Mariel Gramberger

Background/Objectives: Biliary tract cancer (BTC) comprises anatomically and molecularly distinct diseases, yet real-world data integrating molecular testing with clinicopathological characteristics and outcomes after resection remain limited. We evaluated clinical and molecular heterogeneity across the major BTC subtypes in a contemporary surgical cohort. Methods: Consecutive adults undergoing curative-intent resection for intrahepatic (iCCA), perihilar (pCCA), distal (dCCA) cholangiocarcinoma, or gallbladder cancer (GBC) at a single Vienna center between 2019 and 2025 were analyzed at the patient level using the first qualifying resection as the index procedure. Molecular testing (52-gene Oncomine Focus; 50-gene Precision/Genexus), perioperative and pathological outcomes, recurrence, and overall survival (OS) were assessed. Results: The cohort included 145 patients (73 iCCA, 24 pCCA, 22 dCCA, 26 GBC). Molecular profiling was available in 103 patients (71%). IDH1/2 and FGFR2 alterations were confined to iCCA, whereas KRAS alterations were most frequent in pCCA and dCCA. Major morbidity occurred in 54/145 patients (37%) and was highest in pCCA (16/24, 67%); 17 Grade V events were documented. Median OS was 40.0 months and did not differ significantly across anatomical subtypes (log-rank p = 0.250). Cumulative incidence of recurrence likewise did not differ significantly across subtypes when death without prior recurrence was treated as a competing event (Gray’s test p = 0.163). Conclusions: The principal contribution of this real-world cohort is the integration of routine molecular testing with surgical, pathological, treatment, perioperative, and longitudinal outcome data across resected BTC subtypes. Assay coverage and testing selection must be considered when interpreting molecular findings generated in routine practice.

Background: The optimal duration of neoadjuvant therapy for high-risk colorectal liver metastases (CRLM) remains debated. While prolonged chemotherapy may enhance response, it also increases toxicity and risks delaying potentially curative resection. These considerations have raised the question whether a short-course neoadjuvant strategy might achieve sufficient oncologic selection and response while minimizing treatment-related morbidity. Methods: Patients with synchronous or metachronous CRLM who received two cycles of neoadjuvant CAPOX plus bevacizumab followed by curative-intent liver resection treated between 2014 and 2024 at Health Network Vienna, Austria, were included. Clinicopathologic characteristics, treatment tolerability, response assessments (biochemical, radiologic, and pathologic), and survival outcomes were collected and analyzed. Results: A total of 57 patients were included (65% synchronous, 35% metachronous), with the rectum being the most frequent primary tumor site (45.6%). Most liver lesions were 50% tumor marker reduction. Radiologic assessment showed partial response in 31.6% and complete response in 1.7%. Pathologic evaluation revealed TRG 3 as the most common finding (57.1%), followed by TRG 2 in 22.5%. Subgroup analyses demonstrated significantly improved OS and RFS in patients receiving adjuvant therapy and in those with tumors < 5 cm. Conclusion: A two-cycle, short-course regimen of CAPOX plus bevacizumab proved both effective and safe in high-risk CRLM, achieving meaningful biochemical, radiologic, and pathologic responses with acceptable toxicity. This abbreviated approach allowed delivery of neoadjuvant therapy while limiting cumulative treatment-related toxicity, supporting its feasibility as a neoadjuvant strategy in selected high-risk CRLM patients.

(1) Background: The pathological tumor response of the primary tumor to induction chemotherapy in synchronously metastasized colorectal cancer (mCRC) patients has not been investigated. The aim of this study was to compare patients treated with induction chemotherapy combined with vascular endothelial growth factor (VEGF) or with epidermal growth factor receptor (EGFR) antibodies. (2) Methods: We present a retrospective analysis, where we included 60 consecutive patients with potentially resectable synchronous mCRC who received induction chemotherapy combined with either VEGF or EGFR antibodies. The primary endpoint of this study was the regression of the primary tumor, which was assessed by the application of the histological regression score according to Rödel. The secondary endpoints were recurrence-free survival (RFS) and overall survival (OS). (3) Results: A significantly better pathological response and a longer RFS for patients treated with the VEGF antibody therapy compared to those treated with the EGFR antibodies was demonstrated (p = 0.005 for the primary tumor and log-rank = 0.047 for RFS). The overall survival did not differ. The trial was registered with clinicaltrial.gov, number NCT05172635. (4) Conclusion: Induction chemotherapy combined with a VEGF antibody revealed a better pathological response of the primary tumor, leading to a better RFS compared to that with EGFR therapy; this has clinical relevance in patients with potentially resectable synchronously mCRC.