Prediction of the efficacy of immunotherapy by measuring the integrity of cell‐free DNA in plasma in colorectal cancer

• Published in: Cancer science Vol. 107; no. 12; pp. 1825 - 1829
• Main Authors: Kitahara, Masahiro, Hazama, Shoichi, Tsunedomi, Ryouichi, Takenouchi, Hiroko, Kanekiyo, Shinsuke, Inoue, Yuka, Nakajima, Masao, Tomochika, Shinobu, Tokuhisa, Yoshihiro, Iida, Michihisa, Sakamoto, Kazuhiko, Suzuki, Nobuaki, Takeda, Shigeru, Ueno, Tomio, Yamamoto, Shigeru, Yoshino, Shigefumi, Nagano, Hiroaki
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.12.2016; John Wiley and Sons Inc
• Subjects: Aged; Apoptosis; Biomarker; Biomarkers; Biomarkers, Tumor; Cancer; Cancer therapies; Cancer vaccines; Cell size; cell‐free DNA; Chemotherapy; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - blood; Colorectal Neoplasms - diagnosis; Colorectal Neoplasms - mortality; Colorectal Neoplasms - therapy; Cytotoxicity; Deoxyribonucleic acid; DNA; DNA integrity; DNA, Neoplasm - blood; Female; Histocompatibility antigen HLA; Humans; Immunotherapy; Immunotherapy - methods; Kaplan-Meier Estimate; Lymphocytes T; Male; Medical prognosis; Metastases; Middle Aged; Mutation; Neoplasm Metastasis; Neoplasm Staging; Original; Oxaliplatin; Peptides; Prognosis; Proportional Hazards Models; R&D; Research & development; Studies; Treatment Outcome; Tumors; United States > US; cell-free DNA; DNA integrity; Biomarker; colorectal cancer; immunotherapy
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.13085

We previously reported a phase II study of a cancer vaccine using five novel peptides recognized by HLA‐A*2402‐restricted CTL in combination with oxaliplatin‐containing chemotherapy (FXV study) as first‐line therapy for patients with metastatic colorectal cancer and demonstrated the safety and promising potential of our five‐peptide cocktail. The objective of this analysis was to identify predictive biomarkers for identifying patients who are likely to receive a clinical benefit from immunochemotherapy. Circulating cell‐free DNA (cfDNA) in plasma has been reported to be a candidate molecular biomarker for the efficacy of anticancer therapy. Unlike uniformly truncated small‐sized DNA released from apoptotic normal cells, DNA released from necrotic cancer cells varies in size. The integrity of plasma cfDNA (i.e. the ratio of longer fragments [400 bp] to shorter fragments [100 bp] of cfDNA), may be clinically useful for detecting colorectal cancer progression. We assessed plasma samples collected from 93 patients prior to receiving immunochemotherapy. The cfDNA levels and integrity were analyzed by semi‐quantitative real‐time PCR. Progression‐free survival was significantly better in patients with a low plasma cfDNA integrity value than in those with a high value (P = 0.0027). Surprisingly, in the HLA‐A*2402‐matched group, patients with a low plasma cfDNA integrity value had significantly better progression‐free survival than those with a high value (P = 0.0015). This difference was not observed in the HLA‐A*2402‐unmatched group. In conclusion, the integrity of plasma cfDNA may provide important clinical information and may be a useful predictive biomarker of the outcome of immunotherapy in metastatic colorectal cancer. We reported that progression‐free survival was significantly better in patients with a low plasma cfDNA integrity value than in those with a high value. Surprisingly, in the immunochemotherapy group, patients with a low plasma cfDNA integrity value had significantly better progression‐free survival than those with a high value. In conclusion, the integrity of plasma cfDNA may provide important clinical information and may be a useful predictive biomarker of the outcome of immunotherapy in mCRC.