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Background: KIT-directed tyrosine kinase inhibitors such as imatinib have demonstrated benefits in KIT-mutant (KIT+) mucosal, acral, vulvovaginal, and chronically sun-damaged (CSD) melanoma. Dasatinib has superior preclinical activity in comparison with other tyrosine kinase inhibitors against cells with the most common KIT mutation, exon 11 L576P . The ECOG-ACRIN E2607 trial assessed dasatinib in patients with these melanoma subtypes., Methods: Patients received 70 mg of oral dasatinib twice daily. The primary objective for this 2-stage phase 2 trial was response rate. Stage I was open to KIT+ and wild-type KIT (KIT-) mucosal, acral, and CSD melanoma (n = 57). Stage II accrued only KIT+ tumors (n = 30). To enrich the trial for KIT+ tumors, vulvovaginal melanoma was added, and CSD melanoma was removed from eligibility. Secondary objectives included progression-free survival (PFS), overall survival (OS), and safety., Results: From May 2009 to December 2010, the first stage enrolled 57 patients. Among the evaluable patients, 3 of 51 (5.9%) achieved a partial response: all were KIT-. Stage II closed early because of slow accrual (November 2011 to December 2015). In stage II, 4 of 22 evaluable patients (18.2%) had a partial response; the median duration was 4.2 months. The median PFS was 2.1 months (n = 73; 95% confidence interval [CI], 1.5-2.9 months). The median OS was 7.5 months (95% CI, 6.0-11.9 months). In exploratory analyses, no differences were seen in PFS or OS with the KIT status or subtype. Dasatinib was discontinued because of adverse events in 9 of 75 patients (12%)., Conclusions: The dasatinib response rate among KIT+ melanoma patients was low. In view of its clinical activity, it is recommended that imatinib remain the KIT tyrosine kinase inhibitor of choice for unresectable KIT+ melanoma. Cancer 2017;123:2688-97. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

Background: The clinical course of patients with uterine leiomyosarcoma (LMS) is difficult to predict with the currently available categorical staging systems of the American Joint Committee on Cancer (AJCC) and the International Federation of Gynecology and Obstetrics (FIGO). The objective of the current study was to develop and validate a novel, clinically relevant, individualized prognostic model for patients with uterine LMS., Methods: Patients with uterine LMS who presented at the authors' institution from 1982 to 2008 were analyzed. The nomogram model was chosen based on the clinical evidence and statistical significance of the predictors, including age at diagnosis, tumor size, histologic grade, uterine cervix involvement, extrauterine spread, distant metastases, and mitotic index. Five-year overall survival (OS) was the predicted endpoint. The concordance probability (CP) was used as a predictive accuracy measure and compared with the CP of current staging systems. The model was internally validated using 200 bootstrap samples to correct for over fitting., Results: One hundred eighty-five of 270 patients were eligible for the nomogram analysis. The median follow-up was 5.4 years, and the median OS was 3.75 years (95% confidence interval, 3-6 years). The CP of the newly developed nomogram was 0.67 (95% confidence interval, 0.63-0.72). This was superior to predictions based on AJCC and FIGO staging. The bootstrap-validated CP was 0.65 with good calibration accuracy., Conclusions: The authors developed and internally validated a uterine LMS-specific nomogram to predict 5-year OS. This novel, individualized prognostic model outperforms traditionally used categorical staging systems and may be useful for patient counseling and for better selection of patients for adjuvant therapy trials., (Copyright © 2011 American Cancer Society.)

Background: The objective of this study was to compare the human immunodeficiency virus (HIV) viral load (VL) and CD4 counts in patients infected with HIV with and without cervical cancer. The authors hypothesized that HIV-positive women with cervical cancer would have a greater risk of immune suppression., Methods: A case-control study was conducted that included all HIV-positive patients who were seen at the authors' institution from January 1, 1995 to April 20, 2006 with invasive cervical cancer (cases) and without invasive cervical cancer (controls). Patients were included only if they had a CD4 count recorded<6 months before or<3 months after their diagnosis of invasive cervical cancer (cases) or at their last gynecologic examination (controls). Controls were matched to cases on a 4:1 ratio according to current smoking history. Patients were considered immunocompetent if they had both a CD4 count>200 cells/microL and a VL<10,000 copies/mL., Results: In total, 15 cases and 60 controls were identified. The median CD4 count for cases was 208 cells/microL (range, 18-1102 cells/microL) compared with 445 cells/microL (range, 20-1201 cells/microL) for controls (P=.03). The median VL was 16,918 copies/mL (range, 50-214,915 copies/mL) for cases compared with 1430 copies/mL (range, 50-571,000 copies/mL) for controls (P=.15). Only 1 of 14 cases (7%) was immunocompetent compared with 35 of 55 controls (64%; odds ratio, 0.04; 95% confidence interval, 0-0.37; P<.001). This significance was maintained after adjusting for other factors (P=.002)., Conclusions: Women with HIV who were diagnosed with invasive cervical cancer appeared to have a much greater degree of immunosuppression than women with HIV without invasive cervical cancer., (Copyright (c) 2008 American Cancer Society.)