Background: Gallbladder cancer (GBC) is a fatal cancer, and the efficacy of the current standard second-line chemotherapy for GBC is limited. Novel therapies need to be explored. This retrospective analysis was aimed to investigate the outcomes of patients treated at West China Hospital with PD-1 inhibitors combined with nab-paclitaxel-based chemotherapy (nab-paclitaxel monotherapy or nab-paclitaxel plus other cytotoxic agents) in a second-line setting.Methods: Between April 2020 and May 2022, the patients with advanced GBC receiving PD-1 inhibitors combined with nab-paclitaxel-based chemotherapy after resistance to first-line gemcitabine-based chemotherapy at West China Hospital were retrospectively screened.Results: Eleven patients were included, and all received gemcitabine-based chemotherapy as first-line therapy. Eight patients underwent next-generation sequencing (NGS), and all had microsatellite stability (MSS) and a low tumor mutation burden (TMB). Six patients were negative for PD-L1 expression and one patient was positive for PD-L1. Therapeutically relevant genetic alterations were not found. All patients received PD-1 inhibitors in combination with nab-paclitaxel-based chemotherapy as second-line therapy. Pembrolizumab was administered in 3 patients, and sintilimab was administered in eight patients. One patient had no measurable target lesion. Complete response (CR) was observed in one (10.0%) patient, partial response (PR) in four (40%) patients, and stable disease (SD) in four (40%) patients. The median progression-free survival (PFS) was 7.5 (95% CI: 2.5-12.5) months, and the median overall survival (OS) was 12.7 (95% CI: 5.5-19.9) months. The adverse events (AEs) were manageable.Conclusion: Our results suggest that PD-1 inhibitors combined with nab-paclitaxel-based chemotherapy as second-line therapy for advanced GBC might be a potential treatment and deserves further evaluation.

Background: Fruquintinib has demonstrated significant improvement in overall survival (OS) among previously treated metastatic colorectal cancer (mCRC) patients. However, the utilization of fruquintinib has been constrained by various toxicities, such as hand‐foot skin reaction (HFSR) and hypertension, particularly in elderly patients with reduced tolerance to the standard dosage. This study aims to investigate the efficacy and safety of fruquintinib dose‐escalation strategy for elderly refractory mCRC patients.Patients and Methods: This open‐label, single‐arm, phase II trial included patients aged 65 years or over with mCRC who had progressed after two or more lines of chemotherapy. Fruquintinib was administered for 21 consecutive days of a 28‐day treatment cycle. The starting dose of fruquintinib was 3 mg/day and escalated to 4 mg/day in Week 2 and 5 mg/day in Week 3 if no significant drug‐related toxicity was observed. The highest tolerated dose from Cycle 1 would be administered in Cycle 2 and all subsequent cycles. Before commencing treatment, all enrolled patients underwent a G8 questionnaire and comprehensive geriatric assessments. The primary endpoint of the study was progression‐free survival (PFS).Results: A total of 29 patients were enrolled and all started fruquintinib at 3 mg/day. Fifteen patients (51.7%) were subsequently escalated to 4 mg/day and 4 (13.8%) to 5 mg/day. Only four (13.8%) patients discontinued treatment due to adverse events (AEs). The median PFS was 3.8 months (95% CI, 2.7–4.9), and the median OS was 7.6 months (95% CI, 6.5–8.7). Treatment‐related adverse events (TRAEs) were observed in all 29 patients (100%). The most frequently occurring (>10%) TRAEs greater than Grade 3 were HFSR (20.7%), hypertension (20.7%), and diarrhea (10.3%).Conclusion: Our study indicated that a dose of 4 mg/day was well tolerated by most elderly patients, suggesting that fruquintinib dose‐escalation strategy during the first cycle could serve as a viable alternative to the standard 5 mg/day dosing.

Purpose: The patients with advanced mismatch repair deficiency (dMMR) cancers can benefit from programmed cell death 1 (PD-1) pathway blockade, regardless of the tumor type. Little is known about the prevalence of dMMR in intrahepatic cholangiocarcinoma (ICC) and combined hepatocellular-cholangiocarcinoma (cHCC-CC). This study aimed to assess the mismatch repair (MMR)-related protein expression in patients with ICC and cHCC-CC. Patients and Methods: Formalin-fixed, paraffin-embedded tumor specimens were obtained from patients undergoing surgery at the West china Hospital between 2009 and 2017. The immunoreactions for MLH1, MSH2, MSH6, and PMS2 were investigated to determine the MMR status. Results: A total of 97 patients were evaluated, including 73 ICC patients and 24 cHCC-CC patients. The prevalence of dMMR was only found in two cases of 97 patients (2.06%). Both patients are ICC. In 24 cHCC-CC patients, no dMMR was observed. They did not receive an adjuvant chemotherapy after surgery. At the end of the follow-up, one patient was in a tumor-free state, and the other patient had local recurrence and metastasis. After receiving sintilimumab (an immune checkpoint inhibitor [ICI] for PD- 1), the patient had a partial response. Conclusion: DMMR was detected in few patients with ICC and cHCC-CC. Thus, it is not recommended to routinely evaluate the MMR status of patients with ICC or cHCC-CC after surgery, but that of patients with advanced ICC or cHCC-CC should be assessed.

Introduction: Accurate baseline clinical staging is critical to inform treatment decision-making for patients with gastric cancers. Peritoneal metastasis (PM) is the most common form of metastasis in gastric cancer and mainly diagnosed by diagnostic laparoscopy and peritoneal lavage evaluation. However, diagnostic laparoscopy is invasive and less cost-effective. It is urgent to develop a safe, fast and non-invasive functional imaging method to verify the peritoneal metastasis of gastric cancer. The aim of our study was to evaluate the proportion of patients in whom⁶⁸Ga-FAPI-04 positron emission tomography/CT (PET/CT) led to a change in treatment strategy and to assess the diagnostic accuracy of⁶⁸Ga-FAPI-04 PET/CT for the detection of occult peritoneal metastasis compared with laparoscopic exploration.Methods and analysis: In this single-centre, prospective diagnostic test accuracy study, a total of 48 patients with locally advanced gastric or gastro-oesophageal junction adenocarcinoma (cT4a-b, N0-3, M0, based on CT images) who are considering radical tumour surgery will be recruited. All participants will undergo⁶⁸Ga-FAPI-04 PET/CT before the initiation of laparoscopic exploration. The primary outcome is the proportion of patients with occult peritoneal metastatic lesions detected by⁶⁸Ga-FAPI-04 PET/CT, leading to a change in therapy strategy. The secondary outcomes include the diagnostic performance of⁶⁸Ga-FAPI-04 PET/CT for occult peritoneal metastasis, including sensitivity, specificity, accuracy, positive predictive value and negative predictive value.Ethics and dissemination: The study protocol was approved by the Ethics Committee of West China Hospital, Sichuan University (2022-1484). Study results will be presented at public and scientific conferences and in peer-reviewed journals.Trial registration number: ChiCTR2300067591.

Occult peritoneal metastasis (OPM) is common in locally advanced gastric cancer, and accurate detection is critical. This prospective cohort study evaluated the diagnostic accuracy and cost of ⁶⁸Ga-FAPI-04 PET/CT for detecting OPM. Methods: This single-center, prospective cohort study included patients with locally advanced gastric adenocarcinoma. All patients underwent ⁶⁸Ga-FAPI-04 PET/CT before laparoscopic staging, and the diagnosis of OPM was established using laparoscopic staging combined with peritoneal washing cytology as the gold standard. The primary endpoint was the proportion of patients whose treatment intent changed based on ⁶⁸Ga-FAPI-04 PET/CT results. Secondary endpoints included diagnostic accuracy and cost analysis of ⁶⁸Ga-FAPI-04 PET/CT in detecting OPM. Results: In total, 109 patients were recruited between November 2022 and August 2024. ⁶⁸Ga-FAPI-04 PET/CT identified OPM in 17 patients (15.6%), resulting in upstaging to stage IV, with sensitivity, specificity, and diagnostic accuracy of 75.0%, 94.6%, and 91.7%, respectively (area under the curve, 0.83; 95% CI, 0.72–0.94). Economic analysis demonstrated a net cost savings of $979.30 per patient when compared with laparoscopic staging. The combination of ⁶⁸Ga-FAPI-04 PET/CT and laparoscopic staging reduced the need for laparoscopic procedures by 84% and prevented 11% of futile gastrectomies, yielding a minimal cost savings of $232.30 per patient. Conclusion: ⁶⁸Ga-FAPI-04 PET/CT demonstrates high diagnostic accuracy, low cost, and the potential to reduce invasive procedures, making it a promising alternative to laparoscopic staging in patients with locally advanced gastric cancer. Visual Abstract