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Circulating tumor DNA in molecular assessment feasibly predicts early progression of pancreatic cancer that cannot be identified via initial imaging.

ABSTRACT: Molecular assessment using circulating tumor DNA (ctDNA) has not been well-defined. We recruited 61 pancreatic cancer (PC) patients who underwent initial computed tomography (CT) imaging study during first-line chemotherapy. Initial molecular assessment was performed using droplet digital PCR and defined as the change in KRAS-mutated ctDNA before and after treatments, which was classified into five categories: mNT, molecular negative; mCR, complete response; mPR, partial response; mSD, stable disease; mPD, progressive disease. Of 61 patients, 14 diagnosed with PD after initial CT imaging showed significantly worse therapeutic outcomes than 47 patients with disease control. In these 47 patients, initial molecular assessment exhibited significant differences in therapeutic outcomes between patients with and without ctDNA (mPD + mSD vs. mCR + mNT; 13.2 M vs. 21.7 M, P = 0.0029) but no difference between those with mPD and mSD + mCR + mNT, suggesting that the presence of ctDNA had more impact on the therapeutic outcomes than change in its number. Multivariate analysis revealed that it was the only independent prognostic factor (P = 0.0405). The presence of ctDNA in initial molecular assessment predicted early tumor progression and identified PC patients more likely to benefit from chemotherapy.

SUBMITTER: Watanabe F

PROVIDER: S-EPMC10036464 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Circulating tumor DNA in molecular assessment feasibly predicts early progression of pancreatic cancer that cannot be identified via initial imaging.

Watanabe Fumiaki F Suzuki Koichi K Aizawa Hidetoshi H Endo Yuhei Y Takayama Yuji Y Kakizawa Nao N Kato Takaharu T Noda Hiroshi H Rikiyama Toshiki T

Scientific reports 20230323 1

Molecular assessment using circulating tumor DNA (ctDNA) has not been well-defined. We recruited 61 pancreatic cancer (PC) patients who underwent initial computed tomography (CT) imaging study during first-line chemotherapy. Initial molecular assessment was performed using droplet digital PCR and defined as the change in KRAS-mutated ctDNA before and after treatments, which was classified into five categories: mNT, molecular negative; mCR, complete response; mPR, partial response; mSD, stable di ...[more]

PMID: 36959222

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Project description:Patients exhibiting pancreatic cancer possess poor rates of survival. Therefore, the identification of a biomarker that can be measured non-invasively and be used to predict patient outcomes is required for the successful treatment of pancreatic cancer. The present study evaluated serum microRNA (miRNA/miR) profiles in patients exhibiting pancreatic cancer, who were treated with lapatinib and capecitabine in a phase II trial. Serum samples were collected for the measurement of a panel of miRNAs (miR-21, miR-210, miR-221 and miR-7) associated with the epidermal growth factor receptor (EGFR)1 and human epidermal growth factor receptor (HER)2 pathways. Preclinically, human pancreatic cancer PANC-1, MIA PaCa-2 and BXCP-3 cell lines were utilized for miRNA and drug resistance studies. In total, 6/17 patients treated experienced disease progression following 2 cycles of treatment [non-responders (NRS)], while another 6/17 patients exhibited a stable disease state and received >4 cycles of treatment [responders (RS); range, 4-22 cycles]. Five patients withdrew from the study due to severe toxicity or mortality. The mean overall survival time was 6.5 vs. 10.4 months for NRS and RS, respectively. Significant upregulation of serum miRNAs at earlier time points (3-6 weeks) was observed in NRS. miRNA levels increased with cancer progression, and lapatinib and 5-fluorouracil (5-FU; the active form of capecitabine) treatment increased the miRNA levels (specifically miR-210 and miR-221) in the treatment-resistant pancreatic cancer PANC-1 and MIA PaCa-2 cell lines. However, lapatinib and 5-FU treatment did not increase the miRNA levels in the treatment-sensitive BXPC-3 cell line. Inhibition of miR-221 increased the sensitivity of the PANC-1 cells to treatment. In conclusion, an increase in specific serum miRNAs was associated with resistance to lapatinib and capecitabine treatment. Additional investigation is required with regard to the application of the miRNA panel investigated in the present study as a potential predictor of patient responses to anti-EGFR/HER2 treatment.

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Circulating tumor DNA in molecular assessment feasibly predicts early progression of pancreatic cancer that cannot be identified via initial imaging.

Publications

Circulating tumor DNA in molecular assessment feasibly predicts early progression of pancreatic cancer that cannot be identified via initial imaging.

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