Abstract Background Advanced biliary tract cancer (BTC) has a poor prognosis following progression on first-line gemcitabine plus cisplatin. However, evidence comparing second-line chemotherapy regimens remains limited. This study aimed to compare the effectiveness and safety of fluorouracil, leucovorin, and oxaliplatin (FOLFOX); fluorouracil, leucovorin, and irinotecan (FOLFIRI); and capecitabine plus oxaliplatin (CapOx). Patients and Methods Adults with advanced BTC who received first-line gemcitabine plus cisplatin followed by second-line FOLFOX, FOLFIRI, or CapOx between January 2010 and July 2025 were identified from the TriNetX Global Collaborative Network. Patients who subsequently received molecularly targeted therapies were excluded. The study included 825 patients receiving FOLFOX, 184 receiving FOLFIRI, and 149 receiving CapOx; after 1:1 propensity score matching, the respective comparisons included 182 and 149 patients per group. Overall survival (OS) and treatment-related adverse events were compared between the matched cohorts. Results The median OS was comparable between FOLFOX and FOLFIRI (5.7 months vs. 5.8 months, P=.958) and between FOLFOX and CapOx (5.7 months vs. 5.8 months, P=.803). The overall adverse event profiles were also comparable. However, FOLFOX was associated with lower rates of neutropenia but higher rates of thrombocytopenia than FOLFIRI. In contrast, FOLFOX and CapOx demonstrated similar toxicity despite modest differences in anemia and thrombocytopenia. Conclusion This real-world study demonstrates comparable survival outcomes among FOLFOX, FOLFIRI, and CapOx as second-line chemotherapies for advanced BTC. These findings support individualized regimen selection based on patient characteristics and toxicity profiles.
Abstract Precision therapeutics have improved outcomes in gynecologic oncology, but their population-level impact depends on both biological efficacy and reliable treatment delivery. Randomized controlled trials establish causal effects under defined conditions; real-world evidence characterizes implementation and transportability while introducing distinct confounding and measurement challenges. This contextual narrative review integrates pivotal and updated therapeutic studies with clinical, social and translational evidence available through September 2026. Progression-free survival and overall survival are distinct endpoints, whereas effectiveness concerns benefit in routine care; cross-study interpretation requires aligned populations, treatment strategies, follow-up and estimands. The benefits of poly(ADP-ribose) polymerase inhibitors and immunotherapy are examined separately by molecular subgroup and treatment setting. Financial hardship, geographic access, caregiving and health-system constraints can affect initiation, tolerable exposure and continuity. We use the proposed term “social discontinuation” for treatment disruption with a material social contribution, while distinguishing clinical reasons and patient preference. Biological weathering provides plausible links between cumulative adversity and inflammatory, neuroendocrine, epigenetic and immune phenotypes. Human epidemiological associations, translational findings and experimental mechanisms support different inferences; mediation through treatment delivery remains distinct from biological modification of treatment effect. Priorities include justified broader eligibility, prospective social-needs and exposure measurement, responsive symptom management, navigation and hybrid care. Automated extraction and prediction tools require external validation, fairness assessment and prospective clinical-impact evaluation. Integrating randomized and real-world evidence can identify remediable barriers without diminishing the clinical value of effective therapies.
ABSTRACT Background Clinical and molecular features of pancreatic adenocarcinoma (PDAC) according to involved metastatic sites have not been well characterized. Materials and Methods We used the Foundry platform to query information for patients with metastatic PDAC at MD Anderson Cancer Center. Involved metastatic sites were extracted using natural language processing from imaging reports and verified by chart reviews. Overall survival (OS) and next generation sequencing (NGS) data were analyzed. Results In a cohort of 1,095 patients (median overall survival [OS]: 22.8 months), lung-only metastasis was associated with longer median OS (57.6 months, p<0.0001). Patients with metastases not involving the liver had OS of 41.3 months, while liver-only (19.5 months) and multiple sites including liver (19.3 months) had the poorest survival. TP53 mutation rates were higher in liver-involved groups (84–85%) versus lung-only (73%) and non-liver metastases (67%, p<0.0001). Lower rates of GNAS mutations were detected in liver-only (5%) and liver-involved (2%) cases, higher in lung-only (8%) and non-liver (10%, p<0.01). The frequency of KRAS mutation and mutant allele distribution were not significantly different in tissue based NGS. However, in liquid biopsy analysis (n = 240), lung-only metastasis showed the lowest mutation detection (50%), TP53 (23%) and KRAS (10%), compared to liver-only detection rates of 65%, 46%, and 52% respectively (p values: 0.009, 0.02, <0.001). Conclusions Patients with PDAC without liver metastasis have significantly improved OS and lower rates of TP53 mutation. Patients with lung-only metastasis had longer OS, a lower liquid-biopsy positivity rate, and a lower rate of KRAS detection by liquid biopsy; because liquid biopsy may under-detect KRAS in lung-only disease, tumor-tissue sequencing should be prioritized in these patients as KRAS-directed therapies emerge.
Abstract PURPOSE Exocrine pancreatic insufficiency (EPI) is a highly prevalent, yet modifiable determinant of treatment tolerance in pancreatic cancer (PC). Despite its clinical significance, management remains inconsistent due to a lack of oncology-specific guidelines. This project aimed to establish the first U.S. multidisciplinary consensus to standardize pancreatic enzyme replacement therapy (PERT) dosing, education, and longitudinal management in pancreatic oncology. METHODS A mixed-methods design was employed, integrating a parallel literature review, six virtual focus groups with patients and clinicians (n = 28), and a formal modified Delphi process. A multidisciplinary panel of 17 experts, including medical, surgical, and radiation oncologists, advanced practice providers, and oncology dietitians, independently rated and refined draft statements over two iterative rounds. Consensus was defined a priori as ≥ 70% agreement. RESULTS The process yielded 15 final Consensus Statements, all achieving ≥ 81% agreement. This manuscript highlights a critical subset of six statements focusing on clinical application (CS 10–15), which achieved 94%–100% consensus. Recommendations define standardized starting doses (48,000–72,000 lipase units per meal), evidence-based titration protocols, multi-level patient education requirements, and strategies to mitigate financial toxicity and pill burden. CONCLUSION These consensus statements provide a practical, evidence-based framework to reduce provider inertia and practice variability. Broad implementation of these standards offers a vital opportunity to stabilize nutritional status, improve quality of life, and optimize treatment continuity for patients with PC.
Abstract Background Adjuvant CDK4/6 inhibitors have improved outcomes in hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2–) early breast cancer (eBC) in the NATALEE and monarchE trials. However, real‑world evidence on the proportion of candidates for adjuvant CDK4/6 inhibitors and their outcomes within these trial-defined populations remains limited. Materials and Methods We conducted a retrospective, population‑based cohort study including all patients diagnosed with HR+/HER2– eBC in the Hospital District of Helsinki and Uusimaa, Finland, between January 2014 and June 2023. Patients were classified according to NATALEE and/or monarchE eligibility criteria. Outcomes assessed were invasive disease‑free survival (iDFS), distant disease‑free survival (DDFS), and overall survival (OS). Results Among 8,911 patients with HR+/HER2- eBC and a median follow-up of 5.2 years, 40.4% met the NATALEE eligibility criteria and 15.0% met the monarchE criteria. Eligible patients were younger and had higher‑grade tumors and greater proliferation rate than non-eligible patients. Five‑year outcomes were consistently worse in eligible than ineligible patients (NATALEE: iDFS 82.5% vs. 89.6%, DDFS 88.3% vs. 94.5%, OS 90.9% vs. 95.6%; monarchE: iDFS 76.8% vs. 88.4%, DDFS 82.3% vs. 93.8%, OS 86.8% vs. 94.9%). Metastatic progression occurred three‑ to six‑fold more often in eligible patients. In multivariable models, both NATALEE and monarchE eligibility were associated with distant metastasis, and mortality. Conclusion Real-world outcomes among NATALEE and monarchE-eligible patients are consistent with results from phase III trial comparator arms. Trial‑defined eligibility criteria reliably identify patients with substantially poorer prognosis, supporting risk‑adapted adjuvant strategies and the integration of CDK4/6 inhibitors into clinical practice.
