Circulating Tumor Cells and Early Relapse in Node-positive Melanoma.

PURPOSE: There is a need for sensitive, reproducible biomarkers for patients with stage III melanoma to guide clinical decision making. Circulating tumor cells (CTCs) can be detected in patients with melanoma; however, there are limited data regarding their significance in stage III disease. The aim of this study was to determine whether CTCs are associated with early relapse in stage III melanoma. EXPERIMENTAL DESIGN: We prospectively assessed CTCs at first presentation in clinic (baseline) for 243 patients with stage III melanoma. CTCs were measured using the CellSearch System. Relapse-free survival (RFS) was compared between patients with one or more baseline CTC versus those with no CTCs. Log-rank test and Cox regression analysis were applied to establish associations of CTCs with RFS. RESULTS: At least one baseline CTC was identified in 90 of 243 (37%) patients. Forty-five (19%), 67 (28%), 118 (49%), and 13 (5%) patients were stage IIIA, IIIB, IIIC, or IIID, respectively. CTC detection was not associated with substage, or primary tumor characteristics. Multivariable analysis demonstrated that the detection of ≥1 baseline CTC was significantly associated with decreased 6-month RFS [log-rank, P < 0.0001; HR, 3.62, 95% confidence interval (CI), 1.78-7.36; P < 0.0001] and 54-month RFS (log-rank, P = 0.01; HR, 1.69; 95% CI, 1.13-2.54; P = 0.01). CONCLUSIONS: ≥1 CTC was independently associated with melanoma relapse, suggesting that CTC assessment may be useful to identify patients at risk for relapse who could derive benefit from adjuvant therapy.

Circulating Tumor Cells in Stage IV Melanoma Patients.

BACKGROUND: Management of stage IV melanoma patients remains a challenge. In spite of promising new therapies, many patients develop resistance and progression. The aim of this pilot study was to determine if circulating tumor cells (CTCs) are associated with shortened (180-day) progression-free survival (PFS) after a baseline CTC assessment in stage IV melanoma patients. STUDY DESIGN: A baseline CTC assessment was performed in 93 stage IV melanoma patients using a commercially available immunomagnetic system. The presence of 1 or more CTC was considered a positive result. A Cox multivariable regression model was used to evaluate the association between presence of CTCs at baseline and PFS, after adjusting for covariables. Kaplan-Meier curves and a log-rank test were used to summarize and compare unadjusted PFS for patients stratified by CTC positivity. RESULTS: Median follow-up was 17 months; mean age was 55 years. Thirteen of 93 (14%) patients had no evidence of disease (NED) at baseline CTC assessment. One or more CTC was detected in 39 of 93 (42%) of patients at baseline; CTCs were not associated with primary melanoma features or NED status. Twenty-eight of 93 (30%) patients progressed within 180 days of baseline draw, with 20 of 39 (51%) of the CTC-positive patients relapsing compared with 8 of 54 (15%) of the CTC-negative patients. In adjusted Cox models, a significant association was found suggesting worse PFS within 180 days for CTC-positive patients at baseline (vs CTC-negative) (hazard ratio 4.69, 95% CI 1.59 to 13.77, p = 0.005). CONCLUSIONS: One or more CTCs at baseline were associated with progression within 180 days in stage IV melanoma patients. This information warrants further study of CTCs as a means of identifying patients at high-risk for disease progression.

Circulating Tumor Cells in Breast Cancer Patients Treated by Neoadjuvant Chemotherapy: A Meta-analysis.

Background: We conducted a meta-analysis in nonmetastatic breast cancer patients treated by neoadjuvant chemotherapy (NCT) to assess the clinical validity of circulating tumor cell (CTC) detection as a prognostic marker. Methods: We collected individual patient data from 21 studies in which CTC detection by CellSearch was performed in early breast cancer patients treated with NCT. The primary end point was overall survival, analyzed according to CTC detection, using Cox regression models stratified by study. Secondary end points included distant disease-free survival, locoregional relapse-free interval, and pathological complete response. All statistical tests were two-sided. Results: Data from patients were collected before NCT (n = 1574) and before surgery (n = 1200). CTC detection revealed one or more CTCs in 25.2% of patients before NCT; this was associated with tumor size (P < .001). The number of CTCs detected had a detrimental and decremental impact on overall survival (P < .001), distant disease-free survival (P < .001), and locoregional relapse-free interval (P < .001), but not on pathological complete response. Patients with one, two, three to four, and five or more CTCs before NCT displayed hazard ratios of death of 1.09 (95% confidence interval [CI] = 0.65 to 1.69), 2.63 (95% CI = 1.42 to 4.54), 3.83 (95% CI = 2.08 to 6.66), and 6.25 (95% CI = 4.34 to 9.09), respectively. In 861 patients with full data available, adding CTC detection before NCT increased the prognostic ability of multivariable prognostic models for overall survival (P < .001), distant disease-free survival (P < .001), and locoregional relapse-free interval (P = .008). Conclusions: CTC count is an independent and quantitative prognostic factor in early breast cancer patients treated by NCT. It complements current prognostic models based on tumor characteristics and response to therapy.

Exploratory Analyses of Risk Behaviors Among GLBT Youth Attending a Drop-In Center.

This exploratory study examines measures of one drop-in center's efforts to improve health outcomes of gay, lesbian, bisexual, and transgender (GLBT) youth by facilitating out-group secondary social ties. Hatch Youth, located in Houston, Texas, aims to increase self-esteem and decrease negative health outcomes by encouraging GLBT youth to be part of Houston's greater GLBT community. Survey data ( N = 614) collected between October 2003 and April 2013 were entered into logistic regression models. Attending Hatch Youth for 6 or more months was associated with having a social group outside of school (adjusted odds ratio [aOR] = 2.07; 95% confidence interval [CI] = [1.33, 3.20]), being out to that social group (aOR = 2.34; 95% CI = [1.35, 4.03]), and interacting with the GLBT community outside of Hatch Youth (aOR = 2.33; 95% CI = [1.50, 3.54]), when referenced against youth attending less than 1 month. Having a good family relationship in the last 90 days (aOR = 2.48; 95% CI = [1.67, 3.70]) and having a social group outside of school (aOR = 2.57; 95% CI = [1.67, 3.97]) were associated with higher self-esteem. Higher self-esteem was associated with practicing safe sex (aOR = 1.86; 95% CI = [1.25, 2.75]) and not using street drugs (aOR = 0.45; 95% CI = [0.24, 0.83]). Interacting with the GLBT community outside of Hatch Youth was associated with practicing safe sex (aOR = 1.64; 95% CI = [1.12, 2.42]). Drop-in centers can strengthen secondary social ties among youth. Because questions remain about how drop-in centers can assist youth aging out of their programs to find other supportive secondary social ties, additional studies examining similar drop-in centers are needed.

Body mass index mediates the prognostic significance of circulating tumor cells in inflammatory breast cancer.

BACKGROUND: Obesity (BMI≥30) may be an etiologic and prognostic factor in inflammatory breast cancer (IBC). We examined the relationship between BMI, pathologic complete response (pCR), and circulating-tumor-cell (CTC) levels in IBC. METHODS: Cohort included IBC patients diagnosed 2005-2015 who had neoadjuvant chemotherapy during a prospective trial on CTCs and pathologic review describing pCR. Chi-square, logistic regression, and Cox proportional hazards models were used to identify clinicopathologic associations with event-free survival (EFS). RESULTS: Of 73 patients, 61 (84%) had CTC values, 22 (30%) achieved a pCR, and 39 (53%) were obese. There was no difference between obese and non-obese patients for pCR rates (31% vs. 29%, p = 0.90) or presence of CTCs (23% vs. 26%, p = 0.80). Among non-obese patients, CTCs were associated with worse EFS (HR 11.69, p < 0.01), but among obese patients, there was no difference in EFS between those with and without CTCs. CONCLUSIONS: BMI mediates CTCs' prognostic significance in IBC.

Strengthening Social Ties to Increase Confidence and Self-Esteem Among Sexual and Gender Minority Youth.

Sexual and gender minority (SGM) youth too often live in nonsupportive environments. This study reports the influence of social support from primary and secondary social ties on confidence and self-esteem among participants in Hatch Youth, a drop-in group-level intervention for SGM youth. Each 3-hour Hatch Youth meeting consists of a social, educational, and youth-led support hour. Over 14 weeks, these meetings were randomly observed and individual interviews with participating youth ( n = 12) and staff and volunteers ( n = 12) were conducted; data underwent a content analysis. Participants perceived an increase in confidence and self-esteem through enhanced bonding with family and friends, a sense of belonging, and community empowerment because of their involvement with Hatch Youth, suggesting drop-in centers can strengthen secondary social ties and improve confidence and self-esteem.

Social Support, Depression, Self-Esteem, and Coping Among LGBTQ Adolescents Participating in Hatch Youth.

Evidence-based interventions that increase social support have the potential to improve the health of lesbian, gay, bisexual, transgender, and queer (LGBTQ) youth. Hatch Youth is a group-level intervention that provides services four nights a week to LGBTQ youth between 13 and 20 years of age. Each Hatch Youth meeting is organized into three 1-hour sections: unstructured social time, consciousness-raising (education), and a youth-led peer support group. Youth attending a Hatch Youth meeting between March and June 2014 (N = 108) completed a cross-sectional survey. Covariate adjusted regression models were used to examine the association between attendance, perceived social support, depressive symptomology, self-esteem, and coping ability. Compared to those who attended Hatch Youth for less than 1 month, participants who attended 1 to 6 months or more than 6 months reported higher social support (ß1-6mo. = 0.57 [0.07, 1.07]; ß6+mo. = 0.44, 95% confidence interval [CI; 0.14, 0.75], respectively). Increased social support was associated with decreased depressive symptomology (ß = -4.84, 95% CI [-6.56, -3.12]), increased self-esteem (ß = 0.72, 95% CI [0.38, 1.06]), and improved coping ability (ß = 1.00, 95% CI [0.66, 1.35]). Hatch Youth is a promising intervention that has the potential to improve the mental health and reduce risk behavior of LGBTQ youth.

Prognostic Value of Circulating Tumor Cells Identified Before Surgical Resection in Nonmetastatic Breast Cancer Patients.

BACKGROUND: Circulating tumor cells (CTCs) can be identified in approximately 25% of nonmetastatic breast cancer patients, and data are emerging regarding their prognostic significance. We hypothesized that CTCs identified before resection of the primary tumor would predict worse outcomes in nonmetastatic breast cancer patients. STUDY DESIGN: We performed CTC enumerations on 509 patients with nonmetastatic breast cancer as part of an IRB-approved study. The CTCs (per 7.5 mL blood) were identified using the CellSearch System (Janssen). The presence of ≥1 CTC meeting morphologic criteria for malignancy was considered a positive result. Log-rank test and Cox regression analysis were applied to establish the association of CTCs with relapse-free and overall survival. RESULTS: Median follow-up was 48 months and mean age was 53 years. Fifty-nine percent of patients (299 of 509) had tumors larger than 2 cm, and 46% (234 of 509) had positive lymph nodes. One hundred sixty-six patients received neoadjuvant chemotherapy (NACT) before CTC assessment, and 343 patients were chemonaïve. One or more CTC was identified in 43 of 166 (26%) NACT treated patients, and in 81 of 343 (24%) chemonaïve patients. Circulating tumor cells were not associated with tumor size, grade, or lymph node status (p = NS). Detection of 1 or more CTCs predicted decreased relapse-free (log-rank p < 0.001, hazard ratio [HR] 2.72, 95% CI 1.57 to 4.72; p < 0.001) and overall survival (log-rank p = 0.02, HR 2.29, 95% CI 1.12 to 4.67; p = 0.03) at 48 months of follow-up. CONCLUSIONS: One or more CTCs identified before resection of the primary breast tumor predicted worse relapse-free and overall survival, irrespective of primary tumor size, grade, or lymph node positivity.