Advanced sarcomas remain therapeutically challenging. We evaluated treatment implementation and clinical outcomes after molecular tumor board recommendations. We retrospectively analyzed 125 sarcoma patients discussed in our multidisciplinary Molecular and Familial Tumor Board between 2017 and 2023. Clinical benefit was assessed by treatment implementation and by the ratio of progression-free survival on molecularly guided therapy versus the preceding treatment line (PFS2/PFS1). Overall survival (OS) was measured from first board discussion. A total of 252 pathogenic or likely pathogenic variant records across 133 genes were identified. Molecular profiling enabled therapy recommendations in 71 of 125 patients (56.8
Mammography is the standard-of-care for breast cancer (BCA) screening, albeit with significant issues related to tissue density and overdiagnosis of benign conditions leading to a growing interest in alternative blood-based tests. We previously characterized the BF-09 protein biomarker (SAGA-associated factor 29) as a circulating serum BCA antigen. In this feasibility study, we investigated its ability to discriminate between retrospectively collected BCA and non-cancer cases. The serum level of the BF-09 biomarker was measured by ELISA in 261 BCA and 136 controls (43 benign and 93 healthy cases) split between two independent sets. Diagnostic performance was evaluated in each set by receiver operating characteristics curves (ROC), to determine sensitivity (SE), specificity (SP), area under the curve (AUC), negative and positive predictive values. Additional internal validation was done via statistical resampling using bootstrapping and Monte Carlo cross-validation. Performance of the BF-09 biomarker in the training set (71 BCA patients and 56 controls) was characterized by an AUC of 0.92 (95
Evidence of treatment strategies in frail patients (i.e. not fit for combination therapies) with unresectable metastatic colorectal cancer (mCRC) is limited to dose-reduced doublet regimens or oral fluoropyrimidines (FP) with bevacizumab. We conducted a systematic review analyzing evidence for oral FPs with epidermal growth factor receptor (EGFR)-directed monoclonal antibodies for patients with RAS wild-type (WT) mCRC across treatment lines. We searched PubMed and Cochrane Library for phase II and phase III studies evaluating oral FPs (capecitabine, S-1 or trifluridine/tipiracil (FTD/TPI)) plus EGFR-directed monoclonal antibody (panitumumab or cetuximab) in mCRC. Outcomes included efficacy and safety. Seven publications met inclusion criteria (n = 262 patients). First-line data was limited to elderly cohorts receiving capecitabine plus cetuximab or panitumumab with a median progression-free survival (PFS)/median overall survival (OS) of 7.2/17.1 months (cetuximab) and 7.5/23.7 months (panitumumab), respectively. In third-line and beyond, median PFS for the combination of FTD/TPI plus cetuximab or panitumumab ranged from 2.4 (cetuximab) to 5.8 months (panitumumab), and OS from 9.8 (cetuximab) to 14.2 months (panitumumab). S-1 plus cetuximab was associated with a median PFS of 5.5 months and OS of 13.6 months. While capecitabine should not be used together with anti-EGFR antibodies, FTD/TPI in combination with an EGFR-directed antibody appears feasible, shows promising activity and manageable toxicity profile in RAS WT mCRC potentially offering an alternative for frail patients; prospective trials are needed.
Alpha-fetoprotein (AFP) elevation is uncommon in pancreatic ductal adenocarcinoma (PDAC), and its clinicopathological and prognostic significance remains unclear. We retrospectively characterized AFP-elevated PDAC and evaluated its prognostic significance. Patients with pathologically confirmed PDAC treated at our institution over a 10-year period were retrospectively reviewed. Patients with elevated serum AFP at admission were identified, and an institutional cohort of patients with AFP-normal PDAC was included for comparison. Clinicopathological characteristics, treatment patterns, and survival outcomes were evaluated. Restricted cubic spline (RCS) analysis explored the nonlinear association between continuous AFP levels and overall survival (OS) among patients with AFP-elevated PDAC. A total of 50 patients with AFP-elevated PDAC and 93 patients with AFP-normal PDAC were identified. In the cohort with elevated AFP, the median AFP level was 9.0 (7.6, 14.3) ng/ml, and the majority of patients were staged as T4 (16 cases, 37.2
Abstract Following the EV-302/KEYNOTE-A39 study, the combination therapy of enfortumab vedotin and pembrolizumab (EV-P) has been established as a new first-line treatment for metastatic urothelial carcinoma. With increasing use, the documentation and publication of unexpected side effects and complications are essential to systematize procedures. We report on a 56-year-old patient who experienced an extravasation of EV-P during the first cycle due to dislocation of the port catheter from the cephalic vein. Extensive subcutaneous necrosis of the infraclavicular region required surgical debridement and application of a vacuum-assisted closure system, followed by secondary wound healing. The wound healed with a residual scar but no functional impairment or persistent pain. The therapy was resumed via a peripheral venous catheter, and the patient achieved a deep partial response. To our knowledge, this represents the first reported case of central venous EV-P extravasation (CTCAE grade 3) requiring surgical therapy. Because of its cytotoxic payload, EV in particular may pose a high risk of local complications in the context of extravasations.
