Long-Term Survival after Complete Surgical Resection and Adjuvant Immunotherapy for Distant Melanoma Metastases.

BACKGROUND: This phase III study was undertaken to evaluate the efficacy of an allogeneic whole-cell vaccine (Canvaxin™) plus bacillus Calmette-Guerin (BCG) after complete resection of stage IV melanoma. METHODS: After complete resection of ≤5 distant metastases, patients were randomly assigned to BCG+Canvaxin (BCG/Cv) or BCG+placebo (BCG/Pl). The primary endpoint was overall survival (OS); secondary endpoints were disease-free survival (DFS), and immune response measured by skin test (ClinicalTrials.gov identifier: NCT00052156). RESULTS: Beginning in May 1998, 496 patients were randomized. In April 2005, the Data Safety Monitoring Board recommended stopping enrollment due to a low probability of efficacy. At that time, median OS and 5-year OS rate were 38.6 months and 44.9%, respectively, for BCG/Pl versus 31.4 months and 39.6% in the BCG/Cv group (hazard ratio (HR), 1.18; p = 0.250). Follow-up was extended at several trial sites through March 2010. Median OS and 5-year and 10-year survival was 39.1 months, 43.3 and 33.3%, respectively, for BCG/Pl versus 34.9 months, 42.5 and 36.4%, in the BCG/Cv group (HR 1.053; p = 0.696). Median DFS, 5- and 10-year DFS were 7.6 months, 23.8 and 21.7%, respectively, for BCG/Pl versus 8.5 months, 30.0%, and 30.0%, respectively, for the BCG/Cv group (HR 0.882; p = 0.260). Positive DTH skin testing correlated with increased survival. DISCUSSION: In this, the largest study of postsurgical adjuvant therapy for stage IV melanoma reported to date, BCG/Cv did not improve outcomes over BCG/placebo. Favorable long-term survival among study patients suggests that metastasectomy should be considered for selected patients with stage IV melanoma.

Circulating tumor cells in patients with breast cancer dormancy.

PURPOSE: The purpose of this study was to test the hypothesis that circulating tumor cells (CTCs) are present in patients many years after mastectomy without evidence of disease and that these CTCs are shed from persisting tumor in patients with breast cancer dormancy. EXPERIMENTAL DESIGN: We searched for CTCs in 36 dormancy candidate patients and 26 age-matched controls using stringent criteria for cytomorphology, immunophenotype, and aneusomy. RESULTS: Thirteen of 36 dormancy candidates, 7 to 22 years after mastectomy and without evidence of clinical disease, had CTCs, usually on more than one occasion. Only 1 of 26 controls had a possible CTC (no aneusomy). The statistical difference of these two distributions was significant (exact P = 0.0043). The CTCs in patients whose primary breast cancer was just removed had a half-life measured in 1 to 2.4 hours. CONCLUSIONS: The CTCs that are dying must be replenished every few hours by replicating tumor cells somewhere in the tissues. Hence, there appears to be a balance between tumor replication and cell death for as long as 22 years in dormancy candidates. We conclude that this is one mechanism underlying tumor dormancy.

Limitations of the Gail model in the specialized breast cancer risk assessment clinic.

The Gail model is a risk assessment tool that is accurate for general breast cancer risk screening. Because of the limited way that this model incorporates family history information, however, there are concerns that it may underestimate risk for many women attending specialized breast cancer risk assessment clinics. We collected comprehensive breast cancer risk factor information for 213 women attending a specialized breast cancer risk assessment clinic using a modified version of the CancerGene software. Breast cancer risk was calculated using the models of Gail and Claus as well as BRCAPRO and the tables of Bodian (for women with lobular neoplasia). Eighty-six percent of the women had a family history of breast cancer. Although 74% of women had risk factor histories that are thought to confound the Gail model (family history of breast cancer in second-degree relatives, family history of breast cancer before the age of 50, family history of bilateral breast cancer, family history of ovarian cancer, or personal history of lobular neoplasia), the inclusion of other models increased the risk level assignment in only 13% of the cases. We conclude that the Gail model is an appropriate risk assessment tool for most women attending specialized clinics, although the inclusion of models better able to account for family history information and personal history of lobular neoplasia is required to accommodate all women.