Biliary tract malignancies include cholangiocarcinoma and gall bladder cancers. Adenocarcinoma of the Gallbladder is the most common malignancy of the biliary tract and the sixth most common gastrointestinal cancer globally, with a high mortality-to-incidence ratio. Cholangiocarcinoma is an aggressive malignancy of biliary epithelium that may arise anywhere in the biliary tract, from the intrahepatic biliary canaliculi to the terminus where the common bile duct enters the duodenum at the duodenal ampulla. Cholangiocarcinoma is classified by anatomical origin as intrahepatic cholangiocarcinoma (iCCA) or extrahepatic cholangiocarcinoma (eCCA); eCCA is subdivided into perihilar cholangiocarcinoma (pCCA) and distal cholangiocarcinoma (dCCA). More than 95% of cholangiocarcinomas are adenocarcinomas. As per GLOBOCAN 2020 data, there were an estimated 115,949 new cases and 84,695 deaths due to Gall Bladder Cancer (GBC) worldwide, reflecting its aggressive nature and poor prognosis [1]. In India, gallbladder cancer (GBC) is highly prevalent, especially among women in the Northern and Northeastern regions, with the Indo-Gangetic belt identified as a high-risk zone. This clustering is associated with factors like chronic gallstone disease (present in up to 85% of cases), environmental toxins, genetic mutations (e.g., p53, K-ras, EGFR), and infections such as Salmonella typhi. Other risk factors include older age, obesity, porcelain gallbladder, primary sclerosing cholangitis, and unhealthy diets low in vegetables and high in carbohydrates [2–8]. The incidence of cholangiocarcinoma is modest in the western world, between 0.35 to 2 per 100,000 annually; however, in China and Thailand, the incidence can be up to 40 times the rate observed in the United Kingdom and, thus, poses significant public health questions. Cholangiocarcinoma frequently arises in the absence of genetic predisposition and without a clear etiology. The predisposing risk factors include but are not limited to Infestation with liver flukes such as Clonorchis and Opisthorchiasis, primary sclerosing cholangitis, hepatolithiasis, cholelithiasis, and choledocholithiasis and cystic biliary lesions.

Gallbladder cancer (GBC) often presents with non-specific and late presenting symptoms, leading to delayed diagnosis and poor prognosis, which include right upper quadrant pain, nausea, vomiting, anorexia, jaundice, fever, cholangitis,weight oss, cachexia and 1-2% GBC are discovered incidentally. The clinical presentation of cholangiocarcinoma will vary with the location and size of the tumor. Diagnosing cholangiocarcinoma can be difficult, particularly for extrahepatic lesions; available biopsy techniques lack diagnostic sensitivity. Surgical intervention is indicated even without a confirmatory tissue diagnosis in the appropriate clinical setting. All patients with suspected or confirmed cholangiocarcinoma should be evaluated for

distant metastatic disease; almost 75% of patients have nonresectable or metastatic disease at presentation.

Surgical resection remains the only potentially curative treatment, but fewer than 20% of patients are candidates at diagnosis due to late presentation [9]. With regard to chemotherapy, various agents have been discovered and explored in various settings. Biliary tract cancers are considered to be classiscally radioresistant due various genetic and anatomical factors. Evidence is limited to small retrospective series, without robust prospective data [1,2].

Unresectable, non-metastatic biliary tract cancer is defined as locally advanced disease that cannot be surgically removed due to vascular invasion, extensive nodal disease, or poor performance status, but without distant metastasis. It constitutes a distinct clinical group with potentially salvageable outcomes through non-surgical means [9]. Emerging evidence suggests that concurrent chemoradiotherapy (CTRT) may improve locoregional control and survival in this subset. However, prospective data remain limited. The present study aims to address this gap by evaluating the role of definitive CTRT in improving outcomes in unresectable, non-metastatic biliary tract cancer.

While early findings from retrospective and smaller prospective studies are encouraging, there’s still a lack of strong, definitive evidence on the role of concurrent chemoradiotherapy (CTRT) in unresectable, non-metastatic biliary tract cancer. Most available data come from single-center experiences and are limited by small sample sizes, non-randomized designs, and variations in how treatment was delivered.

At present, there’s no clear consensus on key treatment parameters such as the ideal radiation dose, the best chemotherapy agent to pair with RT, or which patients are most likely to benefit. Moreover, many existing studies exclude patients with poor performance status or coexisting medical conditions, making it hard to apply their results to the broader population seen in real-world clinical practice.

These gaps highlight the need for more robust research. A carefully designed prospective cohort study can help fill this void by evaluating outcomes such as overall survival, local disease control, treatment tolerance, and patterns of failure in a clearly defined patient group. By focusing on patients from a high-incidence region and using a consistent treatment approach, the current study aims to generate data that could help refine clinical decision-making and potentially encourage wider use of CTRT in this challenging subset of biliary tract cancer patients. The study aims to evaluate the efficacy of definitive concurrent chemoradiotherapy (CTRT) in patients with unresectable, non-metastatic biliary tract cancer through a prospective cohort study, with a focus on disease control and survival outcomes. The limitation of the proposed study is small sample size and absence of any translational component to the study