Neoadjuvant Treatment Strategies in Unresectable Gallbladder Cancer (GBC) in a Regional Cancer Centre in India: a Prospective Cohort Study.

Artificial Intelligence for Molecular Subtyping in Unresectable Gallbladder Cancer: A Proof-of-Concept Study for CT-based HER2 Status Prediction.

289P Efficacy and safety of camrelizumab plus gemcitabine and oxaliplatin as conversion therapy for unresectable gallbladder cancer: Interim results from a single-arm, phase II prospective clinical study

Introduction: Gall Bladder Cancer (GBC) is associated with poor prognosis, particularly when presenting with jaundice. In these cases, jaundice often indicates advanced disease and precludes curative surgical options. Palliative management with biliary drainage may be the only available option to address symptom relief, restore liver function, and improve Quality Of Life (QOL). The impact of Percutaneous Transhepatic Biliary Drainage (PTBD) on QOL in such patients remains underexplored. Aim: To evaluate the effectiveness of PTBD in improving QOL in patients with advanced GBC and obstructive jaundice, using two validated QOL indices. Materials and Methods: A prospective interventional study in patients with unresectable GBC and jaundice undergoing PTBD was conducted on 70 patients at a tertiary care centre in northern India between 2019 and 2024. Just before and after PTBD, QOL was assessed using FACT-Hep and EORTC QLQ-BIL21/QLQ-C30 at three time points: preprocedure, one month postprocedure, and three months postprocedure. Data were analysed using descriptive statistics and repeated measures ANOVA. Results: Significant improvements were observed in overall QOL and key domains-physical, social, emotional, and functional well-being- between baseline and follow-ups (p<0.05). Jaundice-related symptoms, eating ability, and fatigue showed marked improvement, though pain and anxiety scores remained unchanged. Complications included periprocedural leaks in 22 patients (31.4%), catheter blockage or pull-out in 16 (22.9%), and cholangitis in 8 (11.4%). Conclusion: PTBD effectively improves QOL in patients with advanced GBC by alleviating jaundice-related symptoms and enhancing functional domains, despite procedural complications. Optimising post-procedural care and addressing complications are crucial for maximising palliative benefits in this patient population.

Introduction: Gallbladder cancer (GBC) is an aggressive malignancy with poor prognosis and limited treatment options, especially in Stage III/IV unresectable disease. In India, it predominantly affects women from the North and Northeast, with survival rarely exceeding 6–9 months despite standard care. Homeopathy, widely practiced across India, has shown potential in improving quality of life (QOL) and survival in various cancers when used adjunctively, but evidence in GBC remains scarce. Materials and Methods: This single-blind, randomized, placebo-controlled pilot trial will recruit 30 patients with unresectable GBC at Atal Bihari Vajpayee Regional Cancer Center, Agartala. All participants will be randomized (1:1) to receive either the institutional management protocol (IMP) plus individualized homeopathic medicines or IMP plus placebo for 12 months. The primary outcome is overall survival, assessed monthly over 12 months. Secondary outcomes include tumor response (revised RECIST), QOL (FACT-G questionnaire), performance status (Eastern Cooperative Oncology Group scale), and adverse events (CTCAE v5.0). Data were analyzed on an intention-to-treat basis using Kaplan–Meier survival analysis and log-rank tests, with P < 0.05 considered statistically significant. Results: As a pilot trial, the results will emphasize the feasibility, recruitment, adherence, safety, and preliminary efficacy data of adjunctive homeopathic medicines. Conclusion: This study will explore the feasibility, safety, and potential efficacy of individualized homeopathic medicines as an adjunct to standard care in unresectable GBC. Findings may provide a foundation for larger, definitive randomized controlled trials evaluating homeopathy in advanced GBC management. Trial Registration: CTRI/2025/02/080420.

Background/AimHepatectomy with extrahepatic bile duct resection (Hx+EBDR), pancreaticoduodenectomy (PD), and occasionally hepatopancreaticoduodenectomy (HPD) are required for the treatment of advanced gallbladder cancer (GBC). This study aimed to clarify the clinical value of these extended surgeries for GBC.Patients and MethodsWe retrospectively reviewed the medical records of patients who underwent curative resection (Surg-G, n=59), and their survival rates were compared with those of patients with unresectable GBC who underwent chemotherapy (CTx-G, n=63).ResultsWe performed PD (n=15), Hx+EBDR (n=37), and HPD (n=7). The postoperative complication and death rates were as follows: PD, 40% and 7%, respectively; Hx+EBDR, 89% and 14%, respectively; and HPD, 57% and 0%, respectively. Concomitant vascular resection (VR) was required in 61% of the patients. The 5-year overall survival rate and median survival time (MST) for Surg-G were 25.1% and 26 months, respectively, whereas those for CTx-G were 4.6% and 14.4 months, respectively. There were no significant differences between the surgical procedures. Patients who underwent VR had similar prognoses (5-year overall survival rate and MST: 14.5% and 22.3 months, respectively) as the patients in CTx-G.ConclusionAlthough extended surgery may be considered for patients with GBC, careful patient selection and new therapeutic strategies are required, especially for those requiring VR.

The incidence of gall bladder cancer (GBC), one of the most prevalent bile duct malignancies, differs with ethnicity and geographic location. To treat unresected GBC in the Chinese setting, this study aimed to assess the financial effectiveness of a combination of modified gemcitabine and oxaliplatin. Data from a randomized controlled study in which individuals with metastatic GBC were treated with oxaliplatin and gemcitabine demonstrated improved survival. A Markov model is built to calculate the incremental cost-benefit ratio (ICER) from the viewpoint of Chinese society on the basis of clinical symptoms and disease development. One-way certainty and probability sensitivity analyses are used to describe the uncertainty in the model. Compared with those of fluorouracil (FU) and folinic acid, the utility value of modified oxaliplatin combined with gemcitabine increased by 0.22QALY throughout the course of the 10-year simulation (FA). In a Chinese healthcare setting, the cost-effectiveness ratio (ICER) is $52765.59/QALY, with a 0% chance of cost-benefit at the WTP (willing-to-pay) level of $37697.00/QALY. The ICERs predicted by sensitivity analysis were not significantly affected by cost variations related to the management of Grade 3-4 AEs, the diagnostics used, or hospitalization expenditures. In a Chinese healthcare context, modified gemcitabine coupled with oxaliplatin (mGEMOX) is not a cost-effective treatment option for unresectable GBC.

153P Preliminary activity of camrelizumab plus gemcitabine and oxaliplatin in the transformation of unresectable gallbladder cancer: A single arm, phase II, prospective clinical study

Introduction: Treating advanced Gallbladder Cancer (GBC) poses a substantial therapeutic challenge. Palliative chemotherapy is the primary treatment for patients with unresectable tumours. The effectiveness of this treatment in extending lifespan is limited, usually quantified in a few months, and its accompanying harmful effects can significantly impair overall well-being. As a viable alternative, palliative radiation offers the benefits of shorter treatment duration and a potentially lower risk of harmful side-effects. Its potential in the treatment of advanced GBC has not been fully explored, and the existing medical literature on this topic is scarce. However, the promising aspects of palliative Radiotherapy (RT) suggest a hopeful future for its application in treating unresectable GBC. Aim: To evaluate the Quality of Life (QoL), treatment-related toxicities and tumour response to palliative RT in unresectable GBC. Materials and Methods: A single-arm prospective interventional study was conducted in the Department of Radiation Oncology Outpatient Department (OPD), Sarojini Naidu Medical College, Agra, Uttar Pradesh, India, from September 2022 to May 2024. The present study included all patients with unresectable advanced GBC reported to OPD. Patients who had been previously treated or had ascites or duodenal infiltration were excluded. Twenty-four patients were recruited to receive RT alone (30 Gy in 10 fractions, D1-D10 over two weeks, five fractions per week). Treatment planning was Computed Tomography (CT) scan-guided. Quality of life assessment was based on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and BIL-21 questionnaires, and the Analysis of Variance (ANOVA) test was applied to compare variables. Tumour response was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, and a paired t-test was applied to compare pre and post-treatment values. Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5) was used to monitor toxicity. Descriptive statistics were used to examine patient demographics, baseline characteristics, treatment details and toxicity profiles. Results: Initially, 24 patients were enrolled in the present study, out of which four defaulted before treatment began. The mean age was 49.48±5.2 years. There was a female predominance, with 17 (70.8%) female patients and 7 (29.2%) male patients. The most common stage of the disease was stage IV A, affecting 16 (66.6%) of the patients. The overall QoL score pretreatment was 37.50±21.54, the mid-treatment score was 45.85±11.18, and the post-treatment score was 54.65±16.11. The scores showed improvement but were not statistically significant. A combined tumour response (complete+partial) was achieved in 10 (50%) patients. Treatment-related toxicities were within tolerable limits, with two patients developing cholangitis grade 2. Conclusion: Improvement was observed in the QoL score. Adverse effects were minimal, with a tumour response observed in 50% of patients. Hence, palliative RT showed promising results with the advantage of a short treatment time. However, a study with a larger sample size in different institutes is needed for a clearer picture.

We report a rare case of a patient with initially unresectable gallbladder cancer who underwent conversion surgery with durvalumab in combination with gemcitabine plus cisplatin and achieved an R0 resection. A 68year-old woman was found to have gallbladder cancer and multiple enlarged lymph nodes around the suprapancreatic rim and hepatic hilum invading the proper hepatic artery on computed tomography. The diagnosis was cT3cN2cM0, cStage IVB. After eight cycles of durvalumab in combination with gemcitabine plus cisplatin, all tumor markers became negative, and lymph node invasion of the hepatic artery disappeared. The patient underwent conversion surgery with gallbladder bed resection and regional lymph node dissection. There was no need for hepatic artery reconstruction. Pathology revealed ypT2aypN0ycM0, ypStage IIA, and radical resection was considered. Immunostaining of tissue collected at the time of endoscopic ultrasound-guided tissue acquisition revealed less than 1% programmed death ligand-1 expression. The patient continued adjuvant chemotherapy with single-agent durvalumab every 4weeks and maintained a relapse-free survival of 8months postoperatively. The utility of durvalumab in combination with gemcitabine plus cisplatin in unresectable gallbladder cancer independent of programmed death ligand-1 expression has been confirmed and may be an important option in future multimodal treatment, including conversion surgery.

For the past decade, there have been few chemotherapy options for unresectable biliary tract cancer (BTC). Recently, however, combination therapy with gemcitabine and cisplatin plus S-1 (GCS) has been identified as a promising strategy. This retrospective study analyzes the clinical results of GCS therapy and subsequent conversion surgery (CS). We analyzed the clinical data of 60 consecutive patients who received GCS therapy for unresectable upper BTC at our university hospital during the 5 years between September, 2018 and December, 2022. All patients received GCS therapy as first-line chemotherapy. The response rate was 33.9% and subsequent CS was performed in 35.0%. Of the patients who underwent CS, 81% required more than bisectionectomy of the liver with extrahepatic bile duct resection. The median overall survival of the patients who received GCS therapy and underwent subsequent CS was significantly longer than that of the patients who received GCS therapy alone (28.0 months vs. 12.4 months, respectively; p < 0.001). A decrease in the CA19-9 level 1 month after chemotherapy and RECIST PR were independent positive predictors of CS, whereas unresectable gallbladder cancer and pretreatment ALBI grade 3 were negative predictors of CS. GCS therapy and subsequent CS may contribute to the longer term survival of patients with unresectable upper BTC.

357 Concurrent chemoradiation in unresectable gall bladder cancer: A feasibility analysis to tame young.

Gallbladder cancer, notoriously known for its high malignancy, predominantly requires radical surgery as the treatment of choice. Although laparoscopic techniques have become increasingly prevalent in abdominal surgeries in recent years, the progress of laparoscopic techniques in gallbladder cancer is relatively slow. Due to the anatomical complexity, technical difficulty, and biological features of gallbladder cancer that is prone to metastasis and dissemination, traditional open surgery is still the main surgical approach. This study aims to reappraisal the current state of laparoscopic surgery for gallbladder cancer by appraising clinical practice and research evidence. Laparoscopic surgery for various stages of gallbladder cancer, including early, advanced, incidental, and unresectable gallbladder cancer were discussed. The promise and limitations of laparoscopic techniques are systematically explored.

Outcomes of Self-expandable Metal Stents in Patients With Unresectable Gallbladder Cancer Undergoing Percutaneous Biliary Drainage

Recently, anti-PD-1 antibodies plus lenvatinib has been administered in a series of solid tumors. Yet, the efficacy of chemo-free treatment of this combined therapy has seldom been reported in gallbladder cancer (GBC). The aim of our study was to initially evaluate the efficacy of the chemo-free treatment in unresectable GBCs. We retrospectively collected the clinical data of unresectable GBCs treated using chemo-free anti-PD-1 antibodies plus lenvatinib in our hospital from March 2019 to August 2022. The clinical responses were assessed, and PD-1 expression was evaluated. Our study enrolled 52 patients, with the median progression-free survival being 7.0 months and the median overall survival being 12.0 months. The objective response rate was 46.2% and the disease control rate was 65.4%. The expression of PD-L1 in patients with objective response was significantly higher than those with progression of disease. For patients with unresectable GBC, when not eligible for systemic chemotherapy, chemo-free treatment using anti-PD-1 antibodies with lenvatinib may become a safe and rational choice. The expression of PD-L1 in tumor tissues may be correlated to the objective response, and thus is expected to be a predictor of efficacy, and further clinical studies are certainly needed.

Response Rates and Tolerance for mFOLFIRINOX Regimen in Indian Patients with Metastatic and Unresectable Gall Bladder Cancer - A Prospective Observational Study (Phase II)

Abstract Background: Gallbladder cancer (GBC) has a high incidence rate in the Indo-Gangetic belt and is usually presented in the unresectable advanced or metastatic stage. In this study, we evaluated the response rate and toxicities of the gemcitabine plus capecitabine (GEM-CAP)-based combination chemotherapy in unresectable or metastatic GBC patients. Subjects and Methods: This was an investigator-initiated, single-arm, prospective study conducted on unresectable or metastatic GBC patients at Jaipur, India, for 1 year. All the patients received a GEM-CAP combination chemotherapy regimen which consisted of gemcitabine 1000 mg/m2 intravenously over 30 min on days 1 and 8 and capecitabine at 800 mg/m2 orally twice a day for 14 days, administered every 21 days. The response was evaluated in terms of overall response rate (ORR), tumor control rate (TCR), and progression-free survival (PFS). Both quantitative and qualitative toxicities were assessed. Results: A total of 35 patients were enrolled, of which 3 patients were excluded due to treatment interruption. The mean age of patients was 55 (32–80) years, with the majority being female (77.14%), having an ECOG score of 1 (71.43%), and with Stage IVB disease (77.14%). The ORR was 25%, TCR was 50%, and median PFS was 4 months. Major toxicities noted were Grade I and II hematological and nonhematological toxicities, which were managed adequately. Conclusion: The combination therapy of gemcitabine and capecitabine is reasonable, feasible, and well-tolerated approach for the treatment of unresectable advanced and metastatic GBC patients, a disease that had limited treatment options.

BackgroundConversion surgery, which is defined as chemotherapy or chemoradiotherapy followed by radical surgery, may improve survival of patients with initially unresectable advanced biliary tract cancer, including gallbladder cancer. However, there are few reports on conversion surgery for advanced gallbladder cancer.Case presentationA 69-year-old woman was referred to our hospital with initially unresectable gallbladder cancer with peritoneal carcinomatosis. She underwent gemcitabine plus cisplatin therapy for 9 months. Extended cholecystectomy, resection of the extrahepatic bile duct with regional lymph node dissection, and total omentectomy were then performed as conversion surgery. The patient has survived without recurrence for 19 months postoperatively (31 months after the initial diagnosis) while continuing chemotherapy.ConclusionsThis case suggests that conversion surgery for advanced gallbladder cancer is effective and may be curative for locally advanced disease and distant metastasis such as peritoneal carcinomatosis.

BackgroundConversion surgery for initially unresectable gallbladder cancer is rarely performed due to the low response rate for systemic chemotherapy, and a pathological complete response is seldom achieved.Case presentationA 67-year-old woman with jaundice was referred to our hospital and diagnosed with unresectable gallbladder cancer with extra-regional lymph node metastasis after examinations. After biliary decompression, gemcitabine plus cisplatin therapy was started. The tumor marker levels markedly decreased, and imaging studies revealed a reduction in the primary tumor and metastatic lymph nodes. The primary tumor and metastatic lymph node were still shrunk at 4 years after the start of gemcitabine plus cisplatin therapy, so we decided to perform conversion surgery. Gallbladder bed resection and lymph node dissection were performed. The pathological findings of the resected specimen showed only partial fibrosis in the gallbladder wall and no malignant findings in the dissected lymph nodes, indicating a pathological complete response. As of 24 months after the operation, she is alive without recurrence.ConclusionAlthough there have been only a few reports of conversion surgery for initially unresectable gallbladder cancer, it may be worthwhile to perform chemotherapy with the potential goal of subsequent conversion surgery.

BackgroundSurgical resection of gallbladder cancer with negative margins is the only potentially curative therapy. Most patients with gallbladder cancer are diagnosed in an advanced stage and, despite the availability of several chemotherapies, the prognosis remains dismal. We report a case of locally advanced gallbladder cancer that was successfully treated with effective cisplatin plus gemcitabine, followed by curative resection.Case presentationA 55-year-old Japanese female was hospitalized with right hypochondrial pain. Enhanced computed tomography revealed a 49 × 47 mm mass at the neck of the gallbladder, with suspected invasion of the liver and right hepatic artery. Endoscopic retrograde cholangiopancreatography demonstrated displacement of the upper bile duct. Intraductal ultrasonography showed irregular wall thickening and disappearance of the wall structure in bile ducts from the B4 branch to distal B2 and B3. Percutaneous transhepatic biliary biopsy revealed a poorly differentiated carcinoma. The patient was diagnosed with unresectable gallbladder cancer (T4N0M0 stage IVA). Cisplatin plus gemcitabine chemotherapy was initiated. After six courses of chemotherapy, enhanced computed tomography showed that the mass in the neck of the gallbladder had shrunk to 30 mm, Endoscopic retrograde cholangiopancreatography showed improvement of the hilar duct stenosis. A biopsy of the bile duct mucosa showed no malignant cells in the branch of the left and right hepatic ducts, the left hepatic duct, or the intrapancreatic ducts. The patient underwent conversion surgery with right and segment 4a liver resection, extrahepatic duct resection, and cholangiojejunostomy. The histopathologic diagnosis showed that the tumor cells had shrunk to 2 × 1 mm, and that R0 resection of the T2aN0M0 stage IIA tumor was successful.ConclusionAlthough conversion surgery for gallbladder cancer is rarely possible, curative resection may offer a better prognosis, and it is important to regularly pursue possibilities for surgical resection even during chemotherapy.