Breast cancer has several subtypes, including HER2-positive breast cancer, which is characterized by overexpression of human epidermal growth factor receptor 2 (HER2), aggressiveness, poor prognosis, and high risk of recurrence and metastasis. Brain metastases are a common complication of HER2-positive breast cancer, but brain imaging is not included in the initial staging of this disease. This prospective pilot study aimed to evaluate the usefulness of brain computed tomography (CT) in the initial staging of HER2-positive breast cancer. Fifty-eight patients were enrolled and demographic, clinical, and breast cancer-specific data were collected after the informed consent and ethical approval were obtained. A descriptive analysis was performed. The median age of the patients was 55 years, and the majority had good performance status. Brain CT scans were performed at diagnosis, and no brain metastases were detected in early-stage patients. However, brain CT identified brain metastases in one advanced-stage patient with clinical suspicion. This study suggests that brain CT may have limited utility in the initial staging of early HER2-positive breast cancer, while it could be a valuable tool in advanced cases. Further research is needed, including a higher number of patients to identify those with high risk, which may benefit from brain imaging.

Treatment options for advanced biliary tract cancers (BTCs) progressing after first-line chemoimmunotherapy remain limited. Whether platinum-based chemotherapy reintroduction can restore disease control is unknown. This study evaluates cisplatin-gemcitabine-durvalumab (CGD) reintroduction in patients with advanced BTC progressing during durvalumab maintenance. A multinational cohort of patients with BTC received first-line CGD followed by durvalumab maintenance. Those progressing during maintenance and treated with CGD reintroduction or FOLFOX/XELOX were analyzed. Primary endpoints were overall survival (OS) and progression-free survival (PFS) in the CGD reintroduction group; secondary endpoints included survival outcomes from maintenance and second-line initiation, overall response rate, and disease control rate. Among 1258 patients treated with first-line CGD, 475 received durvalumab maintenance. After disease progression during maintenance (n = 309, 65.1%), 31 patients (6.5%) underwent CGD reintroduction, while 114 (24%) received FOLFOX/XELOX. Baseline characteristics were comparable between groups, except for bilirubin levels. After a median follow-up of 22.6 months [95% confidence interval (CI) 20.0-25.1], median OS was not reached in the reintroduction cohort, while median PFS was 13.3 months (95% CI 9.7-15.8) from first-line initiation. From durvalumab maintenance start, median OS remained not reached and median PFS was 7.1 months (95% CI 4.8-11.3). Following reintroduction, median OS and PFS were 10.5 months (95% CI 8.0-10.5) and 9.0 months (95% CI 5.5-10.2). Compared with FOLFOX/XELOX, CGD reintroduction was associated with significantly improved OS [hazard ratio (HR) 0.47; P = 0.006] and PFS (HR 0.44; P < 0.0001) from first-line therapy start, as well as improved PFS from second-line treatment start (HR 0.60; P = 0.027). These findings were confirmed after multivariable and inverse probability of treatment weighting adjustment. Response outcomes were comparable between groups. This is the first study evaluating CGD reintroduction in patients with BTC progressing during durvalumab maintenance. Although the retrospective design does not allow definitive conclusions, our findings suggest potential benefit in selected patients.

Background: Biliary tract cancers (BTCs) are aggressive malignancies with limited treatment options. The addition of durvalumab or pembrolizumab to cisplatin–gemcitabine improves overall survival (OS), but validated biomarkers of benefit remain limited. Immune-mediated adverse events (imAEs) have been proposed as treatment-emergent clinical correlates of immune activation. Methods: We retrospectively analyzed an international cohort of patients with locally advanced or metastatic BTC treated with first-line cisplatin–gemcitabine plus durvalumab. Primary endpoints were OS and progression-free survival (PFS). The principal exposure was the occurrence of any imAE. A post hoc complete-case Cox model was adjusted for age, sex, primary tumor site, prior surgery, ECOG performance status, disease stage, albumin, bilirubin, and neutrophil-to-lymphocyte ratio (NLR); analyses of individual AEs were exploratory. Exact AE onset dates were not consistently available, precluding a reliable formal time-dependent exposure analysis. Results: A total of 1358 patients were included; all received durvalumab, and 276 (20.3%) developed at least one imAE. In the fully baseline-adjusted model, any imAE remained associated with a lower risk of death (adjusted HR 0.72, 95% CI 0.57–0.92; p = 0.008) and progression or death (adjusted HR 0.63, 95% CI 0.52–0.77; p < 0.001). In exploratory baseline-adjusted analyses of individual imAEs, other imAEs remained associated with OS (HR 0.39, 95% CI 0.24–0.62; p < 0.001) and PFS (HR 0.56, 95% CI 0.40–0.77; p < 0.001), while hypothyroidism remained associated with PFS only (HR 0.65, 95% CI 0.43–0.97; p = 0.034); rash and hyperthyroidism were not independently associated after full baseline adjustment. In AE-focused exploratory models, decreased appetite and hyponatremia were associated with worse outcomes, neutropenia with better outcomes, and ALT elevation with worse PFS. Baseline corticosteroid use was uncommon (n = 21), and all steroid analyses are vulnerable to confounding by indication and exposure-timing bias. Conclusions: Treatment-emergent imAEs may represent potential prognostic markers or clinical correlates of benefit, but they are not validated surrogate endpoints. Prospective studies with precise AE-onset capture are required.