Prognostic risk factors of first recurrence in patients with primary stages I–II cutaneous malignant melanoma – from the population‐based Swedish melanoma register

Lyth, Johan; Falk, Magnus; Maroti, Marianne; Eriksson, Hanna; Ingvar, Christian

doi:10.1111/jdv.14280

Cited by 26 publications

(22 citation statements)

References 33 publications

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“…Whilst stage III melanoma patients have a higher risk of recurrence than stage I [36, 37], in our cohort two of the patients with stage 1 disease and only 1 of the patients with stage III disease at time of diagnosis of the primary, developed metastatic disease. Furthermore tumor thickness has been considered to be an important prognostic risk factor for recurrence [38], however here we report recurrence from primary tumors of 1.1 mm, 1.83 mm and 8.3 mm thickness. Previous studies that have compared time to recurrence with clinical staging as well as host and tumor-dependent variables, have shown that older age, gender (male), thin and non-ulcerated melanomas are each independently associated with a late recurrence (>8 years from time of diagnosis) [7, 8].…”

Section: Discussionmentioning

confidence: 61%

“…Overall, three cases experienced distant disease recurrence during the sample collection period. The BRAF mutation status of these three tumors was determined previously [38] and by Next Generation Sequencing (NGS) using a custom targeted sequencing panel for a third case which was found to be BRAF wild-type. A subset of patients ( n = 27) with no clinical evidence of disease recurrence at last follow-up was selected for ctDNA assessment.…”

Section: Methodsmentioning

confidence: 99%

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Monitoring melanoma recurrence with circulating tumor DNA: a proof of concept from three case studies

et al. 2019

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BackgroundA significant number of melanoma patients experience recurrence to distant sites, despite having had surgical treatment of the primary lesion, with curative intent. Monitoring of patients for early evidence of disease recurrence would significantly improve management of the disease, allowing timely therapeutic intervention. Circulating tumor DNA (ctDNA) is becoming a well-recognized biomarker for monitoring malignancies and has, in a few studies, been shown to signify disease recurrence earlier than conventional methods.MethodsWe performed a retrospective analysis of plasma ctDNA using droplet digital PCR (ddPCR) in 30 primary melanoma patients with tumors harboring BRAF, NRAS or TERT promoter mutations. Mutant specific ctDNA, measured during clinical disease course, was compared with disease status in patients with confirmed disease recurrence (n = 3) and in those with no evidence of disease recurrence (n = 27).ResultsMutant specific ctDNA was detected in all three patients with disease recurrence at the time of clinically confirmed progression. In one case, plasma ctDNA detection preceded clinical identification of recurrence by an interval of 4 months. CtDNA was not detected in patients who were asymptomatic and had no radiological evidence of recurrence.ConclusionsThis study demonstrates promising results for the use of ctDNA as an informative monitoring tool for melanoma patients having undergone tumor resection of an early stage primary tumor. The clinical utility of ctDNA for monitoring disease recurrence warrants investigation in prospective studies as it may improve patient outcome.

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Section: Discussionmentioning

confidence: 61%

Section: Methodsmentioning

confidence: 99%

Monitoring melanoma recurrence with circulating tumor DNA: a proof of concept from three case studies

et al. 2019

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“…Previous studies, based on data from the SweMR, have shown that the majority of recurrences in patients with clinical stage I and II are confirmed within the first years after diagnosis at a median time of 2·3 years. The vast majority of recurrences were diagnosed at body sites easily detected by the patients themselves, which emphasizes the importance of self‐examination education 30,31…”

Section: Discussionmentioning

confidence: 99%

Survival in 31 670 patients with thin melanomas: a Swedish population‐based study*

et al. 2020

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Summary Background The incidence of cutaneous malignant melanoma (CMM) continues to increase in most countries worldwide and the majority are diagnosed with thin tumours (≤ 1 mm). Objectives The aim of the present study was to investigate the melanoma‐specific survival (MSS) as well as conditional MSS (CMSS) in patients with thin CMM in Sweden. Patients and methods Clinical and histological parameters were obtained from the Swedish Melanoma Registry for patients diagnosed with thin CMM between 1990 and 2017. Patients were followed until the end of 2017. MSS as well as CMSS for different thickness groups were calculated using the Kaplan–Meier method and Cox regression analyses were used to calculate for survival differences between thickness groups. Results There were 31 670 patients included for final analyses. The overall 10‐ and 20‐year MSS for thin CMMs was 97% [95% confidence interval (CI) 97–97] and 95% (95% CI 95–96), respectively. From 0·7 mm and above, MSS decreased significantly with increasing thickness level. All thickness groups had an increased survival over time. The lowest CMSS was confirmed for men with 1·0 mm in thickness but their 10‐year CMSS increased steadily over time. Women had overall better MSS as well as CMSS than men. However, the relation between MSS and CMSS was similar for both sexes. Conclusions MSS was confirmed as excellent for patients with thin CMMs in Sweden. Although we could show a decreased MSS for patients with 0·7 mm thickness and above, the long‐term survival and, in addition, a very favourable CMSS for those patients do not support more extended follow‐up programmes than the current recommendations in Sweden.

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“…The risk of recurrence (hazard ratios, HR) was estimated using multivariable Cox regression. All covariables were selected a priori as per our protocol [6,[40][41][42][43][44][45][46][47][48][49]. Models were internally validated by lossless non-parametric bootstrapping by resampling with replacement, with 1000 iterations [50].…”

Section: Statisticsmentioning

confidence: 99%

The neutrophil–lymphocyte ratio and locoregional melanoma: a multicentre cohort study

Robinson

Keeble

et al. 2020

Cancer Immunol Immunother

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Objectives The neutrophil-lymphocyte ratio (NLR) is an inflammatory biomarker which is useful in cancer prognostication. We aimed to investigate the differences in baseline NLR between patients with localised and metastatic cutaneous melanoma and how this biomarker changed over time with the recurrence of disease. Methods This multicentre cohort study describes patients treated for Stage I-III cutaneous melanoma over 10 years. The baseline NLR was measured immediately prior to surgery and again at the time of discharge or disease recurrence. The odds ratios (OR) for sentinel node involvement are estimated using mixed-effects logistic regression. The risk of recurrence is estimated using multivariable Cox regression. Results Overall 1489 individuals were included. The mean baseline NLR was higher in patients with palpable nodal disease compared to those with microscopic nodal or localised disease (2.8 versus 2.4 and 2.3, respectively; p < 0.001). A baseline NLR ≥ 2.3 was associated with 30% higher odds of microscopic metastatic melanoma in the sentinel lymph node [adjusted OR 1.3 (95% CI 1.3, 1.3)]. Following surgery, 253 patients (18.7%) developed recurrent melanoma during surveillance although there was no statistically significant association between the baseline NLR and the risk of recurrence [adjusted HR 0.9 (0.7, 1.1)]. Conclusion The NLR is associated with the volume of melanoma at presentation and may predict occult sentinel lymph metastases. Further prospective work is required to investigate how NLR may be modelled against other clinicopathological variables to predict outcomes and to understand the temporal changes in NLR following surgery for melanoma.

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Prognostic risk factors of first recurrence in patients with primary stages I–II cutaneous malignant melanoma – from the population‐based Swedish melanoma register

Cited by 26 publications

References 33 publications

Monitoring melanoma recurrence with circulating tumor DNA: a proof of concept from three case studies

Monitoring melanoma recurrence with circulating tumor DNA: a proof of concept from three case studies

Survival in 31 670 patients with thin melanomas: a Swedish population‐based study*

The neutrophil–lymphocyte ratio and locoregional melanoma: a multicentre cohort study

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