Age as a predictor of sentinel node metastasis among patients with localized melanoma: an inverse correlation of melanoma mortality and incidence of sentinel node metastasis among young and old patients.

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.

Age as a prognostic factor in patients with localized melanoma and regional metastases.

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.

A chain reaction approach to modelling gene pathways.

BACKGROUND: Of great interest in cancer prevention is how nutrient components affect gene pathways associated with the physiological events of puberty. Nutrient-gene interactions may cause changes in breast or prostate cells and, therefore, may result in cancer risk later in life. Analysis of gene pathways can lead to insights about nutrient-gene interactions and the development of more effective prevention approaches to reduce cancer risk.

Update on the melanoma staging system: the importance of sentinel node staging and primary tumor mitotic rate.

The 7(th) Edition of the AJCC Staging Manual includes a detailed summary of melanoma staging and prognosis. The revisions are summarized in this article, along with details on two key aspects of melanoma staging: the incorporation of mitotic rate of the primary melanoma and the key role of the sentinel lymph node biopsy (SLNB) in determining accurate staging for clinically occult nodal metastases. Primary tumor mitotic rate was introduced as a major criterion for melanoma staging and prognosis that replaces the Clark's level of invasion, and is now proven to be an important independent adverse predictor of survival.

Factors predictive of the status of sentinel lymph nodes in melanoma patients from a large multicenter database.

Background: Numerous predictive factors for cutaneous melanoma metastases to sentinel lymph nodes have been identified; however, few have been found to be reproducibly significant. This study investigated the significance of factors for predicting regional nodal disease in cutaneous melanoma using a large multicenter database.

Methods: Seventeen institutions submitted retrospective and prospective data on 3463 patients undergoing sentinel lymph node (SLN) biopsy for primary melanoma.

Prognostic significance of mitotic rate in localized primary cutaneous melanoma: an analysis of patients in the multi-institutional American Joint Committee on Cancer melanoma staging database.

Purpose: The aim of this study was to assess the independent prognostic value of primary tumor mitotic rate compared with other clinical and pathologic features of stages I and II melanoma.

Methods: From the American Joint Committee on Cancer (AJCC) melanoma staging database, information was extracted for 13,296 patients with stages I and II disease who had mitotic rate data available.

Results: Survival times declined as mitotic rate increased.

Cutaneous melanoma: a model to study cancer metastasis.

Nodal status in melanoma is a critically important prognostic factor for patient outcome. The survival rate drops to <10% when melanoma has spread beyond the regional lymph nodes and includes visceral involvement. In general, the process of melanoma metastasis is progressive in that dissemination of melanoma from the primary site to the regional lymph nodes occurs prior to systemic disease.

Sentinel node positive melanoma patients: prediction and prognostic significance of nonsentinel node metastases and development of a survival tree model.

Background: Completion lymph node dissection (CLND) following positive sentinel node biopsy (SNB) for melanoma detects additional nonsentinel node (NSN) metastases in approximately 20% of cases. This study aimed to establish whether NSN status can be predicted, to determine its effect on survival, and to develop survival tree models for the sentinel node (SN) positive population.

Materials And Methods: Sydney Melanoma Unit (SMU) patients with at least 1 positive SN, meeting inclusion criteria and treated between October 1992 and June 2005, were identified from the Unit database.

Predicting survival outcome of localized melanoma: an electronic prediction tool based on the AJCC Melanoma Database.

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 analysis of prognostic factors among 2,313 patients with stage III melanoma: comparison of nodal micrometastases versus macrometastases.

Purpose: To determine the survival rates and independent predictors of survival using a contemporary international cohort of patients with stage III melanoma.

Patients And Methods: Complete clinicopathologic and follow-up data were available for 2,313 patients with stage III disease in an updated and expanded American Joint Committee on Cancer (AJCC) melanoma staging database. Kaplan-Meier and Cox multivariate survival analyses were performed.

Parametric modeling of localized melanoma prognosis and outcome.

This investigation explored the most suitable parametric model for melanoma prognosis and compared it with the Cox model. Cox-Snell residuals and survival function plots were applied to assess whether the generalized gamma (GG) model was the best-fit parametric model for the data. The GG model is a powerful alternative to the Cox model in prognostic modeling.

Optimal designs for two-arm, phase II clinical trial design with multiple constraints.

Multi-stage Phase II trials are often employed in practice but may not be the best approach when the endpoint of interest is not obtained soon after enrollment and/or when a control arm is desired. We present a new design in which sample size determination includes a control arm and allows for the estimation of response for each treatment as well as estimation of the difference in the response rates. We evaluate this design under varying allocation schemes to treatment arms and response rates for each treatment.

Neurodevelopmental outcomes following ganciclovir therapy in symptomatic congenital cytomegalovirus infections involving the central nervous system.

Background: Ganciclovir protects against hearing deterioration in infants with symptomatic congenital cytomegalovirus (CMV) disease involving the central nervous system (CNS).

Objectives: To assess the neurodevelopmental impact of ganciclovir therapy in this population.

Study Design: 100 neonates were enrolled into a controlled Phase III study of symptomatic congenital CMV involving the CNS, and were randomized to either 6 weeks of intravenous ganciclovir or no treatment.

Turning Access into a web-enabled secure information system for clinical trials.

Background: Organizations that have limited resources need to conduct clinical studies in a cost-effective, but secure way. Clinical data residing in various individual databases need to be easily accessed and secured. Although widely available, digital certification, encryption, and secure web server, have not been implemented as widely, partly due to a lack of understanding of needs and concerns over issues such as cost and difficulty in implementation.

Recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF, sargramostim) administered for 3 years as adjuvant therapy of stages II(T4), III, and IV melanoma.

A hypothesis generating study was conducted to evaluate the safety and efficacy of prolonged (3 y) administration of granulocyte-macrophage colony-stimulating factor (GM-CSF, sargramostim) as surgical adjuvant therapy in patients with melanoma at high risk of recurrence. Ninety-eight evaluable patients with stages II(T4), III, or IV melanoma were given prolonged treatment with GM-CSF after surgical resection of disease. The GM-CSF was administered subcutaneously in 28-day cycles, such that a dose of 125 microg/m2 was delivered daily for 14 days followed by 14 days rest.

Comparison of multivariate adaptive regression splines and logistic regression in detecting SNP-SNP interactions and their application in prostate cancer.

Single nucleotide polymorphism (SNP) interaction plays a critical role for complex diseases. The primary limitation of logistic regressions (LR) in testing SNP-SNP interactions is that coefficient estimates may not be valid because of numerous terms in a model. Multivariate adaptive regression splines (MARS) have useful features to effectively reduce the number of terms in a model.

A four-parameter logistic model for estimating titers of functional multiplexed pneumococcal opsonophagocytic killing assay.

In vitro opsonophagocytosis killing assay (OPA) is widely accepted to quantitate Streptococcus pneumococcal antibodies to serotype-specific pneumococcal capsular polysaccharide (PS). A titer estimation method is needed for large scale data generated by OPA, and it is one component of OPA standardization. In order to improve the reliability of OPA results, we developed a nonlinear fitting method using the Levenberg-Marquardt algorithm with an option of a robust procedure to estimate titers of OPA data.

FCRL2 expression predicts IGHV mutation status and clinical progression in chronic lymphocytic leukemia.

CD38 and ZAP-70 are both useful prognostic markers for B-cell chronic lymphocytic leukemia (CLL), but are variably discordant with IGHV mutation status. A total of 5 human Fc receptor-like molecules (FCRL1-5) have tyrosine-based immunoregulatory potential and are expressed by B-lineage subpopulations. To determine their prognostic potential in CLL, FCRL expression was compared with IGHV mutation status, CD38 and ZAP-70 expression, and clinical features from 107 patients.

Variable selection in logistic regression for detecting SNP-SNP interactions: the rheumatoid arthritis example.

Many complex disease traits are observed to be associated with single nucleotide polymorphism (SNP) interactions. In testing small-scale SNP-SNP interactions, variable selection procedures in logistic regressions are commonly used. The empirical evidence of variable selection for testing interactions in logistic regressions is limited.

Prognosis and determinants of outcome following locoregional or distant recurrence in patients with cutaneous melanoma.

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.

A two-stage binomial test approach of gene identification in oligonucleotide arrays.

Most statistical approaches summarize the probe-level expression data into gene-level measures, which then are used for downstream statistical analyses. However, there are some limitations in using the gene level data for analysis, such as nonhomogeneous probe effects and the interaction effect (e.g.