Background
We postulated that the worse prognosis of melanoma with advancing age reflected more aggressive tumor biology and that in younger patients the prognosis would be more favorable.
Materials ...and Methods
The expanded AJCC melanoma staging database contained 11,088 patients with complete data for analysis, including mitotic rate.
Results
With increasing age by decade, primary melanomas were thicker, exhibited higher mitotic rates, and were more likely to be ulcerated. In a multivariate analysis of patients with localized melanoma, thickness and ulceration were highly significant predictors of outcome at all decades of life (except for patients younger than 20 years). Mitotic rate was significantly predictive in all age groups except patients <20 and >80 years. For patients with stage III melanoma, there were four independent variables associated with patient survival: number of nodal metastases, patient age, ulceration, and mitotic rate. Patients younger than 20 years of age had primary tumors with slightly more aggressive features, a higher incidence of sentinel lymph node metastasis, but, paradoxically, more favorable survival than all other age groups. In contrast, patients >70 years old had primary melanomas with the most aggressive prognostic features, were more likely to be head and neck primaries, and were associated with a higher mortality rate than the other age groups. Surprisingly, however, these patients had a lower rate of sentinel lymph node metastasis per T stage. Among patients between the two age extremes, clinicopathologic features and survival tended to be more homogeneous.
Conclusions
Melanomas in patients at the extremes of age have a distinct natural history.
Purpose
We have previously reported that older patients with clinical stage I and II primary cutaneous. Melanoma had lower survival rates compared to younger patients. We postulated that the ...incidence of nodal metastasis would therefore be higher among older melanoma patients.
Methods
The expanded American Joint Committee on Cancer melanoma staging database contains a cohort of 7,756 melanoma patients who presented without clinical evidence of regional lymph node or distant metastasis and who underwent a sentinel node biopsy procedure as a component of their staging assessment.
Results
Although older patients had primary melanoma features associated with more aggressive biology, we paradoxically observed a significant decrease in the incidence of sentinel node metastasis as patient age increased. Overall, the highest incidence of sentinel node metastasis was 25.8 % in patients under 20 years of age, compared to 15.5 % in patients 80 years and older (
p
< 0.001). In contrast, 5-year mortality rates for clinical stage II patients ranged from a low of 20 % for those 20–40 years of age up to 38 % for those over 70 years of age. Patient age was an independent predictor of sentinel node metastasis in a multifactorial analysis (
p
< 0.001).
Conclusions
Patients with clinical stage I and II melanoma under 20 years of age had a higher incidence of sentinel lymph node metastasis but, paradoxically, a more favorable survival outcome compared to all other age groups. In contrast, patients >70 years had the most aggressive primary melanoma features and a higher mortality rate compared to all other age groups but a lower incidence of sentinel lymph node metastasis.
Background
We sought to develop a reliable and reproducible statistical model to predict the survival outcome of patients with localized melanoma.
Methods
A total of 25,734 patients with localized ...melanoma from the 2008 American Joint Committee on Cancer (AJCC) Melanoma Database were used for the model development and validation. The predictive model was developed from the model development data set (
n
= 14,760) contributed by nine major institutions and study groups and was validated on an independent model validation data set (
n
= 10,974) consisting of patients from a separate melanoma center. Multivariate analyses based on the Cox model were performed for the model development, and the concordance correlation coefficients were calculated to assess the adequacy of the predictive model.
Results
Patient characteristics in both data sets were virtually identical, and tumor thickness was the single most important prognostic factor. Other key prognostic factors identified by stratified analyses included ulceration, lesion site, and patient age. Direct comparisons of the predicted 5- and 10-year survival rates calculated from the predictive model and the observed Kaplan-Meier 5- and 10-year survival rates estimated from the validation data set yielded high concordance correlation coefficients of 0.90 and 0.93, respectively. A Web-based electronic prediction tool was also developed (
http://www.melanomaprognosis.org/
).
Conclusions
This is the first predictive model for localized melanoma that was developed based on a very large data set and was successfully validated on an independent data set. The high concordance correlation coefficients demonstrated the accuracy of the predicted model. This predictive model provides a clinically useful tool for making treatment decisions, for assessing patient risk, and for planning and analyzing clinical trials.
A completely revised staging system for cutaneous melanoma was implemented in 2003. The changes were validated with a prognostic factors analysis involving 17,600 melanoma patients from prospective ...databases. This major collaborative study of predicting melanoma outcome was conducted specifically for this project, and the results were used to finalize the criteria for this evidence-based staging system. In fact, this was the largest prognostic factors analysis of prospectively followed melanoma patients ever conducted. Important results that shaped the staging criteria involved both the tumor-node-metastasis (TNM) criteria and stage grouping for all four stages of melanoma. Major changes in the staging include: (1) melanoma thickness and ulceration are the dominant predictors of survival in patients with localized melanoma (Stages I and II); deeper level of invasion (ie, IV and V) was independently associated with reduced survival only in patients with thin or T1 melanomas. (2) The number of metastatic lymph nodes and the tumor burden were the most dominant predictors of survival in patients with Stage III melanoma; patients with metastatic nodes detected by palpation had a shorter survival compared with patients whose nodal metastases were first detected by sentinel node excision of clinically occult or "microscopic" metastases. (3) The site of distant metastases (nonvisceral versus lung versus all other visceral metastatic sites) and the presence of elevated serum lactate dehydrogenase (LDH) were the dominant predictors of outcome in patients with Stage IV or distant metastases. (4) An upstaging was implemented for all patients with Stage I, II, and III disease when a primary melanoma is ulcerated by histopathological criteria. (5) Satellite metastases around a primary melanoma and in-transit metastases were merged into a single staging entity that is grouped into Stage III disease. (6) A new convention was implemented for defining clinical and pathological staging so as to take into account the new staging information gained from lymphatic mapping and sentinel node biopsy.
BackgroundThis study elucidates the clinical impact of surgical treatment of head and neck squamous cell carcinoma (HNSCC) based on a detailed search of all exons of the TP53 gene and p53 protein ...phenotypic analysis using formalin-fixed paraffin-embedded (FFPE) specimens.MethodsClinically well-annotated FFPE specimens from 317 patients with HNSCC treated by surgery were examined by all-exon TP53 sequencing using a next-generation sequencer and p53 protein phenotype by immunohistochemistry. After excluding human papillomavirus-associated oropharyngeal carcinomas, two risk categories were classified as “p53 adverse function” and “p53 favorable function” based on TP53 mutation status and p53 protein phenotype. Mutation in PIK3CA, AKT, and HRAS was also evaluated by target sequence. Cox proportional hazards regression models were used for statistical analysis of clinical outcomes. Receiver operating characteristic curve analysis was used to determine the optimal surgical margin cutoff for local recurrence. Local control rates were compared between the risk groups using Fisher’s exact test.ResultsMultivariate analysis identified “p53 adverse function” as an independent poor predictor of overall survival, local control, and distant metastasis-free survival. In oral cavity cancer, the optimal surgical margin cutoff associated with local recurrence was 6 mm. In patients with surgical margin > 6 mm, the “p53 adverse function” group demonstrated significantly higher local recurrence rate than the “p53 favorable function” group. PIK3CA, AKT, or HRAS mutation did not correlate with improved overall survival.ConclusionsAll-exon TP53 sequencing and p53 protein phenotype analysis using FFPE specimens can accurately predict clinical outcomes.
A major revision of the American Joint Committee on Cancer (AJCC) stages for melanoma was implemented in 2002 after its validation in multinational cohorts including patients from cancer centers and ...cooperative groups. This staging system has not been validated in a US population-based cohort.
We used 41,417 patients with primary invasive cutaneous melanoma diagnosed between 1988 and 2001 from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) cancer registry to validate the revised AJCC staging system. Survival rates computed from stage-specific Kaplan-Meier curves (time to melanoma-specific death) were compared with the survival rates from 17,600 patients in the original AJCC validation study.
In the SEER cohort, 65% of reported melanomas were < or = 1.00 mm in thickness and 8.7% were more than 4.00 mm compared with 39% and 10% in the AJCC cohort (P < .001), respectively. AJCC stages were able to discriminate among SEER patient groups with different prognosis. However, SEER survival rates were significantly higher than those in the AJCC study and notably so in patients with T1a lesions (< or = 1 mm without ulceration). This population-specific effect remained significant after controlling for lesion thickness in all substages except stage IIA.
Although this national population-based study validates the most recent revision of AJCC stages for melanoma, it emphasizes that survival rates are population specific and found them to be generally higher for SEER compared with AJCC patients. Population-specific survival rates should be used in study designs and decisions about patient-specific interventions.
Objective The study sought to determine the relationship between cytomegalovirus (CMV) viremia during early infancy and clinical and laboratory outcome events, particularly hearing loss in infants ...with symptomatic congenital CMV infection involving the central nervous system (CNS). Study design A total of 147 infant patients were enrolled prospectively in 2 clinical trials evaluating ganciclovir for the treatment of symptomatic congenital CMV infection involving the CNS. Aliquots of serum collected at enrollment in either of the 2 trials were available from 50 of the infants, and the degree of viremia was determined by real-time quantitative polymerase chain reaction. Results Of the 50 infants from whom serum samples were available, 37 had detectable CMV DNA in the serum sample collected at enrollment and were classified as viremic. Viremic infants were more likely to have (1) hearing loss both at enrollment (P = .045) and at the 6-month follow-up testing (P = .035) and (2) other indicators of active CMV disease, including elevated levels of alanine aminotransferase, petechial rash, and organomegaly. Conclusion In children with symptomatic congenital CMV infection involving the CNS, viremia during early infancy is associated with hearing loss and systemic CMV disease.
Objective
Information on prognosis for patients with cutaneous melanoma after locoregional or distant recurrence is sparse and controversial. The aim of this study was to analyze factors influencing ...outcome after the development of a first relapse.
Methods
Information was extracted from the Sydney Melanoma Unit database for 873 melanoma patients with American Joint Committee on Cancer (AJCC) Stage I and II disease treated between 1960 and 2002 who relapsed following treatment of their primary melanoma. Clinical and pathologic factors predicting survival were analyzed using the Cox proportional hazards regression model.
Results
Initial presentation of recurrence was local: 95 patients (10.9%), in transit: 86 patients (9.9%), regional lymph node: 300 patients (34.4%), and distant: 392 patients (44.9%). Independent prognostic factors for survival of the 481 patients with only locoregional recurrence were type of recurrence, primary tumor ulceration, and patient age. Predictors for longer survival in the 392 patients with distant metastasis at the time of first presentation with recurrence were lung vs other sites and diagnosis of relapse after 1990 compared with diagnosis before 1980.
Conclusions
The type of recurrence is the most important prognostic factor in melanoma patients who relapse. Primary tumor ulceration is the most important pathologic predictor. The results of this study suggest that management of distant metastases may have improved over the last 25 years, but many confounders and improved staging techniques make assessment of this unreliable.
The American Joint Committee on Cancer Melanoma Staging Committee proposes major changes to the TNM classification and the stage grouping for cutaneous melanoma. Analyses of prognostic factors by ...major cooperative groups and cancer centers worldwide contributed data and clinical experience to the simplified and evidence‐based recommendations.
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