DeCure for Liver and intrahepatic bile duct neoplasm

Between 1965 and 1969, 77 patients with malignant tumours of the extrahepatic bile ducts were treated at the Lahey Clinic. Of the 68 who underwent exploratory laparotomy, 24 (35 per cent) had a radical procedure; 17 of those survived more than one year, and five were alive more than three years later, three with no evidence of recurrent disease. Forty-one patients received palliative treatment, usually bile-duct decompression, and in 15 cases this was combined with hepatic artery infusion chemotherapy. Sixteen of the palliative group survived more than one year, including nine from the chemotherapy subgroup. Only one palliative patient was alive after more than three years. Overall, 44 per cent survived more than one year, 23 per cent more than two years, and 8 per cent more than three years; mean survival was 13 months. The authors attributed the improvement over an earlier survey to an increase in the radical resection rate from 18 to 31 per cent and to the introduction of hepatic artery infusion chemotherapy in palliative cases.

A retrospective review of 23 patients who received salvage radiotherapy for isolated locoregional recurrence of extrahepatic bile duct cancer after radical surgery reported a median overall survival of 18.4 months and a median progression-free survival of 15.5 months. The median disease-free interval before recurrence was 11.8 months. Radiotherapy was delivered to a median dose of 54 Gy; 18 patients also received concomitant chemotherapy. On multivariate analysis, concomitant chemotherapy was a favourable prognostic factor for progression-free survival, but a prolonged disease-free interval of one year or more was associated with significantly worse overall survival. No grade 3 or higher toxicities were observed. The authors describe these survival outcomes as promising and suggest concurrent chemoradiotherapy can be a viable salvage option in selected patients.

For intrahepatic cholangiocarcinoma, multiple reviews state that surgical resection remains the only curative treatment. Gemcitabine and cisplatin is described as the systemic therapy practice standard for non-resectable disease. Other treatment components mentioned include radiotherapy, hepatic intra-arterial therapy, ablation therapy, molecular targeted therapy, and immunotherapy. Neoadjuvant therapy with liver transplantation is noted as a possible new option for early-stage patients, and radiofrequency ablation or transcatheter arterial chemoembolisation are considered for unresectable or recurrent cases. The reviews emphasise that most patients are diagnosed at an advanced stage when the lesion cannot be resected, and mortality remains high.

What is still missing is prospective evidence that any of the newer modalities — molecular targeted therapy, immunotherapy, or hepatic artery infusion — improve survival in a randomised setting for either extrahepatic or intrahepatic bile duct cancers. The salvage radiotherapy data come from a single-centre retrospective series of 23 patients, and the chemotherapy infusion data from a 1970s cohort with no control group. No trial has yet stratified patients by molecular subtype or defined which subgroups, if any, derive durable benefit from targeted agents. Adequately funded, multi-centre trials with biomarker stratification are needed before any of these approaches can be considered a standard of care.