Outcomes and Risk Factors in Patients with Multiple Primary Melanomas.
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ABSTRACT:
SUBMITTER: Nosrati A
PROVIDER: S-EPMC9191767 | biostudies-literature | 2019 Jan
REPOSITORIES: biostudies-literature
Publications
Outcomes and Risk Factors in Patients with Multiple Primary Melanomas.
Nosrati Adi A Yu Wesley Y WY McGuire Joseph J Griffin Ann A de Souza Juliana Rocha JR Singh Rasnik R Linos Eleni E Chren Mary Margaret MM Grimes Barbara B Jewell Nicholas P NP Wei Maria L ML
The Journal of investigative dermatology 20180719 1
The incidence and patient survival rates of melanoma have increased over the last several decades, with a growing population of patients who develop multiple primary melanomas (MPMs). To determine risk factors for developing MPMs and compare the survival of patients with MPMs to those with single primary melanomas, a prospective, multidisciplinary database of patients with melanoma at a single tertiary care institution was retrospectively reviewed. From 1985 to 2013, 6,963 patients with single p ...[more]
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Project description:Importance:Information on risk factors of subsequent melanomas would be helpful to identify patients at risk after the diagnosis of their first melanomas. Objective:To determine risk factors of subsequent melanomas. Design, Setting, and Participants:In this retrospective case-control study, 1648 participants with histologically verified cutaneous melanoma diagnosed from January 1, 1968, though March 16, 2015, were recruited from a tertiary referral center as part of the Molecular Markers of Melanoma study. CDKN2A was sequenced in 514 and MC1R in 953 participants. Data were analyzed from March 7, 2008, through March 25, 2015. Main Outcomes and Measures:Phenotypic traits and internal and external risk factors for the development of a second, third, or fourth melanoma. Results:In total, 1648 patients (53.6% men; mean [SD] age, 54 [15] years) were enrolled, including 1349 with single and 299 with multiple primary melanoma. Mean (SD) age at recruitment was 57 (15) years for the single-melanoma and 62 (14) years for the multiple-melanoma groups. From the internal risk factors, family history (odds ratio [OR], 1.76; 95% CI, 1.22-2.55; P = .006), CDKN2A high-risk mutations (OR, 4.03; 95% CI, 1.28-12.70; P = .02), and high numbers of nevi as a phenotypic risk factor (ORs, 2.23 [95% CI, 1.56-3.28, P < .001] for 20-30 smaller nevi and 2.56 [95% CI, 1.50-4.36; P = .003] for 20-30 larger nevi) were significantly associated with the risk of developing a subsequent primary melanoma using multivariate logistic regression analysis. Nonmelanoma skin cancer (OR, 2.57; 95% CI, 1.84-3.58; P < .001) and signs of actinic skin damage, particularly on the back (ORs, 1.91 [95% CI, 1.12-3.25; P = .04] for freckling and 1.92 [95% CI, 1.29-3.08; P = .007] for solar lentigines), additionally increased risk of a subsequent melanoma. All those factors were also associated with an earlier development of the second melanoma. Patients with 3 melanomas developed their second melanoma earlier than patients with only 2 melanomas (mean [SD] age, 55 [15] years for those with 2 primary melanomas; 52 [15] years for those with 3 primary melanomas). Time spent outdoors, solarium use, outdoor occupation, and hair color had no significant associations in these models. Conclusions and Relevance:According to the results of this study, internal factors (family history and genetic variants), number of nevi, and actinic damage on the back are more relevant for the development of subsequent melanomas than skin phototype or hair color. Patients with many nevi were younger at the time of the diagnosis of their first melanoma. This finding could help to identify persons at increased risk of developing multiple primary melanomas.
| S-EPMC6439543 | biostudies-literature
Project description:ImportanceMelanoma is one of the most rapidly increasing forms of cancer worldwide. Most studies about survival among patients with melanoma consider only the primary tumor and disregard the potential effect of multiple primary tumors. A better understanding of the prognosis of patients with multiple primary melanoma is important for patient counselling and follow-up strategies.ObjectiveTo describe the epidemiologic features of multiple primary melanoma in patients from the Netherlands.Design, setting, and participantsThis retrospective, population-based cohort study included adults with histologically proven, primary, invasive cutaneous melanoma in the Netherlands between January 1, 2000, and December 31, 2014, with a median follow-up of 75.1 months, using data from PALGA, the Dutch Nationwide Network and Registry of Histopathology and Cytopathology. Follow-up data were retrieved from the Netherlands Cancer Registry. Statistical analysis was performed from August 1, 2018, to September 3, 2018.Main outcomes and measuresA multivariable Cox model with a time-varying covariate was performed to assess overall survival between patients with a single primary melanoma vs those with multiple primary melanomas. Secondary outcomes included incidence of multiple primary melanoma, differences in Breslow thickness, and time between first and second multiple primary melanoma.ResultsOf the 56 929 study patients, 31 916 (56.1%) were female, with a mean (SD) age of 56.4 (16.2) years. A total of 54 645 single primary melanomas and 4967 multiple primary melanomas in 2284 patients were included. The median Breslow thickness decreased from 0.90 mm (interquartile range, 0.55-1.70 mm) for the first melanoma to 0.65 mm (interquartile range, 0.45-1.10 mm) for the second melanoma (P < .001). For their second melanoma, 370 patients (16.2%) had a higher T stage, 1112 (48.7%) had the same T stage, and 802 (35.1%) had a lower T stage. In addition, 841 of 2284 second melanomas (36.8%) in patients with multiple primary melanomas were found during the first year of follow-up, whereas 624 of 2284 (27.3%) were found after 5 years of follow-up. These proportions did not vary when stratified for melanoma stage. Worse overall survival was seen among patients with multiple primary melanomas compared with patients with a single primary melanoma (hazard ratio, 1.31; 95% CI, 1.20-1.42; P < .001).Conclusions and relevanceA significant decrease in Breslow thickness between the first and second multiple primary melanoma was found, and overall survival among patients with multiple primary melanomas was significantly worse than that among patients with a single primary melanoma. These findings suggest that more strict follow-up strategies may be warranted for patients with multiple primary melanomas.
| S-EPMC6596329 | biostudies-literature
Project description:IntroductionMultiple primary melanomas (MPM) occur up to 8% of patients with cutaneous malignant melanoma (CMM). They are often sporadic harbouring several somatic mutations, but also familial cases harbouring a CDKN2A germline mutation have been describe in Caucasian populations. The aim of this study was to investigate the incidence, the distribution patterns and the impact of known and unknown germline and somatic mutations in patients with MPM from Italy.Materials and methodsOne-hundred and two MPM patients were enrolled for germline mutation analysis, and five patients with at least four MPMs were identified for somatic mutation analysis. The demographic, pathologic and clinical features were retrieved from medical records. Molecular analysis for both germline and somatic mutations was performed in genomic DNA from peripheral blood and tissue samples, respectively, through a next generation sequencing approach, using a specific multiple-gene panel constructed by the Italian Melanoma Intergroup for somatic analysis and a commercial cancer hotspot panel for somatic analysis.ResultsCDKN2A mutations were detected in 6/16 (37.5%) and 3/86 (3.5%) MPM cases with and without family history for melanoma, respectively. Furthermore, multiple MC1R and, to a lesser extent, ATM variants have been identified. BAP1 variants were found only in MPM patients from southern Italy. The most frequent somatic variants were the pathogenic BRAFV600E and TP53, followed by KIT, PIK3CA, KDR, and NRAS. Single APC, ERBB4, MET, JAK3 and other variants with unknown function were also detected.ConclusionsCDNK2A mutation is the most relevant susceptibility mutation in Italian patients with MPM, especially those with a family history for CMM. The prevalence of this mutation and other sequence variants identified in this study varies among specific sub-populations. Furthermore, some heterogeneity in driver somatic mutations between sporadic MPMs has been observed, as well as in a number of associated sequence variants the clinical impact of which needs to be further elucidated.
| S-EPMC6683413 | biostudies-literature
Project description:ImportanceLittle is known about survival after a diagnosis of a second or higher-order (multiple) primary melanoma, and no study has explored survival in a population-based sample that included patients with single primary melanomas (SPMs) and multiple primary melanomas (MPMs) of any stage. Because people with a first primary melanoma are known to have an increased risk of being diagnosed with another, evidence for prognosis is needed.ObjectiveTo determine whether survival after diagnosis was better in patients with MPMs than with SPMs, as suggested in a recent study. DESIGN Survival analysis with median follow-up of 7.6 (range, 0.4-10.6) years.SettingThe Genes, Environment, and Melanoma Study enrolled incident cases of melanoma from population-based cancer registries in Australia, Canada, Italy, and the United States. Multiple primary melanomas were ascertained during a longer period than SPM.ParticipantsTwo thousand three hundred seventy-two patients with SPM and 1206 with MPM.ExposureDiagnosis with melanoma.Main outcomes and measuresMelanoma-specific fatality hazard ratios (HR) and 95% confidence intervals associated with clinical and pathological characteristics of SPM, MPM, and both in Cox proportional hazards regression models.ResultsMelanoma thickness was the main determinant of fatality (HR for >4 mm, 7.68 [95% CI, 4.46-13.23]); other independent predictors were ulceration, mitoses, and scalp location. After adjustment for these other predictors, we found little difference in fatality between MPM and SPM (HR for MPM relative to SPM, 1.24 [95% CI, 0.91-1.69; P = .18]). Thicker SPM, however, had higher fatality (HR for >4 mm, 13.56 [95% CI, 6.47-28.40]) than thicker MPM (2.93 [1.17-7.30]).Conclusions and relevanceAlthough overall fatalities due to SPM and MPM were similar, relative fatality for thicker SPM was greater than that for thicker MPM. This finding may offer support for a difference in outcome between patients with SPM and MPM related to factors other than closer surveillance and earlier diagnosis. The better outcomes are worth further exploration.
| S-EPMC3815536 | biostudies-literature
Project description:Background: Melanoma has a complex molecular background and multiple genes are involved in its development and progression. The advent of next generation sequencing platforms has enabled the evaluation of multiple genes at a time, thus unraveling new insights into the genetics of melanoma. We investigated a set of germline mutations able to discriminate the development of multiple primary melanomas (MPM) vs. single site primary melanomas (SPM) using a targeted next generation sequencing panel. Materials and Methods: A total of 39 patients, 20 with SPM and 19 with MPM, were enrolled in our study. Next generation analysis was carried out using a custom targeted sequencing panel that included 32 genes known to have a role in several carcinogenic pathways, such as those involved in DNA repair, pigmentation, regulation of kinases, cell cycle control and senescence. Results: We found a significant correlation between PIK3CA:p.I391M and MPMs, compared to SPMs, p = 0.031 and a trend for the association between CYP1B1: p.N453S and SPMs, compared to MPMs (p = 0.096). We also found that both subgroups shared a spectrum of 9 alterations in 8 genes (CYP1B1: p.N453S, BAP1: p.C39fs, PIK3CA: p.I391M, CDKAL1: c.1226_1227TG, POLE: p.V1161fs, OCA2: p.R419Q, OCA2: p.R305W, MC1R: p.V60L, MGMT: p.L115F), which suggested that these genes may play a role in melanoma development. Conclusions: In conclusion, despite the small cohort of patients, we found that germline mutations, such as those of PIK3CAand CYP1B1, might contribute to the differential development of SPM and MPM.
| S-EPMC7973206 | biostudies-literature
Project description:Multiple primary melanomas (MPM) refer to the occurrence of more than one synchronous or metachronous melanoma in the same individual. The aim of this study was to identify the frequency of MPM and describe the clinical and histopathologic characteristics of patients with MPM. An observational single-center retrospective study was designed based on a cohort of melanoma patients followed in a tertiary care hospital. Fifty-eight (8.9%) patients developed MPM. Most patients were men (65.5%) and the median age at the time of diagnosis of the first melanoma was 71 years old. The median time of diagnosis of the second melanoma from the first melanoma was 10.9 months, and 77.6% of second melanomas were diagnosed within the first 5 years. In total, 29 (50%) and 28 (48.3%) first and second melanomas were located in the trunk, respectively. Concordance of anatomic site between primary and subsequent melanoma was found in 46.6% of the patients. Proportion of in situ melanomas was increasingly higher in subsequent melanomas (from 36.21% of first melanomas to 100% of fifth melanomas). An increasing rate of melanomas with histological regression was observed within subsequent melanomas (from 60.3% of first melanomas to 80% of third melanomas). Our results support the importance of careful long-term follow-up with total body examination in melanoma patients.
| S-EPMC9105033 | biostudies-literature
Project description:BackgroundAlterations in key-regulator genes of disease pathogenesis (BRAF, cKIT, CyclinD1) have been evaluated in patients with multiple primary melanoma (MPM).MethodsOne hundred twelve MPM patients (96 cases with two primary melanomas, 15 with three, and 1 with four) were included into the study. Paired synchronous/asynchronous MPM tissues (N=229) were analyzed for BRAF mutations and cKIT/CyclynD1 gene amplifications.ResultsBRAF mutations were identified in 109/229 (48%) primary melanomas, whereas cKIT and CyclinD1 amplifications were observed in 10/216 (5%) and 29/214 (14%) tumor tissues, respectively. While frequency rates of BRAF mutations were quite identical across the different MPM lesions, a significant increase of cKIT (p<0.001) and CyclinD1 (p=0.002) amplification rates was observed between first and subsequent primary melanomas. Among the 107 patients with paired melanoma samples, 53 (49.5%) presented consistent alteration patterns between first and subsequent primary tumors. About one third (40/122; 32.8%) of subsequent melanomas presented a discrepant pattern of BRAF mutations as compared to incident primary tumors.ConclusionsThe low consistency in somatic mutation patterns among MPM lesions from same patients provides further evidence that melanomagenesis is heterogeneous and different cell types may be involved. This may have implications in clinical practice due to the difficulties in molecularly classifying patients with discrepant primary melanomas.
| S-EPMC4023698 | biostudies-literature
Project description:Esophageal cancer (EC) is a deadly cancer that frequently develops multiple primary cancers (MPCs). However, the risk biomarkers of MPC in EC have hardly been investigated. We retrospectively enrolled 920 subjects with primary EC and analyzed the possible risk factors as well as MPC single-nucleotide polymorphisms (SNPs) from blood DNA. A total of 184 subjects (20.0%) were confirmed to have MPC, 59 (32.8%) had synchronous MPC, and 128 (69.6%) had head and neck cancer. Elderly EC patients have an increased risk of having gastrointestinal cancer (Odds ratio, OR[95% CI]=6.70 [1.49-30.19], p=0.013) and a reduced risk of developing HNC (OR[95% CI]=0.44 [0.24-0.81], p=0.008). MPC risk was also associated with betel nut chewing (OR[95% CI]=1.63, 1.14-2.32], p=0.008), the A allele of ALDH2:rs671 (p=0.074 and 0.030 for GA and AA, respectively), the CC genotype in CISH:rs2239751 (OR[95% CI]=1.99 [1.2-3.32], p=0.008), and the G allele of ERCC5:rs17655 (p=0.001 and 0.090 for GC and CC, respectively). ADH1B:rs1229984 also correlated with MPC risk (p=0.117). Patients carrying four risk SNPs had a 40-fold risk of MPC (OR[95% CI]=40.25 [6.77-239.50], p<0.001) and a 12.57-fold risk of developing second primary cancer after EC (OR[95% CI]=12.57 [1.14-138.8], p=0.039) compared to those without any risk SNPs. In conclusion, hereditary variations in ALDH2, CISH, ERCC5, and ADH1B have great potential in predicting the incidence of MPC in EC patients. An extensive cancer screening program during clinical follow-up would be beneficial for patients with high MPC susceptibility.
| S-EPMC7862767 | biostudies-literature
Project description:IntroductionAutologous hematopoietic stem cell transplantation (ASCT) is a well-established treatment for patients with multiple myeloma (MM), and adequate stem cell collection must be assured before ASCT. However, prediction of poor mobilizers (PMs) is still difficult despite several risk factors for mobilization failure having been identified.MethodsWe retrospectively analyzed MM patients at Taipei Veterans General Hospital in Taiwan who underwent stem cell collection between October 2006 and August 2020. A CD34+ cell collection of <1 × 106 cells/kg was defined as a mobilization failure. The primary endpoint was mobilization failure. The secondary endpoint was overall survival (OS). Odds ratios (ORs) and 95% confidence intervals (CIs) for mobilization failure were calculated using a logistic regression model. The cumulative incidence of mortality was estimated using the Kaplan-Meier method.ResultsIn the multivariate analysis, absolute monocyte count <500/µL (adjusted OR 10.75, 95% CI: 1.82-63.57, p = 0.009), platelet count <150,000/µL (adjusted OR 12.49, 95% CI: 2.65-58.89, p = 0.001) before mobilization, and time interval from diagnosis to stem cell harvest ≥180 days (adjusted OR 7.69, 95% CI: 1.61-36.87, p = 0.011) were risk factors for PMs. PM patients had poorer OS compared to patients with successful stem cell collection in the univariate analysis (log-rank test p = 0.027). The predicted probability of PMs was estimated by the multiple logistic regression model with a sensitivity of 84.6% and a specificity of 84.0%.ConclusionAbsolute monocyte count <500/µL, platelet count <150,000/µL, and treatment duration more than 180 days before stem cell mobilization are risk factors for unsuccessful stem cell collection. Our prediction models have high sensitivity and specificity for mobilization failure prediction and allow for early interventions for possible PMs.
| S-EPMC9912005 | biostudies-literature
Project description:BackgroundSeveral authors have proposed the use of patients with double primary malignancies affecting the same or contralateral organ as a genetically enriched resource of cases for epidemiologic case-control studies in cancer. Such an approach is based on the assumption that the factors that increase the risk of a second primary are the same ones which influence the risk of a first primary. The advantages for statistical power are premised on the assumption that relative risks in survivors of a first primary cancer are similar to relative risks in the unaffected population. We explore these assumptions theoretically and empirically using published data from breast cancer studies involving bilateral breast cancer.MethodsWe conducted a literature review to identify case-control studies of variants in 4 genes known to affect breast cancer risk: CHEK2*1100delC; multiple variants in BRCA1 and BRCA2; and FGFR2 rs2981582. Summary odds ratios were obtained for each of 3 study designs: a conventional case-control design, the design comparing bilateral cases with unilateral controls, and the design comparing bilateral cases with population controls.ResultsThe data show strong patterns of steadily increasing prevalence of risk factors from healthy controls to primary cases to bilateral cases, as expected. Relative risks in survivors of unilateral breast cancer are either the same as in the general population, or modestly attenuated.ConclusionsPatients with double primary malignancies are a very important underused resource for cancer epidemiologic investigation. Such patients are especially useful for broad genome-wide discovery studies, and for studies of rare, strong risk factors such as high penetrance genes.
| S-EPMC3142453 | biostudies-literature