The effect of ovarian imaging on the clinical interpretation of a multivariate index assay.

Objective: The purpose of this study was to investigate the relationship between imaging and the multivariate index assay (MIA) in the prediction of the likelihood of ovarian malignancy before surgery.

Study Design: Subjects were recruited in 2 related prospective, multiinstitutional trials that involved 44 sites across the United States. Women had ovarian imaging, biomarker analysis, and surgery for an adnexal mass.

High-volume ovarian cancer care: survival impact and disparities in access for advanced-stage disease.

Objective: To characterize the impact of hospital and physician ovarian cancer case volume on survival for advanced-stage disease and investigate socio-demographic variables associated with access to high-volume providers.

Methods: Consecutive patients with stage IIIC/IV epithelial ovarian cancer (1/1/96-12/31/06) were identified from the California Cancer Registry. Disease-specific survival analysis was performed using Cox-proportional hazards model.

Resistance to bleomycin in cancer cell lines is characterized by prolonged doubling time, reduced DNA damage and evasion of G2/M arrest and apoptosis.

Background: To establish, characterize and elucidate potential mechanisms of acquired bleomycin (BLM) resistance using human cancer cell lines. Seven BLM-resistant cell lines were established by exposure to escalating BLM concentrations over a period of 16-24 months. IC50 values and cell doubling times were quantified using a real time cytotoxicity assay.

Intraperitoneal chemotherapy from Armstrong to HIPEC: challenges and promise.

The treatment of advanced stage ovarian, primary peritoneal and fallopian tube cancer represents a therapeutic challenge as evidenced by the 70 %-80 % recurrence rate. Our understanding of the synergy between surgical cytoreduction and effective systemic chemotherapy continues to evolve, with research supporting maximal cytoreductive effort followed by intraperitoneal chemotherapy. Specifically, analysis of phase III clinical trials has shown a median survival of 110 months in those treated with intraperitoneal chemotherapy, when surgery results in no visible residual disease.

The prognostic significance of pre- and post-treatment CA-125 in grade 1 serous ovarian carcinoma: a gynecologic Oncology Group study.

Objectives: The study objective was to determine the prognostic significance of serum CA-125 levels in patients with grade 1 serous ovarian carcinoma (SOC) enrolled in a Phase III study.

Methods: An ancillary analysis of a phase III study of women with advanced epithelial ovarian cancer treated with carboplatin/paclitaxel versus triplet or sequential doublet regimens. Grade 1 SOC was used as a surrogate for low-grade serous carcinoma.

Pathologic features associated with resolution of complex atypical hyperplasia and grade 1 endometrial adenocarcinoma after progestin therapy.

Objective: To determine the response of complex atypical hyperplasia (CAH) and well differentiated endometrioid adenocarcinoma of the uterus (WDC) to progestin therapy and whether pre-treatment estrogen and progesterone receptor status predicts outcome.

Methods: We performed a retrospective review encompassing women treated with progestin therapy for CAH or WDC at two institutions. Clinicopathologic, treatment, and recurrence data were recorded.

DNA double-strand break repair pathway choice is directed by distinct MRE11 nuclease activities.

MRE11 within the MRE11-RAD50-NBS1 (MRN) complex acts in DNA double-strand break repair (DSBR), detection, and signaling; yet, how its endo- and exonuclease activities regulate DSBR by nonhomologous end-joining (NHEJ) versus homologous recombination (HR) remains enigmatic. Here, we employed structure-based design with a focused chemical library to discover specific MRE11 endo- or exonuclease inhibitors. With these inhibitors, we examined repair pathway choice at DSBs generated in G2 following radiation exposure.

Intratumoral hypoxia as the genesis of genetic instability and clinical prognosis in prostate cancer.

Intratumoral hypoxia is prevalent in many solid tumors and is a marker of poor clinical prognosis in prostate cancer. The presence of hypoxia is associated with increased chromosomal instability, gene amplification, downregulation of DNA damage repair pathways, and altered sensitivity to agents that damage DNA. These genomic changes could also lead to oncogene activation or tumor suppressor gene inactivation during prostate cancer progression.

Current status and recommendations for the future of research, teaching, and testing in the biological sciences of radiation oncology: report of the American Society for Radiation Oncology Cancer Biology/Radiation Biology Task Force, executive summary.

In early 2011, a dialogue was initiated within the Board of Directors (BOD) of the American Society for Radiation Oncology (ASTRO) regarding the future of the basic sciences of the specialty, primarily focused on the current state and potential future direction of basic research within radiation oncology. After consideration of the complexity of the issues involved and the precise nature of the undertaking, in August 2011, the BOD empanelled a Cancer Biology/Radiation Biology Task Force (TF). The TF was charged with developing an accurate snapshot of the current state of basic (preclinical) research in radiation oncology from the perspective of relevance to the modern clinical practice of radiation oncology as well as the education of our trainees and attending physicians in the biological sciences.

HDAC inhibitor confers radiosensitivity to prostate stem-like cells.

Background: Radiotherapy can be an effective treatment for prostate cancer, but radiorecurrent tumours do develop. Considering prostate cancer heterogeneity, we hypothesised that primitive stem-like cells may constitute the radiation-resistant fraction.

Methods: Primary cultures were derived from patients undergoing resection for prostate cancer or benign prostatic hyperplasia.

Tumor hypoxia as a driving force in genetic instability.

Sub-regions of hypoxia exist within all tumors and the presence of intratumoral hypoxia has an adverse impact on patient prognosis. Tumor hypoxia can increase metastatic capacity and lead to resistance to chemotherapy and radiotherapy. Hypoxia also leads to altered transcription and translation of a number of DNA damage response and repair genes.

miRNA-95 mediates radioresistance in tumors by targeting the sphingolipid phosphatase SGPP1.

Radiation resistance poses a major clinical challenge in cancer treatment, but little is known about how microRNA (miR) may regulate this phenomenon. In this study, we used next-generation sequencing to perform an unbiased comparison of miR expression in PC3 prostate cancer cells rendered resistant to fractionated radiation treatment. One miR candidate found to be upregulated by ionizing radiation was miR-95, the enforced expression of which promoted radiation resistance in a variety of cancer cells.

Reprogramming metabolism with metformin improves tumor oxygenation and radiotherapy response.

Purpose: Tumor hypoxia is a negative prognostic factor in multiple cancers, due in part to its role in causing resistance to radiotherapy. Hypoxia arises in tumor regions distal to blood vessels as oxygen is consumed by more proximal tumor cells. Reducing the rate of oxygen consumption is therefore a potential strategy to reduce tumor hypoxia.

Clinical performance of a multivariate index assay for detecting early-stage ovarian cancer.

Objective: We sought to analyze the effectiveness of a multivariate index assay (MIA) in identifying early-stage ovarian malignancy compared to clinical assessment, CA 125-II, and modified American Congress of Obstetricians and Gynecologists (ACOG) guidelines among women undergoing surgery for an adnexal mass.

Study Design: Patients were recruited in 2 related prospective, multi-institutional trials involving 44 sites. All women had preoperative imaging and biomarker analysis.

Racial disparities and patterns of ovarian cancer surgical care in California.

Objective: To investigate disparities in the frequency of ovarian cancer-related surgical procedures and access to high-volume surgical providers among women undergoing initial surgery for ovarian cancer according to race.

Methods: The California Office of Statewide Health Planning and Development database was accessed for women undergoing a surgical procedure that included oophorectomy for a malignant ovarian neoplasm between 1/1/06 and 12/31/10. Multivariate logistic regression analyses were used to evaluate differences in the odds of selected surgical procedures and access to high-volume centers (hospitals ≥ 20 cases/year) according to racial classification.

Survival in women with grade 1 serous ovarian carcinoma.

Objective: To examine clinicopathologic variables associated with survival among women with low-grade (grade 1) serous ovarian carcinoma enrolled in a phase III study.

Methods: This was an ancillary data analysis of Gynecologic Oncology Group protocol 182, a phase III study of women with stage III-IV epithelial ovarian carcinoma treated with carboplatin and paclitaxel compared with triplet or sequential doublet regimens. Women with grade 1 serous carcinoma (a surrogate for low-grade serous disease) were included in the analysis.

Impact of a multivariate index assay on referral patterns for surgical management of an adnexal mass.

Objective: To determine the impact on referral patterns of using a Multivariate Index Assay, CA125, modified-American College of Obstetricians and Gynecologists referral guidelines, and clinical assessment among patients undergoing surgery for an adnexal mass after initial evaluation by nongynecologic oncologists.

Study Design: Overall, 770 patients were enrolled by nongynecologic oncologists from 2 related, multiinstitutional, prospective trials and analyzed retrospectively. All patients had preoperative imaging and biomarker analysis.

TMPRSS2-ERG status is not prognostic following prostate cancer radiotherapy: implications for fusion status and DSB repair.

Background: Preclinical data suggest that TMPRSS2-ERG gene fusions, present in about 50% of prostate cancers, may be a surrogate for DNA repair status and therefore a biomarker for DNA-damaging agents. To test this hypothesis, we examined whether TMPRSS2-ERG status was associated with biochemical failure after clinical induction of DNA damage following image-guided radiotherapy (IGRT).

Methods: Pretreatment biopsies from two cohorts of patients with intermediate-risk prostate cancer [T1/T2, Gleason score (GS) < 8, prostate-specific antigen (PSA) < 20 ng/mL; >7 years follow-up] were analyzed: (i) 126 patients [comparative genomic hybridization (CGH) cohort] with DNA samples assayed by array CGH (aCGH) for the TMPRSS2-ERG fusion; and (ii) 118 patients [immunohistochemical (IHC) cohort] whose biopsy samples were scored within a defined tissue microarray (TMA) immunostained for ERG overexpression (known surrogate for TMPRSS2-ERG fusion).

High tumor interstitial fluid pressure identifies cervical cancer patients with improved survival from radiotherapy plus cisplatin versus radiotherapy alone.

Radiotherapy (RT) with concurrent cisplatin (CRT) is standard treatment for locally advanced cervical cancer. However, not all patients benefit from the addition of cisplatin to RT alone. This study explored the value of pretreatment tumor interstitial fluid pressure (IFP) and hypoxia measurements as predictors of cisplatin response in 291 patients who were treated with RT (1994-1998) or RT plus concurrent cisplatin (1999-2009).

Adherence to treatment guidelines for ovarian cancer as a measure of quality care.

Objectives: To validate National Comprehensive Cancer Network ovarian cancer guideline adherence as a quality process measure associated with improved survival, and to identify structural health care characteristics predictive of adherence to National Comprehensive Cancer Network guideline care.

Methods: Consecutive patients with epithelial ovarian cancer diagnosed between 1 January 1999 and 31 December 2006 were identified from the California Cancer Registry. Adherence to National Comprehensive Cancer Network guideline care was defined by stage-appropriate surgical procedures and recommended chemotherapy.

Survival impact of complete cytoreduction to no gross residual disease for advanced-stage ovarian cancer: a meta-analysis.

Objective: To quantify the impact of complete cytoreduction to no gross residual disease on overall survival among patients with advanced-stage ovarian cancer treated during the platinum-taxane era.

Methods: PubMed and Cochrane Library databases were searched for all articles on primary cytoreductive surgery for advanced-stage ovarian cancer published from 1/1996 to 7/2011. A total of 18 relevant studies (13,257 patients) were identified for analysis.

Disparities in uterine cancer epidemiology, treatment, and survival among African Americans in the United States.

Objective: The objective of this article is to comprehensively review the scientific literature and summarize the available data regarding the outcome disparities of African American women with uterine cancer.

Methods: Literature on disparities in uterine cancer was systematically reviewed using the PubMed search engine. Articles from 1992 to 2012 written in English were reviewed.