Dataset Information

Pre-operative ctDNA predicts survival in high-risk stage III cutaneous melanoma patients.

ABSTRACT:

Background

The outcomes of patients with stage III cutaneous melanoma who undergo complete surgical resection can be highly variable, and estimation of individual risk of disease recurrence and mortality remains imprecise. With recent demonstrations of effective adjuvant targeted and immune checkpoint inhibitor therapy, more precise stratification of patients for costly and potentially toxic adjuvant therapy is needed. We report the utility of pre-operative circulating tumour DNA (ctDNA) in patients with high-risk stage III melanoma.

Patients and methods

ctDNA was analysed in blood specimens that were collected pre-operatively from 174 patients with stage III melanoma undergoing complete lymph node (LN) dissection. Cox regression analyses were used to evaluate the prognostic significance of ctDNA for distant metastasis recurrence-free survival and melanoma-specific survival (MSS).

Results

The detection of ctDNA in the discovery and validation cohort was 34% and 33%, respectively, and was associated with larger nodal melanoma deposit, higher number of melanoma involved LNs, more advanced stage and high lactate dehydrogenase (LDH) levels. Detectable ctDNA was significantly associated with worse MSS in the discovery [hazard ratio (HR) 2.11 P?ConclusionPre-operative ctDNA predicts MSS in high-risk stage III melanoma patients undergoing complete LN dissection, independent of stage III substage. This biomarker may have an important role in determining prognosis and stratifying patients for adjuvant treatment.

SUBMITTER: Lee JH

PROVIDER: S-EPMC6551453 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Publications

Pre-operative ctDNA predicts survival in high-risk stage III cutaneous melanoma patients.

Lee J H JH Saw R P RP Thompson J F JF Lo S S Spillane A J AJ Shannon K F KF Stretch J R JR Howle J J Menzies A M AM Carlino M S MS Kefford R F RF Long G V GV Scolyer R A RA Rizos H H

Annals of oncology : official journal of the European Society for Medical Oncology 20190501 5

<h4>Background</h4>The outcomes of patients with stage III cutaneous melanoma who undergo complete surgical resection can be highly variable, and estimation of individual risk of disease recurrence and mortality remains imprecise. With recent demonstrations of effective adjuvant targeted and immune checkpoint inhibitor therapy, more precise stratification of patients for costly and potentially toxic adjuvant therapy is needed. We report the utility of pre-operative circulating tumour DNA (ctDNA) ...[more]

PMID: 30860590

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Project description:BackgroundOn the basis of data from a phase 2 trial that compared the checkpoint inhibitor ipilimumab at doses of 0.3 mg, 3 mg, and 10 mg per kilogram of body weight in patients with advanced melanoma, this phase 3 trial evaluated ipilimumab at a dose of 10 mg per kilogram in patients who had undergone complete resection of stage III melanoma.MethodsAfter patients had undergone complete resection of stage III cutaneous melanoma, we randomly assigned them to receive ipilimumab at a dose of 10 mg per kilogram (475 patients) or placebo (476) every 3 weeks for four doses, then every 3 months for up to 3 years or until disease recurrence or an unacceptable level of toxic effects occurred. Recurrence-free survival was the primary end point. Secondary end points included overall survival, distant metastasis-free survival, and safety.ResultsAt a median follow-up of 5.3 years, the 5-year rate of recurrence-free survival was 40.8% in the ipilimumab group, as compared with 30.3% in the placebo group (hazard ratio for recurrence or death, 0.76; 95% confidence interval [CI], 0.64 to 0.89; P<0.001). The rate of overall survival at 5 years was 65.4% in the ipilimumab group, as compared with 54.4% in the placebo group (hazard ratio for death, 0.72; 95.1% CI, 0.58 to 0.88; P=0.001). The rate of distant metastasis-free survival at 5 years was 48.3% in the ipilimumab group, as compared with 38.9% in the placebo group (hazard ratio for death or distant metastasis, 0.76; 95.8% CI, 0.64 to 0.92; P=0.002). Adverse events of grade 3 or 4 occurred in 54.1% of the patients in the ipilimumab group and in 26.2% of those in the placebo group. Immune-related adverse events of grade 3 or 4 occurred in 41.6% of the patients in the ipilimumab group and in 2.7% of those in the placebo group. In the ipilimumab group, 5 patients (1.1%) died owing to immune-related adverse events.ConclusionsAs adjuvant therapy for high-risk stage III melanoma, ipilimumab at a dose of 10 mg per kilogram resulted in significantly higher rates of recurrence-free survival, overall survival, and distant metastasis-free survival than placebo. There were more immune-related adverse events with ipilimumab than with placebo. (Funded by Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00636168 , and EudraCT number, 2007-001974-10 .).

Project description:Importance: Trichiasis surgery programs globally have faced high rates of poor surgical outcomes. Identifying correctable risk factors for improving long-term outcomes is essential for countries targeting elimination of trachoma as a public health problem.Objective: To determine whether the location of trichiatic eyelashes prior to surgery influences development of post-operative trichiasis (PTT) within two years after surgery.Design: Secondary data analysis of four randomized clinical trials evaluating methods to improve trichiasis surgery outcomes. These include the Surgery for Trichiasis, Antibiotics for Recurrence (STAR) trial, Partnership for Rapid Elimination of Trachoma (PRET-Surgery), absorbable versus silk sutures trial, and epilation versus surgery for minor trichiasis trial.Setting: Primary trials were conducted in rural areas of Ethiopia and Tanzania.Interventions or exposures: Trichiasis surgery performed with either the bilamellar tarsal rotation procedure or posterior lamellar rotation procedure.Main outcomes: Prevalence of PTT within two years after surgery, location of trichiatic eyelashes pre-operatively and post-operatively.Results: 6,747 eyelids that underwent first-time trichiasis surgery were included. PTT rates varied by study, ranging from 10-40%. PTT was less severe (based on number of trichiatic eyelashes) than initial trichiasis for 72% of those developing PTT, and only 2% of eyelids were worse at follow up than pre-operatively. Eyelids with central only-trichiasis pre-operatively had lower rates of PTT than eyelids with peripheral only trichiasis in each of the three trials that included severe TT cases. 10% of eyelids with peripheral trichiasis pre-operatively that develop PTT have central TT post-operatively.Conclusions and relevance: Pre-operative central trichiasis is less likely than peripheral trichiasis to be associated with subsequent PTT. Regardless of type of surgery, surgeon skill levels, or pre-operative trichiasis severity, the presence of peripheral trichiasis pre-operatively is associated with higher rates of PTT. Making an incision that extends the length of the eyelid and adequately rotating the nasal and temporal aspects of the eyelid when suturing may help to minimize the chance of developing peripheral PTT.Trial registration: ClinicalTrials.gov PRET: NCT00886015; Suture: NCT005228560; Epilation: NCT00522912.

Dataset Information

Pre-operative ctDNA predicts survival in high-risk stage III cutaneous melanoma patients.

Background

Patients and methods

Results

Publications

Pre-operative ctDNA predicts survival in high-risk stage III cutaneous melanoma patients.

Similar Datasets

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