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Advanced Cholangiocarcinoma With High Tumor Mutation Burden Achieving Complete Response to Immune Check Point
Hirohisa Okabe1,2, Toshiro Masuda3, Hidetoshi Nitta3
1Department of Surgery, Kumamoto Regional Medical Center, Kumamoto, Japan; okabeh@kumamoto-u.ac.jp.
Background/Aim:
Genomic examination of tumor tissue has been clinically accepted, and the identification of actionable mutations for molecular-targeted therapy may provide substantial survival benefit for patients with advanced malignancies.
Case Report:
A female patient in her 60s showed a stenosis of the afferent loop of the small intestine because of circumferential metastatic tumor 14 months after curative surgery for hilar cholangiocarcinoma. Chemotherapy with gemcitabine plus cisplatin was administered for 18 months. An oncopanel examination was performed during chemotherapy, and a high tumor mutation burden was revealed. At 38 months after surgery, a new recurrent tumor, 2.7 cm in size, was observed in the abdominal wall, which was histologically proven to be metastatic adenocarcinoma. Atezolizumab was administered. After three cycles of treatment, treatment was switched to pembrolizumab because of its acceptance by healthcare insurance. The recurrent tumors in the abdominal wall and small intestine disappeared 6 months after the administration of immune checkpoint inhibitor, and the patient has continued pembrolizumab, surviving for 76 months after surgery without any clinical evidence of tumor.
Conclusion:
Immune checkpoint blockade successfully prolonged the survival of a patient with advanced hilar cholangiocarcinoma with high tumor mutation burden, although the optimal number of mutations for such a successful response needs to be clarified.
Insights
Genomic sequencing identified a high tumor mutation burden in advanced hilar cholangiocarcinoma. Immune checkpoint inhibitors led to complete tumor remission and prolonged survival in this patient.
Area of Science:
- Oncology
- Genomics
- Immunotherapy
Background:
- Genomic examination of tumor tissue is crucial for identifying actionable mutations.
- Molecular-targeted therapy can significantly improve survival in advanced malignancies.
Observation:
- A patient with advanced hilar cholangiocarcinoma developed metastatic disease 14 months post-surgery.
- Chemotherapy with gemcitabine plus cisplatin was administered, followed by an oncopanel revealing a high tumor mutation burden.
- Recurrent metastatic adenocarcinoma in the abdominal wall was observed 38 months post-surgery.
Findings:
- The patient received atezolizumab, then pembrolizumab, resulting in the disappearance of recurrent tumors within 6 months.
- The patient has survived for 76 months post-surgery with no clinical evidence of tumor recurrence.
- High tumor mutation burden was associated with a successful response to immune checkpoint inhibitors.
Implications:
- Immune checkpoint blockade can be a viable treatment for advanced hilar cholangiocarcinoma with high tumor mutation burden.
- Further research is needed to determine the optimal mutation burden for predicting response to immunotherapy.
- Personalized medicine approaches integrating genomics and immunotherapy show promise for improving patient outcomes.
