft reperfusion ToD, namely 01:00-07:00 (Night, N = 20), 07:00-13:00 (Morning, N = 49), 13:00-19:00 (Afternoon, N = 69), 19:00-01:00 (Evening, N = 62). Pts characteristics were similar for MELD Score, AFP, tumour numbers, largest tumour diameter, and time elapsed between last treatment and liver transplant in the 4 ToD slots. Median follow-up was 5years [IQR 3.3-5.0]. Recurrence occurred in 33 patients (Night N = 7, 21.2%; Morning N = 2, 6%; Afternoon N = 14, 42.4%; Evening N = 10; 30.3%). DFS differed across reperfusion ToD slots (log-rank p = 0.041), with the most favourable outcomes in the Morning slot, whose pts had improved DFS compared with the three other ToD slots (log-rank p = 0.048). Morning reperfusion was associated with a markedly lower recurrence risk compared to Night reperfusion (HR 0.17, [95% CI, 0.04–0.64]), with consistent trends for afternoon and evening reperfusion. Restricted cubic spline modelling confirmed a circadian pattern, with a nadir of recurrence risk in the early-to-mid afternoon (13:00-15:00) and higher risk estimates toward nighttime reperfusion. Finally, OS differed across reperfusion ToD slots (log-rank p = 0.043), with the most favourable outcomes in the Morning ToD slot. Conclusions: Pts with liver transplant for HCC reperfused in the morning hours had a longer DFS and OS compared to those reperfused at other ToDs. Thus, ToDs could account for significant changes in the recipient’s susceptibility to post-transplant HCC recurrence, possibly resulting from changes in immune responses and/or tumour cell seeding and implantation. These clinically relevant findings warrant further validation in retrospective and prospective pt cohorts and may impact surgical oncology practice.

Efficacy and circulating protein biomarkers of second-line aflibercept plus FOLFIRI according to prior bevacizumab or cetuximab treatment in advanced colorectal cancer (KCSG CO21-21).

3566 Background: Prospective data evaluating second-line aflibercept plus FOLFIRI according to prior bevacizumab (BEV) or cetuximab (CET) exposure and incorporating circulating protein biomarkers remain limited. Methods: This open-label, single-arm, nationwide phase II study (NCT04810585) evaluated aflibercept plus FOLFIRI as second-line with stratification by prior BEV or CET exposure. Seventeen circulating biomarkers were measured by ELISA at baseline and before cycle 4 and analyzed for associations with PFS and OS using Cox models. Plasma proteins were processed using a single-pot solid-phase enhanced SP3 protocol followed by tryptic digestion and analyzed by data-independent acquisition liquid chromatography tandem mass spectrometry, with protein identification and quantification performed using DIA-NN. Results: A total of 159 patients were enrolled (prior BEV, n=83; prior CET, n=76). mPFS was 7.5 months (95% CI, 6.8–8.4), and mOS was 14.4 months (95% CI, 12.9–16.0), with no significant differences by prior biologic therapy (mOS: 13.8 vs 14.7 months for prior BEV vs CET; mPFS: 7.4 vs 7.5 months). Among 146 evaluable patients, the ORR was 28.1% (1 CR [0.7%], 40 PR [27.4%]), and the DCR was 88.4%. The most common TRAEs were proteinuria (47.1%; grade ≥3, 14.0%), neutropenia (43.4%; grade ≥3, 37.5%), nausea (27.2%), and fatigue (24.3%). Baseline PlGF (PFS HR 2.04, q=0.008; OS HR 2.86, q&lt;0.001), IL-8 (PFS HR 1.87, q=0.008; OS HR 2.13, q=0.002), TIMP-1 (PFS HR 1.74, q=0.021; OS HR 3.49, q&lt;0.001), and VEGF-A (PFS HR 1.74, q=0.021; OS HR 1.91, q=0.009) were independently associated with inferior PFS and OS, whereas on-treatment and C1-to-C4 biomarker ratios showed no associations. Enrichment of inflammation/immune related proteins S100A8 (log 2 FC -0.41; p=0.037) and MPO (log 2 FC -1.51; p=0.006), as well as lipid metabolism related proteins APOC3 (log 2 FC -0.58; p &lt;0.001) and APOC2 (log 2 FC -0.47; p=0.003), was observed in patients with prior BEV at baseline. Enrichment of PIGR (log 2 FC -1.21; p&lt;0.001) and OLFM1 (log 2 FC -0.66; p-value &lt;0.001) was observed in PD patients at C4, while SERPINF1 (log 2 FC 0.33; p= 0.003) and FETUB (log 2 FC 0.41; p=0.013) were enriched in PR+CR patients at C4. Further, PIGR expression increased 1.30-fold in PD patients (mean log 2 Δ (C4-C1) = 0.38), compared to a relatively stable expression in PR patients (mean log 2 Δ(C4-C1) = -0.076, p=0.033). Increased PIGR expression at C4 showed an association with inferior OS in Cox models (HR 1.92, p=0.004). Conclusions: Clinical outcomes and safety profiles of aflibercept plus FOLFIRI were comparable regardless of prior BEV or CET exposure. Elevated baseline PlGF, IL-8, TIMP-1 and VEGF-A levels were associated with shorter PFS and OS. Exploratory plasma proteomics identified dynamic PIGR expression as a response-associated biomarker linked to inferior OS. Clinical trial information: NCT04810585 .

Efficacy and safety of recombinant human thrombopoietin (rhTPO) for thrombocytopenia induced by combinatorial interventional, targeted, and immunotherapy in hepatocellular carcinoma (SYNERGY-TPOACT): A retrospective cohort study.

e16250 Background: Combination regimens integrating interventional therapies (TACE/HAIC) with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) are now established as the standard of care for advanced hepatocellular carcinoma (HCC). However, cumulative myelosuppression, specifically severe thrombocytopenia, frequently mandates dose reduction or treatment interruption, thereby compromising clinical outcomes. Although recombinant human thrombopoietin (rhTPO) is well-validated for chemotherapy-induced and immune thrombocytopenia, its utility in this specific setting remains ill- limited. We aimed to evaluate the efficacy and safety of rhTPO in HCC patients undergoing this combinatorial regimen. Methods: This retrospective cohort study assessed 60 HCC patients who developed thrombocytopenia (platelets ≤80×10⁹/L) sequelae to combined interventional, targeted, and immunotherapy at Guizhou Provincial People’s Hospital, China (March 2022-March 2025). All cohorts received subcutaneous rhTPO. The primary endpoint was the overall response rate (ORR), defined as complete response (CR: platelets ≥100×10⁹/L) or partial response (PR: absolute increment ≥25×10⁹/L). Secondary endpoints encompassed platelet kinetics, duration-response analysis, and safety profiles. Results: The cohort was characterized predominantly by BCLC stage C (50.0%) disease and Child-Pugh class B (55.0%) status. Baseline mean platelet count was 51.93×10⁹/L. Following rhTPO administration, the ORR reached 68.3% (CR:38.3%, PR:30.0%). The mean platelet count increased by 47.76×10⁹/L (p &lt; 0.0001, 95% CI: 36.81-58.70). The analysis demonstrated progressive recovery, with mean increments of 25.21×10⁹/L, 42.43×10⁹/L, and 64.91×10⁹/L at days 3, 5, and 7, respectively. Efficacy was consistent across all BCLC stages. Notably, multivariate analysis identified a treatment duration of ≥7 days as an independent predictor of ORR (OR = 7.45, 95%CI: 1.95-28.50, p = 0.003). No treatment-related hepatorenal toxicity or thromboembolic events were observed. Conclusions: rhTPO exhibits significant efficacy and a favorable safety profile in managing thrombocytopenia associated with combinatorial interventional therapy with targeted and immunotherapy in HCC. Our data suggest that a minimum treatment duration of 7 days is pivotal for maximizing platelet recovery, thus facilitating treatment continuity.