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Phase II randomized trial of radiotherapy with pembrolizumab vs. cisplatin for unfavorable-risk p16+ head and neck squamous cell carcinoma (KEYCHAIN).
6016 Background: Standard chemoradiation (CRT) for unfavorable risk p16+ head and neck squamous cell carcinoma (HNSCC) is associated with high rates of toxicity and treatment failure. We hypothesized that concurrent and adjuvant pembrolizumab (pembro) could achieve superior PFS with acceptable toxicity compared to CRT in this population. Methods: KEYCHAIN was an open-label randomized phase II trial conducted at 6 US academic centers. Eligible patients had newly diagnosed unresected p16+ HNSCC with unfavorable risk (AJCC 8 th edition stage II-III oropharynx or stage III-IVB non-oropharynx HNSCC). Patients were randomized 1:1 to RT (70 Gy in 35 fractions) plus pembro (200 mg, 2 weeks prior to RT then every 3 weeks starting day 1 of RT up to 20 total cycles) or RT plus concurrent cisplatin (cis) (100 mg/m 2 every 3 weeks). Age, ECOG status, and oropharynx site were stratification factors. The primary endpoint was PFS, defined as time from randomization to first progression or death from any cause. Primary analysis was in the modified intent-to-treat population, including all patients having ≥ 1 dose of study medication and ≥ 1 efficacy evaluation after baseline. The study design had 80% power with 1-sided α = 0.15 (log-rank test) and planned sample size of 50 analyzable subjects per arm. The study is registered with clinicaltrials.gov (NCT03383094). Results: Between Feb 2019 and Aug 2025, 108 patients were randomized (53 pembro, 55 cis), with 102 analyzable (50 pembro, 52 cis). Median follow-up was 26.5 months. 79% had minimum follow-up of 2 years. At 2 years, there were 7 PFS events and 1 death in the pembro arm, and 14 PFS events and 7 deaths in the cis arm. Two-year PFS was 84% (95% CI: 74-96%) vs. 70% (95% CI: 58-85%) in the pembro vs cis arm (HR 0.57, 95% CI: 0.25-1.31; 1-sided p = 0.09) (see Table). Two-year OS was 98% (95% CI: 94-100%) vs. 85% (95% CI: 76-96%) for pembro vs. cis (HR 0.33, 95% CI: 0.09-1.28; 1-sided p = 0.048). HRs adjusted for T3-4 and N2-3 category were 0.68 (PFS) and 0.31 (OS). As of the latest follow-up, there were 24 total PFS events and 12 deaths. Grade ≥ 3 adverse events definitely or probably related to treatment were 36% vs. 46% in the pembro vs. cis arm. The median number of cycles received in the pembro arm was 18. In the cis arm, 94% completed ≥ 2 cycles. Results by CPS status will be reported when available. Conclusions: Pembro plus RT met the pre-specified significance criterion for improvement in PFS compared to cisplatin plus RT in this phase II trial. A phase III trial of RT with pembrolizumab for unfavorable risk p16+ HNSCC is warranted. Clinical trial information: NCT03383094 . Pembro Cisplatin N 50 52 Mean age 63.5 62.5 Male 87% 89% White 85% 89% Age > 65 42% 35% ECOG 0 83% 70% Oropharynx 94% 96% T1 8% 10% T2 22% 12% T3 38% 38% T4 32% 40% N0 6% 8% N1 42% 29% N2 46% 54% N3 6% 10% 2-yr PFS 84% 70% 2-yr OS 98% 85% Completed RT w/in 56 days 96% 92% Grade ≥ 3 mucositis 18% 17% Grade ≥ 2 mucositis 72% 63% Grade ≥ 3 dysphagia 14% 6% Grade ≥ 2 dysphagia 48% 35%
Neoadjuvant camrelizumab plus apatinib and temozolomide for resectable stage III acral melanoma: Updated CAP 03-NEO trial results and external control comparison.
9571 Background: SWOG1801 and NADINA trials suggested that neoadjuvant therapy may provide greater benefits than adjuvant therapy in melanoma. CAP 03-NEO explores the efficacy and safety of camrelizumab combined with apatinib and temozolomide triple-drug regimen as neoadjuvant therapy in patients (pts) with resectable stage II/III acral melanoma (AM). Methods: This two-stage trial (NCT05512481) aimed to enroll 60 pts with resectable stage II/III AM. Pts received two 4-week cycles of neoadjuvant camrelizumab (200 mg IV Q2W), apatinib (250 mg orally QD), and temozolomide (200 mg/m² IV daily D1–5), followed by surgery and 15 cycles of adjuvant camrelizumab (200 mg Q3W). A total of 30 pts were assessed in stage 1, demonstrating stage III AM benefiting more from neoadjuvant therapy (ASCO 2025, abstract 9512). Therefore, stage 2 exclusively enrolled stage III pts. Endpoints included pathological response, EFS, RFS and DMFS. To further evaluate the neoadjuvant benefit, an external contemporary cohort of stage III AM pts treated with upfront surgery and adjuvant PD-1 inhibitor alone was retrospectively collected for comparison. Propensity score matching (PSM 1:1 nearest neighbor method) and inverse probability of treatment weighting (IPTW) were used to minimize bias. Kaplan-Meier method and Cox regression were performed for survival analysis. Stage 2 results and this post-hoc comparison are reported here. Results: As of Jan. 26, 2026, thirty-one pts in stage 2 were enrolled, with a median follow-up of 13 months. The median age was 60 years (IQR: 49–68). Of 28 pts undergoing surgery, 18 (64.3%) achieved any pathological response, including 10 with major pathological response (7 with pCR, 3 with near pCR), and 8 with pPR. Surgery was canceled for 2 pts due to progressive disease. Neoadjuvant therapy was still ongoing for one patient. The 12-month rates of EFS, RFS and DMFS were 74.4%, 80.3% and 84.0%, respectively. All median values were not reached. As compared to external control cohort (adjuvant treatment alone), both unadjusted and adjusted analyses showed that pts treated with additional neoadjuvant therapy achieved significantly better EFS, RFS and DMFS (Table 1, all p values <0.05). The safety profile between stage 1 and stage 2 were similar and no new safety signal was identified. Conclusions: Stage 2 results and external control comparison of CAP 03-NEO further confirmed the significant benefit of neoadjuvant camrelizumab, apatinib and temozolomide in pts with resectable stage III AM. Clinical trial information: NCT05512481 . HR and 95% CI for EFS, RFS, and DMFS (sample size of stage 2 vs. external control). Survival Unadjusted (31 vs. 50) PSM 1:1 (30 vs. 30) IPTW (31 vs. 50) EFS 0.309 (0.129-0.743) 0.246 (0.078-0.778) 0.317 (0.124-0.810) RFS 0.244 (0.086-0.694) 0.241 (0.071-0.812) 0.242 (0.081-0.728) DMFS 0.286 (0.099-0.822) 0.203 (0.051-0.807) 0.290 (0.094-0.893)
Integrated assessment of cachexia, body composition, and patient-reported outcomes in unplanned hospitalizations of patients with metastatic cancer (PRO-HAND study).
12075 Background: Patients with metastatic cancer hospitalized for unplanned admissions represent a highly vulnerable population with substantial short-term mortality and readmission risk. Cachexia, altered body composition, and patient-reported outcomes (PROs) frequently coexist in this setting, yet their integrated relevance during hospitalization remains insufficiently characterized. Methods: PRO-HAND is a cross-sectional observational study including metastatic cancer patients hospitalized for unplanned admissions between September 2024 and September 2025 who had received systemic anticancer therapy within the preceding 6 months. Cachexia-related indices, bioelectrical impedance analysis (BIA)-derived body composition parameters, and PROs were assessed during hospitalization. Primary outcomes were 30-day mortality, 90-day mortality, and unplanned 30-day hospital readmission. Associations were evaluated using hierarchical multivariable logistic regression models with sequential adjustment for clinical variables, cachexia indices, body composition parameters, and PROs. Results are reported as odds ratios (ORs) with 95% confidence intervals (CIs). Results: A total of 233 patients were included (median age 62 years; 71.2% ECOG ≥2). Median follow-up was 3.35 months. Thirty-day mortality occurred in 21.9%, 90-day mortality in 23.2%, and unplanned 30-day readmission in 57.9%. Lower handgrip strength–based cachexia index (H-CXI) was associated with higher odds of 30-day mortality (OR per 10-unit decrease 1.43; 95% CI 1.19–1.74; p<0.001). ECOG ≥2 and lower phase angle were also associated with early mortality, whereas the composite triglyceride–glucose and inflammation index was not. For 90-day mortality, lower global quality-of-life scores and higher pain burden showed stronger associations than cachexia indices. For unplanned 30-day readmission, a higher total body water/fat-free mass (TBW/FFM) ratio was associated with increased risk. Conclusions: Cachexia severity, body composition abnormalities, and PROs show distinct, outcome-specific associations in metastatic cancer patients hospitalized for unplanned admissions. Integrated assessment during hospitalization may provide complementary clinical information across these domains. Clinical trial identification NCT07167082. Selected baseline characteristics and outcomes. Characteristic n (%) or median (IQR) Age ≥65 years 98 (42.1) ECOG performance status ≥2 167 (71.7) Weight loss ≥10% (6 months) 126 (54.1) H-CXI 34.23 (14.95–71.02) Phase angle, degrees 4.03 (2.95–5.52) FFMI, kg/m² 17.14 (15.48–19.31) FACT-G total score 62 (56–68) Pain score (VAS 0–10) 4 (2–6) Unplanned 30-day readmission 135 (57.9) 30-day mortality 51 (21.9)
Survival in de novo versus metachronous metastatic breast cancer across molecular subtypes: A large real-world, propensity-matched analysis.
e12756 Background: Metastatic breast cancer (MBC) may present as de novo metastatic disease (dnMBC) or as metachronous recurrent metastatic disease (rMBC) following prior early-stage breast cancer. Differences in tumor biology and prior treatment exposure may contribute to survival differences. We compared survival outcomes between dnMBC and rMBC across major breast cancer subtypes using a large real-world database. Methods: We conducted a retrospective, real-world cohort study using the TriNetX research network. Adult female patients (≥18 years) with metastatic breast cancer were identified using structured diagnostic codes. Patients were classified as dnMBC if metastatic disease occurred within 3 months of initial diagnosis and as rMBC if metastatic disease occurred ≥13 weeks after diagnosis. Patients were stratified into four subtypes: HR+/HER2−, HR+/HER2+, HR−/HER2+, and triple-negative breast cancer (TNBC). The primary endpoint was overall survival (OS). Survival was assessed using Kaplan–Meier methods and log-rank tests. Propensity score matching (PSM) was performed within each subtype based on age, race/ethnicity, and major comorbidities. Results: After PSM, cohorts were well balanced. De novo metastatic presentation was consistently associated with superior OS across all subtypes (Table). Across subtypes, dnMBC demonstrated significantly lower mortality risk compared with rMBC, with higher long-term survival and unreached median OS in several groups. Conclusions: In this large real-world, propensity-matched analysis, dnMBC was consistently associated with superior OS compared with rMBC across all major breast cancer subtypes. Timing of metastatic presentation should be considered an important prognostic factor and stratification variable in metastatic breast cancer. Overall survival by breast cancer Subtype (dnMBC vs rMBC). Subtype HR (95% CI) p-value Survival % (dnMBC vs rMBC HR+/HER2- 0.55 (0.51-0.59) <0.0001 55.5 vs 33.1 HR+/HER2+ 0.60 (0.53–0.68) <0.0001 62.8 vs 40.9 HR-/HER2+ 0.62 (0.51–0.76) <0.01 58.8 vs 51.1 TNBC 0.63 (0.56–0.71) <0.0001 50.7 vs 36.4
DLL3-targeted therapy with tarlatamab in small cell lung cancer across lines of therapy: A systematic review of prospective and randomized clinical trials.
e14525 Background: Small-cell lung cancer (SCLC) is an aggressive malignancy with limited treatment options beyond first-line therapy. Delta-like ligand 3 (DLL3) is highly expressed on SCLC tumor cells and is a rational target. Tarlatamab is a first-in-class DLL3-directed bispecific T-cell engager that has demonstrated clinical activity in prospective trials and has received regulatory approval for extensive-stage SCLC. While early-phase studies established activity in previously treated disease, subsequent trials have expanded its relevance into earlier treatment lines. We conducted a systematic review of prospective clinical trials to synthesize the efficacy and safety of tarlatamab. Methods: A systematic literature review was performed in accordance with PRISMA. PubMed, Embase, and major oncology conference proceedings (ASCO, ESMO, AACR) were searched from inception through January 2026 using the terms “tarlatamab,” “DLL3,” “DeLLphi,” and “small-cell lung cancer.” Eligible studies included prospective phase I–III trials evaluating tarlatamab alone or combination regimens. Outcomes included overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), cytokine release syndrome (CRS) and neurologic toxicity. Phase III data were included for contextual relevance but were not pooled with early-phase efficacy outcomes. Results: Prospective evidence included DeLLphi-300 (phase I) and DeLLphi-301 (phase II) monotherapy trials in previously treated SCLC, and phase III trials DeLLphi-304 and DeLLphi-305 evaluating earlier-line strategies. In DeLLphi-301, FDA-reported efficacy included ORR 40% (95% CI, 31–51), median DOR 9.7 months (range, 2.7–20.7+), median PFS 4.9 months in the 10-mg cohort, CRS in approximately 51% (10 mg) and 61% (100 mg) of patients, predominantly grade 1–2. DeLLphi-300 demonstrated activity in heavily pretreated SCLC (ORR ~23–35% across dose cohorts), supporting proof-of-concept for DLL3-directed T-cell redirection. DeLLphi-304 compared tarlatamab monotherapy with standard-of-care chemotherapy in patients progressing on or after one line of platinum-based therapy, met its primary endpoint with a statistically significant OS improvement at interim analysis. DeLLphi-305 is an ongoing randomized phase III study evaluating tarlatamab plus durvalumab versus durvalumab alone as first-line maintenance therapy. Conclusions: Across prospective trials, tarlatamab demonstrates clinically meaningful activity in extensive-stage SCLC with a manageable safety profile characterized by predominantly low-grade CRS and infrequent severe CRS/ICANS with step-up dosing. Early-phase data support its approved use after platinum progression, while emerging phase III evidence suggests potential benefit in earlier treatment settings.
Outcomes and efficacy of neuroendoscopic resection of intraventricular tumors: A systematic review and meta-analysis.
e14107 Background: Intraventricular neoplasms predominantly comprise benign tumors that obstruct cerebrospinal fluid flow, causing hydrocephalus and intracranial hypertension. While open microsurgical approaches have historically served as the standard treatment, neuroendoscopy has emerged as a minimally invasive alternative with potential advantages. However, reported surgical outcomes remain inconsistent, limiting consensus regarding the safety and efficacy of purely neuroendoscopic tumor resection. Methods: A comprehensive systematic review was conducted following PRISMA guidelines. Electronic databases were searched on May 5, 2025, for studies evaluating neuroendoscopic approaches for intraventricular tumor management. Included studies comprised retrospective cohort studies and case series involving adults (≥18 years) with histologically confirmed benign intraventricular brain tumors undergoing purely neuroendoscopic tumor resection. Quality assessment was performed using the Joanna Briggs Institute Critical Appraisal Checklist. Meta-analysis was conducted using random-effects models with appropriate effect measures. Results: Twenty-eight studies encompassing 1,054 patients were included in the meta-analysis. The mean patient age was 36.8 years (range 18-80), with 42% male and 36.8% female participants. Colloid cysts comprised 74% of tumors, followed by craniopharyngiomas (10%) and astrocytomas (3.57%). The pooled gross total resection rate was 80.5% (95% CI: 0.887-0.844, p<0.001), while subtotal resection occurred in 23.9% of cases (95% CI: 0.142-0.374, p<0.001). Mean operative time was 94.12 minutes (95% CI: 84.74-103.51). Intraoperative hemorrhage occurred in 11.0% of patients (95% CI: 0.048-0.242), and the tumor recurrence rate was 12.3% (95% CI: 0.080-0.233). Postoperative outcomes demonstrated excellent survival rates of 97.0% (95% CI: 0.947-0.983), with hydrocephalus resolution in 94.0% of cases (95% CI: 0.859-0.978). New neurological deficits occurred in 12.5% of patients (95% CI: 0.081-0.190), postoperative infections in 8.5% (95% CI: 0.044-0.098), and permanent shunt requirement in 5.9% (95% CI: 0.038-0.098). Conclusions: Neuroendoscopic resection of intraventricular tumors demonstrates favorable outcomes with high gross total resection rates, excellent survival rates, and effective hydrocephalus resolution. The procedure is associated with acceptable complication rates, including low permanent shunt dependency and moderate rates of new neurological deficits. These findings support neuroendoscopy as an effective minimally invasive alternative to traditional microsurgical approaches for appropriately selected intraventricular tumors, particularly colloid cysts and other centrally located lesions. However, careful patient selection and surgeon expertise remain crucial for optimal outcomes.
Uniting providers across institutions to support osteosarcoma care: Insights from 64 cases reviewed through the MIB agents TURBO board.
e13540 Background: TURBO (Tumor Review Board for Osteosarcoma), launched in 2022 by MIB Agents Osteosarcoma Alliance, is a global bi-monthly virtual tumor board designed to support oncology providers managing complex osteosarcoma cases. From February 2022 – November 2025, TURBO held 21 one-hour sessions reviewing 64 cases presented by 50 clinicians from 43 institutions across 8 countries. Summary notes were distributed after each meeting to facilitate the dissemination of expert guidance. Methods: Presenting oncologists submitted standardized case data reflecting patient status at review. Physicians received online surveys 1 week and 6 months post-presentation, assessing TURBO’s usefulness and impact. Results: Demographics reflected the US osteosarcoma population (54.7% male), but skewed younger (76.6% aged 10–24 years). Cases spanned the US; 10 (15.6%) were non-US. More than half (56.3%) were treated at sarcoma centers. Most tumors (64.1%) were lower extremity; metastatic disease was common (82.8%), primarily to the lung (71.9%) and bone (21.9%), with some soft-tissue, CNS, and nodal sites. Disease status at presentation reflected high complexity: 25.0% initial diagnosis, 45.3% progression, and 29.7% recurrence. Most had prior surgery (87.5%) and ≥2 treatment lines (65.6%), with two-thirds (67.2%) receiving ≥4 agents. MAP was the first-line regimen for 84.4%. Common subsequent therapies included ifosfamide/etoposide (39.1%), cabozantinib (23.4%), regorafenib (18.8%), and gemcitabine/docetaxel (17.2%). At presentation, 26.6% had enrolled in ≥1 clinical trial. One week post, 100% of TURBO presenters rated TURBO as very helpful, and 37.5% reported immediate treatment-plan changes. At 6 months, 82.4% reported that the patient received treatment following TURBO, and 70.6% found the discussion helpful in determining the plan. Six-month outcomes were 17.6% NED, 23.5% stable, 35.3% progression, and 23.5% deceased. Physicians valued multidisciplinary input for complex rare cases, gained confidence exploring therapy options, and learned from peers. Recommendations often provided clear guidance, while differing opinions highlighted ongoing uncertainties. At 1 week, 100% rated TURBO as very helpful; 37.5% reported a treatment-plan change, 33.3% maybe, and 29.2% no change. Conclusions: TURBO provides a collaborative forum delivering multidisciplinary expertise to clinicians treating rare high-risk osteosarcoma. Cases reflected a heavily pre-treated, predominantly metastatic population, underscoring the need for shared decision-making. TURBO discussions improved clinician confidence, informed real-time treatment planning, and supported identification of clinical trial options. This scalable international forum strengthens cross-institutional collaboration and may enhance consistency and quality of care in osteosarcoma.
Implementation science insights from a community-embedded cervical cancer screening program integrating high-risk human papillomavirus DNA testing with non-communicable disease screening in rural South India.
1509 Background: The WHO Cervical Cancer Elimination Initiative recommends screening ≥70% of eligible women and linking ≥90% of those with identified disease to treatment. However, in most low- and middle-income countries (LMICs), screening rate remains around 30–40%, and only 40–60% of high-risk human papillomavirus (HR-HPV)–positive women complete colposcopy thereby precluding identification of disease and linking to treatment. To address this gap across the screening–diagnosis–treatment pathway, we implemented a multi-pronged community-based program integrating community participation, self-swab HR-HPV DNA screening at doorsteps, with non-communicable disease (NCD) screening and patient centric treatment linkage. Methods: This longitudinal implementation study was conducted within the Rural Effective Affordable Comprehensive Health (REACH) cohort in Medchal district, Telangana, India. Trained non-physician health workers conducted door-to-door outreach among women aged 25–65 years. Community engagement was supported by a local Community Advisory Board and village influencers, who guided outreach strategies and timing. Counseling and self-collection of vaginal samples were carried out at participants’ homes. Educational content was developed based on prior formative research using the Health Belief Model to address fears, stigma, and misconceptions. Screening for HR-HPV DNA was offered as part of a bundled women’s health package that included blood pressure and diabetes testing. Appointments for both swab collection and colposcopy/biopsy were coordinated and scheduled at the convenience of the community. HR-HPV testing was done using a chip-based PCR platform. Women who tested positive were referred for colposcopy, biopsy, and treatment at an affiliated teaching hospital. Results: Of 1,869 women approached, 1,747 (93.5%) completed HR-HPV self-sampling, surpassing the WHO’s 70% screening target. HR-HPV was detected in 89 women (5.1%). Of these, 64 (71.9%) underwent colposcopy, higher than LMIC averages. All with abnormal findings had biopsies. Four women were diagnosed with high-grade lesions or early invasive cancer, all successfully linked to definitive care or referral, meeting the WHO ≥90% treatment linkage benchmark. Conclusions: Integrating HR-HPV screening with NCD services, enabled by community leadership, doorstep access, and logistical support, achieved high coverage, improved follow-up, and complete linkage to care. This model offers practical, scalable insights for cervical cancer screening programs in rural, resource-limited settings.
Fluoropyrimidine-related cardiotoxicity in patients with <i>DPYD</i> variants: A real-world cohort study.
e24035 Background: Fluoropyrimidines are foundational agents in gastrointestinal oncology but can cause severe toxicity in patients with reduced dihydropyrimidine dehydrogenase (DPD) activity due to DPYD variants. Although complete DPD deficiency is rare, partial deficiency affects an estimated 3–8% of the U.S. population. Fluoropyrimidine-associated cardiotoxicity includes coronary vasospasm, acute coronary syndrome (ACS), arrhythmia and heart failure. Pretreatment DPYD genotyping enables identification of at-risk patients, yet the relationship between DPYD status and cardiotoxicity remains poorly defined. Methods: We conducted a retrospective study of 158 adults receiving fluoropyrimidine-based chemotherapy at Moffitt Cancer Center between 7/2022-12/2025. Pretreatment DPYD genotyping identified patients with decreased-function variants (n = 31) and a comparator group of DPYD wild-type (WT) patients (n = 127). Medical records were reviewed for cardiotoxicity, defined as new-onset ACS, arrhythmia, or left ventricular dysfunction occurring within 30 days of initiating fluoropyrimidine treatment. Characteristics and outcomes were compared between the DPYD- variant and DPYD -WT groups. Results: Cardiotoxicity occurred in 19.4% of DPYD -variant patients compared to 2.4% of the DPYD -WT patients (Fisher’s exact test, p = 0.002). The WT patients who developed cardiotoxicity had higher average baseline cardiovascular risk scores, and 2 experienced ST-elevation ACS. Among DPYD -variant patients who developed cardiotoxicity, 50% carried the *1/*2A ( c.1905+1G > A ) variant and 33% the *1/ c.2846A > T variant. In the variant group, cardiac events occurred with both infusional 5-FU and capecitabine and included arrhythmia, and non-ST-elevation ACS. Notably, 83% of the DPYD -variant patients who developed cardiotoxicity did not receive upfront genotype-guided fluropyrimidine dose-reduction. Following cardiotoxicity, half of the affected DPYD -variant patients resumed therapy with dose-reduction, while the others permanently discontinued treatment. Conclusions: Cardiotoxicity is a potentially life-threatening complication of fluoropyrimidine chemotherapy. In this study, cardiotoxicity occurred significantly more frequently among patients with DPYD deficiency despite lower baseline cardiovascular risk. These findings suggest that DPYD status may confer increased susceptibility to fluoropyrimidine-associated cardiotoxicity and highlight missed opportunities for genotype-guided dose modification. Integration of pretreatment DPYD genotyping, upfront genotype-guided dose reduction, and enhanced cardiac monitoring into standard care may help mitigate this risk. Further prospective and translational studies are needed to clarify the mechanistic links between DPYD activity and cardiotoxicity and to inform genotype-driven treatment strategies.
Preferences and motivations for self-collection HPV testing among cervical cancer screening-eligible U.S. women: A nationally representative study.
e17528 Background: The United States Food and Drug Administration recently approved the human papillomavirus (HPV) self-collection test as a screening option for cervical cancer, a pivotal step toward improving cervical cancer screening rates through patient-centered innovation. However, little is known about population-level preferences for this self-collection screening method, as well as the factors that drive preference for home testing among screening-eligible women. Methods: Study data was derived from the Health Information National Trends Survey (HINTS 7, 2024). The study population included cervical cancer screening-eligible women aged 21 to 65 years, with no prior cervical cancer diagnosis. Prevalence estimates were used to describe preferences for at-home versus clinic-based cervical cancer testing, as well as self-reported reasons for preferring home-based collection. Multiple bivariate logistic regression models were used to investigate associations between respondents’ sociodemographic characteristics and preference for self-collection screening. Results: A total of 2,272 women were included in the analysis, with a mean age of 45.2 years. For race and ethnicity, 48.6% represented Non-Hispanic White, 24.2% Hispanic, 16.3% Non-Hispanic Black, 5.1% Non-Hispanic Asian, and 4.0% Other Non-Hispanics. Overall, 20.2% preferred at-home testing, 60.7% preferred testing in a doctor’s office, and 19.1% were unsure about their preference. The most frequently cited reasons for preferring at-home testing included privacy (65.4%), avoiding time off work (39.7%), avoiding embarrassment (32.9%), saving transport costs (32.2%), and distance to provider (11.6%). Compared with Non-Hispanic White women, Non-Hispanic Black, Hispanic, and Non-Hispanic Asian women had significantly lower odds of preferring home-based testing (OR = 0.39, p < 0.001; OR = 0.63, p = 0.001; and OR = 0.53, p = 0.024), respectively. No significant associations were observed between preference for home testing and age, marital status, weekly working hours, household income, body mass index, or prior cancer diagnosis history. Conclusions: Roughly one in five screening-eligible U.S. women expressed preference for at-home cervical cancer testing, primarily motivated by privacy, interruptions with work, saving cost, and convenience. Preference for self-testing is lower with other races compared to non-Hispanic Whites. Integrating self-collection into national screening programs could be a promising strategy in not only improving screening rates but also reducing structural barriers, improving participation among underserved women, and accelerating progress toward cervical cancer elimination in the United States.
Obese patients with non-small cell lung carcinoma and the intratumor microbiome and immune microenvironment.
e20675 Background: Data that obesity is the primary driver of alterations of intratumor microbiota (IM) is accumulating. A particularly unique relationship exists between obesity and lung cancer risk/recurrence, termed the ‘obesity paradox’, or an inverse association between body mass index (BMI) and lung cancer. More specifically, a high BMI is an independent predictor of decreasing lung cancer risk, better treatment outcomes, and overall longer survival, unlike the negative effect of obesity observed in other cancers. This relationship has not yet been explored in non-small cell lung carcinoma (NSCLC) patients. Methods: In this study, IM samples were collected from formalin-fixed samples from racially and ethnically diverse patients, including obese and non-obese patients (i) obese (tumor = 20 and tumor adjacent normal = 6), (ii)non-obese (tumor = 23, tumor adjacent normal = 8), (ii) negative controls (n = 4). Extracted DNA underwent 16S sequencing, and microbial α- and β-diversity was calculated and compared by obesity status. Differential abundance was calculated. We assessed the association between IM composition, clinicopathological characteristics, and outcomes. After rigorous filtration, all OTUS measuring more than 192 in counts in negative controls are removed. Statistical tests included ANOVA, PERMANOVA, and the Wilcoxon test. p-value < 0.05 was considered statistically significant. Phyloseq and ANCOM-BC were utilized for bioinformatics analysis. In a subset of patients, we determined the relative presence of CD8+ cytotoxic and CD4+ helper/regulatory T-cells in the tumor microenvironment of obese and non-obese patients (n = 10), by immunohistochemistry. Results: Microbial richness, genus number, and beta-diversity were associated with obesity status ( p = 0.006, p = 0.013, and p< 0.0001, respectively). Microbes from the genus Thermi and Flavobacteria are enriched in non-obese patients, regardless of tumor status. Both these microbes are associated with early-stage NSCLC. T-cell evaluation showed a higher prevalence of CD4+ compared to CD8+ cells in the obese group (p = < 0.0001), whereas the non-obese group had a higher number of CD8+ cells (p = 0.097). A higher ratio of CD4+/CD8+ is associated with a better response to immunotherapy. No consistent associations were seen between the IM and any other available demographic and clinical features, including age, sex, genetic ancestry, tumor histology, stage, and overall survival. EGFR status was also not associated with specific microbiota. Conclusions: These results confirm that obese patients harbor a distinct lung IM in NSCLC, irrespective of histologic grade or histologic subtype, and may benefit from immune-based therapies regardless of clinical or pathologic stage. Further characterization of these findings in large, prospective studies is needed to elucidate their potential clinical applications.
AI-powered volumetric and radiomic MRI brain analysis for prognostication and treatment response patterns in ALK+ NSCLC brain metastases: Comparative outcomes of brigatinib versus crizotinib.
e20520 Background: Brigatinib (brig) has demonstrated improved intracranial disease control compared to crizotinib (criz) in ALK+ non-small cell lung cancer (NSCLC). In this study we provide detailed characterization into brain metastases response patterns using volumetric and radiomic analysis as well as predicting intracranial progression-free survival (iPFS), offering a promising, non-invasive approach using standard of care (SOC) imaging. Methods: We retrospectively analyzed 98 ALK+ NSCLC patients with brain metastases from ALTA-1L trial with baseline and first follow-up MRI (T1W post-contrast and T2W/FLAIR). Viable tumor volume, necrosis, and edema were quantified; 225 radiomic features were extracted per scan. Linear mixed-effects models and multivariate survival analyses were employed to correlate radiomics and volumetric change with iPFS, controlling for treatment and patient effects. Lesion-level features were aggregated to the patient level using volume-weighted averaging or by selecting features from the largest lesion. Model performance was assessed using C-index and AUC via cross-validation. Results: Of evaluable patients, 30 received brigatinib (429 lesions) and 40 received crizotinib (752 lesions). Brig treated patients exhibited significantly greater intracranial tumor burden reduction (median -61.6% vs -17.7%) and improved iPFS at 12 months (56.7% vs 7.5%) compared to criz. Brig achieved consistent tumor volume reduction regardless of baseline lesion size, while criz showed only stabilization. Early changes in specific T1PC texture radiomic features (MaxGrad_IH and HGLDE_NGLDM) correlated with long-term iPFS in brigatinib-treated lesions. Baseline radiomic features provided moderate prognostic value (C-index 0.68; AUCs 0.75 for 6-month and 0.72 for 12-month iPFS), with performance enhanced by incorporating longitudinal delta features (C-index 0.80; AUCs 0.84 and 0.87 for 6- and 12-month iPFS, respectively), particularly those derived from FLAIR sequences and aggregated across all lesions. The exploratory lesion-level volumetric response model showed moderate discrimination (AUC 0.70), though impacted by class imbalance. Conclusions: This study highlights the value of AI-powered volumetric and radiomic MRI analysis for non-invasive prognostication and monitoring, using SOC imaging. The study reiterated superior intracranial efficacy of brig over criz across various volumetric response patterns. Longitudinal delta radiomic features, significantly enhance prediction of iPFS compared to baseline features alone in ALK+ NSCLC patients receiving TKI therapy. Brig not only achieves superior intracranial disease control but also enables identification of radiomic markers predictive of long-term benefit, supporting its use as a first-line therapy. Clinical trial information: NCT02737501 .
A phase I trial of emavusertib (CA-4948) in combination with gemcitabine and nab-paclitaxel in metastatic or unresectable pancreatic ductal adenocarcinoma (PDAC).
e16410 Background: Interleukin-1 Receptor Associated Kinase -4 (IRAK4) drives pro-survival NF-kB signaling in PDAC. In preclinical animal models, the oral IRAK4 inhibitor, emavusertib (CA-4948), augments the efficacy of cytotoxic chemotherapy by suppressing cell intrinsic survival mechanisms and prolongs survival when combined with gemcitabine (G)/ nab-paclitaxel (nP) as well as reduces desmoplasia in preclinical models. Methods: This is a multi-institution, Phase I, dose escalation/expansion clinical trial of emavusertib in combination with G/nP as second-line therapy for metastatic or unresectable PDAC (NCI 10522, NCT05685602). The primary objectives of this study are to determine the dose-limiting toxicities (DLTs) and the RP2D of emavusertib in combination with G/nP. Emavusertib is given continuously at escalating doses of DL0 (150 mg p.o. BID), DL1 (200mg BID), and DL2 (250mg BID) with G (1000mg/m 2 i.v.) and nP (125mg/m 2 i.v.) on Days 1 and 8 of every 21-day cycle. DL3 (emavusertib 200mg BID) and DL4 (emavusertib 250mg BID) are given continuously with G/nP on Days 1, 8, and 15 of every 28-day cycle. Dose escalation is according to the BOIN design to determine the MTD of emavusertib in combination with G/nP. Toxicities are graded according to CTCAE v5.0. Response was evaluated according to RECIST v1.1 criteria. Results: We have treated 21 patients in dose escalation (DL0 N = 4, DL1 N = 6, DL2 N = 3, DL3 N = 6, DL4 = 2) with a median number of 3 cycles (range 1-20). To date, there has been one G4 treatment-related adverse event (TRAE) (pancytopenia) at DL0. G3 TRAE includes neutropenia in 10/21 patients (48%), G3 anemia in 4/21 patients (19%), and G3 CPK increase in 1/21 (5%) patients. DLTs occurred at DL1 (G3 CPK increase) and DL3 (G3 diarrhea) while DLTs are currently being assessed in DL4. Fifteen (15) patients are evaluable for response with partial response observed in 3/15 patients (20%), stable disease in 6/15 patients (40%), and progressive disease in 6/15 patients (40%) as their best response, with no complete responses. Objective response rate (ORR) is 20% (3/15 patients), and disease control rate (DCR) is 60% (9/15 patients). Conclusions: At this early stage of the study, emavusertib in combination with G/nP as second-line therapy for metastatic or unresectable PDAC has a manageable toxicity profile and shows encouraging preliminary results with an ORR of 20% and DCR of 60%, compared to historical ORR of 13-17% and DCR of 46-58% for G/nP, respectively. Escalation to DL4 is ongoing, which will be followed by dose expansion at RP2D. Clinical trial information: NCT05685602 .
Mesenteric approach during pancreaticoduodenectomy as modulator of CTC DNA dynamics in pancreatic cancer.
e16464 Background: In pancreatic ductal adenocarcinoma (PDAC), surgical manipulation may facilitate the intraoperative release of circulating tumor cells (CTCs) into the portal venous circulation. The mesenteric approach has been advocated as a strategy to reduce tumor handling and potential tumor cell dissemination; however, its effect on perioperative CTC-related biomarkers has not been fully elucidated. We evaluated perioperative changes in portal venous circulating tumor cell–derived DNA (CTC DNA) to assess the biological impact of surgical approach. Methods: Portal venous blood samples were collected intraoperatively at two time points—immediately after laparotomy and just before specimen removal—in patients undergoing pancreatectomy for PDAC. A total of 107 patients were included: 52 patients underwent the conventional approach and 55 patients underwent the mesenteric-first approach. CTC DNA copy numbers were quantified, and perioperative changes were compared between surgical approaches. Overall survival (OS) was analyzed according to surgical approach and perioperative CTC DNA dynamics. Results: Baseline clinicopathological characteristics and pathological diagnoses were well balanced between the two groups. The mean CTC DNA copy number immediately after laparotomy was 16.0 ± 16.2 copies in the conventional group and 23.7 ± 28.9 copies in the mesenteric-first group. Just before specimen removal, the mean CTC DNA copy number increased to 26.1 ± 29.3 copies in the conventional group, whereas it decreased to 16.3 ± 17.8 copies in the mesenteric-first group. The mean perioperative change in CTC DNA copy number was significantly different between groups, with an increase of +10.1 ± 2.6 copies in the conventional group and a decrease of –7.3 ± 2.6 copies in the mesenteric-first group (p < 0.0001). Despite these marked biological differences, no significant difference in OS was observed between the conventional and mesenteric-first approaches (HR 0.67, 95% CI 0.39–1.13; p = 0.127). Similarly, OS did not differ significantly between patients with increased versus decreased intraoperative CTC DNA copy numbers (HR 0.77, 95% CI 0.45–1.31; p = 0.331). Conclusions: The mesenteric approach was associated with a significant intraoperative reduction in portal venous CTC DNA copy number, suggesting suppression of CTC release during tumor manipulation. Although these perioperative CTC-related changes did not translate into a survival benefit, CTC DNA dynamics may serve as a sensitive biomarker reflecting the biological impact of surgical handling in pancreatic cancer resection. Clinical trial information: NCT03317886 .
Investigating interactions between pharmaceutical industry and oncologists in Africa: A secondary analysis of ONCOTRUST-2 study.
9034 Background: Following the hypothesis-generating ONCOTRUST-1 study, ONCOlogy TRansparency Under Scrutiny and Tracking 2 (ONCOTRUST-2) aimed to compare perceptions, understanding, and behaviors related to conflicts of interest (COI) in oncology between high-income countries (HICs) and low- and middle-income countries. This secondary analysis focuses on African countries versus HICs to explore regional differences in interactions with the pharmaceutical industry. Methods: We conducted a cross-sectional, survey-based study over two years (January 2024–January 2026). Participants were oncologists practicing in Africa or HICs. Outcomes included perceptions of industry-oncologists’ interactions, recognition of COI scenarios requiring disclosure, and self-reported behaviors. Comparisons used Chi-squared or Fisher’s exact tests as appropriate. Results: A total of 331 oncologists were included (Africa n=133; HIC n=188; 52% women). Most respondents were specialists (61.3%), followed by professors (22.1%) and trainees (15.1%). HIC oncologists reported better understanding of evidence-based medicine (EBM) than African oncologists (p=0.002). Overall ability to identify all COI scenarios requiring declaration did not differ (p=0.45), but HIC oncologists more frequently recognized consulting/advisory roles, direct payments/honoraria, expert testimony, personal funding, and travel/conference support as declarable COI (all p<0.01). No group differences were observed for sample drugs, institutional research funding, gifts, or food/beverage paid by industry (all p>0.05). Self-reported COI disclosure prevalence was similar between groups (p=0.67), and travel/conference support from pharmaceutical industry did not differ (p=0.14). African oncologists reported fewer consulting honoraria (p=0.001) and lower amounts (p<0.001) and less research funding (p=0.02), but more receipt of drug samples (p=0.001). Compared with HIC peers, African oncologists reported poorer disclosure practices (less reporting in publications when COI existed, p=0.001; less disclosure before presentations, p<0.0001). Moreover, African oncologists reported more prescription pressure from industry (p=0.013) and lower perceived objectivity in trial appraisal when COI exist (p=0.056). Interestingly, HIC oncologists more often endorsed adopting new drugs despite weak clinical-trial evidence (p=0.003). Knowledge of COI regulations/policies was lower in Africa (p<0.0001). Across both groups, support was strong for clearer COI policies, education, and online COI databases. Conclusions: African and HIC oncologists showed difference in recognition of specific COI types, disclosure behavior, and policy awareness. Strengthening COI education and implementing clear enforceable policies are therefore needed.
Career fulfillment and intent to leave among oncology physicians: A global survey.
9009 Background: Burnout among U.S. oncologists has risen from 34% (2013) to 59% (2023), with global estimates of 32–45%. However, burnout is often studied in isolation rather than alongside fulfillment, distress, and intent to leave, limiting understanding of workforce attrition. With ~20% of US oncologists leaving clinical roles over the past decade, factors driving workforce attrition require a precise evaluation across international settings. Methods: An anonymous, cross-sectional global survey distributed via professional email (Oct–Dec 2025) assessed burnout using validated Maslach Burnout Inventory (MBI) items and evaluated associations with professional fulfillment, career regret, and intent to leave clinical practice among oncology physicians. Descriptive statistics were performed, with χ²/Fisher’s exact tests for categorical comparisons and multivariable logistic regression to identify independent factors associated with fulfillment and intent to leave. Results: A total of 306 participants were included (156 non-U.S. and 150 U.S.). Clinical workload was substantial: 33.0% reported ≥5 clinic half-days per week, and 57.7% reported ≥5 inpatient service weeks annually. Administrative burden was also common, with 45.6% independently performing peer-to-peer appeals and 53.8% reporting feeling overwhelmed by this responsibility. Career satisfaction was reported by 70.6%, while job-related stress was highly prevalent (71.9%). Work frequently extended beyond scheduled hours, with 48.0% reporting moderate-to-excessive after-hours electronic medical record use. More than one-quarter of respondents (27.4%) expressed regret about pursuing a career in oncology, most attributed to poor work–life balance (69.3%) and burnout (65.3%). Despite these challenges, 50.5% reported frequent professional fulfillment and 21.7% reported very high fulfillment, particularly among U.S.-based vs. non-U.S. physicians (62.7% vs 25.0%, P < 0.001). Overall, 45% reported ever considering leaving practice; frequent intent to leave was higher among U.S.-based physicians (15.3% vs 7.1%, P = 0.034) [Table 1]. Conclusions: Oncologists experience a fulfillment–distress paradox, reporting meaningful professional fulfillment despite high stress, administrative burden, career regret, and intent to leave practice. This “professional dissonance” suggests that meaning and identity in oncology may persist despite insufficient institutional support but may remain fragile over time. Systems-level approaches addressing workload, professional culture, and identity formation are needed to improve physician well-being and workforce retention. Key outcomes by region. Outcome (often/always) Non-US(n=156) US(n=150) p-value Fulfillment high 39 (25.0%) 94 (62.7%) <0.001 Consider leaving high 11 (7.1%) 23 (15.3%) 0.034
Causes of death in patients with lymphoplasmacytic lymphoma.
e19079 Background: Lymphoplasmacytic lymphoma (LPL) is an indolent type of B-cell non-Hodgkin lymphoma. In the majority of cases, it presents as Waldenström Macroglobulinemia (WM), which is defined by the presence of bone marrow involvement and IgM monoclonal gammopathy. There are limited data regarding the causes of death in patients with LPL / WM. Methods: We conducted a retrospective review of 82 consecutive LPL patients followed in our Hematology/Oncology clinic between January 2000 and December 2025. Patients with IgM-MGUS were excluded from the analysis. Results: The median age at diagnosis was 72 years (range, 43-96), and 51 patients (62%) were male. The paraprotein was IgM-kappa, IgM-lambda, and other (IgA, biclonal IgM-kappa + IgM-lambda, or absent) in 55 (67%), 22 (27%), and 5 (6%) patients, respectively. Patients received a variety of chemotherapy and targeted agents, alone or in combination, with the most frequently administered being rituximab (n=36), corticosteroids (n=17), zanubrutinib (n=10), ibrutinib (n=8), bortezomib (n=7), bendamustine (n=6), chlorambucil (n=6), cyclophosphamide (n=6), carfilzomib (n=4), fludarabine (n=3), and others (n=7). Death occurred in 32 (39%) patients. The most common cause of death was infection (n=10), associated with chemotherapy in only 1 case. The second most frequent cause was metastatic cancer other than LPL: lung (n=4), prostate (n=3), squamous cell skin cancer (n=1), and acute myelogenous leukemia (n=1). Five patients died of comorbidities unrelated to LPL, and 2 patients died of traumatic causes. Only 5 (6%) patients died as a direct result of LPL, due to untreated hypercalcemia (n=2), thrombocytopenia (n=2), and anemia (n=1). Of note, the LPL of these 5 patients was intentionally left untreated, because of poor performance status due to advanced age and significant comorbidities, including dementia. Conclusions: In our experience of 82 consecutive LPL patients followed over 25 years, none died directly from LPL when able to receive appropriate therapy.
Malignant hemangiopericytoma: A National Cancer Database study of demographic and socioeconomic factors.
e22628 Background: Malignant hemangiopericytoma (HPC) is a rare and solitary fibrous tumor arising from pericytes surrounding small blood vessels. Annual incidence in the United States is estimated at 0.6 per million for cases originating in the CNS. Prior case series reported prognosis is poor, with high rates of local recurrence (87%) and metastasis (64%). Definitive diagnosis typically requires tissue biopsy due to nonspecific imaging and histologic features. To address the limitation of large-scale data, the National Cancer Database (NCDB) was analyzed to characterize demographic and socioeconomic factors for an epidemiologic evaluation in patients with malignant HPC. Methods: This retrospective cohort study included patients with histologically-confirmed malignant HPC (N = 1,648) (ICD-O-3 code - 9150) within the 2004–2020 NCDB. Demographic factors (age, sex, race, Hispanic status, educational attainment, insurance status, facility type, location of facility, and Charlson-Deyo score) were analyzed by descriptive statistics, and incidence trends were interpreted in regression analysis. Results: The incidence of HPC remained stable over the study period, with no meaningful temporal trend observed (R^2 = 0.04). Patients were diagnosed at a mean age of 52.7 years (SD = 16.2), with a near equal sex distribution (51.5% female). Patients were predominantly non-Hispanic (89.3%), White (83.3%), residing in metropolitan areas (53.2%) with private insurance (56.4%). Additionally, 38.5% of patients resided in the highest income quartile (≥$74,063). Comorbidity burden was low in this cohort (78.6% with a Charlson–Deyo Score 0). Cerebral meninges was the most common primary site (24.8%), with most tumors considered borderline (41.6%) or malignant/invasive (45.0%). Radiation therapy served as the primary treatment (54.1%). Treatment often occurred at academic/research programs (41.3%) or comprehensive community cancer programs (22.5%). Ninety-day survival following primary surgery was high (98.2%). Estimated overall survival was 93.0% at two years, 80.2% at five years, and 58.9% at ten years, with a mean survival of 132.2 months. Conclusions: To the best of our knowledge, this is the first NCDB analysis on malignant HPC, demonstrating near-equal sex distribution. Analysis revealed patients were more likely to be female, non-Hispanic, in the top income quartile, have private insurance, and reside in populated metropolitan areas. Most patients received care at academic/research institutions, with radiation therapy as the primary treatment. These patterns highlight the need for deeper investigation into how demographic and socioeconomic factors shape diagnostic timing, guide treatment selection, and influence long-term outcomes of this rare malignancy.
Efficacy and safety of anlotinib and sintilimab combined with GEMOX in advanced combined hepatocellular-cholangiocarcinoma (cHCC-CCA): A prospective phase II study.
e16203 Background: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary liver cancer with poor prognosis and no standardized standard-of-care for advanced disease. While immunotherapy-based combinations have improved outcomes in hepatocellular carcinoma and biliary tract cancer separately, evidence for cHCC-CCA remains limited. We hypothesized that a triplet regimen integrating chemotherapy, targeted therapy, and immunotherapy would improve outcomes. We present results from a phase II study evaluating anlotinib and sintilimab combined with gemcitabine and oxaliplatin (GEMOX) in advanced cHCC-CCA. Methods: This prospective, single-arm, phase II study enrolled patients with advanced or metastatic cHCC-CCA who were either treatment-naïve or had progressed on prior systemic therapy. Patients received gemcitabine ($1000\ mg/m^2$ IV, D1, D8) and oxaliplatin ($85\ mg/m^2$ IV, D1) combined with anlotinib (8 mg PO, D1–14) and sintilimab (200 mg IV, D1) every 3 weeks for 6 cycles. This was followed by maintenance with anlotinib and sintilimab until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) per RECIST v1.1. Secondary endpoints included safety, progression-free survival (PFS), and overall survival (OS). Results: Between December 2023 and November 2025, 12 patients were enrolled. Seven patients (58.3%) had received at least one prior line of systemic therapy. Per RECIST v1.1, the confirmed ORR was 58.3% (7/12) and the disease control rate (DCR) was 91.7% (11/12). The median PFS was 6.3 months (95% CI, 1.5–11.9). Median OS was not reached; the 6-month and 12-month OS rates were 91.7% and 71.3%, respectively. Grade 3/4 treatment-related adverse events included neutropenia, thrombocytopenia, and elevated transaminases, which were manageable with dose adjustments or supportive care. No treatment-related deaths occurred. Conclusions: The combination of GEMOX, anlotinib, and sintilimab demonstrates promising antitumor activity and a manageable safety profile in patients with advanced cHCC-CCA, including those who have progressed on prior therapies. These results support further investigation in larger cohorts. Clinical trial information: NCT06033118 .
Integrative genomic profiling of Indian brain tumors: Prognostic markers and actionable therapeutic opportunities.
e14096 Background: Brain tumors are aggressive malignancies with substantial genetic heterogeneity, complicating prognosis and treatment. Comprehensive mutation profiling via next-generation sequencing enables robust molecular classification and identification of prognostic biomarkers and potential therapeutic targets, guiding precision medicine beyond conventional chemotherapy and radiotherapy. Methods: Retrospective analysis of 94 brain tumor samples from patients who opted for CGP with 4baseCare’s comprehensive gene panels. Results: Demographics: Predominantly male (62.7%); 67.0% aged ≥40 years. Histology: Glioblastoma constituted 55% of cases; remaining tumors encompassed diverse gliomas. Mutational landscape: TP53 mutations most frequent (42%), followed by TERT (26%) and PTEN (25%), with TERT/PTEN mutations co-occurring in 11% of samples. Recurrent mutations observed in EGFR , PIK3CA , NF1 , RB1 (each 14%). Additional mutations included MTHFR , POLE , ATM , and MSH6 (approximately 10% each). IDH1 mutations were present in 14% of the cohort, enriched in glioma subtypes; glioblastoma were largely IDH -wild type. Tumor mutational burden (TMB) was low (≤10 mutations/Mb) in majority (91.6%) of samples in a subset (n=48). Conclusions: Brain tumors remain challenging to treat, with targeted and biomarker-guided options currently limited and reliance on conventional chemotherapy for majority of patients. This study defines prognostic and predictive biomarkers that can refine risk stratification and guide therapy in selected patients. Key markers include: RB1 mutations associated with improved overall survival; TERT and PTEN alterations linked to worse prognosis; IDH1 mutations associated with better prognosis and potentially enhanced treatment response; POLE , ATM , and MSH6 alterations indicating potential resistance to temozolomide and implications for alternative strategies; and druggable pathways such as PI3K/AKT/mTOR for biomarker-defined subgroups. Overall, these genomic insights lay the groundwork for integrating CGP into routine brain oncologic care to optimize risk stratification, personalize treatment decisions, and identify candidates for biomarker-guided trials.