Medicine and Health Sciences Commons^™

Preservation Of Immune Function In Cervical Cancer Patients During Chemoradiation Using A Novel Integrative Approach., Susan Lutgendorf, Elizabeth Mullen-Houser, Daniel Russell, Koen De Geest, Geraldine Jacobson, Laura Hart, David Bender, Barrie Anderson, Thomas Buekers, Michael Goodheart, Michael Antoni, Anil Sood, David Lubaroff

David P Bender

Patients receiving chemoradiation for cervical cancer are at risk for distress, chemoradiation-related side-effects, and immunosuppression. This prospective randomized clinical trial examined effects of a complementary therapy, Healing Touch (HT), versus relaxation training (RT) and usual care (UC) for (1) supporting cellular immunity, (2) improving mood and quality of life (QOL), and (3) reducing treatment-associated toxicities and treatment delay in cervical cancer patients receiving chemoradiation. Sixty women with stages IB1 to IVA cervical cancer were randomly assigned to receive UC or 4 ×/weekly individual sessions of either HT or RT immediately following radiation during their 6-week chemoradiation treatment. Patients completed psychosocial …

A Phase Ii Evaluation Of Tirapazamine Plus Cisplatin In The Treatment Of Recurrent Platinum-Sensitive Ovarian Or Primary Peritoneal Cancer: A Gynecologic Oncology Group Study., Allan Covens, John Blessing, David Bender, Robert Mannel, Mark Morgan

David P Bender

OBJECTIVES: To estimate the anti-tumor activity, nature and degree of toxicity of tirapazamine in combination with cisplatin in patients with recurrent platinum-sensitive ovarian or primary peritoneal cancers.

METHODS: Eligible consenting patients had to have recurrent epithelial ovarian or primary peritoneal carcinoma with measurable disease. Patients were not allowed to have received any additional cytotoxic chemotherapy for management of recurrent or persistent disease, including re-treatment with initial chemotherapy regimens. Patients must have been platinum-sensitive, meaning a treatment-free interval of >6 months after response to a platinum-based regimen. The RECIST criteria were used for parameters of response. Tirapazamine was administered at a …

Diurnal Cortisol Dysregulation, Functional Disability, And Depression In Women With Ovarian Cancer., Aliza Weinrib, Sandra Sephton, Koen De Geest, Frank Penedo, David Bender, Bridget Zimmerman, Clemens Kirschbaum, Anil Sood, David Lubaroff, Susan Lutgendorf

David P Bender

BACKGROUND: Multiple alterations in circadian rhythms have been observed in cancer patients, including the diurnal rhythm of the adrenal hormone cortisol. Diurnal cortisol alterations have been associated with cancer-related physiological processes as well as psychological stress. Here we investigate alterations in diurnal cortisol rhythm in ovarian cancer patients, and potential links with depression, life stress, and functional disability.

METHODS: Women (n = 177) with suspected ovarian cancer completed questionnaires and collected salivary cortisol 3× daily for 3 consecutive days before surgery. One hundred women were subsequently diagnosed with ovarian cancer and 77 with benign disease. In addition, healthy women (n …

Sleep Disturbance, Cytokines, And Fatigue In Women With Ovarian Cancer., Lauren Clevenger, Andrew Schrepf, Desire Christensen, Koen De Geest, David Bender, Amina Ahmed, Michael Goodheart, Frank Penedo, David Lubaroff, Anil Sood, Susan Lutgendorf

David P Bender

Pro-inflammatory cytokines, such as interleukin-6 (IL-6), have been implicated in the underlying processes contributing to sleep regulation and fatigue. Despite evidence for sleep difficulties, fatigue, and elevations in IL-6 among women with ovarian cancer, the association between these symptoms and IL-6 has not been investigated. To address this knowledge gap, we examined relationships between sleep disturbance, fatigue, and plasma IL-6 in 136 women with ovarian cancer prior to surgery. These relationships were also examined in 63 of these women who were disease-free and not receiving chemotherapy one year post-diagnosis. At both time-points, higher levels of IL-6 were significantly associated with …

Social Isolation Is Associated With Elevated Tumor Norepinephrine In Ovarian Carcinoma Patients., Susan Lutgendorf, Koen De Geest, Laila Dahmoush, Donna Farley, Frank Penedo, David Bender, Michael Goodheart, Thomas Buekers, Luis Mendez, Gina Krueger, Lauren Clevenger, David Lubaroff, Anil Sood, Steve Cole

David P Bender

Noradrenergic pathways have been implicated in growth and progression of ovarian cancer. Intratumoral norepinephrine (NE) has been shown to increase with stress in an animal cancer model, but little is known regarding how tumor NE varies with disease stage and with biobehavioral factors in ovarian cancer patients. This study examined relationships between pre-surgical measures of social support, depressed mood, perceived stress, anxiety, tumor histology and tumor catecholamine (NE and epinephrine [E]) levels among 68 ovarian cancer patients. We also examined whether associations observed between biobehavioral measures and tumor catecholamines extended to other compartments. Higher NE levels were found in advanced …

A Single-Institution Evaluation Of Factors Important In Fallopian Tube Carcinoma Recurrence And Survival., Alireza Shamshirsaz, Thomas Buekers, Koen De Geest, David Bender, Gideon Zamba, Michael Goodheart

David P Bender

OBJECTIVE: The aim of this study was to identify prognostic factors and markers that influence clinical outcomes in patients with primary fallopian tube carcinoma at a single tertiary health care center. These prognostic factors may be of clinical importance and can subsequently be included in future clinical trials. MATERIALS AND METHODS: A retrospective review of our Tumor Registry and Gynecologic Oncology database was conducted to include any patients with a diagnosis of fallopian tube carcinoma between the years 1994 and 2005. We identified clinicopathological data to evaluate factors important in recurrence, disease-specific and overall survival. Kaplan-Meier curves were generated, and …

Serum Ca 125 Is An Independent Prognostic Factor In Cervical Adenocarcinoma, David Bender, J. Sorosky, R. Buller, A. Sood

David P Bender

OBJECTIVE: The purpose of this study was to determine the prognostic significance of a pretreatment serum CA 125 value in patients who were diagnosed with adenocarcinoma of the cervix. STUDY DESIGN: All patients who were diagnosed with adenocarcinoma or adenosquamous carcinoma of the cervix and treated definitively between 1986 and 1998 were eligible. The relationship between pretreatment serum CA 125 values and various clinical factors was evaluated. RESULTS: Seventy-three patients had pretreatment CA 125 drawn, with values that ranged from 5 to 683 U/mL and all patients were included in this study. A CA 125 value of >or=30 U/mL was …

A Phase Ii Study Of Vorinostat In The Treatment Of Persistent Or Recurrent Epithelial Ovarian Or Primary Peritoneal Carcinoma: A Gynecologic Oncology Group Study, S. Modesitt, M. Sill, J. Hoffman, David Bender

David P Bender

PURPOSE: This multi-institutional phase II trial assessed the activity and toxicity of a new histone deacetylase inhibitor, vorinostat (suberoylanilide hydroxamic acid--SAHA) in patients with recurrent or persistent epithelial ovarian or primary peritoneal carcinoma. PATIENTS AND METHODS: Women with recurrent or persistent epithelial ovarian or primary peritoneal carcinoma who were platinum-resistant/refractory (progression-free interval <12 months since platinum) were eligible for trial entry if they had measurable disease, a good performance status, and good overall organ function. Women were treated with a 400 mg daily oral dose of vorinostat and continued on treatment until disease progression or unacceptable toxicity. The primary endpoints …

Intestinal Lymphangiectasia Mimicking Primary Peritoneal Carcinoma., Jennifer Steines, Joshua Larson, Neal Wilkinson, Patricia Kirby, Michael Goodheart

Jennifer C. Steines Wagemester

Intestinal lymphangiectasia is an obstruction of the lymphatic system. We report on a patient with mesenteric adenopathy and an elevated CA125 level, which were suspicious for peritoneal carcinoma. Further evaluation and bowel resection identified intestinal lymphangiectasia. This disease should be considered in patients with mesenteric adenopathy and a small bowel mass.

Endocrine Cancer Risks For Women During The Perimenopause And Beyond., Kimberly Leslie, N. Kumar

Kimberly K. Leslie

Cancer and its link to reproductive hormones is an area of intense concern for our patients and has been the subject of much speculation. But if estrogen causes breast cancer, for example, most women would eventually develop the disease. We know this is not the case! Actually, estrogen and progesterone have been linked to a decrease as well as an increase in cancer, depending upon the type of tumor under investigation. The purpose of this manuscript is to review the data supporting those relationships.

Cadherins, Catenins And Cell Cycle Regulators: Impact On Survival In A Gynecologic Oncology Group Phase Ii Endometrial Cancer Trial, M. Singh, K. Darcy, W. Brady, R. Clubwala, Z. Weber, J. Rittenbach, A. Akalin, C. Whitney, R. Zaino, N. Ramirez, Kimberly Leslie

Kimberly K. Leslie

OBJECTIVE: We evaluated the clinical relevance of catenins, cadherins and cell cycle regulators in stage IV or recurrent endometrial carcinoma in a multi-center phase II trial (GOG protocol #119). METHODS: Tissue microarrays of metastatic or recurrent (n=42) tumor were developed and immunohistochemistry was performed. Average expression (percent staining x intensity) was assessed in tumor epithelium ((E)) and stroma ((S)) and categorized into tertiles (T1, T2, T3) for E-cadherin(E), N-cadherin(E), alpha-catenin(E), beta-catenin(E), gamma-catenin(E), p120-catenin(E) and Ki-67(E); as negative, below median or above median for p16(E), p27(E) and CD44(S); or as negative or positive for p53(E), Ki-67(S) and APC(S) (adenomatous polyposis coli). …

A Phase Ii Evaluation Of Lapatinib In The Treatment Of Persistent Or Recurrent Epithelial Ovarian Or Primary Peritoneal Carcinoma: A Gynecologic Oncology Group Study, A. Garcia, M. Sill, H. Lankes, A. Godwin, R. Mannel, D. Armstrong, R. Carolla, M. Liepman, N. Spirtos, E. Fischer, Kimberly Leslie

Kimberly K. Leslie

OBJECTIVE: Activation and dimerization of the ERBB family play a role in the pathogenesis and progression of ovarian cancer. We conducted a phase II trial to evaluate the activity and tolerability of lapatinib in patients with recurrent or persistent epithelial ovarian cancer (EOC) and to explore the clinical value of expression levels of epidermal growth factor receptors (EGFR), phosphorylated EGFR, HER-2/neu, and Ki-67, and the presence of EGFR mutations. METHODS: Eligible patients had recurrent or persistent EOC or primary peritoneal carcinoma, measurable disease, and up to 2 prior chemotherapy regimens for recurrent disease. Patients were treated with lapatinib 1500 mg/day. …

Effect Of Tamoxifen On Endometrial Histology, Hormone Receptors, And Cervical Cytology: A Prospective Study With Follow-Up, Kimberly Leslie, S. Walter, K. Torkko, J. Stephens, C. Thompson, M. Singh

Kimberly K. Leslie

OBJECTIVES: Our major hypothesis for these studies was that tamoxifen's varied effects on the endometrium might be due in part to differences in effect on estrogen and progesterone receptors [ER, progesterone receptor isoform A (PRA), and progesterone receptor isoform B (PRB)]. We aimed to evaluate the changes in histology in serial endometrial biopsies (Em bx), Papanicolaou smears (Pap smears), and endometrial ultrasounds as well as changes in the expression of ER, PRA, and PRB in response to tamoxifen. We propose that understanding and correlating the dynamics of receptor expression with histologic and cytologic changes will help us better understand the …

Phase Ii Trial Of Bevacizumab In Recurrent Or Persistent Endometrial Cancer: A Gynecologic Oncology Group Study, C. Aghajanian, M. Sill, K. Darcy, B. Greer, D. Mcmeekin, P. Rose, J. Rotmensch, M. Barnes, P. Hanjani, Kimberly Leslie

Kimberly K. Leslie

PURPOSE: Bevacizumab, a recombinant humanized monoclonal antibody against vascular endothelial growth factor-A (VEGF-A), has clinical activity in multiple tumor types. We conducted a phase II trial to assess the activity and tolerability of single-agent bevacizumab in recurrent or persistent endometrial cancer (EMC). PATIENTS AND METHODS: Eligible patients had persistent or recurrent EMC after receiving one to two prior cytotoxic regimens, measurable disease, and Gynecologic Oncology Group performance status of

Gpr30: A Novel Indicator Of Poor Survival For Endometrial Carcinoma, H. Smith, Kimberly Leslie, M. Singh, C. Qualls, C. Revankar, N. Joste, E. Prossnitz

Kimberly K. Leslie

OBJECTIVE: This study was undertaken to evaluate the relationship between GPR30, classical steroidal receptor expression, and clinical outcome in patients with endometrial carcinoma. STUDY DESIGN: Immunohistochemistry was used to investigate the expression of GPR30, estrogen, progesterone, epidermal growth factor receptors and Ki-67 in 47 consecutive consenting patients with endometrial carcinoma diagnosed between 1997 and 2001. Results were correlated with clinical and pathologic predictors of adverse outcome and survival. RESULTS: GPR30 correlated positively with epidermal growth factor receptor (P = .005), but negatively with progesterone (P = .05) receptor expression. GPR30 overexpression occurred more frequently in tumors with deep myometrial invasion, …

Association Of Intimate Partner Violence And Childhood Sexual Abuse With Cancer-Related Well-Being In Women, Ann L. Coker, Diane R. Follingstad, Lisandra S. Garcia, Corrine M. Williams, Timothy N. Crawford, Heather M. Bush

Obstetrics and Gynecology Faculty Publications

BACKGROUND: Limited evidence suggests that intimate partner violence (IPV) may be associated with poorer cancer outcomes. We hypothesized that timing and type of IPV as well as childhood sexual abuse (CSA) may negatively affect depression, perceived stress, and cancer-related well-being.

METHODS: This was a cross-sectional study of women diagnosed with either breast, cervical, or colorectal cancer in the prior 12 months included in the Kentucky Cancer Registry. Consenting women were interviewed by phone (n=553). Multivariate analysis of covariance (MANCOVA) was used to determine the association between IPV (37% lifetime prevalence) and type, timing, and the range of correlated cancer-related well-being …

Response To An Abnormal Ovarian Cancer-Screening Test Result: Test Of The Social Cognitive Processing And Cognitive Social Health Information Processing Models, Michael A. Andrykowski, Edward J. Pavlik

Behavioral Science Faculty Publications

All cancer screening tests produce a proportion of abnormal results requiring follow up. Consequently, the cancer-screening setting is a natural laboratory for examining psychological and behavioural response to a threatening health-related event. This study tested hypotheses derived from the social cognitive processing and cognitive-social health information processing models in trying to understand response to an abnormal ovarian cancer (OC) screening test result. Women (n = 278) receiving an abnormal screening test result a mean of 7 weeks earlier were assessed prior to a repeat screening test intended to clarify their previous abnormal result. Measures of disposition (optimism, informational coping style), …