Dataset Information

Rapid response of stage IV colorectal cancer with APC/TP53/KRAS mutations to FOLFIRI and Bevacizumab combination chemotherapy: a case report of use of liquid biopsy.

ABSTRACT: BACKGROUND:Liquid biopsies of blood plasma cell free DNA can be used to monitor treatment response and potentially detect mutations that are present in resistant clones in metastatic cancer patients. CASE PRESENTATION:In our non-interventional liquid biopsy study, a male patient in his fifties diagnosed with stage IV colorectal cancer and polytope liver metastases rapidly progressed after completing chemotherapy and deceased 8?months after diagnosis. Retrospective cell free DNA testing showed that the APC/TP53/KRAS major clone responded quickly after 3?cycles of FOLFIRI + Bevacizumab. Retrospective exome sequencing of pre-chemotherapy and post-chemotherapy tissue samples including metastases confirmed that the APC/TP53/KRAS and other major clonal mutations (GPR50, SLC5A, ZIC3, SF3A1 and others) were present in all samples. After the last chemotherapy cycle, CT imaging, CEA and CA19-9 markers validated the cfDNA findings of treatment response. However, 5?weeks later, the tumour had rapidly progressed. CONCLUSION:As FOLFIRI+Bevacizumab has recently also been associated with sustained complete remission in a APC/TP53/KRAS triple-mutated patient, these driver genes should be tested and monitored in a more in-depth manner in future patients. Patients with metastatic disease should be monitored more closely during and after chemotherapy, ideally using cfDNA.

SUBMITTER: Hendricks A

PROVIDER: S-EPMC6942307 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Rapid response of stage IV colorectal cancer with APC/TP53/KRAS mutations to FOLFIRI and Bevacizumab combination chemotherapy: a case report of use of liquid biopsy.

Hendricks Alexander A Rosenstiel Philip P Hinz Sebastian S Burmeister Greta G Röcken Christoph C Boersch Kathrin K Schafmayer Clemens C Becker Thomas T Franke Andre A Forster Michael M

BMC medical genetics 20200103 1

<h4>Background</h4>Liquid biopsies of blood plasma cell free DNA can be used to monitor treatment response and potentially detect mutations that are present in resistant clones in metastatic cancer patients.<h4>Case presentation</h4>In our non-interventional liquid biopsy study, a male patient in his fifties diagnosed with stage IV colorectal cancer and polytope liver metastases rapidly progressed after completing chemotherapy and deceased 8 months after diagnosis. Retrospective cell free DNA te ...[more]

PMID: 31900123

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Project description:BackgroundAdvanced biliary tract cancer (BTC) has a poor prognosis. Gemcitabine with platinum chemotherapy was the standard first-line chemotherapeutic regimen until the recent addition of anti-PD-1/PD-L1 antibodies. After disease progression, the only second-line chemotherapy that has demonstrated a survival benefit versus supportive care is FOLFOX (folinic acid, fluorouracil, and oxaliplatin), with a modest benefit. This study aimed to assess the efficacy and safety of second-line FOLFIRI (folinic acid, fluorouracil, and irinotecan) combined with bevacizumab for advanced BTC.MethodsThis single-center retrospective study enrolled patients with metastatic BTC (intrahepatic cholangiocarcinoma [ICC], extrahepatic cholangiocarcinoma [ECC], or gallbladder carcinoma) that progressed after first-line gemcitabine-based chemotherapy. FOLFIRI-bevacizumab was administered intravenously every 2 weeks [folinic acid 200 mg/m², fluorouracil 400 mg/m² (bolus), fluorouracil 2400 mg/m² (46-h continuous intravenous infusion), irinotecan 180 mg/m², and bevacizumab 5 mg/kg] until unacceptable toxicity, patient refusal, or disease progression.ResultsOverall, 28 patients received the FOLFIRI-bevacizumab regimen after gemcitabine-based chemotherapy. The median overall survival (OS) was 9.0 months (95% CI 6.4-16.5). The OS rate was 39.3% (95% CI 24.8-62.3) and 10.7% (95% CI 3.7-32.1) at 12- and 24-months respectively. The median progression-free survival (PFS) was 5.2 months (95% CI 3.1-10.2) with FOLFIRI-bevacizumab. The PFS rates at 12 months and 24 months were 17.9% (95% CI 8.19-39.5] and 10.7% (95% CI 3.7-31.2), respectively. The overall response rate (ORR) to FOLFIRI-bevacizumab was 23.1%, with a disease control rate (DCR) of 69.3%. Grade 3-4 adverse events (sAE) were reported in 20 patients (71.4%) treated with FOLFIRI-bevacizumab.ConclusionFOLFIRI-bevacizumab as a second-line treatment for advanced BTC after gemcitabine-based chemotherapy showed efficacy and safety with a promising tumor response rate in this retrospective single-center study.

Project description:BackgroundNon-small cell lung cancer (NSCLC) patients treated with first-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) almost always acquire resistance, and the development of novel techniques analyzing circulating tumor DNA (ctDNA) have made it possible for liquid biopsy to detect genetic alterations from limited amount of DNA with less invasiveness. While a large amount of patients with EGFR exon 21 p.Thr790 Met (T790M) benefited from osimertinib treatment, acquired resistance to osimertinb has subsequently become a growing challenge.MethodsWe performed tissue and liquid rebiopsy on 50 patients with EGFR-mutant NSCLC who acquired resistance to first-generation EGFR-TKIs. Plasma samples underwent droplet digital PCR (ddPCR) and next-generation sequencing (NGS) examinations. Corresponding tissue samples underwent NGS and Cobas® EGFR Mutation Test v2 (Cobas) examinations.ResultsOf the 50 patients evaluated, the mutation detection rates of liquid biopsy group and tissue biopsy group demonstrated no significant differences (41/48, 85.4% vs. 44/48, 91.7%; OR=0.53, 95% CI=0.15 to 1.95). Overall concordance, defined as the proportion of patients for whom at least one identical genomic alteration was identified in both tissue and plasma, was 78.3% (36/46, 95% CI=0.39 to 2.69). Moreover, our results showed that almost half of the patients (46%, 23/50) resistant to first-generation EGFR-TKI harbored p.Thr790 Met (T790M) mutation. 82.6% (19/23) of the T790M positive patients were analyzed by liquid biopsy and 60.9% (14/23) by tumor tissue sequencing. Meanwhile, a wide range of uncommon mutations was detected, and novel mechanisms of osimertinib resistance were discovered. In addition, 16.7% (2/12) of the T790M positive patients with either TP53 R237C or KRAS G12V failed to benefit from the subsequent osimertinib treatment.ConclusionOur results emphasized that liquid biopsy is applicable to analyze the drug resistance mechanisms of NSCLC patients treated with EGFR-TKIs. Moreover, we discovered two uncommon mutations, TP53 R273C and KRAS G12V, which attenuates the effectiveness of osimertinib.

Dataset Information

Rapid response of stage IV colorectal cancer with APC/TP53/KRAS mutations to FOLFIRI and Bevacizumab combination chemotherapy: a case report of use of liquid biopsy.

Publications

Rapid response of stage IV colorectal cancer with APC/TP53/KRAS mutations to FOLFIRI and Bevacizumab combination chemotherapy: a case report of use of liquid biopsy.

Similar Datasets

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