Pathological complete response in advanced intrahepatic cholangiocarcinoma was achieved through tri-modal therapy: A case report and review of literature

Abstract

Background: Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignancy with limited treatment options and a poor prognosis, particularly in unresectable or metastatic cases. Tri-modal strategies combining systemic chemotherapy, targeted therapies, and immune checkpoint inhibitors have demonstrated synergistic effects in converting unresectable ICC to resectable status and improving patient survival.

Case summary: A 39-year-old male presented with unresectable stage IIIB ICC (cT3N1M0), abdominal pain, and elevated carbohydrate antigen (CA) 19-9 levels. He received tri-modal therapy consisting of gemcitabine-oxaliplatin hepatic arterial infusion chemotherapy (GEMOX-HAIC), lenvatinib (8 mg daily), and toripalimab (160 mg every three weeks). After five cycles, significant tumor shrinkage and normalization of CA19-9 levels enabled a left hepatectomy. Complications, including biliary stenosis and liver abscesses, were managed with biliary stenting and percutaneous drainage, which allowed for the continuation of chemotherapy. Postoperative pathological examination confirmed a pathological complete response. At the last follow-up, the patient had maintained 29 months of disease-free survival post-resection and was continuing postoperative therapy.

Conclusion: This case highlights the potential of a tri-modal therapy combining GEMOX-HAIC, lenvatinib, and toripalimab to convert unresectable ICC to a resectable status, thereby potentially improving patient survival by surgical resection. Further clinical trials investigating this regimen are warranted.

Keywords: Case report; Hepatic arterial infusion chemotherapy; Intrahepatic cholangiocarcinoma; Lenvatinib; Surgery; Toripalimab.

Figure 1

Serial contrast-enhanced computed tomography imaging during the treatment course. A: Pre-chemotherapy baseline computed tomography (CT) showing a 13-cm hypodense mass (blue arrow) with heterogeneous enhancement in the left hepatic lobe, exhibiting mild to moderate peripheral enhancement and left portal branch encasement (orange arrow); B: Follow-up CT after 3 cycles of combined therapy demonstrating a significant reduction in tumor diameter to 6.5 cm (blue arrow), with attenuated enhancement compared to baseline and alleviated left portal branch involvement (orange arrow); C: Post-resection CT at 24-month follow-up revealing no evidence of tumor recurrence; D: Post-resection CT at 29-month follow-up confirming the absence of tumor recurrence.

Figure 2

Histopathological and immunohistochemical features of the liver tumor biopsy. A: Hematoxylin and eosin staining (× 10) reveals adenocarcinoma with cuboidal tumor cells arranged in glandular patterns; B: Immunohistochemical staining for CK7 is positive, confirming biliary differentiation.

Figure 3

Serial carbohydrate antigen 19-9 monitoring during treatment shows that carbohydrate antigen 19-9 decreased significantly after two cycles of combined therapy, returned to the normal range after three cycles, and remained within the normal range during postoperative follow-up.

Figure 4

Contrast-enhanced computed tomography imaging of the hepatic abscess, demonstrating diffuse hepatic parenchymal edema, with a characteristic targetoid peripheral rim enhancement encircling the hypodense abscess wall and a central non-enhancing hypodense area indicative of liquefactive necrosis.

Figure 5

Tumor pathology. A: Gross resected tumor specimen; B: Hematoxylin and eosin staining, × 10. Tissue was necrotic; no residual viable tumor was detected.

Figure 6

Clinical timeline depicting the sequence of initial diagnosis, implementation of GEMOX-HAIC combined with lenvatinib and toripalimab therapy, complication management, subsequent surgical resection, and post-operative follow-up. CT: Computed tomography.

Figure 7

Pre-chemotherapy hepatic arteriography. A and B: The left hepatic artery is the dominant feeding artery of the tumor, demonstrating marked luminal dilation, serpentine tortuosity, and proliferative branching encircling the tumor in the early and middle arterial phases; C: Prominent tumor staining is observed in the late arterial phase during microcatheter angiography.