ABSTRACT: Isolated limb infusion (ILI) is a minimally invasive technique of delivering regional chemotherapy in patients with advanced melanoma or soft-tissue sarcoma of the limb. We report the final results of the first clinical trial of ILI in North America (NCT00004250). Eligible patients had recurrent melanoma or unresectable soft-tissue sarcoma of the limb. Angiographic catheters were positioned just above the knee or elbow of the extremity. General anesthesia was performed, a proximal tourniquet inflated, and a normothermic, low flow, hypoxic infusion of melphalan and dactinomycin circulated through the involved limb for 20 min. Tumor response and morbidity were assessed using standard criteria. Thirty-seven patients were accrued to the trial and 44 ILIs were performed (eight patients had two ILIs); one patient was not treated. Of the 32 evaluable patients, 17 (53%) had a significant response at 3 months: 25% of patients had a complete response and 28% of patients had a partial response. The median duration of complete response was 1 year (5-32 months). Morbidity was acceptable, with peak erythema, edema, and pain experienced at 2 weeks and considered 'moderate' in most patients. No patients developed compartment syndrome or required amputation because of ILI. ILI is well tolerated. More than half of the treated patients experienced a complete or partial response.
Melanoma research 05/2009; 19(2):106-11. · 2.06 Impact Factor
ABSTRACT: The pathologic status of the sentinel lymph node (SLN) is a powerful prognostic factor for patients with intermediate thickness melanoma. We hypothesize that a high number of SLNs identified may be associated with poor outcome.
We evaluated the impact of number of SLNs removed in patients undergoing SLN mapping for cutaneous melanoma at our institution between 1996 and 2006. We excluded patients with multiple primary or synchronous primary lesions (n = 144) to eliminate any chance of erroneous association between a SLN and the wrong primary melanoma. We also excluded patients with in-transit disease (n = 37) and one patient in whom no SLN was identified, leaving 970 patients. We evaluated factors associated with the number of SLNs removed by multivariate Poisson regression and determined whether an increased number of SLNs was associated with poorer overall (OS) or recurrence-free survival (RFS).
Clinical factors independently associated with increased number of SLNs were younger age and head and neck primary site. Pathologic factors associated with an increased number of SLNs were lymphovascular invasion and increased Breslow thickness. There was no association between number of SLNs removed and OS or RFS in all patients or in patients with negative SLNs (n = 803).
The number of SLNs identified during staging of the regional nodal basin for primary melanoma is not an independent prognostic factor. Drainage to multiple SLNs is more common in the setting of an increased Breslow depth and lymphovascular invasion suggesting that tumors with these adverse features may enhance peritumoral lymphangiogenesis.
Annals of Surgical Oncology 03/2009; 16(4):948-52. · 4.17 Impact Factor
ABSTRACT: Survival of patients with stage IV melanoma is poor. In the current American Joint Committee on Cancer (AJCC) staging system, site of distant disease and lactate dehydrogenase (LDH) are the only prognostic factors included for stage IV disease. We sought to validate the current AJCC staging system in a contemporary, prospectively collected cohort of patients and explore additional factors that may influence prognosis.
Our prospective database was searched to identify patients with stage IV melanoma; only patients seen at our institution before developing stage IV disease were included (n = 589). Demographic, clinical, and tumor characteristics were abstracted. Univariate and multivariate assessment of prognostic factors associated with survival were performed by Cox regression.
Overall median survival was 9 months. Differential survival by AJCC substage was observed (P < .001). For each site of disease described within the AJCC staging system, an abnormal LDH level was associated with a poorer prognosis. By multivariate analysis, older age at diagnosis (as a continuous variable, hazard ratio [HR] 1.02, 95% confidence interval [95% CI]) 1.01-1.02), an abnormal LDH (HR 1.42, 95% CI 1.11-1.82), site of disease (lung HR 1.22, 95% CI .89-1.66; other viscera 1.61, 95% CI 1.18-2.21), more than one organ involvement (HR 1.27, 95% CI 1.01-1.60), and more than one metastasis (HR 2.27, 95% CI 1.65-3.14) were independently associated with poorer survival. Sex, antecedent stage, and disease-free interval were not statistically significant.
In our patient cohort, the AJCC staging system was valid. The strongest predictor of survival-the number of metastases present at the diagnosis of stage IV disease-represents a variable to consider in future staging systems.
Annals of Surgical Oncology 07/2008; 15(7):2034-41. · 4.17 Impact Factor
ABSTRACT: Patients with subungual melanoma (SM) often experience delayed diagnosis and present with deep primary lesions. Breslow depth of the primary lesion is often unknown before definitive resection, thus complicating treatment planning.
Patients with SM treated at our institution from 1992 to 2004 were identified from our prospective melanoma database. Clinical and pathologic factors were reviewed; Student t test and Kaplan-Meier method were used for statistical analysis.
Forty-nine patients were identified; most were female (63%). The median age was 66 years (range 24 to 83). The most common site was the great toe (n = 21), followed by the thumb (n = 15). Eight patients had in situ disease; 6 were treated initially with wide local excision, and 4 of these eventually required amputation. The median Breslow depth of invasive lesions was 2.1 mm (range .2 to 11). Toe lesions were thicker than finger lesions (mean 3.5 vs 2.5 mm, P = .005). Patients with invasive SM of the toe had a less favorable outcome than those with finger lesions (5-year overall survival 40% vs 72%, respectively; P = .05). Sentinel lymph node (SLN) biopsy was performed in 30 patients and was positive in 5 (17%); all underwent completion lymphadenectomy. Median Breslow depth in patients with positive SLN was 4 mm (range 1.2 to 11). Four of 5 patients with positive SLN developed recurrence (median 16 months); 3 patients died of disease within 40 months.
Patients with SM present distinct therapeutic challenges. They continue to present with deep primary melanoma, particularly on the toe. Undertreatment of early disease is associated with local recurrence.
American journal of surgery 03/2008; 195(2):244-8. · 2.36 Impact Factor
ABSTRACT: Histological evidence of primary tumor regression (RG) is observed in 35% or fewer patients with cutaneous melanoma. Some advocate a lower threshold for sentinel lymph node (SLN) biopsy when RG is present.
We identified 1,349 patients presenting to our center with clinically localized cutaneous melanoma between 1995 and 2004. Of these, 344 demonstrated histological RG in their primary melanoma. A retrospective analysis of their medical records was performed to obtain clinical and pathological information.
The median Breslow depth for the 344 patients with RG was 1.1 mm versus 1.5 mm for 1,005 patients with no regression (NRG) (P < 0.005). SLN biopsy was performed in 64% of patients with RG and 72% without. Positive SLN was more common in those with NRG than in those with RG (18% vs 10%, P = 0.005). Only one RG patient with thin melanoma (</=1 mm, Clark IV) had a positive SLN. When stratified by Breslow depth, patients with RG had lower rates of SLN positivity in all groups (</=1.0mm, >1.0 and </=2.0mm, >2 and </=4 mm, and >4.0 mm). Recurrence was more common in patients with NRG (21% vs 12%; P < 0.005). Both local and systemic recurrence occurred more commonly in patients with NRG (4% vs 1%, P = 0.002 and 8% vs 3%, P < 0.005, respectively)
The presence of histological RG in a primary melanoma predicts neither SLN positivity when stratified by Breslow depth nor increased risk of recurrence when compared with melanomas with NRG.
Annals of Surgical Oncology 01/2008; 15(1):316-22. · 4.17 Impact Factor
ABSTRACT: We reviewed a contemporary, single-institution experience to evaluate the natural history of stage-IV melanoma metastatic to the lung and identify factors predictive of survival.
A search of our prospective database was performed to identify patients with stage-IV melanoma and pulmonary metastases as the initial disease site; only patients seen at our institution prior to developing stage-IV disease and in whom treatment response was available were included. Patients' demographic, clinical, and treatment variables were recorded. Cox regression was used to identify factors independently predictive of survival.
The study cohort was comprised of 122 patients. Median survival was 14 months (5-year survival of 8%). Clinical factors at time of diagnosis of stage IV independently predictive of survival were a solitary pulmonary metastasis (HR 2.7, CI 1.6-4.4, P<0.0005) and absence of extra-pulmonary disease (HR 1.9, CI 1.2-3.1, P = 0.01). Among treatment factors, only metastasectomy was independently predictive of survival (HR 0.42, CI 0.21-0.87, P = 0.02). Of the patients, 26 (21%) underwent metastasectomy, with a median survival of 40 months compared with 13 months in patients not selected for surgical treatment. Of these 26, 23 (88%) experienced recurrence at a median of 5 months after the procedure. No survival difference was seen between responders and non-responders to systemic therapy (P = 0.55).
In stage-IV melanoma with pulmonary metastases, a solitary metastasis and absence of extra-pulmonary disease are predictive of survival. While these factors are often present in patients selected for pulmonary metastasectomy, this independently predicts survival. However, response to systemic therapy does not correlate with a survival difference.
Annals of Surgical Oncology 10/2007; 14(10):2847-53. · 4.17 Impact Factor
ABSTRACT: Sentinel lymph node biopsy (SLNB) has become well accepted in management of patients with primary cutaneous melanoma. An understanding of the pattern of recurrence after SLNB is helpful in coordinating a rational plan of follow-up in these patients. We sought to determine the site and timing of initial recurrence and post-recurrence survival after SLNB.
Stage I/II melanoma patients who underwent SLNB during 1991-2004 were identified from a prospective single-institution database. Site and date of first recurrence after SLNB were recorded. Patterns of recurrence after SLNB and post-recurrence survival were analyzed.
One thousand and forty-six patients underwent SLNB. The sentinel lymph node (SLN) was positive in 164 patients (16%). Median follow-up was 36 months for survivors. Median and 3-year relapse-free survival for SLN-positive patients were 41 months and 56%, and for SLN-negative patients were not reached and 87%, respectively (P < .0001). Of the SLN-positive patients, 47% experienced recurrence, compared with 14% SLN-negative patients. The pattern of recurrence stratified by SLN status was similar between the two groups (P = NS). After recurrence, the site of recurrence was the only significant prognostic factor influencing survival (P < .0001).
Although SLN-positive patients experience recurrence far earlier and more frequently than SLN-negative patients, the pattern of recurrence is similar. After recurrence, its site is the primary determinant of survival.
Annals of Surgical Oncology 06/2007; 14(6):1934-42. · 4.17 Impact Factor
ABSTRACT: Tumor-infiltrating lymphocytes (TILs) are considered a manifestation of the host immune response to tumor, but the influence of TILs on outcome remains controversial. Studies evaluating the prognostic significance of TILs were published before routine examination of draining lymph nodes by sentinel lymph node (SLN) biopsy, the most important predictor of survival in patients with melanoma. The prognostic implications of TILs were re-evaluated in a large group of patients undergoing SLN biopsy at our institution.
All patients who underwent SLN mapping for primary cutaneous melanoma between January 1996 and July 2005 were evaluated. Univariate and multivariate analyses were performed to assess factors that predict SLN positivity and survival. Factors analyzed included Breslow thickness, ulceration, anatomic site, sex, Clark level, age, mitotic rate, and the presence (brisk or nonbrisk) or absence of TIL.
Eight hundred eighty-seven patients underwent SLN mapping, and a SLN was identified in 875 patients (98.8%). The SLN was positive for tumor in 156 patients (17.6%). Multivariate analysis revealed that only Breslow thickness (P < .0001), ulceration (P = .0004), male sex (P = .03), and absent TILs (P = .0003) were independently predictive of the presence of SLN metastases. In melanomas with a brisk TIL infiltrate, the probability of a positive SLN was 3.9% as compared with 26.2% for melanomas in which TILs were absent. TILs were not an independent predictive factor for survival.
The absence of TILs, together with increasing Breslow thickness, presence of ulceration and male sex, predicts SLN metastasis in patients undergoing SLN biopsy for primary cutaneous melanoma.
Journal of Clinical Oncology 03/2007; 25(7):869-75. · 18.37 Impact Factor
ABSTRACT: Cutaneous Malignant Melanoma causes over 75% of skin cancer-related deaths, and it is clear that many factors may contribute to the outcome. Matrix Metalloproteinases (MMPs) play an important role in the degradation and remodeling of the extracellular matrix and basement membrane that, in turn, modulate cell division, migration and angiogenesis. Some polymorphisms are known to influence gene expression, protein activity, stability, and interactions, and they were shown to be associated with certain tumor phenotypes and cancer risk.
We tested seven polymorphisms within the MMP-9 gene in 1002 patients with melanoma in order to evaluate germline genetic variants and their association with progression and known risk factors of melanoma. The polymorphisms were selected based on previously published reports and their known or potential functional relevance using in-silico methods. Germline DNA was then genotyped using pyrosequencing, melting temperature profiles, heteroduplex analysis, and fragment size analysis.
We found that reference alleles were present in higher frequency in patients who tend to sunburn, have family history of melanoma, higher melanoma stage, intransit metastasis and desmoplastic melanomas among others. However, after adjustment for age, sex, phenotypic index, moles, and freckles only Q279R, P574R and R668Q had significant associations with intransit metastasis, propensity to tan/sunburn and primary melanoma site.
This study does not provide strong evidence for further investigation into the role of the MMP-9 SNPs in melanoma progression.
BMC Medical Genetics 02/2007; 8:10. · 2.33 Impact Factor
ABSTRACT: The matrix metalloproteinases (MMPs) are enzymes that cleave various components of the extracellular matrix (ECM) and basement membranes. MMPs are expressed in melanocytes and their overexpression has been linked to tumor development, progression and metastasis. At the genetic level, the following functional promoter polymorphisms are known to modify the gene transcription: -1306 C/T and -735 C/T in the MMP2 gene, and -1171 5A/6A in the MMP3 gene. Functional polymorphisms in MMP genes' promoter regions may modulate the risk for melanoma progression.
We evaluated MMP2 and MMP3 germline polymorphisms in a group of 1002 melanoma patients using PCR-based methods, including fragment size analysis and melting temperature profiles. Two-sided Chi-Square, Cochran-Armitage tests for trend, Fisher's exact tests, and Kendall's Tau tests were performed to evaluate the associations between genotype and various clinical and epidemiologic factors. Multivariate analyses were conducted using logistic regression, adjusting for known melanoma confounders such as age, sex, phenotypic index, moles, freckles, and race. Survival estimates were computed using the Kaplan-Meier method and differences in survival were assessed using the log rank test.
All genotypes were in Hardy-Weinberg equilibrium. After adjustment for age, sex and phenotypic characteristics of melanoma risk, no significant associations were identified with the clinical, pathological, and epidemiological variables studied. The melting profile for MMP2 -735 C/T identified a new change in one sample. A new PCR-amplification followed by direct sequencing confirmed a heterozygote G to A substitution at position -729.
This study does not provide strong evidence for further investigation into the role of the MMP2 and MMP3 variants in melanoma progression.
Journal of Negative Results in BioMedicine 02/2007; 6:9. · 1.47 Impact Factor
ABSTRACT: Isolated limb infusion (ILI) is a minimally invasive technique of delivering regional chemotherapy in patients with advanced melanoma or soft tissue sarcoma of the limb. Reports from Australia of efficacy similar to that of isolated limb perfusion prompted us to conduct a phase II trial to evaluate the efficacy and safety of ILI.
Eligible patients had American Joint Committee on Cancer stage IIIB or IIIC melanoma or unresectable soft tissue sarcoma of the limb. Angiographic catheters were positioned just above the knee or elbow of the extremity. General anesthesia was performed, a proximal tourniquet was inflated, and a normothermic, low-flow, hypoxic infusion of melphalan and dactinomycin was circulated through the involved limb for 20 minutes. The tumor response was assessed by using standard criteria at 3 months. Morbidity was determined in the hospital and at 2, 6, and 12 weeks.
Twenty-five patients were accrued to the trial, and 32 ILIs were performed (8 patients had 2 ILIs); 1 patient was not treated. Of the 22 assessable patients, 11 (50%) had a significant response at 3 months: 23% of patients had a complete response, and 27% of patients had a partial response. The median duration of complete response was 1 year (range, 6-32 months). Morbidity was acceptable. Peak morbidity occurred at 2 weeks and was considered moderate in most patients. Limb edema and erythema were common. No patient developed compartment syndrome or required amputation.
ILI is well tolerated. Half of the patients experienced a complete or partial response.
Annals of Surgical Oncology 09/2006; 13(8):1123-9. · 4.17 Impact Factor
ABSTRACT: [(18)]F Fluorodeoxyglucose-positron emission tomography (PET) scanning provides functional imaging based on glucose uptake by tumors. Melanoma is a glucose-avid malignancy, and preoperative PET scanning in melanoma patients has the potential to guide appropriate treatment.
We performed a prospective trial to evaluate the clinical utility of whole-body fluorine 18-labeled deoxyglucose-PET scanning used in addition to standard imaging (contrast-enhanced computed tomographic [CT] imaging of the chest, abdomen, and pelvis) in preoperative stage IIC (T4N0M0), III (any T, N1 to N3, M0), and IV (any T, any N, M1) melanoma patients. Pathologic or clinical follow-up within 4 to 6 months of the imaging studies was used to determine the accuracy of preoperative PET and CT scan findings.
Preoperative imaging findings led to a change in clinical management in 36 (35%) of 103 patients. In 32 (89%) of these patients, the information was accurate. Findings on PET scan alone (14 of 36; 39%) or in combination with CT (20 of 36; 56%) resulted in a treatment change in most patients (34 of 36; 94%). The most common decision was to cancel the operation (19 of 36; 53%). PET scanning was more sensitive than CT scanning in detecting occult disease (68% vs. 48%; P=.05), but both tests were highly specific (92% vs. 95%; P=.7, PET vs. CT).
PET scanning facilitates the appropriate management of high-risk melanoma patients being considered for operative intervention. PET imaging in addition to CT scanning should be strongly considered before operation in patients at high risk for occult metastatic disease.
Annals of Surgical Oncology 05/2006; 13(4):525-32. · 4.17 Impact Factor
ABSTRACT: The objectives of the current study were to examine how the estimated stage-specific survival is altered in the 2002 American Joint Committee on Cancer (AJCC) melanoma staging system compared with the 1997 AJCC staging system and to contrast the predictive accuracy of the 2 staging systems.
There were 5847 consecutive melanoma patients who presented to Memorial Sloan-Kettering Cancer Center from 1996 to 2004 and who were entered prospectively into a data base. These patients were staged according to both the 1997 and 2002 AJCC staging criteria. Overall survival estimates were determined using the Kaplan-Meier method. The overall predictive accuracy of the two staging systems was compared using concordance estimation.
In total, 1035 patients were shifted to a lower stage in the 2002 staging system, whereas only 15 patients were upstaged. The number of patients with Stage I melanoma increased by 697 under the 2002 system (n = 2166 patients) compared with the 1997 system (n = 1463 patients). Because of the changes in 2002, the estimated 5-year overall survival for patients with Stage II melanoma decreased considerably, from 79% (1997) to 64% (2002). With the initiation of subgroups in 2002, it became apparent that patients with Stage III melanoma were very heterogeneous in terms of their survival probabilities (5-yr overall survival ranged from 70% in patients with Stage IIIA disease to 24% in patients with Stage IIIC disease). Furthermore, in the 2002 system, there was substantial prognostic overlap between Stage II and Stage III. Despite the increased complexity of the 2002 system, the 2 staging systems had similar concordance estimates: 58% for the 1997 staging system compared with 58% (ignoring the subgroups) and 59% (with subgroups) for the 2002 system.
Estimates of stage-specific survival were altered substantially by the changes made in the 2002 AJCC staging system for melanoma, particularly for Stage II. Stage subgroups that were added in the 2002 system resulted in a large diversity of risk within Stage III. This must be taken into account to stratify patients properly for clinical trials. The increased complexity of the 2002 system did not improve its predictive ability over the simpler 1997 system, highlighting the importance of developing individualized risk-prediction models.
Cancer 02/2006; 106(1):163-71. · 4.77 Impact Factor
ABSTRACT: The course and outcome of metastatic uveal melanoma are not well described. We evaluated the survival of our patients with metastatic uveal melanoma, described factors that correlated with survival, and evaluated the influence of screening tests on time of detection and survival.
All patients with metastatic uveal melanoma seen at Memorial Sloan-Kettering Cancer Center between 1994 and 2004 were identified from our database. We recorded date of initial diagnosis, date of metastatic disease, date of last follow-up, site of the first metastasis, how the first metastasis was discovered, treatment, and outcome of therapy.
The estimated median survival of the 119 patients analyzed was 12.5 months; 22% of patients were alive at 4 years. Five variates correlated independently with prolonged survival: Lung/soft tissue as only site of first metastasis, treatment with surgery or intrahepatic therapy, female sex, age younger than 60, and a longer interval from initial diagnosis to metastatic disease. Discovering metastatic disease in asymptomatic patients did not correlate with overall survival; 89% of patients had a single organ as the site of first metastasis. Although liver was the most common site, 39.5% of patients had nonliver sites, most commonly lung, as the first site of metastasis.
A substantial subset of patients with metastatic uveal melanoma survive more than 4 years with metastatic disease. Data on variates of survival and site of first metastasis may guide strategies for screening patients, although our data failed to show a survival advantage in discovering asymptomatic metastatic disease.
Journal of Clinical Oncology 12/2005; 23(31):8076-80. · 18.37 Impact Factor
ABSTRACT: The incidence of multiple primary melanomas ranges from 1.3% to 8.0% in large retrospective reviews; however, the impact of certain risk factors is not understood.
To determine the incidence of multiple primary melanomas (MPM) from a prospective, single-institution, multidisciplinary database, and to describe the clinical and pathological characteristics and risk factors specific to these patients.
Review of a prospectively maintained database at Memorial Sloan-Kettering Cancer Center in New York, NY.
A total of 4484 patients diagnosed with a first primary melanoma between January 1, 1996, and December 31, 2002.
Incidence of and risk factors for MPM.
Three hundred eighty-five patients (8.6%) had 2 or more primary melanomas, with an average of 2.3 melanomas per MPM patient. Seventy-eight percent had 2 primary melanomas. For 74% of patients, the initial melanoma was the thickest tumor. Fifty-nine percent presented with their second primary tumor within 1 year. Twenty-one percent of MPM patients had a positive family history of melanoma compared with only 12% of patients with a single primary melanoma (SPM) (P<.001). Thirty-eight percent of MPM patients had dysplastic nevi compared with 18% of SPM patients (P<.001). The estimated cumulative 5-year risk of a second primary tumor for the entire cohort was 11.4%, with almost half of that risk occurring within the first year. For patients with a positive family history or dysplastic nevi, the estimated 5-year risk of MPM was significantly higher at 19.1% and 23.7%, respectively. The most striking increase in incidence for the MPM population was seen for development of a third primary melanoma from the time of second primary melanoma, which was 15.6% at 1 year and 30.9% at 5 years.
The incidence of MPM is increased in patients with a positive family history and/or dysplastic nevi. These patients should undergo intensive dermatologic screening and should consider genetic testing.
JAMA The Journal of the American Medical Association 10/2005; 294(13):1647-54. · 30.03 Impact Factor
The incidence of multiple primary melanomas ranges from 1.3% to 8.0%
in large retrospective reviews; however, the impact of certain risk factors
is not understood.Objectives
To determine the incidence of multiple primary melanomas (MPM) from
a prospective, single-institution, multidisciplinary database, and to describe
the clinical and pathological characteristics and risk factors specific to
these patients.Design and Setting
Review of a prospectively maintained database at Memorial Sloan-Kettering
Cancer Center in New York, NY.Patients
A total of 4484 patients diagnosed with a first primary melanoma between
January 1, 1996, and December 31, 2002.Main Outcome Measures
Incidence of and risk factors for MPM.Results
Three hundred eighty-five patients (8.6%) had 2 or more primary melanomas,
with an average of 2.3 melanomas per MPM patient. Seventy-eight percent had
2 primary melanomas. For 74% of patients, the initial melanoma was the thickest
tumor. Fifty-nine percent presented with their second primary tumor within
1 year. Twenty-one percent of MPM patients had a positive family history of
melanoma compared with only 12% of patients with a single primary melanoma
(SPM) (P<.001). Thirty-eight percent of MPM patients
had dysplastic nevi compared with 18% of SPM patients (P<.001). The estimated cumulative 5-year risk of a second primary
tumor for the entire cohort was 11.4%, with almost half of that risk occurring
within the first year. For patients with a positive family history or dysplastic
nevi, the estimated 5-year risk of MPM was significantly higher at 19.1% and
23.7%, respectively. The most striking increase in incidence for the MPM population
was seen for development of a third primary melanoma from the time of second
primary melanoma, which was 15.6% at 1 year and 30.9% at 5 years.Conclusions
The incidence of MPM is increased in patients with a positive family
history and/or dysplastic nevi. These patients should undergo intensive dermatologic
screening and should consider genetic testing.
Figures in this Article
The phenomenon of multiple primary tumors occurring within a single
organ or organ system has been well documented.1 Whether
this is a function of an increased genetic susceptibility of the individual
patient (eg, in familial polyposis and colorectal cancer), consistent exposure
to a common exogenous promoter of malignancy (eg, cigarette smoke and lung
cancer), or a combination of these 2 factors varies from one patient to the
next and from one organ system to the next. Malignant melanoma epitomizes
much of what is known about multiple primary tumors.
In 2005, there will be an estimated 62 000 new cases of invasive
melanoma and an estimated 7600 deaths due to melanoma in the United States.2 Melanoma is the fifth leading cancer in men and the
sixth leading cancer in women in the United States.2 The
incidence of melanoma continues to rise at about 3.0% per year in the United
States, with an estimated lifetime risk for an individual of 1.4%.1- 2 This increasing incidence puts a larger
portion of the population at risk not only for 1 primary melanoma but also
for subsequent primary melanomas.3 Among patients
with a history of a primary melanoma, retrospective reviews report the incidence
of a second primary tumor to range from 0.2% to 8.6%3- 13 (Table 1). The Surveillance, Epidemiology, and
End Results (SEER) database from 1996-2001 includes 22 688 patients with
a single melanoma and 465 patients with more than 1 melanoma, for an incidence
Table Grahic Jump LocationTable 1. Summary of Previous Studies+View Large |
Save Table |
Download Slide (.ppt)
View in Article Context
Since Pack et al5 first described the
phenomenon of multiple primary melanomas (MPM) in 1952, patients with this
disease have not been well characterized. The clinical manifestations of MPM
are broad. While 63% to 88% of patients with MPM are reported to have 2 primary
tumors,3,5- 10 a
patient with as many as 48 separate primary melanomas has been reported.6
Several risk factors associated with the development of MPM have been
identified. These include a positive family history of MPM and a personal
history of dysplastic nevi (DN), atypical moles that are risk markers but
nonobligate precursors of melanoma.12- 16 Among
patients with MPM, 18% to 38% are reported to have a positive family history
of melanoma4,11 and 38% to 46%
are reported to have a history of dysplastic nevi.3- 4 However,
few longitudinal cohort-defined databases have prospectively recorded known
risk factors for all patients with melanoma to assess the impact of these
risk factors on the development of MPM.
The main difficulty in estimating the incidence of MPM is that it requires
careful follow-up of large populations of melanoma patients over long periods
of time, with specific effort to capture antecedent, synchronous, or subsequent
This is the first study, to our knowledge, to use a prospective, multidisciplinary,
single-institution database to identify the characteristics of patients at
risk of developing MPM. This study defines the estimated incidence of MPM
among a cohort of consecutive patients treated for melanoma at a tertiary
cancer referral center. Specific patient characteristics, prospectively collected,
included family history and presence of DN. Tumor characteristics were evaluated
with specific attention to the number of melanomas diagnosed, the time course
over which melanomas were diagnosed, the timing of the thickest melanomas
(initial vs subsequent), the location of subsequent melanomas, and the prevalence
of melanoma in situ. In addition, these characteristics among MPM patients
were compared with those of patients with single primary melanoma (SPM) in
the same prospective database.
JAMA The Journal of the American Medical Association 294(13):1647-1654. · 30.03 Impact Factor