Open AccessPrediction of the efficacy of immunotherapy by measuring the integrity of cell‐free DNA in plasma in colorectal cancer
Author(s) -
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
Publication year - 2016
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13085
Subject(s) - colorectal cancer , oxaliplatin , biomarker , cancer , dna , cell free fetal dna , medicine , immunotherapy , cancer research , oncology , human leukocyte antigen , immunology , biology , antigen , genetics , pregnancy , fetus , prenatal diagnosis
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 (cf DNA ) 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 cf DNA (i.e. the ratio of longer fragments [400 bp] to shorter fragments [100 bp] of cf DNA ), may be clinically useful for detecting colorectal cancer progression. We assessed plasma samples collected from 93 patients prior to receiving immunochemotherapy. The cf DNA levels and integrity were analyzed by semi‐quantitative real‐time PCR . Progression‐free survival was significantly better in patients with a low plasma cf DNA 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 cf DNA 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 cf DNA may provide important clinical information and may be a useful predictive biomarker of the outcome of immunotherapy in metastatic colorectal cancer.