OVARIAN CANCER and US

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Tuesday, November 10, 2015

Association of Preoperative Thrombocytosis and Leukocytosis With Postoperative Morbidity and Mortality Among Patients With Ovarian Cancer



Abstract


OBJECTIVE:

To examine whether preoperative thrombocytosis or leukocytosis is associated with increased postoperative morbidity or mortality.

METHODS:

Patients with ovarian cancer undergoing primary surgery from 2005 to 2012 were identified from the American College of Surgeons National Surgical Quality Improvement Project. Thrombocytosis was defined as platelets greater than 450,000/mm and leukocytosis as white blood cells greater than 10,000/mm. We examined 30-day postoperative complications and mortality. Descriptive statistics and adjusted multivariable logistic regression were used for analysis.

RESULTS:

We identified 1,072 patients. The incidence of thrombocytosis was 9.6%, leukocytosis was 18.7%, and 4.9% had both.

Morphological and Immunohistochemical Reevaluation of Tumors Initially Diagnosed as Ovarian Endometrioid Carcinoma With Emphasis on High-grade Tumors



abstract

 Ovarian endometrioid carcinomas (OEC) of low grade have characteristic morphologic features, but high-grade tumors can mimic high-grade serous and undifferentiated carcinomas. We reviewed tumors initially diagnosed as OEC to determine whether a combination of pathologic and immunohistochemical features can improve histologic subclassification. Tumors initially diagnosed as OEC were reviewed using World Health Organization criteria. We also noted the presence of associated confirmatory endometrioid features (CEFs): (i) squamous metaplasia; (ii) endometriosis; (iii) adenofibromatous background; and (iv) borderline endometrioid or mixed Mullerian component. A tissue microarray was constructed from 27 representative tumors with CEF and 14 without CEF, and sections were stained for WT-1, p16, and p53. Of 109 tumors initially diagnosed as OEC, 76 (70%) tumors were classified as OEC. The median patient age was 55 years, and 75% of patients were younger than 60 years. Ninety-two percent presented with disease confined to the pelvis, and 87% of tumors were unilateral. The median tumor size was 11.8 cm. Only 3% of tumors were high grade (grade 3of 3). Eighty percent of cases had at least 1 CEF, and 59% had at least 2 CEFs. Eleven percent overexpressed p16, 0% overexpressed p53, and 3% expressed WT-1. Only 10% of patients died of disease at last follow-up. Thirty-three (33) tumors, or 30% of tumors originally classified as endometrioid, were reclassified as serous carcinoma (OSC). The median patient age was 54.5 years, and 59% of patients were younger than 60 years of age. Only 27% had disease confined to the pelvis at presentation, 52% of tumors were unilateral, and the median tumor size was 8 cm. Associated squamous differentiation, endometrioid adenofibroma, and endometrioid or mixed Mullerian borderline tumor (CEFs) were not present in any case, but 6% of patients had endometriosis. Approximately one half of the reclassified OSC demonstrated SET-pattern morphology (combinations of glandular, cribriform, solid, and transitional cell-like architecture) and were immunophenotypically indistinguishable from OSCs with papillary architecture. Sixty percent of OSC overexpressed p16, 50% overexpressed p53, and 82% expressed WT-1. At last follow-up, 52% had died of disease. Compared with OSC, OEC patients more frequently presented below 60 years of age (P=0.046), had low-stage tumors (P<0.001), were more frequently unilateral (P<0.001), more frequently had synchronous endometrial endometrioid carcinomas (P<0.001); and had no evidence of disease at last follow-up (P<0.001). Their tumors were of lower grade (P<0.001), had more CEFs (P<0.001), and less frequently overexpressed p16 and p53 (P=0.003 and P<0.001, respectively) and less frequently expressed WT-1 (P<0.001). This analysis emphasizes the diagnostic value of CEFs, the presence of a low-grade gland-forming endometrioid component, and WT-1 negativity, as valid, clinically relevant criteria for a diagnosis of OEC. Glandular and/or cribriform architecture alone may be seen in both OECs and OSCs and are therefore not informative of diagnosis. Further study is needed to elaborate the characteristics of the exceedingly rare high-grade OEC.

Plasma biomarker analysis of ovarian cancer patients undergoing immunotherapy with therapeutic cancer vaccine DPX-Survivac



Journal for ImmunoTherapy of Cancer
 

Background

Immune based therapies for cancer are emerging as promising strategies to treat a number of malignancies. A more thorough biomarker assessment of the patients may provide insights into the variability in response to such immune therapies. In a Phase I/Ib clinical trial with the survivin-targeting vaccine DPX-Survivac, we showed the induction of robust immune responses in ovarian cancer patients. In this study, we investigated the potential of proteomic and metabolomic analysis of plasma to identify surrogate biomarkers for efficacy, recurrence and adverse events (AE) in vaccine recipients.....

Monday, November 09, 2015

Calls for more funding for rare cancers



(Australia) media
 

AN AUSTRALIAN medical expert says a different approach to treatment of rare cancers is needed, with research showing rare cancers contribute to 30% of deaths from the disease while less than 20% of funding goes to them.
University of South Australia's Professor Ian Olver said in the Medical Journal of Australia, published Monday, that research showed more than 80% of cancer research funding went to blood cancers and five solid cancers (breast, colorectal, prostate, melanoma and lung), while rare cancers such as pancreatic, ovarian and brain received less funding.
Rare cancers are defined as having fewer than six cases per 100,000 head of population a year.
"If less research is being performed to provide data, and the low incidence of rare cancers makes large randomised clinical trials impractical, there are few evidence-based guidelines regarding rarer cancers to which clinicians can refer," Prof Olver said.
He said ovarian cancer was a good example of how approaches to rare cancer treatment needed to evolve.
He said common cancers which had improved survival rates, including breast and bowel, had screenings for early detection.
But a population screening test would be difficult to achieve for ovarian cancer, he said.
"The heterogeneity of ovarian cancer suggests that a population screening test based on a panel of biomarkers will be difficult to achieve."

Is Neoadjuvant Chemo Justified in Ovarian Cancer?



Onclive

.... Herzog said ongoing studies, including the NCIC CTG OV.21 and MRC-UK ICON8 trials, are hoping to add further clarity to the use of neoadjuvant chemotherapy in ovarian cancer....

Dose Delays, Dose Reductions, and Relative Dose Intensity in Patients With Cancer Who Received Adjuvant or Neoadjuvant Chemotherapy in Community Oncology Practices



abstract

Background: A wide variety of myelosuppressive chemotherapy regimens are used for the treatment of cancer in clinical practice. Neutropenic complications, such as febrile neutropenia, are among the most common side effects of chemotherapy, and they often necessitate delays or reductions in doses of myelosuppressive agents. Reduced relative dose intensity (RDI) may lead to poorer disease-free and overall survival.  
Methods: Using the McKesson Specialty Health/US Oncology iKnowMed electronic health record database, we retrospectively identified the first course of adjuvant or neoadjuvant chemotherapy received by patients without metastases who initiated treatment between January 1, 2007, and March 31, 2011. For each regimen, we estimated the incidences of dose delays (≥7 days in any cycle of the course), dose reductions (≥ 15% in any cycle of the course), and reduced RDI (<85% over the course) relative to the corresponding standard tumor regimens described in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines).  
Results: This study included 16,233 patients with 6 different tumor types who received 1 of 20 chemotherapy regimens. Chemotherapy dose delays, dose reductions, and reduced RDI were common among patients treated in community oncology practices in the United States, but RDI was highly variable across patients, regimens, and tumor types (0.486–0.935 for standard tumor regimen cohorts). Reduced RDI was more common in older patients, obese patients, and patients whose daily activities were restricted.  
Conclusions: In this large evaluation of RDI in US clinical practice, physicians frequently administered myelosuppressive agents at dose intensities lower than those of standard regimens.

Editorial: Silicone Gel Breast Implants: What We Know About Safety After All These Years



partial view 

Controversy over the safety of silicone breast implants has been raging for more than half a century. In this issue, Balk and colleagues report a comprehensive systematic review on long-term health outcomes in women with silicone gel breast implants. The editorialists note that given the absence of solid evidence for association between silicone implants and well-defined disease, we should refocus research efforts to understand the symptoms that some women with implants report.

Editorial: Working Toward a Solution: The Unanswered Questions About Silicone Gel Breast Implants



partial view (subscriber based publication)

Long-Term Health Outcomes in Women with Silicone Gel Breast Implants: A Systematic ReviewLong-Term Health Outcomes With Silicone Gel Breast Implants



abstract: Long-Term Health Outcomes in Women with Silicone Gel Breast Implants: A Systematic ReviewLong-Term Health Outcomes With Silicone Gel Breast Implants | Annals of Internal Medicine

 
Background: Silicone gel breast implants were removed from the U.S. market for cosmetic use in 1992 owing to safety concerns. They were reintroduced in 2006, with a call for improved surveillance of clinical outcomes.
Purpose: To systematically review the literature regarding specific long-term health outcomes in women with silicone gel breast implants, including cancer; connective tissue, rheumatologic, and autoimmune diseases; neurologic diseases; reproductive issues, including lactation; offspring issues; and mental health issues (depression and suicide).

5 Reasons Why The Future Looks Bright For Humans And Bleak For Cancer (article)



(media) article: Joan Massagué
 


Sunday, November 08, 2015

Immunotherapy Not Ready for Prime Time in Ovarian Cancer



Markman: onclive

Early promising responses seen with immune checkpoint inhibitors for patients with ovarian cancer still need to be validated in larger randomized trials before a conclusion is made regarding their true efficacy, according to a presentation by Maurie Markman, MD, at the 33rd Annual Chemotherapy Foundation Symposium.

 “The checkpoint inhibitors are not ready for prime time yet in ovarian cancer. It's not because there's evidence that they don't work—it's just that there's no evidence at all,” said Markman, president of Medicine and Science at the Cancer Treatment Centers of America. “You could not think of a more appropriate tumor type to explore the concept of immunotherapy than ovarian cancer. Unfortunately, as we've all learned, it's much more complicated.”....

Different Types Of Ovarian Cancer Have Different Causes



science news
 
.....Professor Charlie Swanton, Chair of the 2015 NCRI Cancer Conference, said, "We've known for some time that the number of children a woman has, and her use of contraception, can influence her risk of ovarian cancer, so this research provides important further detail about different types of the disease.
"Ovarian cancer - like many other cancers - is not one disease, but different diseases that are grouped together because of where they start. It's important to know what affects the risk of different types of ovarian cancer and what factors impact this. We now need to understand the mechanisms behind these findings to develop some way to extend this lower risk to all women, regardless of how many children they have."

ImmunoGen (IMGN) Refines Drug Targeting for Ovarian Cancer Patients (Based on these new findings, ImmunoGen is planning a phase II study of mirvetuximab soravtansin which will enroll ovarian cancer patients with tumors containing medium and high levels of folate receptors. The study is expected to start before the end of the year (mirvetuximab soravtansin)



financial news

..... Based on these new findings, ImmunoGen is planning a phase II study of mirvetuximab soravtansin which will enroll ovarian cancer patients with tumors containing medium and high levels of folate receptors. The study is expected to start before the end of the year.

A comparison of the toxicity and tolerability of two IP chemotherapy regimens for advanced-stage epithelial ovarian cancer



 Blogger's Note: abstract does not detail followup period eg. PFS

Abstract
 

OBJECTIVES:

Randomized controlled trials (RCTs) in optimally cytoreduced epithelial ovarian cancer (EOC) patients have demonstrated an impressive survival benefit of intraperitoneal (IP) platinum over intravenous (IV), but its use has been limited by significant toxicity from cisplatin. The aim of this study was to compare the toxicity and tolerability of IP cisplatin to IP carboplatin in women with optimally cytoreduced EOC.

METHODS:

Retrospective analysis of 141 women with EOC who underwent optimal surgical cytoreduction followed by IV paclitaxel and IP cisplatin or IP carboplatin was performed. Toxicities of the two treatment regimens were compared. As a secondary outcome, overall survival (OS) and progression-free survival (PFS) probabilities were obtained using the Kaplan-Meier estimate; the log-rank test was used to compare survival curves.

RESULTS:

Of the 141 patients, 77 (54.6%) received IP cisplatin and 64 (45.4%) received IP carboplatin. Eighty-six percent received at least 4cycles of IP chemotherapy. IP cisplatin was associated with significantly more grade 3 nausea and vomiting (10.4% vs 1.6%, p=0.033), grade 3 neuropathy (7.8% vs 0%, p=0.013) and grade 2-3 neutropenia (22.1% vs 9.4%, p=0.042). No difference in PFS (p=0.602) or OS (p=0.107) was found between the groups.

CONCLUSION:

IP chemotherapy had a high completion rate in both groups of patients. IP carboplatin required a less resource intense protocol and was tolerated better than IP cisplatin with less gastrointestinal, neurologic and hematologic toxicities.

Prevalence of sexual dysfunction after risk-reducing salpingo-oophorectomy



abstract


OBJECTIVES:

To determine the prevalence of sexual dysfunction in women after risk-reducing salpingo-oophorectomy (RRSO) and to assess factors which may influence sexual wellbeing following this procedure.

METHODS:

This work is a cross-sectional study of women who underwent RRSO at a tertiary gynecologic oncology unit between January 2009 and October 2014. Data collection involved a comprehensive questionnaire including validated measures of sexual function, sexual distress, relationship satisfaction, body image, impact of event, menopause specific quality of life, and general quality of life. Participants were invited to undergo blood testing for serum testosterone and free androgen index (FAI).