Measurement of circulating free DNA in squamous cell carcinoma of the anus and relation to risk factors and recurrence

Lefèvre, Anna Cecilie; Kronborg, C.; Sørensen, Brita Singers; Krag, Susanne; Serup-Hansen, Eva; Spindler, Karen Lise Garm

doi:10.1016/j.radonc.2020.06.045

Cited by 8 publications

(33 citation statements)

References 32 publications

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“…This method is simple, rapid and inexpensive. The method has proved feasible in patients with locally advanced rectal cancer (14), mCRC (15,16) and squamous cell carcinoma of the anus undergoing chemoradiotherapy (17).…”

Section: Introductionmentioning

confidence: 99%

Total cell‑free DNA measurement in metastatic colorectal cancer with a fast and easy direct fluorescent assay

et al. 2022

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Treatment for metastatic colorectal cancer (mCRC) is focused on prolonging survival and maintaining quality of life. It is important to establish prognostic and predictive markers to avoid extended, ineffective treatment. The aim of the present study was, by a novel approach, to analyze the association between cell-free (cf)DNA levels and outcome in patients receiving systemic therapy for incurable mCRC. The study was a prospective non-interventional biomarker study for patients receiving standard of systemic treatment for mCRC. Patients with mCRC, who, according to standard guidelines, were considered for treatment with EGFR inhibitors, were included. The cfDNA levels in consecutive plasma samples were measured by a direct fluorescence assay. The study included 47 patients. Blood samples were available at baseline (n=47); prior to the third treatment cycle (n=31); the first (n=33), second (n=22) and third response evaluation during treatment (n=17); and at progression (n=22). The disease control rate was 42 and 91% in patients with high (≥75th percentile of baseline cfDNA levels) and low cfDNA levels (<75th percentile of baseline cfDNA levels), respectively (P<0.001). Median progression-free survival (PFS) was 3.8 and 8.5 months in patients with high and low cfDNA levels, respectively (hazard ratio=3.03, 95% CI 1.46-6.29, P<0.01). Median overall survival (OS) was 5.0 and 26.6 months in patients with high and low cfDNA levels, respectively (hazard ratio=3.48, 95% CI 1.44-8.44, P<0.01). In the multivariate analysis, baseline cfDNA levels remained a significant predictor of PFS and OS. In conclusion, cfDNA is a promising prognostic tool in the personalized treatment of mCRC. cfDNA levels were estimated by a simple, rapid and inexpensive method (OPTIPAL II: ClinicalTrials.gov identifier no. NCT03750175; registered November 21, 2018).

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Section: Introductionmentioning

confidence: 99%

Total cell‑free DNA measurement in metastatic colorectal cancer with a fast and easy direct fluorescent assay

et al. 2022

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“…Most tumors were P16 positive (82%). Patients were treated as previously presented [ 9 , 13 ]. Radiotherapy comprised dose levels of 64Gy/32 fractions ( n = 58), 60Gy/30 fractions ( n = 17) and 54-50Gy/27-25 fractions ( n = 12), one patient received 48Gy/30 fractions.…”

Section: Resultsmentioning

confidence: 99%

“…Patients with newly diagnosed SCCA at Department of Oncology, Aarhus University Hospital, Denmark, were included in the prospective clinical data and biobank collection study “Plan-A”, Ethical Committee no. 1-10-72-79-16, as described previously [ 9 , 13 ].…”

Section: Methodsmentioning

confidence: 99%

“…Circulating free DNA (cfDNA) is a mixture of normal cell DNA fragments and tumor DNA fragments (ctDNA) [ 12 ] in the blood. The constant release and fast elimination make ctDNA a timely marker for early evaluation and detection of recurrence after primary therapy [ 13 , 14 , 15 , 16 , 17 ]. In HPV related tumors, as most SCCA [ 3 ], ctDNA measured as serum HPV or plasma HPV (pHPV), has been detected in blood samples from patients with oropharynx cancer, cervical cancer, and in smaller studies for SCCA [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ].…”

Section: Introductionmentioning

confidence: 99%

“…(B) 20 patients with slow pHPV elimination pattern. (C)13 patients with molecular persistent disease. In (D), the relation between the pattern and treatment outcome are outlined, including 22 patients with undetectable pHPV and the 21 patients who were excluded due to insufficient repeated pHPV measurements.…”

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confidence: 99%

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The Clinical Value of Measuring Circulating HPV DNA during Chemo-Radiotherapy in Squamous Cell Carcinoma of the Anus

Lefèvre

Pallisgaard

Kronborg

et al. 2021

Cancers

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Background and purpose: Circulating tumor DNA (ctDNA) is investigated in various cancers. In squamous cell carcinoma of the anus (SCCA) infection with human papilloma virus (HPV) is found in around 90% of cases and here, plasma HPV (pHPV) can be used as ctDNA. Preliminary data have proved the ability to detect pHPV16 and -18 in SCCA. We have developed a highly sensitive method for measurement of six relevant pHPV subtypes, to investigate the elimination pattern of pHPV during chemo-radiotherapy (CRT) for SCCA and its clinical value. Material and methods: Patients treated at Aarhus University Hospital from 2016–2020 were included. P16 status in the primary biopsy was measured and 82% of patients had P16 positive tumor. Blood samples were collected prior to treatment (PT), mid treatment (MT), end of therapy (EOT), and during follow-up (FU). An in-house multiplex digital droplet PCR method measured pHPV subtypes 16, 18, 31, 33, 51, 58. Results: Samples from 88 patients were drawn PT (n = 73), MT (n = 72), EOT (n = 64) and during FU (n = 41). Plasma HPV was detectable in 52 patients and PT pHPV levels correlated to tumor stages. Three elimination patterns were observed during CRT with correlation to outcome: fast responders with no local or distant failures (0/12); slow responders with high risk of local failures (4/20), no distant failures; persistent molecular responders with high risk of distant failures (4/13), but no local failures, p < 0.01. Conclusion: During CRT, pHPV can divide patients with SCCA into three groups with significantly different risk of failure. The use of pHPV can potentially assist in clinical treatment decision.

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Treatment of Squamous Cell Carcinoma of the Anus, Unresolved Areas and Future Perspectives for Research: Perspectives of Research Needs in Anal Cancer

Guren

Sebag‐Montefiore

Franco

et al. 2021

Clinical Colorectal Cancer

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Measurement of circulating free DNA in squamous cell carcinoma of the anus and relation to risk factors and recurrence

Cited by 8 publications

References 32 publications

Total cell‑free DNA measurement in metastatic colorectal cancer with a fast and easy direct fluorescent assay

Total cell‑free DNA measurement in metastatic colorectal cancer with a fast and easy direct fluorescent assay

The Clinical Value of Measuring Circulating HPV DNA during Chemo-Radiotherapy in Squamous Cell Carcinoma of the Anus

Treatment of Squamous Cell Carcinoma of the Anus, Unresolved Areas and Future Perspectives for Research: Perspectives of Research Needs in Anal Cancer

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