Association between tumor size and Breslow's thickness in malignant melanoma: a cross-sectional, multicenter study.

The aim of this study was to assess the potential role of tumor diameter in explaining variations in tumoral invasion and in the initial prognosis for patients with malignant melanoma (MM). This was a multicenter, cross-sectional study that recruited between 2000 and 2009 patients with primary in-situ MM (Tis) and invasive cutaneous MM. Tis and MMs with a Breslow's thickness less than 1 mm (T1) were grouped (Tis-T1) and tumors with a Breslow's thickness 1 mm or more were also analyzed in combination (T2-T4). The tumor size was measured after routine formalin tissue fixation. Primary outcomes were the correlation between Breslow's thickness and tumor size, and the role of tumor size in explaining variations in Breslow's thickness, as assessed by the Pearson correlation test and logistic binary regression with calculation of the odds ratios. A total of 1610 MM patients were included and analyzed. The Pearson correlation between tumor size and Breslow's thickness was 0.42, with a determination coefficient of R2=0.18 (P>0.01). Correlations between tumor size and thickness were stronger in patients aged 30-60 years (r=0.42, R2=0.1764, P<0.001) and in tumors arising on the upper limbs (r=0.55, R2=0.3025). The odds ratio of identifying a T2-T4 stage MM in patients with tumors larger than 1 cm in size was 2.76 (95% confidence interval 2.25-3.39, P<0.001). Even though a direct, positive, and strong association between tumoral size and Breslow's thickness might be expected in melanoma cases, the strength of this association has been moderate. Tumor size explains a low burden of the variation observed in the Breslow's thickness.

Role of age and sex in the diagnosis of early-stage malignant melanoma: a cross-sectional study.

Age and sex have been identified as predictors of outcome in malignant melanoma (MM). This aim of this multicentre, cross-sectional study was to analyse the role of age and sex as explanatory variables for the diagnosis of thin MM. A total of 2430 patients with MM were recruited. Cases of in situ-T1 MM were more frequent than T2-T4 MM (56.26% vs. 43.74%). Breslow thickness increased throughout decades of life (analysis of variance (ANOVA) p < 0.001), with a weak correlation between Breslow thickness and patient's age (r = 0.202, p < 0.001). Breslow thickness was significantly less in women (1.79 vs. 2.38 mm, p = 0.0001). Binary logistic regression showed a significant (p < 0.001) odds ratio for age 0-29 years (1.18), and 30-59 years (1.16), and for women (1.09). Age and sex explained 3.64% of the variation observed in Tis-T1 frequency (R2 = 0.0364). Age and sex appear to explain a low percentage of the variation in the early detection of MM.

The role of accessibility policies and other determinants of health care provision in the initial prognosis of malignant melanoma: a cross-sectional study.

BACKGROUND: The prognostic benefit of health care service provision and delivery policies for patients with malignant melanoma (MM) is not yet clear. OBJECTIVE: To analyze the role of health care provision determinants in the initial prognosis of MM. METHODS: A multicenter cross-sectional study was conducted at 14 public hospitals and recruited 3550 patients with MM between 2000 and 2009. The study variables were analyzed using univariate and multivariate models to identify their role in the variations observed. RESULTS: In a 10-year period, the number of patients with MM increased by 78.54%, with primary in situ MM (Tis) or MMs with a Breslow thickness <1 mm (T1) representing 51.72% of the total number of MMs in 2000, increasing to 62.23% by the end of the study period (P = .005). Among the variables that explained the variation in MM frequency the year of diagnosis after 2004 (univariate odds ratio [OR], 1.43 [P < .001]; multivariate OR, 1.36 [P = .005]) and diagnosis in centers with specific fast-track referral systems (univariate OR, 1.24 [P = .01]; multivariate OR, 1.59 [P = .025]) were shown to explain the increasing frequency of Tis-T1 MM. LIMITATIONS: The primary potential limitation of this study is its retrospective nature. CONCLUSION: Health care provision policies and interventions aimed at improving accessibility to specialized care appear to explain the increasing frequency of Tis-T1 MM.

New insights into the role of the immune microenvironment in breast carcinoma.

Recently, immune edition has been recognized as a new hallmark of cancer. In this respect, some clinical trials in breast cancer have reported imppressive outcomes related to laboratory immune findings, especially in the neoadjuvant and metastatic setting. Infiltration by tumor infiltrating lymphocytes (TIL) and their subtypes, tumor-associated macrophages (TAM) and myeloid-derived suppressive cells (MDSC) seem bona fide prognostic and even predictive biomarkers, that will eventually be incorporated into diagnostic and therapeutic algorithms of breast cancer. In addition, the complex interaction of costimulatory and coinhibitory molecules on the immune synapse and the different signals that they may exert represent another exciting field to explore. In this review we try to summarize and elucidate these new concepts and knowledge from a translational perspective focusing on breast cancer, paying special attention to those aspects that might have more significance in clinical practice and could be useful to design successful therapeutic strategies in the future.

Isolated limb perfusion for malignant melanoma: systematic review on effectiveness and safety.

BACKGROUND: Isolated limb perfusion (ILP) involves the administration of chemotherapy drugs directly into a limb involved by locoregional metastases. Unresectable locally advanced melanoma of the limbs represents one of the clinical settings in which ILP has demonstrated benefits. METHODS: A systematic review of the literature on ILP for patients with unresectable locally advanced melanoma of the limbs was conducted. MEDLINE, EMBASE, and Cochrane database searches were conducted to identify studies fulfilling the following inclusion criteria: hyper- or normothermic ILP with melphalan with or without tumor necrosis factor (TNF) or other drugs providing valid data on clinical response, survival, or toxicity. To allocate levels of evidence and grades of recommendation the Scottish Intercollegiate Guidelines Network system was used. RESULTS: Twenty-two studies including 2,018 ILPs were selected with a clear predominance of observational studies (90.90%) against experimental studies (9.10%). The median complete response rate to ILP was of 58.20%, with a median overall response rate of 90.35%. ILP with melphalan yielded a median complete response rate of 46.50%, against a 68.90% median complete response rate for melphalan plus TNF ILP. The median 5-year overall-survival rate was 36.50%, with a median overall survival interval of 36.70 months. The Wieberdink IV and V regional toxicity rates were 2.00% and 0.65%, respectively. CONCLUSIONS: ILP is effective in achieving clinical responses in patients with unresectable locally advanced melanoma of the limbs. The disease-free and overall survival rates provided by ILP are acceptable. ILP is safe, with a low incidence of severe regional and systemic toxicity.

Economic evaluation of a store-and-forward teledermatology system for skin cancer patients.

We conducted an economic analysis of a store-and-forward teledermatology system for the routine triage of skin cancer patients. A cost-identification, cost-effectiveness and sensitivity analysis under a societal perspective was used to compare teledermatology with the conventional care alternative. In the period March 2004 to July 2005, a total of 2009 teledermatology referrals were managed from 12 Primary Care Centres (PCCs) of the public health system. The unit cost was of Euro 79.78 per patient in teledermatology, and Euro 129.37 per patient in conventional care (P < 0.005), with an incremental cost of Euro 49.59 per patient in favour of teledermatology. The cost ratio between teledermatology and conventional care was 1.6. There was a significant inverse relation between the unit cost in each participating PCC and the number of teleconsultations transmitted from them (P < 0.001). Teledermatology resulted in a more cost-effective, or dominant, methodology. In a public health system equipped with an intranet, the routine use of teledermatology in skin cancer clinics is a cost-effective method of managing referrals.

Teledermatology-based presurgical management for nonmelanoma skin cancer: a pilot study.

BACKGROUND: To date, no previous experiences of teledermatology (TD) as a preoperative management facility have been published. OBJECTIVE: The objective was to evaluate a store-and-forward TD (SFTD) system aimed at the presurgical management of nonmelanoma skin cancer patients. METHODS AND MATERIALS: This was a multicenter, longitudinal, descriptive, and evaluative pilot study. Patients included in the TD-based surgical referral system presented with a nonmelanoma skin cancer or a fast-growth vascular tumor suitable for surgery under local anesthesia. Waiting intervals and on-the-day cancellation rates were evaluated and compared with a sample of patients managed through the conventional system. The accuracy of the diagnoses yielded and of the surgical techniques planned through teleconsultation was also calculated. RESULTS: A total of 134 patients were enrolled in the study. The mean waiting interval was 26.10 days [95% confidence interval (CI), 24.51-27.70] in patients managed through TD and 60.57 days (95% CI, 56.20-64.93 days; n=92; p < .001) in the conventional system. On-the-day surgery cancellation was 2.99% (95% CI, 1.52%-4.46%) for the TD series and 8.85% (95% CI, 5.62%-11.81%; p<.005) in the conventional system. The accuracy of the telediagnoses was kappa=0.86 (95% CI, 0.83-0.89). The agreement rate between the surgical technique planned through teleconsultation and the technique finally performed was kappa=0.75 (95% CI, 0.04-0.79). CONCLUSION: SFTD has been demonstrated to be effective and accurate as a preoperative tool for nonmelanoma skin cancer, avoiding unnecessary visits to the hospital and shortening the waiting intervals to the surgical treatment.

Store-and-forward teledermatology in skin cancer triage: experience and evaluation of 2009 teleconsultations.

OBJECTIVE: To evaluate a store-and-forward teledermatology system aimed at the routine triage of patients with skin cancer. DESIGN: A multicenter, longitudinal, 4-phase, descriptive and evaluation study of a referred sample of patients attended through teleconsultation between March 2004 and July 2005 (n = 2009). Clinical and dermoscopical examination and histopathological study were considered the gold standard. SETTING: A skin cancer unit of a public university hospital and 12 primary care centers in southern Spain. PATIENTS: The study population comprised patients with circumscribed lesions fulfilling at least 1 of the following criteria: changes in ABCD criteria (asymmetry, border irregularity, color variegation, and diameter >6 mm), recent history, multiple melanocytic lesions, symptoms, and/or patient's application for surgical treatment and concern about moles. INTERVENTIONS: Diagnosis, diagnostic category (malignant lesions, high-risk lesions, benign lesions, special lesions, and other lesions), diagnostic confidence level on a 3-point scale, and management decision (referral vs nonreferral) were listed after the evaluation of each teleconsultation. A face-to-face evaluation and biopsy of selected patients were performed. MAIN OUTCOME MEASURES: The filtering percentage, as the percentage of patients not referred to the face-to-face clinic, as well as waiting intervals and pick-up or skin cancer detection rates were evaluated as effectiveness indicators. Reliability measures (kappa agreement), accuracy, and diagnostic performance indicators (validity) were also evaluated. RESULTS: The filtering percentage was 51.20% (95% confidence interval [CI], 49.00%-53.40%). The waiting interval to attend the clinic was 12.31 days (95% CI, 8.22-16.40 days) through teledermatology and 88.62 days (95% CI, 38.42-138.82 days; P<.001) for the letter referral system. Pick-up rates were 2.02% (95% CI, 1.10%-2.94%) for malignant melanoma and 27.94% (95% CI, 24.98%-30.90%) or 1:3.71 for patients with any malignant or premalignant lesion. Intraobserver agreement was kappa = 0.91 (95% CI, 0.89-0.93) for the management decision and kappa = 0.95 (95% CI, 0.94-0.96) for the diagnosis. Interobserver concordance was kappa = 0.83 (95% CI, 0.78-0.88) for the management decision and kappa = 0.85 (95% CI, 0.79-0.91) for the diagnosis. Accuracy was kappa = 0.81 (95% CI, 0.78-0.84). Sensitivity was 0.99 (95% CI, 0.98-1.00); specificity, 0.62 (95% CI, 0.56-0.69); pretest likelihood, 0.42 (95% CI, 0.37-0.47); positive posttest likelihood, 0.65 (95% CI, 0.61-0.69); and negative posttest likelihood, 0.01 (95% CI, 0.00-0.05). CONCLUSION: Store-and-forward teledermatology has demonstrated in this series to be an effective, accurate, reliable, and valid approach for the routine management of patient referrals in skin cancer and pigmented lesion clinics.