Targeted deep sequencing contributes to guiding personalized targeted therapy for advanced biliary tract cancer patients with non‑radical resection: A real‑world study

Oncol Rep. 2020 Apr;43(4):1089-1102. doi: 10.3892/or.2020.7491. Epub 2020 Feb 6.

Abstract

Targeted therapy based on specific genetic alterations has been proven to be an effective treatment for various types of cancer. In the present study, we aimed to explore the efficacy of personalized targeted therapy guided by targeted deep sequencing for patients with advanced biliary tract cancer (BTC) after non‑radical resection. Targeted deep sequencing was performed on 49 patients with BTC, to whom biologic agents were recommended. Among 32 patients with stage IV and R2 resection (a non‑radical resection), 21 patients underwent conventional chemotherapy (mGEMOX), while the remaining 11 patients received a personalized targeted agent. The genomic landscape of the 49 patients with BTC was determined and the results showed that genetic alterations were enriched in the ERBB family and cell cycle pathway. After a median follow‑up of 12 months, the 11 BTC patients with personalized targeted therapy showed a median progression‑free survival (PFS) of 4.5 months (2.5‑20.5 months), a median overall survival (OS) of 12.9 months (4.7‑24.8 months) and a disease control rate (DCR) of 63.6%. In the other 21 BTC patients, who were undergoing conventional chemotherapy, the BTC patients had a median PFS of 1.5 months (0.5‑11.6 months), a median OS of 4.1 months (1.3‑18.4 months), and a DCR of 33.3%. In addition, 36.4% of the patients in the personalized targeted therapy group experienced grade >2 treatment‑related toxicity vs. 19.0% of patients in the conventional chemotherapy group. This real‑world study suggests that targeted deep sequencing contributes to the guidance of personalized targeted therapy based on individual actionable mutations, which may benefit advanced BTC patients undergoing non‑radical resection.

Keywords: personalized targeted therapy; biliary tract cancer; non radical resection; targeted deep sequencing; prognosis.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biliary Tract Neoplasms / drug therapy*
  • Biliary Tract Neoplasms / pathology
  • Biliary Tract Neoplasms / surgery
  • Class I Phosphatidylinositol 3-Kinases / antagonists & inhibitors
  • Class I Phosphatidylinositol 3-Kinases / genetics
  • Dasatinib / administration & dosage
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics
  • Everolimus / administration & dosage
  • Female
  • Gemcitabine
  • Genes, Neoplasm*
  • High-Throughput Nucleotide Sequencing / methods*
  • Humans
  • Imatinib Mesylate / administration & dosage
  • Lapatinib / administration & dosage
  • Male
  • Middle Aged
  • Molecular Targeted Therapy / methods*
  • Mutation*
  • Neoplasm Staging
  • Organoplatinum Compounds / administration & dosage
  • Receptor, ErbB-2 / antagonists & inhibitors
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-3 / antagonists & inhibitors
  • Receptor, ErbB-3 / genetics
  • Receptor, ErbB-4 / antagonists & inhibitors
  • Receptor, ErbB-4 / genetics
  • Survival Rate
  • Treatment Outcome

Substances

  • Organoplatinum Compounds
  • Lapatinib
  • Deoxycytidine
  • Imatinib Mesylate
  • Everolimus
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • EGFR protein, human
  • ERBB2 protein, human
  • ERBB3 protein, human
  • ERBB4 protein, human
  • ErbB Receptors
  • Receptor, ErbB-2
  • Receptor, ErbB-3
  • Receptor, ErbB-4
  • Dasatinib
  • Gemcitabine