Accurate risk stratification of intraductal papillary mucinous neoplasms (IPMNs) remains clinically challenging. This study evaluates a structured imaging-based scoring approach for IPMN risk stratification, referred to as the Tübingen Dignity Score (TDS), and compares its diagnostic performance with established methods.

In this retrospective study, imaging findings from patients with suspected IPMN were analyzed using MRI, CT, and ultrasound. The TDS was applied as an imaging-based scoring system. Diagnostic performance was assessed in a histopathological subset and compared with MRI-based assessment and Fukuoka criteria.

MRI showed high sensitivity (94.4%) but limited specificity (57.1%). Fukuoka criteria showed high sensitivity (100%) and high specificity (91.3%) in this cohort, although with a lower positive predictive value. In contrast, the TDS showed high specificity (100%) and positive predictive value, but lower sensitivity (40%), reflecting a different diagnostic profile. These findings indicate a trade-off between sensitivity and specificity across the evaluated approaches. However, the limited number of malignant cases limits the robustness and generalizability of these estimates.

The TDS may serve as a complementary, imaging-based tool within a multimodal diagnostic framework for IPMN. Its potential value lies in supporting clinical decision-making in selected cases, particularly where established criteria yield inconclusive results. Given the limited sample size, retrospective single-center design, and exploratory nature of this study, external prospective multicenter validation is required before routine clinical application can be recommended.

Background/Objectives: Tumor-infiltrating lymphocyte (TIL) therapy is an important option for patients with metastatic melanoma progressing after standard systemic therapy, but real-world data on treatment delivery, toxicity monitoring, and immune recovery remain limited. We evaluated clinical outcomes, treatment tolerance, immune reconstitution, and cardiac biomarker dynamics across three Mayo Clinic sites. Methods: We retrospectively analyzed adults with metastatic melanoma who received lymphodepleting chemotherapy followed by TIL infusion and high-dose interleukin-2 (IL-2) between April 2024 and December 2025. Clinical outcomes, treatment delivery, and adverse events were assessed. Longitudinal immune monitoring included CD4 and CD8 T-cell counts, CD4:CD8 ratio, and immunoglobulin G (IgG) at baseline and follow-up. In a prespecified cardiac sub-cohort, high-sensitivity troponin (hs-Tn) was measured during IL-2 administration to evaluate associations with cardiac events and IL-2 interruption. Results: Thirty-six patients underwent TIL infusion. The objective response rate was 50.0%, including complete responses in 13.9%, and the disease control rate was 72.2%. Median progression-free survival was 3.61 months, and median overall survival was 12.94 months. M1d disease was associated with inferior overall survival on univariable analysis (HR 6.55, 95% CI 2.03-21.17; p = 0.002), with attenuation after multivariable adjustment. Receipt of ≥3 IL-2 doses was associated with longer overall survival on univariable analysis (HR 0.20, 95% CI 0.06-0.64; p = 0.007), but this association also attenuated after adjustment. Longitudinal immune monitoring demonstrated persistent CD4 lymphopenia through 6 months, sustained inversion of the CD4:CD8 ratio, and declining IgG at months 3 and 6. In the cardiac sub-cohort (24 patients; 87 IL-2 doses), post-dose hs-Tn ≥15 ng/L was associated with clinically significant cardiac events (OR 9.6, 95% CI 1.5-60.6; p = 0.016) and IL-2 interruption (OR 3.4, 95% CI 1.1-10.7; p = 0.036). For cardiac events, hs-Tn ≥15 ng/L had 100% sensitivity and 100% negative predictive value. Conclusions: In routine practice, TIL therapy was feasible and active in metastatic melanoma. M1d disease identified a subgroup with poor survival, peri-dose hs-Tn showed promise as a tool to support safer IL-2 delivery, and prolonged CD4 suppression with IgG decline suggests that recovery after TIL therapy extends beyond initial hematologic reconstitution. These findings support prospective validation of biomarker-guided IL-2 monitoring and extended post-treatment immune surveillance.

The fifth annual pan-tumour Early Age Onset Cancer (EAOC) Symposium, held in November 2025 and organized by the Colorectal Cancer Resource & Action Network (CCRAN), convened clinicians, researchers, policymakers, patients, and caregivers to address the rising incidence of cancers in individuals under 50 years. In addition to discussions around diagnostic and therapeutic advances for patients with late-stage disease, content centered on addressing critical gaps along the EAOC care continuum, including (i) diagnostic delays related to limited awareness and suboptimal primary care pathways, (ii) screening eligibility criteria for colorectal cancer (CRC) that no longer reflect current disease epidemiology, and (iii) insufficient age-appropriate infrastructure to meet the EAOC population's unique unmet needs with respect to psychosocial support, fertility counseling, financial navigation, and survivorship planning. The symposium generated consensus recommendations such as the embedding of EAOC education into medical training curricula to increase the index of suspicion of EAOC in primary care, lowering the CRC screening age to 45 years to match this population's rising disease incidence, and expanding multidisciplinary adolescent and young adult (AYA) and EAOC programs-including through the use of virtual models-to ensure that patients receive coordinated, comprehensive, equitable and age-appropriate care across the country.

A subgroup of adolescent and young adult patients (AYAs; 18 to 39 years at diagnosis) face an uncertain or poor cancer prognosis (UPCP). Previous qualitative research identified dual coping pathways in this population: engagement in life versus the reality of premature death. This study examines whether similar psychosocial profiles can be identified through quantitative data, aiming to differentiate patient experiences and identify characteristic features of each cluster. Additionally, this study examines the association between cluster membership and social support needs to understand psychosocial disparities.

Eligible participants completed questionnaires assessing physical, psychosocial, and existential outcomes related to their disease and prognosis. An ensemble clustering approach was applied, including evaluation of clustering tendency and multiple algorithms, with stable clusters identified through majority voting. Associations with social support needs were analyzed using Fisher's exact test.

Data from 155 AYAs with a UPCP were included. The mean age at diagnosis was 31.2 years, with glioma (34.8%) and breast cancer (17.4%) as the most common diagnoses. Two distinct clusters were identified: one (22%) characterized by poorer functional outcomes and fewer protective factors (e.g., hope, meaning in life), and another cluster (78%) with better functioning and less frequent needs for social support (p < 0.00043).

Findings revealed divergent psychosocial profiles within the AYA-UPCP population, highlighting the importance of early identification of vulnerable subgroups. Strengthening protective factors may enhance resilience and reduce unmet support needs. Validation in larger, external datasets is needed to confirm these pathways and guide tailored supportive care strategies.

Patients with acute myeloid leukemia (AML) experience severe infections frequently during and after chemotherapy. The purpose of this study was to develop an early risk assessment tool to identify newly diagnosed AML patients at high risk of developing sepsis during the early phase of induction chemotherapy.

The records of 192 newly diagnosed AML patients from February 2017 to December 2023 at our institution were retrospectively reviewed. Kaplan-Meier survival analysis was performed to explore the prognosis difference between groups with or without sepsis. Mann-Whitney U test, Chi-square test, and multivariable logistic regression analysis were used to identify independent risk factors and establish a nomogram for early risk stratification of sepsis. The predictive accuracy of the nomogram was evaluated using the area under the curve (AUC), calibration curves, and concordance index (C-index). The nomogram is intended for application on days 3-5 of induction chemotherapy.

Multivariate logistic regression identified TP53 mutation, elevated aspartate aminotransferase (AST) and C-reactive protein (CRP) at diagnosis, increased procalcitonin (PCT), and higher urea levels post-induction as independent risk factors for sepsis progression. The bootstrap-corrected AUC was 0.892 (C-index 0.892). The bias-corrected calibration curve was close to the ideal line, demonstrating strong consistency between actual observations and predictions. Patients with sepsis experienced a poorer prognosis (p < 0.001) both at 1-year and 5-year survival rates. The incidence rates of pneumonia and invasive fungal infection were higher in the sepsis group.

We developed a nomogram for early identification of sepsis risk in newly diagnosed AML patients during their initial induction chemotherapy. This tool may assist clinicians in identifying patients requiring close monitoring and intensive supportive care.

Allogeneic hematopoietic cell transplantation (allo-HCT) improves survival in patients with acute myeloid leukemia (AML); however, posttransplant relapse remains the most common cause of treatment failure and death. Limited data exist on posttransplant health care resource utilization (HCRU) and costs, particularly for patients initiating maintenance therapy.

To describe HCRU and costs among commercially insured patients, Medicaid enrollees from participating US states, and Medicare-eligible beneficiaries with employer-sponsored supplemental coverage who received maintenance therapy after allo-HCT compared with those receiving allo-HCT alone.

We conducted a retrospective cohort study of patients with AML who underwent allo-HCT using claims data from the Merative MarketScan database from October 1, 2015, to March 31, 2024. Patients receiving maintenance therapy were identified by a claim for 1 of the following agents after allo-HCT: azacitidine, decitabine, enasidenib, gemtuzumab ozogamicin, gilteritinib, glasdegib, ivosidenib, midostaurin, quizartinib, sorafenib, or venetoclax. Groups were balanced using inverse probability treatment weighting (IPTW) based on baseline characteristics. We assessed differences in all-cause monthly HCRU and costs. HCRU included emergency department (ED) visits, inpatient (IP) admissions, outpatient (OP) visits, and hospital length of stay throughout the 12-month follow-up period. Poisson and negative binomial regression models estimated event rates. Per patient per month mean costs were reported with SEs, and between-group differences were assessed using mean differences, bootstrapped 95% CIs, and P values. Cumulative costs were summarized using the mean with bootstrapped 95% CIs and the median. IPTW-weighted mean monthly costs were also calculated for each cohort. Transfusion burden was also evaluated.

Of the 373 patients who met the inclusion criteria, 43 were prescribed maintenance therapy following allo-HCT. The maintenance therapy group demonstrated significantly higher HCRU across service types. Both office (incidence rate ratio [IRR] = 3.23, P = 0.004) and OP visits (IRR = 4.26, P < 0.001) were more than tripled compared with the allo-HCT-only group, and IP admissions rose by 34% (IRR = 1.34, P = 0.034). Specialist clinic and ED visit rates were higher but not statistically significant (IRR = 3.03, P = 0.060 and IRR = 1.51, P = 0.483, respectively). Health care costs transitioned from predominantly IP at transplant to mostly pharmacy-driven by month 4, with similar trends across both groups. The maintenance therapy group had significantly higher per patient per month pharmacy costs ($6,433.81 vs $3,132.51, P = 0.002). Blood transfusion requirements were minimal in both groups. Weighted mean length of stay was significantly longer in the allo-HCT-only cohort compared with the maintenance therapy group (26.53 [SE = 1.29] vs 21.40 [SE = 1.21] days, respectively), with a mean difference of -5.13 days (95% CI = -8.60 to -1.65; P = 0.004).

Those who received maintenance therapy following allo-HCT had higher IP admission and OP use rates and incurred more pharmacy costs. These findings highlight the need to balance the clinical benefits of maintenance therapy with its increased demands on health care resources.

Immune checkpoint inhibitors (ICIs) are widely used in advanced non-small cell lung cancer (NSCLC) but can lead to immune-related adverse events (irAEs) that may disrupt care. Although irAEs are well described clinically, there is limited evidence quantifying their downstream health care use and costs in Medicare beneficiaries with advanced NSCLC.

To evaluate health care use and costs associated with clinically impactful irAEs among older adults receiving ICI therapy.

Using Surveillance, Epidemiology, and End Results-Medicare data, we identified patients (fee-for-service beneficiaries) aged 66 to 85 years with advanced NSCLC and who initiated nivolumab, pembrolizumab, or atezolizumab, alone or in combination with each other or chemotherapy, between 2015 and 2017 (patient identification window), with follow-up through 2019. These agents represent ICIs approved for advanced NSCLC during the identification period. Clinically impactful irAEs were defined using irAE diagnosis codes accompanied by evidence of systemic immunosuppressant use and treatment interruption and were modeled as a time-varying exposure. Health care use and costs were assessed using weighted longitudinal models accounting for time-varying confounding (marginal structural models with stabilized inverse probability weights). Two-part generalized estimating equations estimated per-patient-per-month (PPPM) and cumulative outcomes over 6, 12, and 24 months, with sensitivity analyses including models incorporating ICI drug costs and alternative approaches to account for censoring.

Among 4,867 patients, 1,667 (34.3%) experienced a clinically impactful irAE. Adjusted all-cause health care use was higher among patients with irAEs (mean 15.8 [SE = 0.12] vs 12.0 [SE = 0.12] visits PPPM; difference, 3.9; 95% CI = 2.9-4.8), with more than double the odds of inpatient hospitalization (odds ratio, 2.21; 95% CI = 2.15-2.29). Adjusted all-cause medical costs averaged $16,042 (SE = 14.7) vs $12,721 (SE = 13.1) PPPM (difference, $3,322; 95% CI = $3,283-$3,361), driven primarily by inpatient care ($2,922; 95% CI = $2,903-$2,941). At 24 months, cumulative costs per patients were $846,013 (SE = 12,786) for patients with irAEs compared with $751,606 (SE = 11,358) for those without (difference, $94,407; 95% CI = $91,606-$97,207). Findings were consistent in sensitivity analyses.

Clinically impactful irAEs were associated with substantially higher health care use and costs among older adults with advanced NSCLC receiving ICIs, with inpatient care accounting for most excess costs. These findings have implications for managed care strategies focused on toxicity monitoring, hospitalization prevention, and value-based ICI management.

Many patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer (eBC) experience recurrence despite treatment with adjuvant endocrine therapy; recurrences bear a substantial cost and can impact life expectancy and quality of life.

To estimate the lifetime clinical and economic value of ribociclib for the treatment of patients with HR+/HER2- stage II/III eBC at high risk of recurrence including select node-negative and all node-positive patients.

A 4-state Markov model comparing ribociclib+nonsteroidal aromatase inhibitor (NSAI) with NSAI alone estimated the expected lifetime costs and effectiveness for patients with eBC (mean age = 53 years). High risk of recurrence in HR+/HER2- eBC was based on the NATALEE trial criteria: all node-positive and node-negative patients with tumor size larger than 5 cm or 2-5 cm with Grade 3 or Grade 2 and high genomic risk. Model outcomes included invasive disease-free survival (IDFS), locoregional recurrence (LR), distant recurrence (DR), overall survival, adjuvant treatment costs, adverse event costs, disease management costs by health state, and DR treatment costs. Patient-level IDFS for the first 4.5 years observed in the NATALEE trial was parametrically extrapolated thereafter. DR and LR progression risks and treatment utilization patterns were obtained from the literature. Model outputs included total costs, quality-adjusted life-years (QALYs), life-years (LYs), equal-value LYs (evLYs), and the incremental cost-effectiveness ratio (ICER) of ribociclib+NSAI vs NSAI when using IDFS as the effectiveness outcome.

Ribociclib+NSAI improved IDFS (13.08 vs 11.09 years) and reduced DR (DR state = 1.28 vs 2.35 years), generating QALY gains of 0.68 (ribociclib+NSAI = 11.45; NSAI = 10.77), LY gains of 0.69 (ribociclib+NSAI = 14.98; NSAI = 14.29), and evLY gains of 0.75 (ribociclib+NSAI = 11.52; NSAI = 10.77). Total lifetime incremental costs were $52,385 (ribociclib+NSAI = $831,433; NSAI = $779,047). The ICER was $77,448/QALY, and the probability of ribociclib+NSAI being cost-effective was 68.5% at a willingness to pay of $150,000/QALY.

Based on model estimation, ribociclib+NSAI is projected to be a cost-effective therapy in the United States vs NSAI alone by reducing the rate of high-cost metastatic recurrences and increasing QALYs.

Among the estimated 234,580 patients diagnosed with lung or bronchus cancer in 2024, an estimated 66%, or 154,823 patients, were diagnosed with advanced or metastatic non-small cell lung cancer (mNSCLC). More than half of patients have a genomic variant that can be treated with targeted therapy. Despite widespread evidence supporting the survival benefits of biomarker-driven management of patients with mNSCLC, real-world implementation of precision oncology has not kept pace with recommendations.

To quantify the potential survival deficit from underutilization of precision oncology (genomic testing and matched therapy) for patients with newly diagnosed mNSCLC in the United States.

We developed a simulation model comparing Observed Practice with Optimal Practice in which all eligible patients receive biomarker testing and appropriate treatment. We assessed a mix of 3 testing pathways assessed: (1) guideline-concordant biomarker testing consistent with National Comprehensive Cancer Network (NCCN) Guideline recommendations, (2) nonguideline biomarker testing, and (3) no biomarker testing. Input values and probabilities for each pathway were obtained from published data. Survival deficit was estimated as life-years lost in Observed Practice vs Optimal Practice.

Among the estimated 92,401 patients with new metastatic adenocarcinoma or large cell carcinoma histology, 49,427 patients were projected to have at least 1 of the 10 NCCN-recommended mutations with a known targeted first-line therapy. Among those harboring actionable mutations, 46,757 were assumed to be identified and treated with precision-matched targeted therapy (PMTT) in Optimal Practice vs 28,177 in Observed Practice. The 46,757 patients receiving PMTT in Optimal Practice realized a total of 113,417 life-years, a gain of 20,901 over the patients treated in Observed Practice.

Among patients with mNSCLC in the United States, suboptimal use of recommended panel testing and implementation of precision medicine for newly diagnosed mNSCLC is associated with life-years lost. Investments in effective programs that improve adherence to NCCN guideline recommendations and test-concordant therapy would result in increased life expectancy for up to 20,000 patients annually.

Human papillomavirus (HPV) causes multiple cancers. Understanding HPV-related cancer burden may help implement effective strategies for cancer prevention. The aim was to examine incidence and survival trends of eight HPV-related cancer sites in Estonia and estimate the number of cases attributable to HPV. Patient/material and methods: The Estonian Cancer Registry provided data on all cases of eight HPV-related cancer sites diagnosed in Estonia during 1995-2022. Age-standardized incidence trends were analyzed using joinpoint regression, estimating annual percentage change (APC). The number of HPV-attributable cases was estimated using internationally derived site-specific attributable fractions, as tumor HPV status was not available. Five-year relative survival ratios were calculated from national life tables.

In all, 11,266 cases of HPV-related cancer sites were diagnosed, of which 6,263 were estimated to be attributable to HPV; over 40% occurred before age 55. In women, estimated average annual number of HPV-attributable cases nearly quadrupled for oropharyngeal cancer (OPC) and tripled for anal cancer. A significant increase in OPC and anal cancer incidence was observed among women (APC 10.0 and 3.8, respectively). Cervical cancer incidence declined after 2012 (APC -5.6). Survival improved for OPC in men (from 13 to 44%) and vaginal cancer in women (from 45 to 73%).

HPV-related cancer patterns in Estonia are shifting from cervical to non-cervical cancers. Increasing oropharyngeal and anal cancer incidence highlights the need for prevention strategies beyond cervical screening alone. Strengthening HPV vaccination uptake and sustaining organized cervical screening are critical for reducing future cancer burden.