Dataset Information

Circulating tumour DNA dynamics predict recurrence in stage III melanoma patients receiving neoadjuvant immunotherapy.

ABSTRACT:

Background

Neoadjuvant therapy improves recurrence-free survival (RFS) in resectable stage III cutaneous melanoma. However, accurately predicting individual recurrence risk remains a significant challenge. We investigated circulating tumour DNA (ctDNA) as a biomarker for recurrence in measurable stage IIIB/C melanoma patients undergoing neoadjuvant immunotherapy.

Methods

Plasma samples were collected pre-neoadjuvant treatment, pre-surgery and/or six weeks post-surgery from 40 patients enrolled in the OpACIN-neo and PRADO clinical trials. Patients received two cycles of ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) before surgery. Cell free DNA (cfDNA) underwent unbiased pre-amplification followed by tumour-informed mutation detection using droplet digital polymerase chain reaction (ddPCR) with the Bio-Rad QX600 PCR system.

Results

Pre-treatment ctDNA was detectable in 19/40 (48%) patients. Among these, 17/19 (89%) zero-converted within six weeks of surgery and none recurred. Positive ctDNA post-surgery (N = 4), irrespective of pre-treatment ctDNA status, was 100% predictive of recurrence (sensitivity 44%, specificity 100%). Furthermore, ctDNA cleared prior to surgery in 7/9 (78%) patients who did not recur, warranting further investigation into ctDNA-guided surgical management.

Conclusion

Post-surgery ctDNA positivity and zero-conversion are highly predictive of recurrence, offering a window for personalised modification of adjuvant therapy.

SUBMITTER: Chan WY

PROVIDER: S-EPMC11337884 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Publications

Circulating tumour DNA dynamics predict recurrence in stage III melanoma patients receiving neoadjuvant immunotherapy.

Chan Wei Yen WY Lee Jenny H JH Stewart Ashleigh A Diefenbach Russell J RJ Gonzalez Maria M Menzies Alexander M AM Blank Christian C Scolyer Richard A RA Long Georgina V GV Rizos Helen H

Journal of experimental & clinical cancer research : CR 20240821 1

<h4>Background</h4>Neoadjuvant therapy improves recurrence-free survival (RFS) in resectable stage III cutaneous melanoma. However, accurately predicting individual recurrence risk remains a significant challenge. We investigated circulating tumour DNA (ctDNA) as a biomarker for recurrence in measurable stage IIIB/C melanoma patients undergoing neoadjuvant immunotherapy.<h4>Methods</h4>Plasma samples were collected pre-neoadjuvant treatment, pre-surgery and/or six weeks post-surgery from 40 pati ...[more]

PMID: 39169411

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Project description:BackgroundPatients with stage II to III breast cancer have a high recurrence rate. The early detection of recurrent breast cancer remains a major unmet need. Circulating tumor DNA (ctDNA) has been proven to be a marker of disease progression in metastatic breast cancer. We aimed to evaluate the prognostic value of ctDNA in the setting of neoadjuvant therapy (NAT).MethodsPlasma was sampled at the initial diagnosis (defined as before NAT) and after breast surgery and neoadjuvant therapy(defined as after NAT). We extracted ctDNA from the plasma and performed deep sequencing of a target gene panel. ctDNA positivity was marked by the detection of alterations, such as mutations and copy number variations.ResultsA total of 95 patients were enrolled in this study; 60 patients exhibited ctDNA positivity before NAT, and 31 patients exhibited ctDNA positivity after NAT. A pathologic complete response (pCR) was observed in 13 patients, including one ER(+)Her2(-) patient, six Her2(+) patients and six triple-negative breast cancer (TNBC) patients. Among the entire cohort, multivariate analysis showed that N3 classification and ctDNA positivity after NAT were independent risk factors that predicted recurrence (N3, hazard ratio (HR) 3.34, 95% confidence interval (CI) 1.26 - 8.87, p = 0.016; ctDNA, HR 4.29, 95% CI 2.06 - 8.92, p < 0.0001). The presence of ctDNA before NAT did not affect the rate of recurrence-free survival. For patients with Her2(+) or TNBC, patients who did not achieve pCR were associated with a trend of higher recurrence (p = 0.105). Advanced nodal status and ctDNA positivity after NAT were significant risk factors for recurrence (N2 - 3, HR 3.753, 95% CI 1.146 - 12.297, p = 0.029; ctDNA, HR 3.123, 95% CI 1.139 - 8.564, p = 0.027). Two patients who achieved pCR had ctDNA positivity after NAT; one TNBC patient had hepatic metastases six months after surgery, and one Her2(+) breast cancer patient had brain metastasis 13 months after surgery.ConclusionsThis study suggested that the presence of ctDNA after NAT is a robust marker for predicting relapse in stage II to III breast cancer patients.

Dataset Information

Circulating tumour DNA dynamics predict recurrence in stage III melanoma patients receiving neoadjuvant immunotherapy.

Background

Methods

Results

Conclusion

Publications

Circulating tumour DNA dynamics predict recurrence in stage III melanoma patients receiving neoadjuvant immunotherapy.

Similar Datasets

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