Early dynamics of circulating tumor DNA predict chemotherapy responses for patients with esophageal cancer

• Published in: Carcinogenesis (New York) Vol. 42; no. 10; pp. 1239 - 1249
• Main Authors: Fujisawa, Ryosuke, Iwaya, Takeshi, Endo, Fumitaka, Idogawa, Masashi, Sasaki, Noriyuki, Hiraki, Hayato, Tange, Shoichiro, Hirano, Tomomi, Koizumi, Yuka, Abe, Masakazu, Takahashi, Tomoko, Yaegashi, Mizunori, Akiyama, Yuji, Masuda, Mari, Sasaki, Akira, Takahashi, Fumiaki, Sasaki, Yasushi, Tokino, Takashi, Nishizuka, Satoshi S
• Format: Journal Article
• Language: English
• Published: UK Oxford University Press 26.10.2021
• Subjects: Aged; Aged, 80 and over; Antineoplastic Agents - therapeutic use; Circulating Tumor DNA - blood; Esophageal Neoplasms - blood; Esophageal Neoplasms - drug therapy; Esophageal Neoplasms - genetics; Esophageal Squamous Cell Carcinoma - blood; Esophageal Squamous Cell Carcinoma - drug therapy; Esophageal Squamous Cell Carcinoma - genetics; Female; Gene Frequency; Humans; Male; Middle Aged; Mutation; Polymerase Chain Reaction - methods; Treatment Outcome
• ISSN: 0143-3334; 1460-2180
• DOI: 10.1093/carcin/bgab088

Abstract We investigated whether early circulating tumor DNA (ctDNA) changes, measured using digital PCR (dPCR), can predict later chemotherapy responses in esophageal squamous cell cancer (ESCC). We compared the dynamics of ctDNA and tumor volumes during chemotherapy in 42 ESCC. The accuracy of predictions of later chemotherapy responses was evaluated by the ratio of the variant allele frequency of ctDNA (post-/pre-ctDNA) and the total tumor volume (post-/pre-volume) before and after an initial chemotherapy cycle using a receiver-operating characteristic curve analysis. Total positive and negative objective responses (ORs) were defined as either >50 or ≤50% reductions, respectively, in the total tumor volume at the end of first-line chemotherapy. Mutation screening of 43 tumors from 42 patients revealed 96 mutations. The pretreatment dPCR-ctDNA data were informative in 38 patients, using 70 selected mutations (1–3 per patient). The areas under the curve (AUCs) for the post-/pre-volume and post-/pre-ctDNA levels used in predicting the total OR were 0.85 and 0.88, respectively. The optimal cutoff value of post-/pre-ctDNA was 0.13. In 20 patients with post-/pre-volume ≥50%, the total OR could be predicted by the post-/pre-ctDNA with high accuracy; the AUC by post-/pre-ctDNA was higher than that by post-/pre-volume (0.85 versus 0.76, respectively). Patients with low post-/pre-ctDNA (n = 18) had a significantly better overall survival rate than those with high post-/pre-ctDNA (n = 20; P = 0.03). Early ctDNA changes after an initial cycle of chemotherapy predict later responses to treatment with high accuracy in ESCC patients. Early circulating tumor DNA dynamics using digital PCR that targeted individual tumor-specific mutations predict later chemotherapy responses more accurately than tumor volume change seen through computed tomography before and after the initial cycle in esophageal squamous cell cancer patients. Graphical Abstract Graphical Abstract