The BRCA1/2-directed miRNA signature predicts a good prognosis in ovarian cancer patients with wild-type BRCA1/2

open access

Paclitaxel/carboplatin with or without sorafenib in the first-line treatment of patients with stage III/IV epithelial ovarian cancerry

open access: Paclitaxel/carboplatin with or without sorafenib in the first-line treatment of patients with stage III/IV epithelial ovarian cancer: a randomized phase II study of the Sarah Cannon Research Institute

".....Unfortunately, interpretation of the results is hindered since the trial accrued slowly and was closed after 85 of a planned 120 patients had been randomized. However, comparisons of the efficacy of the two regimens showed no differences in overall response rates, PFS, or overall survival. The PFSs for both groups of  patients (paclitaxel/carboplatin/sorafenib, 15.4 months; paclitaxel/carboplatin, 16.3 months) were similar to those previously reported using standard therapy for advanced ovarian cancer. As anticipated, the patients who received sorafenib had more toxicity. The additional toxicity consisted primarily of well described sorafenib-related toxicity including skin toxicity, hand–foot syndrome, mucositis, and hypertension. The difficulty in tolerating the sorafenib-containing regimen resulted in a high rate of sorafenib dose reductions and discontinuations, and may have had an adverse impact on the efficacy of the regimen..........

 As more evidence accumulates, it is evident that sorafenib is not the angiogenesis inhibitor-of-choice in the treatment of patients with advanced ovarian cancer.

Anti-vascular therapies in ovarian cancer: moving beyond anti-VEGF approaches

Abstract

 Resistance to chemotherapy is among the most important issues in the management of ovarian cancer. Unlike cancer cells, which are heterogeneous as a result of remarkable genetic instability, stromal cells are considered relatively homogeneous. Thus, targeting the tumor microenvironment is an attractive approach for cancer therapy. Arguably, anti-vascular endothelial growth factor (anti-VEGF) therapies hold great promise, but their efficacy has been modest, likely owing to redundant and complementary angiogenic pathways. Components of platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), and other pathways may compensate for VEGF blockade and allow angiogenesis to occur despite anti-VEGF treatment. In addition, hypoxia induced by anti-angiogenesis therapy modifies signaling pathways in tumor and stromal cells, which induces resistance to therapy. Because of tumor cell heterogeneity and angiogenic pathway redundancy, combining cytotoxic and targeted therapies or combining therapies targeting different pathways can potentially overcome resistance. Although targeted therapy is showing promise, much more work is needed to maximize its impact, including the discovery of new targets and identification of individuals most likely to benefit from such therapies.

Contraceptive methods and ovarian cancer risk among Chinese women: A report from the Shanghai women's health study

International Journal of Cancer

Oral contraceptive (OC) use is associated with reduced ovarian cancer risk; however, associations with other contraceptive methods, such as intrauterine device (IUD) and tubal ligation (TL), are less clear. Women in China differ from western women in regard to mechanisms and duration of use of contraception. This study was undertaken to evaluate associations between contraceptive methods and ovarian cancer risk using data from the prospective Shanghai Women's Health Study...... A total of 174 epithelial ovarian cancer cases were found to occur among 70,259 women that were followed for a total of 888,258 person years. The majority of women had ever used any contraception (77.0%), including IUD use (55.6%), OC use (20.4%), TL (14.7%), and contraceptive shots (2.6%). Ever use of any contraception was associated with a non-significant reduction in ovarian cancer risk (HR: 0.86, 95% CI: 0.60-1.24). Longer duration of IUD use was associated with lower ovarian cancer risk (P-value for trend=0.04). Compared to never users, women with durations of IUD use longer than the median (20 years) were 38% less likely to develop ovarian cancer (HR: 0.62, 95% CI: 0.40-0.97). Based on the high prevalence and long duration of IUD use among Chinese women, we estimate a preventive fraction of 9.3%, corresponding to approximately 16 ovarian cancer cases. High prevalence of long-term IUD use may therefore contribute to the low incidence of ovarian cancer observed in China. 

Is it time to curb the charity fear factor?

The Cancer Blog

Validation of Family Cancer History Data in High-Risk Families: The Influence of Cancer Site, Ethnicity, Kinship Degree, and Multiple Family Reporters

abstract

Information on family cancer history (FCH) is often collected for first-degree relatives, but more extensive FCH information is critical for greater accuracy in risk assessment. Using self-reported diagnosis of cancer as the gold standard, we examined differences in the sensitivity and specificity of relative-reported FCH by cancer site, race/ethnicity, language preference, and kinship degree (1,524 individuals from 557 families; average number of relatives per family = 2.7). We evaluated the impact of FCH data collected in 2007-2013 from multiple relatives by comparing mean values and proportions for the number of relatives with any cancer, breast cancer, or ovarian cancer as reported by a single relative and by multiple relatives in the same family. The sensitivity of FCH was lower in Hispanics, Spanish-speaking persons, and third-degree relatives (e.g., for all cancers, sensitivities were 80.7%, 87.4%, and 91.0% for third-, second-, and first-degree relatives, respectively). FCH reported by multiple relatives included a higher number of relatives with cancer than the number reported by a single relative (e.g., mean increase of 1.2 relatives with any cancer), with more relatives diagnosed with any cancer, breast cancer, and ovarian cancer in 52%, 36% and 12% of families, respectively. Collection of FCH data from multiple relatives may provide a more comprehensive picture of FCH and may potentially improve risk assessment and preventive care.

© The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.

Costs and Benefits of Opportunistic Salpingectomy as an Ovarian Cancer Prevention Strategy

abstract

 OBJECTIVE:: 

To conduct a cost-effectiveness analysis of opportunistic salpingectomy (elective salpingectomy at hysterectomy or instead of tubal ligation).

METHODS::

A Markov Monte Carlo simulation model estimated the costs and benefits of opportunistic salpingectomy in a hypothetical cohort of women undergoing hysterectomy for benign gynecologic conditions or surgical sterilization. The primary outcome measure was the incremental cost-effectiveness ratio. Effectiveness was measured in terms of life expectancy gain. Sensitivity analyses accounted for uncertainty around various parameters. Monte Carlo simulation estimated the number of ovarian cancer cases associated with each strategy in the Canadian population.

RESULTS::

Salpingectomy with hysterectomy was less costly ($11,044.32±$1.56) than hysterectomy alone ($11,206.52±$29.81) or with bilateral salpingo-oophorectomy ($12,626.84±$13.11) but more effective at 21.12±0.02 years compared with 21.10±0.03 and 20.94±0.03 years, representing average gains of 1 week and 2 months, respectively. For surgical sterilization, salpingectomy was more costly ($9,719.52±$3.74) than tubal ligation ($9,339.48±$26.74) but more effective at 22.45±0.02 years compared with 22.43±0.02 years (average gain of 1 week) with an incremental cost-effectiveness ratio of $27,278 per year of life gained. Our results were stable over a wide range of costs and risk estimates. Monte Carlo simulation predicted that salpingectomy would reduce ovarian cancer risk by 38.1% (95% confidence interval [CI] 36.5-41.3%) and 29.2% (95% CI 28.0-31.4%) compared with hysterectomy alone or tubal ligation, respectively.

CONCLUSION::

Salpingectomy with hysterectomy for benign conditions will reduce ovarian cancer risk at acceptable cost and is a cost-effective alternative to tubal ligation for sterilization. Opportunistic salpingectomy should be considered for all women undergoing these surgical procedures.

Risk Factors for Early-Occurring and Late-Occurring Incisional Hernias After Primary Laparotomy for Ovarian Cancer

abstract

OBJECTIVE::

To evaluate a cohort of gynecologic oncology patients to discover risk factors for early- and late-occurring incisional hernia after midline incision for ovarian cancer.

METHODS::

We collected retrospective data from patients undergoing primary laparotomy for ovarian cancer at the University of Wisconsin Hospitals and Clinics from 2001 to 2007. Patient characteristics and potential risk factors for hernia formation were noted. Physical examination, abdominal computerized assisted tomography scans, or both were used to detect hernias 1 year after surgery (early hernia) and 2 years after surgery (late hernia).

RESULTS::

There were 265 patients available for the 1-year analysis and 189 patients for the 2-year analysis. Early and late hernia formation occurred in 9.8% (95% confidence interval [CI] 6.2-12%) and an additional 7.9% (95% CI 4.1-12%) of patients, respectively. Using multiple logistic regression, poor nutritional status (albumin less than 3 g/dL) and suboptimal cytoreductive surgery (1 cm or greater residual tumor) were significantly associated with the formation of early incisional hernia after midline incision (P<.001 for both). Late hernia formation was associated only with age 65 years or older (P=.01).

CONCLUSION::

The formation of early incisional hernias after midline incision is associated with poor nutritional status and suboptimal cytoreductive surgery, whereas late hernia formation is associated with advanced age. LEVEL OF EVIDENCE:: II.

Unexpected Gynecologic Malignancy Diagnosed After Hysterectomy Performed for Benign Indications

abstract


 OBJECTIVE:: 

To define the incidence of unexpected gynecologic malignancies among women who underwent hysterectomy for benign indications.

METHODS::

We conducted a data analysis of hysterectomy cases from a quality and safety database maintained by the Michigan Surgical Quality Collaborative, a statewide group of hospitals that voluntarily reports perioperative outcomes. Cases were abstracted from January 1, 2013, through December 8, 2013. Benign preoperative surgical indications included pelvic mass, family history of cancer, hyperplasia without atypia, prolapse, endometriosis, pelvic pain, abnormal uterine bleeding, or leiomyomas. Women with a surgical indication of cancer, cervical dysplasia, or hyperplasia with atypia were excluded.

RESULTS::

During the study period, 7,499 women underwent a hysterectomy and 85.24% (n=6,360) were performed for benign indications. The incidence of unexpected gynecologic malignancy among hysterectomies performed for benign indications was 2.7% (n=172) and included ovarian, peritoneal, and fallopian tube cancer (n=69 [1.08%]), endometrial cancer (n=65 [1.02%]), uterine sarcoma (n=14 [0.22%]), metastatic cancer (n=13 [0.20%]), and cervical cancer (n=11 [0.17%]). The most common indications for hysterectomy were leiomyomas and abnormal uterine bleeding. There was no difference in the mean age (46.86±10.57 compared with 47.0±10.76 years, P=.96) of women with unexpected sarcoma compared with benign disease. Women with unexpected sarcoma were more likely to have a history of venous thromboembolism and preoperative blood transfusion, but this did not reach statistical significance.

CONCLUSION::

The 2.7% incidence of unexpected gynecologic malignancy includes a 0.22% incidence of uterine sarcoma and 1.02% incidence of endometrial cancer. No reliable predictors of uterine sarcoma exist and caution is warranted in preoperative planning for hysterectomy. LEVEL OF EVIDENCE:: II.

Genomic Vision Achieves Major Milestone with Delivery of New High-Throughput Genome Analyzer to Quest Diagnostics

business news

Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis - The Lancet Neurology

The Lancet Neurology

Ovarian Cancer: New Measure of Benefit Proposed - HOPE study

medscape

.....Conditional disease-free survival, however, takes into account changes in the probability of remaining disease-free over time, as well as the amount of time since achieving remission, Dr Diergaarde explained.....

.....Although conditional disease-free survival always increases as the number of years spent in remission increases, certain subgroups in this study experienced larger increases, Alexia Iasonos, PhD, a biostatistician at the Memorial Sloan Kettering Cancer Center in New York City, pointed out in an accompanying podcast.

Mammary and rectal metastases from an ovarian cancer: report of two cases and review of literature

article: open access

See referee responses

 Conclusion

To our knowledge, this is the first case reported in literature that describes both rectal- and breast metastases mimicking an inflammatory breast cancer, that derived from a serous papillary ovarian cancer. Our second case illustrates the role of PET-CT in detecting subclinical metastases, which leads to an increase in the diagnosis of uncommon sites of secondary dissemination of ovarian cancer. The differential diagnosis between a primary and a secondary breast cancer is crucial to provide the appropriate treatment. Unfortunately, the occurrence of breast metastases in an ovarian carcinoma is linked to an extensive disease and a poor prognosis.

Role of the folate receptor in ovarian cancer treatment: evidence, mechanism, and clinical implications

abstract

Folate can be transported into the cell by the reduced folate carrier (RFC), the proton-coupled folate transporter (PCFT), or the folate receptor (FR), of which various isoforms exist. While the RFC and PCFT are expressed by many normal cells, the FR is present only in a small proportion of normal tissues. In these tissues, the FR expression level is often low and restricted to the apical surface of polarized epithelial cells. In contrast, FR is expressed on the blood-accessible basal and lateral membranes of many types of epithelial cancer. Considering that FR is expressed in few nonmalignant cell types on luminal membranes generally not accessible for molecules transported in the blood, FR is considered a promising antitumor target. As FR expression seems associated with tumor progression and prognosis, anticancer therapies targeting FR are currently being developed, such as farletuzumab (Morphotek, Exton, PA, USA), IMGN853 (ImmunoGen, Waltham, MA, USA), vintafolide, and EC1456 (both Endocyte Inc., West Lafayette, IN, USA). FR expression could be used as a response-predictive biomarker for these treatments. The ability to identify patients and treat them with an effective therapy based on the known expression of the tumor marker would, indeed, be the next step in predictive medicine for these patients. This review summarizes the role of FR in ovarian cancer and the value of FR as a prognostic biomarker for ovarian cancer and a response-predictive biomarker for folate-targeted therapeutics.

Adnexal Mass in the Postmenopausal Patient

Abstract

The adnexal mass in a postmenopausal patient poses an important diagnostic and management dilemma for primary care providers and gynecologists. Postmenopausal women are at a significantly increased risk of gynecologic malignancy; yet even in this population the majority of adnexal masses are benign. Evaluation and management of these lesions centers on the identification of malignancy, especially ovarian cancer, while avoiding unnecessary intervention in patients with benign lesions. Tumor markers and imaging can help in the evaluation of adnexal mass in postmenopausal women. Transvaginal ultrasound has long been considered the imaging modality of choice for the evaluation of adnexal masses. Particularly in the setting of high frequency utilization of transvaginal probes, which project high quality images allowing for detailed descriptions of the macroscopic appearance of the mass, and remains the least expensive of all imaging modalities currently available. For adnexal masses that are highly suspicious for cancer, women should be referred a gynecologic oncologist and facility for optimal care.

The Prognostic Role of Optimal Cytoreduction in Advanced, Bowel Infiltrating Ovarian Cancer

abstract

Aim: In locally advanced ovarian cancer with bowel involvement appropriate surgical treatment is still controversial.

Objective was to delineate factors to select those most likely to benefit from radical surgery in patients with locally advanced ovarian cancer.

Methods: Therefore, we retrospectively evaluated 207 consecutive patients with primary stage IIB-IV ovarian cancer who underwent primary surgery between 2000 and 2007. Every patient received stage-related surgery and adjuvant platinum-based chemotherapy. Median follow-up was 53.5 months. Data collected included stage, histology, extent of cytoreduction and type of bowel resection. Univariate survival analyses were performed to investigate variables associated with outcome.

Results: Optimal cytoreduction (OCR) (R ≤ 1 cm) was achieved in 76.8%. Most patients presented histologic grade 2/3 (96.6%), serous ovarian cancers (84.1%) and lymph node involvement (52.2%). Complete cytoreduction (R = 0 mm) has significant best prognostic impact in FIGO IIB-IV (p = .026).

Regarding bowel involvement, bowel resection was performed in 82 patients (39.6%). In this subgroup of patients complete cytoreduction led to significant better overall survival than R > 0 mm-1 cm, even in FIGO IIIC-IV patients (p = .027); this fact is independent of bowel resection. Noticeably, for survival bowel resection achieving residual tumor mass below 1 cm was also one main prognostic factor and even recurrence rate was associated with residual tumor mass.

Conclusion: Our findings suggest that the major prognostic factor in patients with advanced ovarian cancer needing colorectal resection is completeness of cytoreduction. Therefore, in advanced ovarian cancer patients, multivisceral surgery is indicated to achieve OCR (R ≤ 1 cm) with or without bowel resection with best prognostic impact.

Breast and ovarian cancer survivors' experience of participating in a cognitive-existential group intervention addressing fear of cancer recurrence

abstract

 PURPOSE: 

Currently, very few clinical approaches are offered to cancer survivors dealing with fear of cancer recurrence (FCR). This paper provides an overview of cancer survivors' experience and satisfaction after taking part in a six-week, cognitive-existential (CE) group intervention that aimed to address FCR.

METHOD:

In this qualitative descriptive study, 12 women with breast or ovarian cancer provided in-depth interviews of their experience in taking part in the CE group intervention.

RESULTS:

Analysis of their accounts revealed struggles to face their fears. Yet, by embracing their group experience, the women learned how to confront their fears and gain emotional control. The women reported that the group work was highly valuable.

CONCLUSION:

From the women's analysed accounts, the authors have proposed recommendations for changes to the group work process before moving the study to a full clinical trial. The study's findings also provide valuable insights to other cancer survivor groups who may also be experiencing FCR.

Endogenous estrogens and the risk of breast, endometrial, and ovarian cancersI

abstract

Data from laboratory and epidemiologic studies support a relationship between endogenous hormones and the increased risk of several female cancers. In epidemiologic studies, consistent associations have been observed between risk of breast, ovarian and endometrial cancers and reproductive and hormonal risk factors such as high postmenopausal body mass index (BMI) and postmenopausal hormone use, which suggest the importance of endogenous hormones in the etiology of these diseases. The relationship between circulating estrogen levels in postmenopausal women and the risk of breast cancer is well established, with an approximately 2-fold higher risk among women in the top 20-25% (versus bottom 20-25%) of levels. However, data evaluating the relationship between endogenous estrogens and premenopausal breast cancer risk are more limited and less consistent. Two studies to date have evaluated the relationship between circulating estrogens and breast cancer risk by menstrual cycle phase at blood collection and only one study has examined this relationship by menopausal status at diagnosis. Three prospective studies have evaluated circulating estrogen levels and endometrial cancer risk in postmenopausal women, with consistent strong positive associations reported (with relative risks of 2-4 comparing high versus low hormone levels), while this relationship has not been studied in premenopausal women. Compared to breast and endometrial cancers, reproductive and hormonal characteristics such as postmenopausal hormone use are generally weaker and less consistent risk factors for ovarian cancer, and the only small prospective study conducted to date indicated a non-significant positive relationship between circulating estrogen levels and ovarian cancer risk. In this review, we summarize current evidence and identify key areas to be addressed in future epidemiologic studies of endogenous estrogens and the risk of breast, endometrial, and ovarian cancers.

Evaluation of the Effectiveness of a Surgical Checklist in in Medicare patients (Michigan/Ontario)

abstract

Background:
Surgical checklists are increasingly used to improve compliance with evidence-based processes in the perioperative period. Although enthusiasm exists for using checklists to improve outcomes, recent studies have questioned their effectiveness in large populations.

Objective:
We sought to examine the association of Keystone Surgery, a statewide implementation of an evidence-based checklist and Comprehensive Unit–based Safety Program, on surgical outcomes and health care costs.

Methods:
We performed a study using national Medicare claims data for patients undergoing general and vascular surgery (n=1,002,241) from 2006 to 2011. A difference-in-differences approach was used to evaluate whether implementation was associated with improved surgical outcomes and decreased costs when compared with a national cohort of nonparticipating hospitals. Propensity score matching was used to select 10 control hospitals for each participating hospital. Costs were assessed using price-standardized 30-day Medicare payments for acute hospitalizations, readmissions, and high-cost outliers.

Results:
Keystone Surgery implementation in participating centers (N=95 hospitals) was not associated with improved outcomes. Difference-in-differences analysis accounting for trends in nonparticipating hospitals (N=950 hospitals) revealed no differences in adjusted rates of 30-day mortality [relative risk (RR)=1.03; 95% confidence intervals (CI), 0.97–1.10], any complication (RR=1.03; 95% CI, 0.99–1.07), reoperations (RR=0.89; 95% CI, 0.56–1.22), or readmissions (RR=1.01; 95% CI, 0.97–1.05). Medicare payments for the index admission increased following implementation ($516 average increase in payments; 95% CI, $210–$823 increase), as did readmission payments ($564 increase; 95% CI, $89–$1040 increase). High-outlier payments ($965 increase; 95% CI, $974decrease to $2904 increase) did not change.

Conclusions:
Implementation of Keystone Surgery in Michigan was not associated with improved outcomes or decreased costs in Medicare patients.

BMJ Blogs: Richard Smith: Dying of cancer is the best death (readers' comments included

 Note: this certainly garned much in the way of responses

BMJ Blogs

Non-Steroidal Anti-Inflammatory Drugs Use Is Associated with Reduced Risk of Inflammation-Associated Cancers: NIH-AARP Study

open access

.....Non-steroidal anti-inflammatory drug (NSAID) use, especially of aspirin, has been linked to reduced risk of cancers in several, [5]–[8] but not all [5]–[11] observational studies. Data from clinical trials of NSAIDs have shown that NSAID use can lower ovarian and colorectal cancer risk [12]–[15]. However, the role of NSAID use in less common cancers is unclear due to the small numbers of these cancers in previous studies. In addition, cancers that have inflammation-related causes in common have not been jointly evaluated. Evaluating these cancers as a group could help eliminate some of the uncertainty from previous studies and elucidate the role of NSAIDs in inflammation-related cancers.....

Conclusions

After accounting for potential selection bias, our data showed an inverse association between NSAID use and alcohol-related, infection-related, obesity-related, and smoking-related cancers and support the hypothesis that inflammation is related to an increased risk of certain cancers.

All in the Family: Barriers and Motivators to the Use of Cancer Family History Questionnaires and the Impact on Attendance Rates

Abstract

Data has demonstrated that family history questionnaires (FHQs) are an invaluable tool for assessing familial cancer risk and triaging patients for genetic counseling services. Despite their benefits, return rates of mailed FHQs from newly referred patients remain low, suggesting potential barriers to their use. To investigate this, a total of 461 participants, 239 who completed a FHQ (responders) and 222 who did not (non-responders), were surveyed at a subsequent appointment regarding potential barriers and motivators to using the FHQ. With respective rates of 51 and 56 %, there was no significant difference in the proportion of responders and non-responders who reported difficulty in completing the FHQ; however, for both groups factors related to family dynamics (large family size, lack of contact with relatives, and lack of knowledge of family history) were reported as major variables confounding completion of the FHQ. Responders were also significantly more likely to have a personal diagnosis of cancer (p = 0.02) and to report that their physician had discussed the reason for the appointment with them (p = 0.01). Overall, 19 % of non-responders returned their FHQ after being mailed an appointment letter and 67 % attended their scheduled genetic counseling appointment. These findings demonstrate that difficulty completing the FHQ is not inherent to its design but due to difficulty accessing one's family history, and that mailed appointment letters are a highly successful way to increase attendance rates in the non-responder population. Furthermore, these results demonstrate the important role that referring physicians play in the utilization of genetic counseling services.

HE4 as biomarker for the differentiation between epithelial ovarian cancer and ovarian metastases of gastrointestinal origin

abstract

OBJECTIVE:

About 5-15% of all malignant ovarian tumors are metastases from other malignancies such as gastrointestinal tumors, breast cancer or melanoma. Also other gynecological tumors can metastasize to the ovaries. It is crucial to differentiate between primary epithelial ovarian cancer (EOC) and ovarian metastases because different treatment is required. The clinical value of Human Epididymal secretory protein 4 (HE4) as a serum biomarker in primary ovarian cancer has been established. The use of HE4 in the differentiation between primary ovarian cancer and ovarian metastases from other malignancies has never been investigated.

METHODS:

HE4, CA125 and CEA were measured in 192 patients with EOC (n=147) or ovarian metastases (n=40). Univariate and multivariate logistic regression analyses were done. Sensitivity, specificity and area under the curve (AUC) were calculated for all markers and ratios hereof using receiver operating characteristics methodology.

RESULTS:

Median serum HE4 concentration was significantly higher in patients with EOC compared to patients with ovarian metastases (431 pmol/L vs 68 pmol/L, p<0.001). HE4 and CEA were independent factors in differentiating between EOC and ovarian metastases (both p<0.001) while CA125 was not (p=0.33). The HE4^2.5/CEA ratio demonstrated the highest discriminative value (ROC-AUC 0.94) compared to HE4, CEA, CA125 or CA125/CEA ratio (0.88, 0.78, 0.80 and 0.89 respectively) and showed a specificity of 82.5% at set sensitivity of 90% in discriminating EOC from ovarian metastases.

CONCLUSION:

HE4 can be used in combination with CEA to make the distinction between EOC and ovarian metastases from gastrointestinal origin.

Surgical staging and prognosis in serous borderline ovarian tumours (BOT): A subanalysis of the AGO ROBOT study : British Journal of Cancer

Abstract

Background:

Incomplete surgical staging is a negative prognostic factor for patients with borderline ovarian tumours (BOT). However, little is known about the prognostic impact of each individual staging procedure.

Methods:

Clinical parameters of 950 patients with BOT (confirmed by central reference pathology) treated between 1998 and 2008 at 24 German AGO centres were analysed. In 559 patients with serous BOT and adequate ovarian surgery, further recommended staging procedures (omentectomy, peritoneal biopsies, cytology) were evaluated applying Cox regression models with respect to progression-free survival (PFS).

Results:

For patients with one missing staging procedure, the hazard ratio (HR) for recurrence was 1.25 (95%-CI 0.66–2.39; P=0.497). This risk increased with each additional procedure skipped reaching statistical significance in case of two (HR 1.95; 95%-CI 1.06–3.58; P=0.031) and three missing steps (HR 2.37; 95%-CI 1.22–4.64; P=0.011). The most crucial procedure was omentectomy which retained a statistically significant impact on PFS in multiple analysis (HR 1.91; 95%-CI 1.15–3.19; P=0.013) adjusting for previously established prognostic factors as FIGO stage, tumour residuals, and fertility preservation.

Conclusion:

Individual surgical staging procedures contribute to the prognosis for patients with serous BOT. In this analysis, recurrence risk increased with each skipped surgical step. This should be considered when re-staging procedures following incomplete primary surgery are discussed.

It is not all about BRCA: Cullin-Ring ubiquitin Ligases in ovarian cancer

British Journal of Cancer - open access (technical)

Mutations in the BRCA1 and BRCA2 genes predispose individuals to the development of breast and ovarian cancers. As a result, biochemical functions of BRCA1 and BRCA2 proteins are being characterised in great detail. These studies have prompted the use of PARP inhibitors to treat BRCA1 and BRCA2-deficient ovarian cancers. This example of synthetic lethality represents a conceptual progress made recently in the approach to cancer treatment and is being currently tested in multiple clinical trials. Other than BRCA1 and BRCA2, many other factors might influence the survival of ovarian cancer patients. Currently, ovarian cancer remains the fifth most common cancer in the United Kingdom among women. Recent evidence suggests benefit in the modulation of the ubiquitin-proteasome system for the treatment of ovarian cancer. In this manuscript, we review the role of Cullin-Ring ubiquitin Ligases (CRLs) in the pathogenesis of ovarian cancer and their potential therapeutic exploitation. CRLs comprise a large family of proteins that, like kinases, might represent ideal candidates for targeted therapy and provide a large repertoire for the development of new anti-cancer compounds......

" An accumulating body of evidence suggests strongly that multiple genetic aberrations work independently or together to confer survival ability to cancer cells. In summary, it is only the combination of functional studies and genomic signatures that will allow us to make progress in ovarian cancer treatment. In the future, we will need to learn how diverse pathways interact and integrate them in order to predict the development of drug resistance by cancer cells."

Consumer guide to hospice - Washington Post

Washington Post

'Hospices vary widely in ways that can affect patient care.

The Washington Post has gathered data largely from government sources on more than 3,000 hospices that participate in Medicare, which pays for the vast majority of hospice care in this country. No single factor can predict the quality of a hospice’s care, and these figures do not offer a complete picture of any single hospice. But consumers can benefit from knowing how a hospice compares to others on these important measures......

Select a state below to explore its hospices or read on to learn more about a hospice's important traits.

See Post coverage about hospices.  |  Click here to learn how to use this guide.

Contraception May Reduce BRCA-Associated Ovarian Cancers

Cancer Network

Next-Generation Sequencing of the BRCA1 and BRCA2 Genes for the Genetic Diagnostics of Hereditary Breast and/or Ovarian Cancer

abstract

Genetic testing for hereditary breast and/or ovarian cancer mostly relies on laborious molecular tools that use Sanger sequencing to scan for mutations in the BRCA1 and BRCA2 genes. We explored a more efficient genetic screening strategy based on next-generation sequencing of the BRCA1 and BRCA2 genes in 210 hereditary breast and/or ovarian cancer patients. We first validated this approach in a cohort of 115 samples with previously known BRCA1 and BRCA2 mutations and polymorphisms. Genomic DNA was amplified using the Ion AmpliSeq BRCA1 and BRCA2 panel. The DNA Libraries were pooled, barcoded, and sequenced using an Ion Torrent personal genome machine sequencer. The combination of different robust bioinformatics tools allowed detection of all previously known pathogenic mutations and polymorphisms in the 115 samples, without detecting spurious pathogenic calls. We then used the same assay in a discovery cohort of 95 uncharacterized hereditary breast and/or ovarian cancer patients for BRCA1 and BRCA2. In addition, we describe the allelic frequencies across 210 hereditary breast and/or ovarian cancer patients of 74 unique definitely and likely pathogenic and uncertain BRCA1 and BRCA2 variants, some of which have not been previously annotated in the public databases. Targeted next-generation sequencing is ready to substitute classic molecular methods to perform genetic testing on the BRCA1 and BRCA2 genes and provides a greater opportunity for more comprehensive testing of at-risk patients.

Precision Medicine Meets Public Health: Population Screening for BRCA1 and BRCA2

(requires paid subscription to view in full)  BRCA1 and BRCA2

7th Asian Oncology Summit and 11th Annual Conference of the Organisation for Oncology and Translational Research

conference notice

 Last chance to submit abstracts: January 9, 2015

Please remember to submit abstracts for the 2015 Asian Oncology Summit (AOS) ‘Cause and effect: aetiology and medicine working together to improve health’ by Friday, January 9, 2015.

Abstracts are invited for short oral contributions and poster presentations alongside the invited lectures on the following topics.

• Prevention
  
• Palliative care
  
• Gastrointestinal cancer
  
• Breast cancer
  
• Genitourinary cancer
  
• Lung cancer
  
• Translational oncology
  
• Haematological oncology
  
• Supportive oncology
  
• Melanoma
  
• Sarcoma
  
• Head and neck cancer
  
• Health economics
  
• Radiation oncology
  
• Gynaecological cancer
  
• Pharmacoeconomics
  
• Health-care delivery
  
• Molecular pathology
  
• Endocrine late effects of cancer

End of cancer-genome project prompts rethink

Scientific American

"... On December 2, Staudt announced that once TCGA is completed, the NCI will continue to intensively sequence tumours in three cancers: ovarian, colorectal and lung adenocarcinoma. It then plans to evaluate the fruits of this extra effort before deciding whether to add back more cancers....

Don’t blame the flu for ER congestion

The Globe and Mail

".... We are told, in public service announcements from health regions, in press releases from hospitals and in newspaper headlines, that the flu is to blame.
That’s B.S.
Our emergency rooms are overflowing because of bad planning and misplaced priorities........

TIME: Most Cancer Is Beyond Your Control

 Note: it is very unfortunate that the original research paper is NOT open access; includes comments on ovarian and other cancers eg. colon, brain etc...

TIME

Commentary: The bad luck of cancer

The bad luck of cancer (requires subscription for full access)

Biomedicine

The bad luck of cancer

"Bert Vogelstein and Cristian Tomasetti of Johns Hopkins University have put forth a mathematical analysis of the genesis of cancer that suggests many cases are not preventable.

Hopkins Medicine: Bad Luck of Random Mutations Plays Predominant Role in Cancer, Study Shows - 01/01/2015

Hopkinsmedicine

Release Date: January 1, 2015

Scientists from the Johns Hopkins Kimmel Cancer Center have created a statistical model that measures the proportion of cancer incidence, across many tissue types, caused mainly by random mutations that occur when stem cells divide. By their measure, two-thirds of adult cancer incidence across tissues can be explained primarily by “bad luck,” when these random mutations occur in genes that can drive cancer growth, while the remaining third are due to environmental factors and inherited genes.

“All cancers are caused by a combination of bad luck, the environment and heredity, and we’ve created a model that may help quantify how much of these three factors contribute to cancer development,” says Bert Vogelstein, M.D., the Clayton Professor of Oncology at the Johns Hopkins University School of Medicine, co-director of the Ludwig Center at Johns Hopkins and an investigator at the Howard Hughes Medical Institute.

“Cancer-free longevity in people exposed to cancer-causing agents, such as tobacco, is often attributed to their ‘good genes,’ but the truth is that most of them simply had good luck,” adds Vogelstein, who cautions that poor lifestyles can add to the bad luck factor in the development of cancer.

The implications of their model range from altering public perception about cancer risk factors to the funding of cancer research, they say. “If two-thirds of cancer incidence across tissues is explained by random DNA mutations that occur when stem cells divide, then changing our lifestyle and habits will be a huge help in preventing certain cancers, but this may not be as effective for a variety of others,” says biomathematician Cristian Tomasetti, Ph.D., an assistant professor of oncology at the Johns Hopkins University School of Medicine and Bloomberg School of Public Health. “We should focus more resources on finding ways to detect such cancers at early, curable stages,” he adds.

In a report on the statistical findings, published Jan. 2 in Science, Tomasetti and Vogelstein say they came to their conclusions by searching the scientific literature for information on the cumulative total number of divisions of stem cells among 31 tissue types during an average individual’s lifetime. Stem cells “self-renew,” thus repopulating cells that die off in a specific organ.

It was well-known, Vogelstein notes, that cancer arises when tissue-specific stem cells make random mistakes, or mutations, when one chemical letter in DNA is incorrectly swapped for another during the replication process in cell division. The more these mutations accumulate, the higher the risk that cells will grow unchecked, a hallmark of cancer. The actual contribution of these random mistakes to cancer incidence, in comparison to the contribution of hereditary or environmental factors, was not previously known, says Vogelstein.

To sort out the role of such random mutations in cancer risk, the Johns Hopkins scientists charted the number of stem cell divisions in 31 tissues and compared these rates with the lifetime risks of cancer in the same tissues among Americans. From this so-called data scatterplot, Tomasetti and Vogelstein determined the correlation between the total number of stem cell divisions and cancer risk to be 0.804. Mathematically, the closer this value is to one, the more stem cell divisions and cancer risk are correlated.

“Our study shows, in general, that a change in the number of stem cell divisions in a tissue type is highly correlated with a change in the incidence of cancer in that same tissue,” says Vogelstein. One example, he says, is in colon tissue, which undergoes four times more stem cell divisions than small intestine tissue in humans. Likewise, colon cancer is much more prevalent than small intestinal cancer.

“You could argue that the colon is exposed to more environmental factors than the small intestine, which increases the potential rate of acquired mutations,” says Tomasetti. However, the scientists saw the opposite finding in mouse colons, which had a lower number of stem cell divisions than in their small intestines, and, in mice, cancer incidence is lower in the colon than in the small intestine. They say this supports the key role of the total number of stem cell divisions in the development of cancer.

Using statistical theory, the pair calculated how much of the variation in cancer risk can be explained by the number of stem cell divisions, which is 0.804 squared, or, in percentage form, approximately 65 percent.

Finally, the research duo classified the types of cancers they studied into two groups. They statistically calculated which cancer types had an incidence predicted by the number of stem cell divisions and which had higher incidence. They found that 22 cancer types could be largely explained by the “bad luck” factor of random DNA mutations during cell division. The other nine cancer types had incidences higher than predicted by "bad luck" and were presumably due to a combination of bad luck plus environmental or inherited factors.

   

“We found that the types of cancer that had higher risk than predicted by the number of stem cell divisions were precisely the ones you’d expect, including lung cancer, which is linked to smoking; skin cancer, linked to sun exposure; and forms of cancers associated with hereditary syndromes,” says Vogelstein.

“This study shows that you can add to your risk of getting cancers by smoking or other poor lifestyle factors. However, many forms of cancer are due largely to the bad luck of acquiring a mutation in a cancer driver gene regardless of lifestyle and heredity factors. The best way to eradicate these cancers will be through early detection, when they are still curable by surgery,” adds Vogelstein.

The scientists note that some cancers, such as breast and prostate cancer, were not included in the report because of their inability to find reliable stem cell division rates in the scientific literature. They hope that other scientists will help refine their statistical model by finding more precise stem cell division rates.

The research was funded by the Virginia and D. K. Ludwig Fund for Cancer Research, the Lustgarten Foundation for Pancreatic Cancer Research, the Sol Goldman Pancreatic Cancer Research Center, and the National Institutes of Health’s National Cancer Institute (grants P30-CA006973, R37-CA43460, RO1-CA57345 and P50-CA62924).

###

On the Web:

• Read the study in Science: DOI: 10.1126/science.1260825

revised: The simple math that explains why you may (or may not) get cancer

 Abstract 

Abstract
 
Some tissue types give rise to human cancers millions of times more often than other tissue types. Although this has been recognized for more than a century, it has never been explained. Here, we show that the lifetime risk of cancers of many different types is strongly correlated (0.81) with the total number of divisions of the normal self-renewing cells maintaining that tissue’s homeostasis. These results suggest that only a third of the variation in cancer risk among tissues is attributable to environmental factors or inherited predispositions. The majority is due to “bad luck,” that is, random mutations arising during DNA replication in normal, noncancerous stem cells. This is important not only for understanding the disease but also for designing strategies to limit the mortality it causes.

Editor's Summary

Crunching the numbers to explain cancer

Why do some tissues give rise to cancer in humans a million times more frequently than others? Tomasetti and Vogelstein conclude that these differences can be explained by the number of stem cell divisions. By plotting the lifetime incidence of various cancers against the estimated number of normal stem cell divisions in the corresponding tissues over a lifetime, they found a strong correlation extending over five orders of magnitude. This suggests that random errors occurring during DNA replication in normal stem cells are a major contributing factor in cancer development. Remarkably, this “bad luck” component explains a far greater number of cancers than do hereditary and environmental factors.

Science/AAAS | News

"...For Vogelstein, one major message is that cancer often cannot be prevented, and more resources should be funneled into catching it in its infancy. “These cancers are going to keep on coming,” he says.
Douglas Lowy, a deputy director of the National Cancer Institute in Bethesda, Maryland, agrees, but also stresses that a great deal of “cancer is preventable” and efforts to avert the disease must continue.
Although the randomness of cancer might be frightening, those in the field see a positive side, too. The new framework stresses that “the average cancer patient … is just unlucky,” Clevers says. “It helps cancer patients to know” that the disease is not their fault."
 

Professional risk factors associated with the cancer of the ovary.Literature review. (asbestos)

abstract

 The aim of this work was to review the available literature on occupational risk factors associated with ovarian cancer. A PubMed search was performed using an algorithm with the following search terms: ovary, ovarian, exposure, work, occupation. Relevant articles were selected through assessment of titles and abstracts as well as through the reference lists of related articles. A total of 54 studies were selected for this review, including 17 studies on asbestos exposure and risk of ovarian cancer and, 16 studies on other occupational factors (5 cohort studies and 11 case control studies). An increased risk of ovarian cancer has been reported for several occupations (teachers, administration employees, nurses, religious workers) and various industrial sectors (biomedical research, telephony industry, hairdresser and beautician, printing factories) with inconsistent results. Moreover, in many of these studies, individual risk factors of ovarian cancers were not considered. Despite methodological limitations of published studies, a significantly increased risk for ovarian cancer associated with asbestos exposure have been consistently reported.

A systematic review of the incidence and prevalence of cancer in multiple sclerosis

Abstract

BACKGROUND:

Studies of cancer incidence and prevalence in multiple sclerosis (MS) have produced conflicting results.

OBJECTIVE:

To estimate the incidence and prevalence of cancer in persons with MS and review the quality of included studies.

RESULTS:

We identified 38 studies. Estimates for incidence and prevalence varied substantially for most cancers. In population-based studies, cervical, breast, and digestive cancers had the highest incidence. The risk of meningiomas and urinary system cancers appeared higher than expected, while the risks of pancreatic, ovarian, prostate and testicular cancer were lower than expected.

Conclusion: The complexity of understanding cancer risk in MS is augmented by inconsistencies in study design, and the relative paucity of age, sex and ethnicity-specific risk estimates from which the strong impact of age on the incidence of cancers can be assessed.

Genetic counseling content: How does it impact health behavior? - PubMed - NCBI

Note: abstract provides no reference to Lynch Syndrome

abstract

 Women with hereditary breast-ovarian cancer face decisions about screening (transvaginal ultrasound, CA125, mammography, breast exams) and proactive (before cancer) or reactive (after cancer) surgery (oophorectomy, mastectomy). The content of genetic counseling and its relation to these key health behaviors is largely unexamined. Ashkenazi Jewish women (n = 78) were surveyed through the process of genetic testing and had audiorecorded counseling sessions available for Linguistic Inquiry and Word Count analysis. Proportions for participant and counselor cognitive and affective content during sessions were used as primary predictor variables in linear mixed models for change in intentions for screening and treatment and in self-reported screening. Cognitive and affective content were important predictors of behavior. Counselor cognitive content was associated with ovarian screening. An interaction effect also emerged for CA-125, such that counselor cognitive content plus participant cognitive content or counselor affective content were associated with more screening. Teasing out the factors in risk communication that impact decision-making are critical, and affect from a risk communicator can spur action, such as cancer screening.

Systematic evaluation of bevacizumab in recurrent ovarian cancer treatment

abstract

Purpose: This study aimed to evaluate the efficacy and safety of bevacizumab in the treatment of recurrent ovarian cancer.

Methods: The Cochrane Library, MEDLINE, and EMBASE were searched. Data regarding the use of bevacizumab in recurrent ovarian cancer were collected from randomized controlled trials (RCTs). Data were evaluated with the Cochrane systematic method, and statistical analysis was performed with the RevMan 5.2 software. Two RCTs comprising a total of 845 patients were included.

Results: Bevacizumab combined with conventional chemotherapy prolonged the progression-free survival (PFS) (hazard ratio [HR] 0.48; 95% confidence interval [CI], 0.41-0.56), without significantly altering the overall survival (OS) (HR 1.03; 95% CI 0.79-1.33). Adverse events (NCI-CTCAE v.4.0) associated with bevacizumab were ≥ grade 3 hypertension (relative risk [RR] 2.30; 95% CI 1.39-3.83) and bleeding (RR 4.76; 95% CI 1.38-16.37).

Conclusions: Bevacizumab prolonged the PFS of patients with recurrent ovarian cancer. Additional high-quality randomized controlled trials are needed to verify these results.

NICE publish draft guidance, reducing access to ovarian cancer drugs

UK

Low-dose aspirin use and the risk of ovarian cancer in Denmark

abstract

Background A comprehensive body of evidence has shown that aspirin has cancer-preventive effects, particularly against gastrointestinal cancer, but its effects on the risk of ovarian cancer are less well established. This nationwide case-control study examined the association between low-dose aspirin and the risk of ovarian cancer. 

Patients and methods We identified all patients in the Danish Cancer Registry aged 30–84 years old with a histologically verified first diagnosis of epithelial ovarian cancer during 2000–2011. Each patient was sex- and age-matched to 15 population controls using risk-set sampling. Prescription use, comorbidity, reproductive history and demographic characteristics data were obtained from nationwide registries. Use of low-dose (75–150 mg) aspirin was defined according to dose and duration and consistency of use. Conditional logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for the association between low-dose aspirin use and the risk of epithelial ovarian cancer, both overall and for specific histological types. 

Results For 4,103 ovarian cancer cases and 58,706 population controls, the adjusted OR for epithelial ovarian cancer associated with ever use (≥2 prescriptions) of low-dose aspirin was 0.94 (95% CI: 0.85–1.05). ORs for epithelial ovarian cancer were lower with the use of 150 mg aspirin tablets (OR=0.82; 95% CI: 0.68–0.99) and with long-term use (≥5 years) of low-dose aspirin (OR=0.77; 95% CI: 0.55–1.08). Continuous long-term use of low-dose aspirin, defined as close consecutive prescriptions, was associated with a further reduction in OR (0.56; 95% CI: 0.32–0.97). For histological types of epithelial ovarian cancer, the strongest inverse associations with low-dose aspirin use were seen for mucinous and endometrioid tumours. 

Conclusion This nationwide case-control study indicates that low-dose aspirin use may be associated with reduced risk of epithelial ovarian cancer.

Short-Term Risk of Colorectal Cancer in Individuals With Lynch Syndrome: A Meta-Analysis

abstract

Purpose For carriers of germline mutations in DNA mismatch repair genes, the most relevant statistic for cancer prevention is colorectal cancer (Lynch syndrome) risk, particularly in the short term.

Clearer Picture of PMS2-Associated Lynch Syndrome Is Emerging

Commentary/link to original article - JCO

Primary peritoneal carcinoma after prophylactic oophorectomy in women with a family history of ovarian cancer - Cancer Genetics and Epigenetics

open access

Background According to previous reports, primary peritoneal carcinoma indistinguishable from primary ovarian adenocarcinoma had developed in five women with a history of familial ovarian cancer who had undergone prophylactic oophorectomy.

Methods The records from the Gilda Radner Familial Ovarian Cancer Registry were reviewed for instances of prophylactic oophorectomy and cases of primary peritoneal carcinoma occurring after prophylactic oophorectomy.

Results From 2011 through July 2012, the Gilda Radner Familial Ovarian Cancer Registry accessioned 931 families (a total of 2221 cases of familial ovarian cancer). Currently, 324 women in these families have undergone prophylactic oophorectomy as a preventive measure against the subsequent development of ovarian cancer. Primary peritoneal carcinoma indistinguishable histologically from primary ovarian adenocarcinoma has developed in six of these women 1-27 years after prophylactic oophorectomy.

Conclusions Based on this finding and other reports of such primary peritoneal carcinoma, a prospective international study is planned. This study will compare the incidence of peritoneal carcinoma in first- or second-degree relatives who underwent prophylactic oophorectomy because of a family history of ovarian cancer with that of those who did not undergo prophylactic oophorectomy.

The complete article is available as a Provisional PDF if requested. The fully formatted PDF and HTML versions are in production.

Neurotoxicity Research (journal homepage)

pay-per-view journal (abstracts available)

Neurotoxicity in Ovarian Cancer Patients on GOG 218

abstract

Neurotoxicity in Ovarian Cancer Patients on Gynecologic Oncology Group (GOG) Protocol 218: Characteristics Associated with Toxicity and the Effect of Substitution with Docetaxel: An NRG Oncology/Gynecologic Oncology Group study.

OBJECTIVES:

To describe characteristics associated with neurotoxicity (NT) in advanced ovarian cancer patients treated on Gynecologic Oncology Group 218 and examine effect of substituting docetaxel for paclitaxel in these patients.

METHODS:

The development of NT was defined as Common Toxicity Criteria grade (G) ≥1. The association between substitution with docetaxel and NT improvement was explored with generalized estimating equations adjusting for treatment cycle and NT grading at previous cycle.

RESULTS:

Of 1,864 evaluable patients, 1,329 (71%) developed G≥1 NT during the study. Nearly half appeared within the first two cycles of chemotherapy, with 31% experiencing G≥2. Older patients or those with worse quality of life (QoL) scores at baseline (p<0.05) were more likely to experience NT. One-hundred-six patients received docetaxel as substitute for paclitaxel. Of them, 47 patients started with docetaxel at cycle one due to reaction to paclitaxel (n=32), fear of NT (n=4), other reasons (n=11), whereas 59 patients switched to docetaxel during cycle 2-6 due to NT (n=32), reaction to paclitaxel (n=19), and other reasons (n=8). Although the protocol instructed otherwise, the majority continued paclitaxel despite G≥2 NT symptoms. There was no evidence that substitution with docetaxel improved NT (Odds Ratio): 1.57; 95% CI 0.98-2.54; p>0.05). Of 59 patients who switched to docetaxel, only seven (12%) discontinued taxane prior to chemotherapy completion. A roughly equal chance of worsening NT was reported on paclitaxel (6%) as on docetaxel (5%).

CONCLUSIONS:

Age and worse QoL at baseline are associated with NT. Substitution of docetaxel did not improve NT symptoms.

Racial disparity in 30-day morbidity and mortality after surgery for ovarian cancer

abstract

CONCLUSIONS:

African American race was not an independent predictor of poor 30-day outcomes. Interestingly, AAs with OC are underrepresented in quality-seeking hospitals. Efforts to minimize this racial disparity should target optimization of comorbidities and improving access to high-volume centers for AA women.

Televised medical talk shows—what they recommend and the evidence to support their recommendations

open access -  the BMJ

The Year in Gynecologic Cancer: Bevacizumab and Beyond

medscape

• The Year In Medicine 2014

Medscape Oncology > Markman on Oncology

Maurie Markman, MD

audio/videos: 2014 THE THERAPEUTIC Potential of Novel PARP Inhibitors in the clinic - ovarian cancerINIC

 Note: requires sign-in/password (free)

Imedex

European recommendations for biomarker-based chemoprevention trials

open access-ecancermedicalscience


 Abstract

Chemoprevention or the now more preferred ‘cancer prevention’ is the long-term administration of a biological or chemical agent to reduce the risk of cancer. This approach has long been active in individuals at high risk of developing breast or colon cancer. The aim of this expert meeting was to review the current status of the field of cancer prevention and potential, emerging biomarkers specifically focusing on breast, colon, and lung cancer but also with sessions on ovary and prostate.......

A survey of treatment approaches of malignant ascites in Germany and Austria (gasto/gyn/medonc)

Abstract

BACKGROUND: 

Malignant ascites (MA) is a common manifestation of advanced cancer. Currently, there are no evidence-based guidelines for the management of MA. We conducted a survey with physicians throughout Germany and Austria, to get an overview of current approaches and opinions in the treatment of MA.

METHODS:

One hundred and twenty-eight medical oncologists (MO), gastroenterologists (GE), and gynecologists (GYN) completed an electronic questionnaire consisting of 33 questions.

CONCLUSIONS:

Repeated PC is the main pillar of treatment of MA; its effect is only temporary and requires significant hospital resources. Further treatment strategies of MA have to be evaluated in prospective studies. Targeted therapies like catumaxomab and VEGF inhibitors should be integrated into these.

Canadian doctors preparing for ‘all eventualities’ in case top court strikes down ban on assisted suicide

media

Distribution and case-fatality ratios by cell-type for ovarian carcinomas: A 22-year series....

abstract
 Distribution and case-fatality ratios by cell-type for ovarian carcinomas: A 22-year series of 562 patients with uniform current histological classification

Highlights

•

Among 562 ovarian cancers classified by cell-type, high grade serous carcinoma and its variants accounted for 85% of tumor deaths

•

Reproducibility of cell-type designation among gynecologic pathology experts was excellent

•

1.7% of type II tumors (high grade serous carcinomas and variants) were FIGO stage I with comprehensive surgical staging

---

Background

Ovarian carcinoma is comprised of several different cell types reflecting different clinicopathologic features. Pathologic criteria for distinguishing cell types have evolved, and therefore non-contemporary literature on ovarian cancer may have limited current relevance. A new dualistic model of pathogenesis that distinguishes type I (endometrioid, mucinous, clear cell and low grade serous carcinomas) from type II (high grade serous carcinomas and carcinosarcomas) tumors has become widely accepted.

Methods

A cohort of 562 patients with invasive ovarian carcinoma from a large community hospital practice was reviewed. Cell type, FIGO stage, mortality and interpathologist diagnostic reproducibility were analyzed.

Results

Advanced stage ovarian carcinomas were type II in 86% of cases while low stage tumors were most often type I. Only 1.7% of type II tumors were confirmed to be stage I with comprehensive surgical staging. Type II tumors accounted for 85% of deaths, and clear cell carcinomas, 5% of deaths. Cell type-specific case-fatality ratios for type II tumors were 62% and 79% for high grade serous carcinoma and carcinosarcoma, respectively. For type I tumors, case-fatality ratios were 38%, 36%, 27% and 13% for low grade serous, clear cell, endometrioid and mucinous carcinomas, respectively. The kappa value for diagnostic reproducibility among 3 gynecologic pathologists was 0.83.

Conclusions

Current diagnostic criteria confirm that high grade serous carcinoma and carcinosarcoma account for the vast majority (85%) of ovarian cancer deaths. Cell type designation is highly reproducible among gynecologic pathologists. Type II tumors are rarely stage I (< 2%) when comprehensively staged by a gynecologic oncologist.

Prevalence of Germline Mutations in Cancer Predisposition Genes in Patients with Pancreatic Cancer

abstract

BACKGROUND:& Aims: 

We investigated the prevalence of germline mutations in APC, ATM, BRCA1, BRCA2, CDKN2A, MLH1, MSH2, MSH6, PALB2, PMS2, PRSS1, STK11, and TP53 in patients with pancreatic cancer.

METHODS:

The Ontario Pancreas Cancer Study enrolls consenting participants with pancreatic cancer from a province-wide electronic pathology database; 708 probands were enrolled from April 2003 through August 2012. To improve precision of BRCA2 prevalence estimates, 290 probands were randomly selected from 3 strata, based on family history of breast and/or ovarian cancer, pancreatic cancer, or neither. Germline DNA was analyzed by next-generation sequencing using a custom multiple-gene panel. Mutation prevalence estimates were calculated from the sample for the entire cohort.

RESULTS:

Eleven pathogenic mutations were identified: 3 in ATM, 1 in BRCA1, 2 in BRCA2, 1 in MLH1, 2 in MSH2, 1 in MSH6, and 1 in TP53. The prevalence of mutations in all 13 genes was 3.8% (95% confidence interval, 2.1%-5.6%). Carrier status was significantly associated with breast cancer in the proband or first-degree relative (P<.01), and colorectal cancer in the proband or first-degree relative (P<.01), but not family history of pancreatic cancer, age of diagnosis, or stage at diagnosis. Of patients with a personal or family history of breast and colorectal cancer, 10.7% (4.4%-17.0%) and 11.1% (3.0%-19.1%) carried pathogenic mutations, respectively.

CONCLUSIONS:

A small but clinically important proportion of pancreatic cancer is associated with mutations in known predisposition genes. The heterogeneity of mutations identified in this study demonstrates the value of using a multiple-gene panel in pancreatic cancer.

Is the endometrial evaluation routinely required in patients with adult granulosa cell tumors of the ovary?

abstract

 OBJECTIVE: 

granulosa cells tumors (GCTs) are the most common estrogen-secreting ovarian tumors; perhaps due to the persistent hyperestrogenism, a wide spectrum of associated endometrial pathologies ranging from endometrial hyperplasia to carcinoma has been documented in patients with GCTs. The aim of this study is to evaluate the incidence of endometrial pathologies in a large series of GCTs patients treated in MITO centers.

METHODS:

a retrospective multi-institutional review of patients with granulosa cell tumors of the ovary treated or referred to MITO centers was conducted. Descriptive statistics were used to characterize the patient population and to assess the association of GCT and endometrial abnormalities at the time of diagnosis; multivariate regression analysis was also performed to identify independent predictors of endometrial abnormalities.

RESULTS:

a total of 150 patients with primary adult GCT was identified. During the preoperative assessment, endometrial pathology was found in 35.9% of symptomatic patients and in 90.9% of asymptomatic women with endometrial thickening at transvaginal ultrasound. At the time of surgery, hyperplasia was documented in 29.2% of patients, whereas endometrial cancer occurred in 7.5% of patients. Almost all of the patients (97.6%) with endometrial hyperplasia were older than 40 years. All patients with endometrial cancer were older than 40 years and postmenopausal.

CONCLUSIONS:

endometrial carcinoma/atypical hyperplasia were commonly observed in GCT patients>40 years; based on these data, endometrial sampling should be performed in symptomatic women at least 40 years of age. In asymptomatic women<40 years, endometrial sampling is of low yield.

A multicenter, non-randomized, phase II study of docetaxel and carboplatin administered every 3 weeks as 2nd line chemotherapy in patients with first relapse of platinum sensitive epithelial ovarian, peritoneal or fallopian tube

open access

Conclusions

The three-weekly regimen of docetaxel in combination with carboplatin was feasible and active as second-line treatment of platinum-sensitive ovarian, peritoneal and Fallopian tube cancer. The major toxicity was neutropenia, while the frequency of peripheral neuropathy was low.

Metronomic oral cyclophosphamide (MOC) in the salvage therapy of heavily treated recurrent ovarian cancer patients

open access

Incidence of breast and gynaecological cancers by ethnic group in England, 2001-2007

open access

 Conclusions

Our study provides evidence that the risk of breast and gynaecological cancers varies by ethnic group and that those groups typically grouped together are not homogenous with regards to their cancer risk. Furthermore, several of our findings cannot be readily explained by known risk factors and therefore warrant further investigation.

Skin Cancer Risk in BRCA1/2 Mutation Carriers

abstract

 Women with BRCA1/2 mutations have an elevated risk of breast and ovarian cancer. These patients and their clinicians are often concerned about their risk for other cancers, including skin cancer. Research evaluating the association between BRCA1/2 mutations and skin cancer is limited and has produced inconsistent results. Herein, we review the current literature on the risk of melanoma and non-melanoma skin cancers in BRCA1/2 mutation carriers. No studies have shown a statistically significant risk of melanoma in BRCA1 families. BRCA2 mutations have been linked to melanoma in large breast and ovarian cancer families, though a statistically significant elevated risk was reported in only one study. Five additional studies have shown some association between BRCA2 mutations and melanoma, while four studies did not find any association. With respect to non-melanoma skin cancers, studies have produced conflicting results. Given the current state of medical knowledge, there is insufficient evidence to warrant increased skin cancer surveillance of patients with a confirmed BRCA1/2 mutation or a family history of a BRCA1/2 mutation, in the absence of standard risk factors. Nonetheless, suspected BRCA1/2 mutation carriers should be counseled about skin cancer risks and may benefit from yearly full skin exams.

Very late recurrence (after more than 20 years) of epithelial ovarian carcinoma: case report and literature review

  "Lifelong follow-up is critically important for ovarian cancer patients."
  (Opinion - and clinical/research reporting)


abstract

PURPOSE:

To present a case of very late (more than 20 years) recurrence of epithelial ovarian carcinoma and to review the pertinent literature. We encountered a 50-year-old patient who, at the age of 22, underwent cytoreductive surgery and adjuvant chemotherapy for stage III serous ovarian carcinoma. She recurred after 28 years and underwent secondary surgery and chemotherapy.

METHOD:

A PubMed search of the English literature containing the following key words: ovarian cancer, late recurrence, late relapse, late metastasis was performed.

RESULTS:

Only five cases (including the present one) with recurrence after more than 20 years are so far on record. Of these, four patients were 33 years old or younger and had advanced stage at diagnosis. Time to recurrence ranged from 21 to 28 years. All patients had serous carcinoma and three had recurrence in lymph nodes.

CONCLUSIONS:

Very late recurrence is an extremely rare event and may result from either regrowth of dormant tumor cells or from development of a new cancer. Lifelong follow-up is critically important for ovarian cancer patients.

Music therapy in cancer patients: fact or fiction?

open access

Future Oncology - Index: Themed Content: Minimizing morbidity in radiation oncology

Index

Best of the Radiosurgery Society® Scientific Meeting 2014: stereotactic radiosurgery/stereotactic body radiotherapy treatment of extracranial and intracranial lesions

Research Article

Chest wall and rib irradiation and toxicities of early-stage lung cancer patients treated with CyberKnife stereotactic body radiotherapy

Special Report

The promise of combining radiation therapy and immunotherapy: morbidity and toxicity

Review

Radiation oncology: physics advances that minimize morbidity

Radioprotective agents for radiation therapy: future trends

Radiobiological modifiers in clinical radiation oncology: current reality and future potential

The use of angiotensin II receptor antagonists to increase the efficacy of radiotherapy in cancer treatment

Radiogenomics: the search for genetic predictors of radiotherapy response

Minimizing morbidity in radiation oncology: a special issue from Future Oncology

Future Medicine

New ways to successfully target tumor vasculature in ovarian cancer

abstract

Purpose of review: The aim of this article was to review the recent literature on potential therapeutic strategies for overcoming resistance to antivascular endothelial growth factor drugs in ovarian cancer.

Recent findings: Although clinical benefits of antivascular endothelial growth factor therapy were observed in ovarian cancer treatment trials, this use yielded only modest improvement in progression-free survival and, with the exception of cediranib, no effect on overall survival. Adaptive resistance and escape from antiangiogenesis therapy is likely a multifactorial process, including induction of hypoxia, vascular modulators, and immune response. New drugs targeting the tumor vasculature or other components of the surrounding microenvironment have shown promising results.

Summary: When to start and end antiangiogenesis therapy and the choice of optimal treatment combinations remain controversial. Further evaluation of personalized novel angiogenesis-based therapy is warranted. Defining the critical interaction of these agents and pathways and the appropriate predictive markers will become an increasingly important objective for effective treatment.

Combining images and genetic data proves gene loss behind aggressive ovarian cancers - PTEN

media

 Cancer Research UK scientists have shown that loss of a gene called PTEN triggers some cases of an aggressive form of ovarian cancer, called high-grade serous ovarian cancer, according to a study published in Genome Biology today.....

FDA Approves Olaparib (Lynparza) for BRCA Ovarian Cancer

medscape

Olaparib Approved in Europe for BRCA Ovarian Cancer (2015 in U.S.?)

medscape

Preclinical Efficacy for AKT Targeting in Clear Cell Carcinoma of the Ovary

abstract

The aim of this study was to determine the role of AKT as a therapeutic target in ovarian clear cell carcinoma (CCC), an aggressive, chemoresistant histological subtype of ovarian cancer. AKT activation was assessed by immunohistochemistry (IHC) using human tissue microarrays of primary ovarian cancers, comprised of both CCC and serous adenocarcinoma (SAC). The growth-inhibitory effect of AKT-specific targeting by, the small molecule inhibitor, perifosine was examined using ovarian CCC cell lines in vitro and in vivo. Finally, the activity of perifosine was examined using in CCC-derived tumors that had acquired resistance to anti-VEGF or chemotherapeutics like bevacizumab or cisplatin, respectively. Interestingly, AKT was frequently activated both in early-stage and advanced-stage CCCs.

Treatment of CCC cells with perifosine attenuated the activity of AKT targeted therapy for ovarian clear cell carcinoma. AKT-mTORC1 signaling, inhibited proliferation, and induced apoptosis. The effect of perifosine was more profound under conditions of high AKT activity compared to low AKT activity. Increased AKT activation and enhanced sensitivity to perifosine were observed in the context of cisplatin-resistant CCC. Treatment with perifosine concurrently with cisplatin significantly enhanced the anti-tumor effect of cisplatin. Moreover, perifosine showed significant anti-tumor activity in CCC-derived tumors that had acquired resistance to bevacizumab or cisplatin. Collectively, these data reveal that AKT is frequently activated in ovarian CCCs and is a promising therapeutic target in aggressive forms of ovarian cancer.

Implications: AKT-targeted therapy has value in a front-line setting as well as a second-line treatment for recurrent disease developing after platinum-based chemotherapy or bevacizumab treatment.

Interactions of Multitargeted Kinase Inhibitors and Nucleoside Drugs: Achilles Heel of Combination Therapy?

abstract (technical)

Multitargeted tyrosine kinase inhibitors (TKI) axitinib, pazopanib, and sunitinib are used to treat many solid tumors. Combination trials of TKIs with gemcitabine, a nucleoside anticancer drug, in pancreas, renal, lung, ovarian, and other malignancies resulted in little benefit to patients. ........An additional unwanted interaction may be reduced FLT uptake in tumor tissues that could lead to aberrant conclusions regarding tumor response.

 fluorothymidine (FLT)

Targeting those with decreased meaning and peace: a supportive care opportunity

abstract

PURPOSE:

To evaluate if an individual's level of meaning/peace (M/P) predicts various quality of life (QOL) and mental well-being measures. To identify targets that might enhance the overall spiritual well-being and QOL of ovarian cancer patients.

METHODS:

Multi-site analysis of women with newly diagnosed stages II-IV ovarian, primary peritoneal, or fallopian tube cancer. Patients completed the following surveys: Functional Assessment of Chronic Illness Therapy-Ovarian (FACT-O), Functional Assessment of Chronic Illness Therapy-Spiritual (FACIT-Sp), Edmonton Symptom Assessment System (ESAS), Hospital Anxiety and Depression Scale (HADS), Templer's Death Anxiety Scale (DAS), Herth Hope Index (HHI), and Brief Multidimensional Measure of Religiousness/Spirituality (BMMRS). Linear regression models were created to examine the effect of M/P (FACIT-Sp) upon QOL, symptoms, and other measures of mental well-being. These models adjusted for the effect of site, race, age, stage, anaphylaxis to chemotherapy, and partner status as potential confounders.

RESULTS:

This study enrolled 104 patients from three separate sites. After adjusting for potential confounders, it was found that higher M/P predicted better QOL (FACT-O) (p < 0.0001). Higher M/P also predicted decreased death anxiety, depression, and anxiety (p ≤ 0.005). Finally, higher M/P predicted increased hope and coping scores (p ≤ 0.0005).

CONCLUSIONS:

Level of M/P is associated with several important mental and physical health states. This information may allow providers to identify patients at increased risk for mental/physical distress and may facilitate early referral to targeted psychotherapy interventions focused on improving patient QOL and decreasing anxiety and depression.

Predictive factors for the presence of malignant transformation of pelvic endometriosis

abstract

OBJECTIVES:

To determine predictive factors for the presence of malignant transformation in ovarian endometriotic cysts.

STUDY DESIGN:

This was an IRB approved, case control study analyzing patient data from 2004 to 2013. Pathology database records were searched to identify patients with benign endometrioma and ovarian carcinoma arising in the background of endometriosis. Inclusion criteria required each patient to have a preoperative diagnosis of adnexal mass and no other findings concerning for malignancy. Patient clinical records were queried for preoperative symptoms, serum CA125 levels and radiologic findings. Pathologic data were collected including histology, tumor grade and stage.

RESULTS:

A total of 138 patients met inclusion criteria; 42 women with ovarian cancer arising in the background of endometriosis and 96 women with benign endometrioma. Women diagnosed with ovarian cancer were significantly older than women with endometriosis (53.6 vs. 39.2 years). There was no difference in presence of symptoms between the two groups. Women with malignant tumors were found to have significantly larger cysts (14cm vs. 7.5cm; p<0.0001) that were more often multilocular (45.7% vs. 12.2%; p<0.0001), and contained solid components (77.1% vs. 14.5%; p<0.0001). Among patients that were observed prior to surgery there was a significant difference in the change in size of the mass over time with 4.2cm increase for cases vs. 1.0cm increase for controls (p=0.02). Multiple logistic regression analysis indicated that for every 5 years increase in age there was an adjusted OR of 2.17 (p=0.003). An age of 49 years or greater had an 80.6% sensitivity (95% CI: 62.5-92.5%) and an 82.9% specificity (95% CI: 67.9-92.8%) for malignancy, and solid component on imaging had an adjusted OR of 23.7 (p<0.0001). Serum CA125 levels tended to be higher in patients with malignant tumors but did not reach statistical significance with a mean of 204.9 vs. 66.9 (p=0.1).

CONCLUSIONS:

Significant predictors for malignant transformation of endometriosis include cyst characteristics and age. Women above the age of 49 with multilocular cysts and solid components are at high risk for malignant transformation of endometriosis. Serum CA125 level is not a significant predictor of malignant transformation.