GC plus BV followed by BV until progression resulted in a statistically significant improvement in PFS compared with GC plus PL in platinum-sensitive ROC.
Background
Natural killer (NK) cells derived from patients with cancer exhibit diminished cytotoxicity compared with NK cells from healthy individuals. We evaluated the tumor response and in vivo expansion of allogeneic NK cells in recurrent ovarian and breast cancer.
Methods
Patients underwent a lymphodepleting preparative regimen: fludarabine 25 mg/m2 × 5 doses, cyclophosphamide 60 mg/kg × 2 doses, and, in seven patients, 200 cGy total body irradiation (TBI) to increase host immune suppression. An NK cell product, from a haplo-identical related donor, was incubated overnight in 1000 U/mL interleukin (IL)-2 prior to infusion. Subcutaneous IL-2 (10 MU) was given three times/week × 6 doses after NK cell infusion to promote expansion, defi ned as detection of ≥ 100 donor-derived NK cells/µL blood 14 days after infusion, based on molecular chimerism and flow cytometry.
Results
Twenty (14 ovarian, 6 breast) patients were enrolled. The median age was 52 (range 30–65) years. Mean NK cell dose was 2.16 × 107 cells/kg. Donor DNA was detected 7 days after NK cell infusion in 9/13 (69%) patients without TBI and 6/7 (85%) with TBI. T-regulatory cells (Treg) were elevated at day +14 compared with pre-chemotherapy (P = 0.03). Serum IL-15 levels increased after the preparative regimen (P = <0.001). Patients receiving TBI had delayed hematologic recovery (P = 0.014). One patient who was not evaluable had successful in vivo NK cell expansion.
Conclusions
Adoptive transfer of haplo-identical NK cells after lymphodepleting chemotherapy is associated with transient donor chimerism and may be limited by reconstituting recipient Treg cells. Strategies to augment in vivo NK cell persistence and expansion are needed.
A B S T R A C T PurposeTo determine the safety of sentinel lymph node biopsy as a replacement for inguinal femoral lymphadenectomy in selected women with vulvar cancer.
Patients and MethodsEligible women had squamous cell carcinoma, at least 1-mm invasion, and tumor size Ն 2 cm and Յ 6 cm. The primary tumor was limited to the vulva, and there were no groin lymph nodes that were clinically suggestive of cancer. All women underwent intraoperative lymphatic mapping, sentinel lymph node biopsy, and inguinal femoral lymphadenectomy. Histologic ultra staging of the sentinel lymph node was prescribed.
ResultsIn all, 452 women underwent the planned procedures, and 418 had at least one sentinel lymph node identified. There were 132 node-positive women, including 11 (8.3%) with false-negative nodes. Twenty-three percent of the true-positive patients were detected by immunohistochemical analysis of the sentinel lymph node. The sensitivity was 91.7% (90% lower confidence bound, 86.7%) and the false-negative predictive value (1-negative predictive value) was 3.7% (90% upper confidence bound, 6.1%). In women with tumor less than 4 cm, the false-negative predictive value was 2.0% (90% upper confidence bound, 4.5%).
ConclusionSentinel lymph node biopsy is a reasonable alternative to inguinal femoral lymphadenectomy in selected women with squamous cell carcinoma of the vulva.
Purpose
Despite initial sensitivity to chemotherapy, ovarian cancers (OVCA) often develop drug-resistance, which limits patient survival. Using specimens and/or genomic data from 289 patients and a panel of cancer cell lines, we explored genome-wide expression changes that underlie the evolution of OVCA chemo-resistance and characterized the BCL2 antagonist of cell death (BAD) apoptosis pathway as a determinant of chemo-sensitivity and patient survival.
Experimental Design
Serial OVCA cell cisplatin treatments were performed in parallel with measurements of genome-wide expression changes. Pathway analysis was performed on genes associated with increasing cisplatin-resistance (EC50). BAD-pathway expression and BAD-protein phosphorylation were evaluated in patient samples and cell lines as determinants of chemo-sensitivity and/or clinical outcome and as therapeutic targets.
Results
Induced in vitro OVCA cisplatin-resistance was associated with BAD-pathway expression (P < 0.001). In OVCA cell lines and primary specimens, BAD-protein phosphorylation was associated with platinum-resistance (n = 147, P < 0.0001) and also with overall patient survival (n = 134, P = 0.0007). Targeted modulation of BAD-phosphorylation levels influenced cisplatin sensitivity. A 47-gene BAD-pathway score was associated with in vitro phosphorylated-BAD levels and with survival in 142 patients with advanced-stage (III/IV) serous OVCA. Integration of BAD-phosphorylation or BAD-pathway score with OVCA surgical cytoreductive status was significantly associated with overall survival by log-rank test (P = 0.004 and <0.0001, respectively).
Conclusion
The BAD apoptosis pathway influences OVCA chemo-sensitivity and overall survival, likely via modulation of BAD-phosphorylation. The pathway has clinical relevance as a biomarker of therapeutic response, patient survival, and as a promising therapeutic target.
The current study examines gender differences in victim and crime characteristics in an effort to determine the extent to which sexual assault is a similar experience for men and for women. Data from a routine structured interview was obtained from medical charts of 842 women and 128 men seen at an urban hospital-based rape treatment center. Demographic characteristics were similar, although males were more like to identify as gay or bisexual, and women were more likely to be of minority ethnicity. Men were more likely to report acute psychiatric symptoms, a history of psychiatric disorder, and a history of psychiatric hospitalization. Women were more likely to experience vaginal or anal penetration, to sustain injuries, and to make a police report. Implications for services for both men and women are discussed.
Purpose: To define the use of complementary and alternative medicine (CAM) in individuals presenting for care at a comprehensive cancer center. Patients and Methods: A total of 17 639 individuals presenting to an NCI-designated Comprehensive Cancer Center (and consortium sites) completed a questionnaire regarding CAM use. Data were analyzed using the univariate χ2 test to assess CAM use associated with a number of variables, including cancer status, age, gender, marital status, ethnicity, race, employment, and education level. Results: Eighty-seven percent of individuals who completed the CAM survey acknowledged CAM therapy use within the previous 12 months. Of the 5 broad categories of CAM, the most commonly used were biologically based approaches (14 759/17 639 [83.67%]), mind-body interventions (4624/17 485 [26.45%]), manipulative and body-based therapies (3957/17 537 [22.56%]), alternative medical systems (429/15 952 [2.69%]), and energy therapies (270/15 872 [1.7%]). CAM use was more prevalent among women, non-Hispanics, Caucasians, patients 60 to 69 years of age, and those who are married, have a higher level of education, and are employed (P < .005). Conclusions: This is the largest report of CAM use in individuals presenting for care at a comprehensive cancer center. Our analysis revealed that a very high percentage of patients utilize CAM. Because many of these CAM interventions are not studied in oncology patients, additional research on safety, efficacy, and mechanisms of action are essential. Furthermore, it is important that oncologists understand CAM modalities and counsel their patients about their use.
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