Heidi E. Gibbons

Platinum/taxane‐based chemotherapy with or without radiation therapy favorably impacts survival outcomes in stage I uterine papillary serous carcinoma

A study was undertaken to determine recurrence patterns and survival outcomes of stage I uterine papillary serous carcinoma (UPSC) patients.

Radiation therapy compared with pelvic node resection for node-positive vulvar cancer: a randomized controlled trial.

OBJECTIVES: To report long-term survival and toxicity of radiation compared with pelvic node resection for patients with groin node–positive vulvar cancer. METHODS: A Gynecologic Oncology Group protocol enrolled 114 patients randomly allocated to postoperative pelvic and groin radiation (45–50 Gy, n=59) or to ipsilateral pelvic node resection (n=55) after radical vulvectomy and inguinal lymphadenectomy. Retrospective analyses for 114 enrolled patients included both risk of progression and death after treatment and assessment of toxicity. RESULTS: Median age was 70 years. Median survivor follow-up was 74 months. The relative risk of progression was 39% in radiation patients (95% confidence interval [CI] 0.17–0.88, P=.02). Fourteen intercurrent deaths occurred after radiation as compared with only two after pelvic node resection, narrowing 6-year overall survival (51% compared with 41%, hazard ratio 0.61 [95% CI 0.30–1.3], P=.18). However, the cancer-related death rate was significantly higher for pelvic node resection compared with radiation (51% compared with 29% at 6 years, hazard ratio 0.49 [95% CI 0.28–0.87], P=.015). Six-year overall survival benefit for radiation in patients with clinically suspected or fixed ulcerated groin nodes (P=.004) and two or more positive groin nodes (P<.001) persisted. A ratio of more than 20% positive ipsilateral groin nodes (number positive/number resected) was significantly associated with contralateral lymph node metastasis, relapse, and cancer-related death. Late chronic lymphedema (16% compared with 22%) and cutaneous desquamation (19% compared with 15%) were balanced after radiation and pelvic node resection. CONCLUSION: Radiation after radical vulvectomy and inguinal lymphadenectomy significantly reduces local relapses and decreases cancer-related deaths. Late toxicities remained similar after radiation or pelvic node resection. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00898352. LEVEL OF EVIDENCE: I

Feasibility and effectiveness of a lifestyle intervention program in obese endometrial cancer patients: A randomized trial

OBJECTIVE The majority of endometrial cancer survivors (ECS) are obese and at risk for premature death. The purpose of this study was to assess feasibility of a lifestyle intervention program for promoting weight loss, change in eating behaviors, and increased physical activity in obese ECS. STUDY DESIGN Early stage ECS (n=45) were randomized to a 6-month lifestyle intervention (LI; n=23) or usual care (UC; n=22). The LI group received group and individual counseling for 6 months. The primary endpoint was weight change. Secondary endpoints were physical activity, [Leisure score index (LSI)] and nutrient intake (3-day food records). Quantitative vitamin C and folate intake were used to assess fruit/vegetable intake. RESULTS Recruitment was 29%, adherence (LI group) was 73% and 84% of participants completed follow-up assessments. At 12 months, the intervention group lost 3.5 kg compared to a 1.4 kg gain in the control group [mean difference=-4.9 kg; 95% CI: -9.0 to -0.9 kg; p=.018] and had an increased LSI score of 16.4 versus -1.3 in the control group from baseline [mean group difference=17.8; 95% CI=7.1 to 28.4; p=.002]. There were no differences in vitamin C and folate intake. The LI group had lower intake of kilocalories, although differences were not significant. CONCLUSION(S) A lifestyle intervention program in obese ECS is feasible and can result in sustained behavior change and weight loss over a 1-year period.

Activation of P2X7-mediated apoptosis Inhibits DMBA/TPA-induced formation of skin papillomas and cancer in mice

BackgroundThe study tested the hypothesis that apoptosis can prevent and control growth of neoplastic cells. Previous studies in-vitro have shown that the pro-apoptotic P2X7 receptor regulates growth of epithelial cells. The specific objective of the present study was to understand to what degree the P2X7 system controls development and growth of skin cancer in vivo, and what cellular and molecular mechanisms are involved in the P2X7 action.MethodsSkin neoplasias in mice (papillomas, followed by squamous spindle-cell carcinomas) were induced by local application of DMBA/TPA. Experiments in-vitro utilized cultured epidermal keratinocytes generated from wild-type or from P2X7-null mice. Assays involved protein immunostaining and Western blots; mRNA real-time qPCR; and apoptosis (evaluated in situ by TUNEL and quantified in cultured keratinocytes as solubilized DNA or by ELISA). Changes in cytosolic calcium or in ethidium bromide influx (P2X7 pore formation) were determined by confocal laser microscopy.Results(a) Co-application on the skin of the P2X7 specific agonist BzATP inhibited formation of DMBA/TPA-induced skin papillomas and carcinomas. At the completion of study (week 28) the proportion of living animals with cancers in the DMBA/TPA group was 100% compared to 43% in the DMBA/TPA+BzATP group. (b) In the normal skin BzATP affected mainly P2X7-receptor – expressing proliferating keratinocytes, where it augmented apoptosis without evoking inflammatory changes. (c) In BzATP-treated mice the degree of apoptosis was lesser in cancer than in normal or papilloma keratinocytes. (d) Levels of P2X7 receptor, protein and mRNA were 4–5 fold lower in cancer tissues than in normal mouse tissues. (e) In cultured mouse keratinocytes BzATP induced apoptosis, formation of pores in the plasma membrane, and facilitated prolonged calcium influx. (f) The BzATP-induced apoptosis, pore-formation and augmented calcium influx had similar dose-dependence for BzATP. (g) Pore formation and the augmented calcium influx were depended on the expression of the P2X7 receptor, while the BzATP-induced apoptosis depended on calcium influx. (h) The BzATP-induced apoptosis could be blocked by co-treatment with inhibitors of caspase-9 and caspase-3, but not of caspase-8.Conclusion(a) P2X7-dependent apoptosis is an important mechanism that controls the development and progression of epidermal neoplasia in the mouse. (b) The P2X7-dependent apoptosis is mediated by calcium influx via P2X7 pores, and involves the caspase-9 (mitochondrial) pathway. (c) The diminished pro-apoptotic effect of BzATP in mouse cancer keratinocytes is possibly the result of low expression of the P2X7 receptor. (d) Activation of P2X7-dependent apoptosis, e.g. with BzATP could be a novel chemotherapeutic growth-preventive modality for papillomas and epithelial cancers in vivo.

Stage II uterine papillary serous carcinoma: Carboplatin/paclitaxel chemotherapy improves recurrence and survival outcomes

OBJECTIVES To determine recurrence patterns and survival outcomes of stage II uterine papillary serous carcinoma (UPSC) patients treated by various modalities with an emphasis on carboplatin/paclitaxel-based chemotherapy (CT)+/-radiotherapy (RT). METHODS A retrospective, multi-institution study of women with stage II UPSC diagnosed from 1992 to 2006 was performed. All patients underwent comprehensive surgical staging. Treatment included observation (OBS), RT (vaginal brachytherapy, whole pelvic and/or whole abdominal therapy), or >or=3 cycles carboplatin/paclitaxel alone or with RT. Recurrence and survival outcomes were determined. RESULTS We identified 55 subjects: 10 treated with OBS, 26 with RT alone and 19 with CT+/-RT. After a median follow-up of 33 mos (range, 10-119), 20 recurrences (36%) were observed. There was an overall difference in recurrence based upon treatment (p=.013). Specifically, all CT+/-RT treated patients had a lower risk of recurrence (11%) compared to patients treated by RT alone (50%) or OBS (50%). No patients treated with both CT+RT (n=12) experienced a recurrence. Treatment with CT was also associated with a decreased risk of recurrence on multivariate analysis (p=.015). Most recurrences were extra-pelvic (70%), occurred within 2 years (85%) and were not salvageable (84%). Five-year progression-free survival was 86% in chemotherapy-treated patients versus 41% in those not receiving chemotherapy (p=.010); overall survival was 88% in chemotherapy-treated patients versus 64% in those not receiving chemotherapy (p=.115). CONCLUSIONS Stage II UPSC patients have a significant risk for unsalvageable, extra-pelvic recurrence. However, treatment with platinum/taxane therapy+/-RT appears to reduce this risk and is associated with improved progression free survival outcomes.

A randomized trial of a lifestyle intervention in obese endometrial cancer survivors: quality of life outcomes and mediators of behavior change

BackgroundTo examine the effects of a 6 month lifestyle intervention on quality of life, depression, self-efficacy and eating behavior changes in overweight and obese endometrial cancer survivors.MethodsEarly stage endometrial cancer survivors were randomized to intervention (n = 23) or usual care (n = 22) groups. Chi-square, Students t-test and repeated measures analysis of variance were used in intent-to-treat analyses. Outcomes were also examined according to weight loss.ResultsMorbidly obese patients had significantly lower self-efficacy, specifically when feeling physical discomfort. There was a significant improvement for self-efficacy related to social pressure (p = .03) and restraint (p = .02) in the LI group. There was a significant difference for emotional well-being quality of life (p = .02), self-efficacy related to negative emotions (p < .01), food availability (p = .03), and physical discomfort (p = .01) in women who lost weight as compared to women who gained weight. Improvement in restraint was also reported in women who lost weight (p < .01).ConclusionThis pilot lifestyle intervention had no effect on quality of life or depression but did improve self-efficacy and some eating behaviors.Trial Registrationhttp://www.clinicaltrials.gov; NCT00420979

Assessment of factors that contribute to decreased quality of life in gynecologic oncology group ovarian cancer trials

The objective of this study was to assess which quality‐of‐life (QOL) line items on the Functional Assessment of Cancer Therapy‐Ovarian (FACT‐O) were associated with low QOL in women who were receiving chemotherapy for ovarian cancer.

Improved tolerance of primary chemotherapy with reduced-dose carboplatin and paclitaxel in elderly ovarian cancer patients

OBJECTIVE Elderly cancer patients are less likely to tolerate chemotherapy. We sought to compare the toxicity profiles and outcomes of elderly ovarian cancer patients treated with standard versus reduced-dose i.v. carboplatin/paclitaxel. METHODS A retrospective, multi-center analysis of women > or = 70 years with papillary serous ovarian/primary peritoneal cancers diagnosed from 1994-2005 was performed. Reduced-dose (RD) patients received carboplatin AUC 4-5 and paclitaxel 135 mg/m(2); standard-dose (SD) patients received carboplatin AUC 5-6 and paclitaxel 175 mg/m(2). Patient variables collected included age, stage, performance status (PS), cytoreductive status, Charlson comorbidity scores, and growth factor administration. RESULTS One-hundred patients met the study criteria. RD patients (n=26) were significantly older than SD patients (n=74; median age 77.0 versus 74.7, respectively, p=0.014). No differences were noted in stage, comorbidity scores, cytoreductive status or growth factor administration between cohorts. Incidence of grade 3-4 neutropenia was higher in the SD group (54.1% versus 19.2%; p=0.002). SD patients were more likely to experience cumulative toxicity (p=0.003) and required delays in therapy (p=0.05). Although PS was poorer in SD patients (p=0.02), on multivariate analysis, only the administration of the SD regimen predicted toxicity (p=0.008). There were no differences in progression-free or overall survival between cohorts (median follow-up: 34 months). On multivariate analysis, age (p=0.004) and PS (p=0.008) had a significant impact on survival. CONCLUSION(S) This preliminary data suggests that reduced-dose carboplatin/paclitaxel may be better tolerated but equally effective as the standard regimen in elderly ovarian cancer patients. Age, performance status and other geriatric parameters should be considered when dosing chemotherapy in the elderly.

Adjuvant treatment and survival in obese women with endometrial cancer: An international collaborative study

OBJECTIVE The purpose of this study was to determine the impact of patient weight on the frequency of surgical staging lymphadenectomy and pelvic radiation. Adverse effects, disease relapse, and survival outcomes were investigated. STUDY DESIGN Records of 766 women who underwent surgery for presumed corpus-confined endometrial cancer were reviewed. Body mass index (BMI) was calculated to categorize women as obese (BMI, > or = 30 kg/m2) or nonobese (BMI, < 30 kg/m2). Radiation-related toxicity was scored retrospectively. Median duration of follow-up period was 38 months. Chi2, logistic regression, correlation, Kaplan-Meier, and Cox multivariate proportional hazards were used for analysis. RESULTS Lymphadenectomy was completed as often in nonobese as obese women (P = .24). Adjuvant pelvic radiation treatment was administered more often in nonobese women (P = .01). Among 681 women with endometrioid histopathologic findings, 4-year cancer-related survival in obese women was 10% higher than all cause deaths, compared with 6% in nonobese women. CONCLUSION Obesity was not a barrier to lymphadenectomy, but did influence adjuvant pelvic radiation use.

Indicators of survival duration in ovarian cancer and implications for aggressiveness of care.

Ovarian cancer patients frequently receive chemotherapy near the end of life. The purpose of the current study was to develop indicators that characterize those ovarian cancer patients who have a short life span.