open access: (U.S.) The Cost of Initial Care for Medicare Patients With Advanced Ovarian Cancer

open access

 Prior studies documenting the costs of care for patients with ovarian cancer have either used a brief period of time, or have described costs for a particular treatment type.^6–8 Our objectives were to use the SEER-Medicare data set to describe the costs of care for patients with ovarian cancer in the first year after diagnosis, evaluate differences in costs depending on treatment approach, and evaluate factors responsible for variation.

 Conclusions: The financial burden of caring for patients with ovarian cancer is substantial. Treatment that is consistent with NCCN recommendations for treating advanced ovarian cancer, which is shown to have improved outcomes, is not associated with higher cost.

Adopting a Uniform Approach to Site Assignment in Tubo-Ovari... : International Journal of Gynecological Pathology

Abstract

There is currently sufficient evidence that nonuterine high-grade serous carcinoma (HGSC) originates in the fallopian tube in the majority of cases, but this is not uniformly reflected in our diagnostic terminology. This is because there remains wide variation in awareness and acceptance of this evidence, which conflicts with traditional views on origin. Accurate disease classification is fundamental to routine clinical practice and research, particularly at a time when exciting new approaches to therapy, early detection, and prevention are appearing on the horizon. We feel the time has come to minimize individual and institutional variations in practice, and agree on an evidence-based approach to uniform terminology and primary site assignment. In this paper we put forward a proposal for a unified approach based on published research evidence and discuss the reasons why it is vital to agree on a uniform protocol. We propose the term “Tubo-ovarian HGSC” in preference to “pelvic” or “Müllerian,” as it accurately reflects the origin of this disease in the vast majority of cases, and is unambiguous, distinguishing it clearly from uterine serous carcinoma and ovarian low-grade serous carcinomas. A detailed protocol for primary site assignment is presented for different scenarios, which is easy to follow and has been developed with a view to promoting a uniform approach worldwide.

Immunohistochemistry in the Diagnosis of Mucinous Neoplasms...

abstract
 Immunohistochemistry in the Diagnosis of Mucinous Neoplasms Involving the Ovary: The Added Value of SATB2 and Biomarker Discovery Through Protein Expression Database Mining

Immunohistochemistry is frequently used to identify ovarian mucinous neoplasms as primary or metastatic; however, there is significant overlap in expression patterns. We compared traditional markers (CK7, CK20, CDX2, PAX8, estrogen receptor, β-catenin, MUC1, MUC2, and MUC5AC) to 2 novel proteins identified through mining of the Human Protein Atlas expression database: SATB2 and POF1B. The study cohort included 49 primary gastrointestinal (GI) mucinous adenocarcinomas (19 colorectal, 15 gastric, 15 pancreatobiliary), 60 primary ovarian mucinous neoplasms (19 cystadenomas, 21 borderline tumors, 20 adenocarcinomas), and 19 metastatic carcinomas to the ovary (14 lower and 5 upper GI primaries). Immunohistochemistry was performed on tissue microarrays, scored and interpreted as negative (absent or focal/weak) or positive. Metastatic tumors were frequently unilateral (42.8% of tumors from lower and 40% of tumors from upper tract) and ≥10 cm (85.7% of tumors from lower and 80% of tumors from upper tract). CK7 was positive in 88.5% upper GI and 88.3% primary ovarian compared with 24.3% lower GI neoplasms. CK20 and CDX2 were positive in 84.8% and 100% of lower GI tumors, respectively; however, expression was also common in upper GI (CK20 42.8%, CDX2 50%) and primary ovarian neoplasms (CK20 65.7%, CDX2 38.3%). Conversely, SATB2 was more specific for lower GI origin, being positive in 78.8% lower GI but only 11.5% upper GI and 1.7% primary ovarian neoplasms. PAX8 expression was common in primary ovarian neoplasms (75% of all neoplasms, 65% of carcinomas); only 1 (1.5%) GI tumor was positive. MUC2 and β-catenin were frequently positive in lower GI tumors (96.9% and 51.5%, respectively). Estrogen receptor expression was only seen in primary ovarian neoplasms (13.3%).

Recurrent Pseudomembranous Colitis in an Ovarian Cancer Patient Undergoing Carboplatin Chemotherapy

Clostridium difficile colitis or pseudomembranous colitis is colitis (inflammation of the large intestine) resulting from infection with Clostridium difficile, a spore-forming bacterium. It causes an infectious diarrhea called C. difficile associated diarrhea (CDAD).

open access

 Abstract

Background. Diarrhea is a common problem in ovarian cancer patients undergoing chemotherapy and Clostridium difficile infection has been identified as a cause. The proper diagnosis and treatment of diarrhea are critical to patient care, especially to prevent the serious complications from a severe Clostridium difficile infection (CDI). Case. We present a heavily pretreated ovarian cancer patient who developed recurrent pseudomembranous colitis while receiving carboplatin chemotherapy. Despite treatment with oral metronidazole for fourteen days, the patient’s diarrhea relapsed and colonoscopy revealed extensive pseudomembranous colitis. The infection eventually resolved with the combination of oral vancomycin and metronidazole.  
Conclusions. Diarrhea is a common problem in patients undergoing chemotherapy for ovarian cancer. Management requires obtaining the proper diagnosis. Clostridium difficile associated pseudomembranous colitis must be part of the differential diagnosis. Treatment must be sufficient to prevent relapses of the Clostridium difficile infection to prevent serious consequences in an already vulnerable patient population.

1. Introduction

Clostridium difficile infection (CDI) was recognized in 1978 as the etiology of antibiotic associated diarrhea and subsequent pseudomembranous colitis [1, 2]. In modern practice, clinical suspicion for CDI remains high when a patient develops diarrhea in close temporal relation to a course of antibiotics. However, in addition to antibiotics, chemotherapy has been confirmed as an independent risk factor for development of CDI and recently chemotherapy has become an established independent risk factor for healthcare associated Clostridium difficile colonization [3, 4]. The purpose of this paper is to describe a case of recurrent Clostridium difficile pseudomembranous colitis associated with single agent carboplatin chemotherapy in a woman with ovarian cancer......

Clinicopathologic features of ovarian neoplasms with emphasis on borderline ovarian tumors: an institutional perspective (Pakistan)

abstract:
Clinicopathologic features of ovarian neoplasms with emphasis on borderline ovarian tumors: an institutional perspective

BACKGROUND:
 

Ovarian cancer is the most lethal gynecologic malignancy and it represents third most common malignancy in Karachi (after breast and oral cancer). Due to lack of well established cancer registry in our country, changing trends of ovarian tumors has not been determined. Therefore we aimed to establish the current trends and classification of ovarian tumors in our setup according to latest WHO guidelines.

METHODS:

We retrospectively analyzed 162 cases of ovarian tumors that underwent surgical resection from January 2009 till December 2014. Specimens were received in histopathology department, Liaquat National hospital and cases were examined by senior histopathologists and classified according to latest WHO guidelines. Various histopathologic parameters including capsular invasion, omental and lymph node meatstasis along with uterine and fallopian tube involvement were determined apart from tumor type and grade.

RESULTS:

Mean age at diagnosis was 35.8 years (± 15.5). surface epithelial tumors were most common, 109 cases (67.2 %) followed by germ cell tumors, 44 cases (27.1 %) and sex cord stromal tumors, 8 cases (4.9 %). Serous tumors were most common surface epithelial tumors with 90 % benign morphology. On the other hand, mucinous tumors showed a higher percentage of borderline and malignant features (16.7 and 14.6 % respectively). Higher incidence of capsular invasion and omental metastasis was noted in endometroid and serous carcinoma compared to mucinous tumors.

CONCLUSIONS:

We noted a higher frequency of young age ovarian cancers in our set up. Serous and endometroid carcinomas were found to be associated with adverse prognostic factors like capsular invasion and omental metastasis. Moreover a significantly higher proportion of ovarian tumors constitute mucinous histology including borderline tumors. Whether this represents a changing trend towards biology of these tumors in this part of the world needs to be uncovered by further studies.

With OVA1 Sales Slumping, Vermillion Looks Ahead to Overa | GenomeWeb

genomeweb
 

Mar 24, 2016

NEW YORK (GenomeWeb) –

 Vermillion this month published a clinical study detailing Overa's performance in the American Journal of Obstetrics and Gynecology and now plans to begin offering the test through an early-access program designed to generate additional performance, outcome, and health economic data, Vermillion President and CEO Valerie Palmieri said on a conference call this week following release of the company's Q4 and full-year 2015 earnings results.
One of the key areas in which Overa improves upon OVA1 is specificity and positive predictive value, which have proven a stumbling block for the first-generation test. In the AJOG study, the test distinguished between benign and malignant masses with specificity of 69 percent and positive predictive value of 40 percent, compared to 54 percent specificity and PPV of 31 percent for OVA1.
The sensitivity and negative predictive value of the two tests, meanwhile, were equivalent.
"We had very strong negative predictive value with OVA1, but marginal positive predictive value, and now we have a test that has both," Palmieri said on this week's call.
As Laura Havrilesky, a gynecologic oncologist at Duke University, explained to GenomeWeb in a 2011 interview, low specificity was an issue for OVA1 in that it meant the test was identifying likely benign patients as likely malignant, which, in turn, meant Ob-Gyns were passing patients on to gynecologic oncologists for surgeries that they could have done themselves.
"Looking at those [specificity] numbers, if you were sitting in your general Ob-Gyn practice, they might be a little concerning – 'A lot of my benign cases are going to go out the door because I'm doing this test on everybody,'" she said.

brief report: clinical utility of an elevated-risk multivariate index assay score in ovarian cancer patients

abstract
 

Objective: Early involvement of specialists is associated with improved survival in ovarian cancer patients. However, only 33-60% of patients are currently being referred. A more effective strategy to get patients with an elevated risk of ovarian cancer to gynecologic oncologists is needed. The objective of this study was to evaluate the clinical utility of a multivariate index assay, OVA1, by assessing its ability to drive referral of ovarian cancer patients to gynecologic oncologists prior to their first surgical intervention.

 

Research design and methods: Information on patients who received an OVA1 test was collected retrospectively from 22 obstetricians/gynecologists through a chart review. Physicians were recruited from a variety of practices and hospitals representing major geographic regions within the United States. Clinical utility of OVA1 was assessed by examining the rate at which obstetricians/gynecologists involved a gynecologic oncologist for patients with elevated-risk OVA1 results prior to first surgical intervention.

 

Results: A total of 136 patients with elevated-risk OVA1 results were assessed, of which 122 underwent surgery to remove an adnexal mass. Prior to surgery, 98 (80%) of the patients were referred to a gynecologic oncologist with an additional 11 (9%) having a gynecologic oncologist available if required by intra-operative findings. Primary ovarian cancer was found in 65 (53%) patients, and gynecologic oncologists performed 61 (94%) of the initial surgeries these patients. Similar results were found in premenopausal and postmenopausal patients.

 

Conclusions: A high proportion of patients with an elevated-risk OVA1 results were referred to a gynecologic oncologist prior to their initial surgery. Nearly all of the patients who had primary ovarian malignancies were appropriately referred to gynecologic oncologists, highlighting the clinical utility of OVA1. Nearly all patients identified with ovarian cancer received their initial surgery by a gynecologic oncologist - demonstrating a higher rate of gynecologic oncologist involvement in comparison to past studies. The study may be limited by unintentional bias in physician response and recall.

Routine ureteric stenting before cytoreductive surgery plus HIPEC in managing peritoneal carcinomatosis from gyn malignancies

Blogger's Note: in general terms the acknowledged 'best' imaging for ureters is CT urogram

abstract
  Routine ureteric stenting before cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy in managing peritoneal carcinomatosis from gynecologic malignancies: a single-center experience. (authors: Saudia Arabia/Egypt)

BACKGROUND:

Iatrogenic ureteric injury is a rare, yet serious operative complication in gynecologic procedures and associated with substantial morbidities such as prolonged hospitalization, additional financial-based ureter-related repairing procedures, impaired renal function, and compromised quality of life. Direct visual identification of ureters can be very challenging in managing patients with primary advanced or recurrent disseminated intraperitoneal gynecologic malignancies, who are referred to complex procedures such as cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).

AIMS:

To report our single-center experience (feasibility and morbidity) with prophylactic ureteric stents as a routine practice before CRS+HIPEC procedure in managing peritoneal carcinomatosis (PC) from gynecologic malignancies.

METHODS:

From June-2010 to March-2014, all patients with gynecologic-related PC, managed with CRS+HIPEC, and underwent prophylactic ureteric stents. The data were retrospectively abstracted and analyzed.

RESULTS:

Fifty-three patients were identified. Almost all PC cases were secondary/recurrence presentations (90.6 %) and originated from ovarian cancer (84.9 %). Optimal cytoreduction microscopic residual disease) was achieved in 35 patients (60 %). Average insertion time of ureteric stents was 8.9 ± 3.3 min. Fifty-two patients (98.1 %) received bilateral ureteric stents. Forty-nine patients (92.5 %) had their ureteric stents removed by the end of procedure. No patient experienced major peri-operative urinary tract-related complications.

CONCLUSIONS:

Prophylactic ureteric stents appeared to be feasible, potentially safe, and could reduce the risk of iatrogenic ureteric injuries without incurring an increase in urinary tract-related complications. Prophylactic ureteric stenting does not eliminate the necessity for competent anatomical knowledge, meticulous retroperitoneal dissection and direct intra-operative visualization of ureters.

Hormone Receptors in Serous Ovarian Carcinoma: Prognosis, Pathogenesis

open access

 Clinical Medicine Insights: Oncocology 2016

Abstract

A few breakthroughs have been accomplished for the treatment of ovarian cancer, the most deadly gynecologic carcinoma, in the current era of targeted oncologic treatment. The estrogen receptor was the first target of such treatments with the introduction of tamoxifen four decades ago in breast cancer therapeutics. Attempts to duplicate the success of hormonal therapies in ovarian cancer met with mixed results, which may be due to an inferior degree of hormone dependency in this cancer. Alternatively, this may be due to the failure to clearly identify the subsets of ovarian cancer with hormone sensitivity. This article reviews the expression of hormone receptors by ovarian cancer cells, the prognostic value of these expressions, and their predictive capacity for response to hormonal agents. The possible ways ahead are briefly discussed.

Table 1. Estrogen Receptor α (ERα) expression and prognostic value in serous ovarian carcinoma

Table 2. Progesterone Receptor (PR) expression and prognostic value in serous ovarian carcinoma.

 In addition, there is a need to better target specific subsets of the disease based on histologies and genetic profiles instead of treating all ovarian cancers as a uniform disease, which is clear that it is not.82 ERβ and GPER1, PR and its subtypes, and the GnRH receptor are also potential targets of hormone agents that provide opportunities for fine-tuning therapies.

Evaluation and Management of Ultrasonographically Detected Ovarian Tumors in Asymptomatic Women

abstract

Data from screening trials indicate that a significant percent of asymptomatic women older than 50 years of age will develop ovarian abnormalities that are detectable by ultrasonography. Most of these abnormalities are benign, and many will resolve spontaneously. However, the risk of ovarian cancer, particularly in postmenopausal women, is of concern. The goal is to use a diagnostic and treatment algorithm that will reliably detect ovarian cancer at the earliest possible stage while limiting the number of women undergoing surgery for benign disease. The combination of morphology indexing and serum biomarker analysis can accurately predict the risk of malignancy in most ovarian tumors. Ovarian tumors with cystic or septate morphology are at minimal risk of malignancy and can be followed with serial ultrasonography evaluations, thereby avoiding the morbidity and cost of surgery. Complex or solid ovarian tumors with a high morphology index score, or those with increasing biomarker production, are at a high risk of malignancy, and patients with these tumors should be referred to a gynecologic oncologist for further evaluation and treatment.

Association Between Menopausal Estrogen-Only Therapy and Ovarian Carcinoma Risk

Abstract

Authors:
 ¹Departments of Preventive Medicine and Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, California; the University of Texas School of Public Health, Houston, Texas; the Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital, and the Harvard T. H. Chan School of Public Health, Boston, Massachusetts; the Department of Public Health Sciences, the University of Virginia, Charlottesville, Virginia; the Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, and the University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; the Department of Epidemiology, the Geisel School of Medicine at Dartmouth, Hanover, New Hampshire; Women's Cancer, Institute for Women's Health, University College London, London, United Kingdom; the Center for Cancer Prevention and Translational Genomics and Cancer Prevention and Control, Samuel Oschin Comprehensive Cancer Institute, the Department of Biomedical Sciences, and the Community and Population Health Research Institute, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California; the Department of Chronic Disease Epidemiology, Yale University School of Public Health, New Haven, Connecticut; the Department of Obstetrics, Gynecology, and Reproductive Sciences, Division of Gynecologic Oncology, University of Pittsburgh School of Medicine, the Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, and the Women's Cancer Research Program, Magee-Womens Research Institute and University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania; the Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York; the Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina; the Department of Epidemiology, University of Washington, and the Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington; the Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, and the Molecular Unit, Department of Pathology, Herley Hospital, and the Department of Gynecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; the Cancer Epidemiology Program, University of Hawaii Cancer Center, and the Department of Obstetrics and Gynecology, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii; the Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York; and the Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, Michigan.

OBJECTIVE: To describe the association between postmenopausal estrogen-only therapy use and risk of ovarian carcinoma, specifically with regard to disease histotype and duration and timing of use.

METHODS: We conducted a pooled analysis of 906 women with ovarian carcinoma and 1,220 women in a control group; all 2,126 women included reported having had a hysterectomy. Ten population-based case-control studies participating in the Ovarian Cancer Association Consortium, an international consortium whose goal is to combine data from many studies with similar methods so reliable assessments of risk factors can be determined, were included. Self-reported questionnaire data from each study were harmonized and conditional logistic regression was used to examine estrogen-only therapy's histotype-specific and duration and recency of use associations.

RESULTS: Forty-three and a half percent of the women in the control group reported previous use of estrogen-only therapy. Compared with them, current or recent estrogen-only therapy use was associated with an increased risk for the serous (51.4%,) and endometrioid (48.6%,) histotypes. In addition, statistically significant trends in risk according to duration of use were seen among current or recent postmenopausal estrogen-only therapy users for both ovarian carcinoma histotypes (Ptrend<.001 for serous and endometrioid). Compared with women in the control group, current or recent users for 10 years or more had increased risks of serous ovarian carcinoma (36.8%,) and endometrioid ovarian carcinoma (34.9%,).

CONCLUSION: We found evidence of an increased risk of serous and endometrioid ovarian carcinoma associated with postmenopausal estrogen-only therapy use, particularly of long duration. These findings emphasize that risk may be associated with extended estrogen-only therapy use.

Hormone Use After Nonserous Epithelial Ovarian Cancer: Overall/Disease-Free Survival

abstract

OBJECTIVE: To evaluate whether hormone therapy (HT) after nonserous epithelial ovarian cancer is associated with a decrease in overall and disease-free survival.

METHODS: We conducted a retrospective cohort study. The Manitoba Cancer Registry and Drug Programs Information Network were searched to find all women with known nonserous epithelial ovarian, fallopian tube, or primary peritoneal cancer between 1995 and 2010 who had used HT after treatment. Women who did not receive treatment or had no follow-up were excluded.

RESULTS: Three hundred ninety-one patients met the inclusion criteria. Seventeen patients were excluded because the patients did not receive treatment for cancer, and 17 were excluded for lack of follow-up. A total of 94 women received HT after treatment, and 263 women did not. The average age was 57.8 years. In HT users younger than 55 years of age, disease-free survival is improved according to both the multivariable landmark analysis (n=68/145, and the time-varying Cox regression analysis (n=42/158, when adjusting for International Federation of Gynecology and Obstetrics stage and need for chemotherapy. There is no statistical difference in overall survival in this age group. No associations between HT use and overall survival or disease-free survival were found among women aged 55 years and older.

CONCLUSION: After treatment for nonserous epithelial ovarian cancer, hormone therapy is not associated with decreased disease-free or overall survival.

Farletuzumab Shows Limited Efficacy in Relapsed Ovarian Cancer

cancer news
 
Maintenance farletuzumab following chemotherapy in combination with farletuzumab did not improve progression-free survival (PFS) for women with recurrent ovarian cancer, according to results from a study published in the Journal of Clinical Oncology.¹
However, this global, multicenter, phase 3 study showed that risk for progression was reduced by 51% in a subset of patients with CA-125 not more than 3 times the upper limit of normal (ULN).
“These observations provide a dose-efficacy relationship for farletuzumab, and hence, proof of principle,” corresponding author Ignace Vergote, MD, chairman of the Leuven Cancer Institute, University Hospital Leuven, Belgium, told Cancer Therapy Advisor.
For women with epithelial ovarian cancer that has relapsed following initial response to a platinum-based regimen, treatment options are limited to further chemotherapy-based regimens.

Risk-adjusted benchmarking of surgical complications for ten UK gynaecological oncology centres allows fairer comparison (UK)

Blogger's Note: see abstract for further stats/adjusted for ease of reading

abstract:
Benchmarking of surgical complications in gynaecological oncology: prospective multicentre study - Burnell - 2016 - BJOG: An International Journal of Obstetrics & Gynaecology 

Objective

To explore the impact of risk-adjustment on surgical complication rates (CRs) for benchmarking gynaecological oncology centres.

Design

Prospective cohort study.

Setting

Ten UK accredited gynaecological oncology centres.

Population

Women undergoing major surgery on a gynaecological oncology operating list.

Methods

Patient co-morbidity, surgical procedures and intra-operative (IntraOp) complications were recorded contemporaneously by surgeons for 2948 major surgical procedures. Postoperative (PostOp) complications were collected from hospitals and patients. Risk-prediction models for IntraOp and PostOp complications were created using penalised (lasso) logistic regression using over 30 potential patient/surgical risk factors.

Main outcome measures

Observed and risk-adjusted IntraOp and PostOp CRs for individual hospitals were calculated. Benchmarking using colour-coded funnel plots and observed-to-expected ratios was undertaken.

Results

Overall, IntraOp CR was 4.7% and PostOp CR was 25.7%. The observed CRs for all hospitals were under the upper 95% control limit for both IntraOp and PostOp funnel plots. Risk-adjustment and use of observed-to-expected ratio resulted in one hospital moving to the >95–98% CI (red) band for IntraOp CRs. Use of only hospital-reported data for PostOp CRs would have resulted in one hospital being unfairly allocated to the red band. There was little concordance between IntraOp and PostOp CRs.

Conclusion

The funnel plots and overall IntraOp (≈5%) and PostOp (≈26%) CRs could be used for benchmarking gynaecological oncology centres. Hospital benchmarking using risk-adjusted CRs allows fairer institutional comparison. IntraOp and PostOp CRs are best assessed separately. As hospital under-reporting is common for postoperative complications, use of patient-reported outcomes is important.

Tweetable abstract

Risk-adjusted benchmarking of surgical complications for ten UK gynaecological oncology centres allows fairer comparison.

The complexities of benchmarking surgical complications in gynaecological oncology - (UK/GOG) mini review

Blogger's Note: the patient safety communities will invariably (also) understand the role of campaigns such as 'sorry' and 'to err is human' which really is the underlying theme here

2016 - BJOG

 Author Information

1. Division of Gynecologic Oncology, Women's Cancer Center of Nevada, Las Vegas, NV, USA

1. Linked article: This is a mini commentary on Burnell M et al. To view this article visit http://dx.doi.org/10.1111/1471-0528.13994
   
    30 MAR 2016
   
   

   Burnell et al. (BJOG 2016; DOI: 10.1111/1471-0528.13994), in an attempt to establish benchmarks for potential use as future standards when evaluating quality of care provided by the individual physician, subspecialties, or hospital services, have undertaken a significant statistical endeavour using the data previously reported by Iyer et al. (Br J Cancer 2015;112:475–84). The authors’ use of complex statistical analyses has been tempered by their noting the shortcomings of the methods used and more importantly, their care to apply this analysis in a clinically meaningful context. Iyer et al. compiled intra-operative and postoperative complications as well as co-morbidities associated with surgery undertaken by gynaecological cancer services in ten major UK centres. These raw data have been used to construct benchmarks and to identify, with some limitations, institutions with higher and lower rates of complications, while not neglecting the institutional degree of surgical complexity. Given the relative paucity of data the authors were not able to extend this analysis to the individual surgeon.

   At first glance, establishment of benchmarks seems logical and important, as it contributes to the patients’ right to transparency regarding healthcare and a potential pathway to improve physician and institutional performance. In the USA, Gynecologic Oncology Group (GOG) trial results are not separated by institution, much less by the individual physician. Potentially this is problematic because these are publically funded trials and it is argued that the public has the right to know outcomes associated with specific institutions. Burnell et al. begin to address this issue. Complete transparency in healthcare sounds like a panacea, but there are potential risks associated with it. Specifically, it could lead to surgeons undertaking only low-risk procedures so as to lower their individual and institutional complication rates. This could become problematic in patients with ovarian cancer because rendering them free of disease requires highly complex surgery, which accordingly is associated with increased peri-operative complications, but also with improved overall survival. The authors do not address this most important of issues. Perhaps that institution with the highest rate of complications also has the highest overall survival; these two issues are inseparable.

   Using these data to identify individual surgeons or institutions in need of remedial training or instruction might be even more complicated. The premise of such benchmarking requires underlying honesty on the part of the surgeon and the institution and if the response to such reporting is seen as punitive, as opposed to educational or constructive, then it is doubtful that reporting will be forthright. This potential scenario requires a built-in mechanism for remedial training for surgeons who may fall below acceptable standards of care. Similarly, hospitals must be given an opportunity to correct any deficiencies. Accordingly, as these benchmarks are established, reporting of substandard performance should probably be limited to those failing to correct identified deficiencies.

   The last area that may be adversely affected by such reporting is resident education. Undoubtedly, if complications are going to be publically associated with individual surgeons, consultants will probably be less inclined to ‘turn cases over to the trainee’ and the long-term impact of this potentially outweighs any benefit associated with the transparency of reporting.

   In summary, this effort should be applauded, but application of this principle should be undertaken with considerable forethought.
   

   “for there is nothing either good or bad, but thinking makes it so”

   William Shakespeare

There are too many studies, new study finds | Science | News | The Independent

UK News 

Science is drowning in studies, and it took a study to expose it.
In a paper entitled 'Attention decay in science', professors from universities in Finland and California conclude that "the exponential growth in the number of scientific papers makes it increasingly difficult for researchers to keep track of all the publications relevant to their work.
"Consequently," the say, "the attention that can be devoted to individual papers, measured by their citation counts, is bound to decay rapidly."
While this particular study relates to the booming number of academic papers and journals, it's a trend we can probably all relate to.
Content is snowballing in the information age, its volume weakening the impact and longevity of each individual thing, be it a study, opinion, fact, tweet or utterance.
While this disposability of content is usually talked about with regards to culture - music, films, TV etc - the study shows the insidious effect it could have on science.
With the exponential growth in the number of scientific literature inevitably accelerating the turnover of papers due to the finite capacity of scholars to keep track of it, important data, research and theories could be overlooked

Amid Public Feuds, A Venerated Medical Journal (NEJM) Finds Itself Under Attack

ProPublica (including public comments)

A widely derided editorial, a controversial series of articles and delayed corrections have prompted critics to question the direction of the New England Journal of Medicine. 

ELITE Provides Reassurance About Estrogen in Early Menopause (not surgical menipause)

medscape

In terms of the clinical implications, based on this trial we can't say that hormone therapy should now be used for prevention of heart disease and other chronic disease events in younger women, because the trial used a surrogate endpoint and there could be other effects of hormone therapy. There is a very complex balance of benefits and risks in terms of venous thrombosis, stroke, breast cancer, and other outcomes.
However, this trial does provide further reassurance about the use of estrogen for the treatment of moderate to severe hot flashes, night sweats, and other menopausal symptoms in early menopause, as well as further evidence that concerns about coronary risk should not be used as a reason for denying hormone therapy treatment to women in early menopause who have these symptoms and are otherwise appropriate candidates for treatment.

Striving for Safe, Effective, Affordable Care for Cancer Survivors With Chronic Pain: Another Kind of Moonshot

Another Kind of Moonshot

 The guideline produced 3 items addressing when to initiate or continue opioids for chronic pain; 4 items about opioid selection, dosage, follow-up, and duration; and 5 items related to assessing risk and addressing the harms of opioid use (Box). Opioid use in cancer care and end-of-life care were excluded from the guidelines. Nevertheless, these recommendations are relevant to the oncology and palliative care community because of the growing population of cancer survivors, many of whom are living with serious chronic pain.

Editorial: Clinical Application of Liquid Biopsies

JAMA Network open access

(Ontario - OHA lacks of transparency) New OHA Guidance Document: Addressing Interim Access Requests for Physician-Assisted Death

Healthscape.ca 

 To access this resource, please visit the OHA Knowledge Center Library (OHA member login required).

Skin Manifestations of ovarian Malignancy - Google Search

Google Search (past year)

Seminars in Oncology - cutaneous (skin) manifestations in cancer patients

Seminars in Oncology (abstracts Feb 2016)

• Cutaneous manifestations in leukemia patients
• Cutaneous manifestations of breast cancer
• Cutaneous Manifestations of Genito-Urinary Malignancy
• Cutaneous manifestations of lung cancer
• Varied Skin Manifestations of Malignancy: Critical Clues in Diagnosis and Treatment
• Skin manifestations associated with kidney cancer
• Cutaneous manifestations associated with melanoma
• The cutaneous manifestations of gastrointestinal malignancy
• Soft tissue sarcomas in skin: presentations and management
• Skin manifestations of endocrine and neuroendocrine tumors
• Cutaneous Manifestations of Non-Targeted and Targeted Chemotherapies
• Cutaneous manifestations of multiple myeloma and other plasma cell proliferative disorders
• Partnering with Skin to Outsmart Cancer: Following Leads Provided by Tumor-Specific T Cells
• Cutaneous manifestations in neuro-oncology: clinically relevant tumor and treatment associated dermatologic findings
• Cutaneous manifestations and management of hematologic neoplasms
• Cutaneous squamous cell carcinomas in solid organ transplant recipients: emerging strategies for surveillance, staging, and treatment

INFOGRAPHICS AICR | American Institute for Cancer Research (all cancers)

INFOGRAPHICS 

Ludwig Cancer Research and CRI initiate clinical trial of immunotherapy for ovarian cancer

medical news
 April 6, 2016

 Ludwig Cancer Research and the Cancer Research Institute (CRI) have launched a Phase 1/2 clinical trial of combination immunotherapy for advanced ovarian cancer. The international, multicenter trial is led by George Coukos, director of the Ludwig Institute for Cancer Research, Lausanne and Brad Monk, director of Gynecologic Oncology at St. Joseph's Hospital and Medical Center. The study is being conducted through the CVC Trials Network, which is jointly managed by Ludwig and CRI, in collaboration with MedImmune, the global biologics research and development arm of AstraZeneca, and the biopharmaceutical company VentiRx Pharmaceuticals Inc.....

 Patients enrolled in the trial will be treated with the chemotherapeutic drug pegylated liposomal doxorubicin (PLD), which is the current standard of care for ovarian cancer after the failure of platinum therapy. They will also receive durvalumab and motolimod, with the Phase 1 and 2 portions of the trial running successively. The primary objective of the Phase 1 cohort of the study is to evaluate the safety and optimal dosage of the combination. The Phase 2 cohort of the trial will measure the efficacy of the treatment by evaluating the number of patients whose tumors have not progressed at six months.

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(Breast & Ovarian) Lattice Biologics/Sunnybrook Research Institute Commence Study to Develop New Cancer Screening Methods

press release



Study Using Patient-Derived Cells Within Human Extracellular Matrix (ECM) to Replicate Heterogeneous Tumor Microenvironments Aims to Improve Breast and Ovarian Cancer Treatment by Decreasing Anti-cancer Drug Failure Rates on a Large-Scale

SCOTTSDALE, AZ--(Marketwired - March 30, 2016) -  Lattice Biologics Ltd. (TSX VENTURE: LBL)(OTCBB: BLVKF) ("Lattice Biologics" or the "Company") is pleased to announce it has entered into an Industry Sponsored Collaboration Agreement with Sunnybrook Research Institute ("SRI") in Toronto, Ontario titled, "Conditional Reprogramming of Epithelial Cells to Determine Mechanisms of Resistance and Drug Sensitivity" (the "Study"). The purpose of the Study is to develop new research methods, including the creation of new instruments to make cellular measurements, and the validation of methods to determine mechanisms of resistance and drug sensitivity. The successful identification of such new methods would lead to commercialization of high content screening (HCS) chemosensitivity testing for cancer patients.

"We are extremely pleased to be working with such a prestigious partner as Sunnybrook Research Institute to develop a personalized approach for cancer diagnostics," states Guy Cook, Chief Executive Officer of Lattice Biologics Ltd.

"Lattice Biologic's ECM technology is revolutionary in its unparalleled ability to accurately recreate complex tumor microenvironments because it allows us to grow biopsies from patients' own cancer tumors in the laboratory, subject the tumors to multiple anti-cancer agents, and observe the resulting behaviors all while sustaining natural conditions.

"This will provide a never-before-seen understanding of how individual patients' tumors respond to specific treatments, allowing physicians to prescribe anti-cancer treatments with new accuracy. This level of personalized medicine will change the entire cancer  treatment game......

Colorectal Tumors from Different Racial and Ethnic Minorities Have Similar Rates of Mismatch Repair Deficiency (Lynch Syndrome)

abstract

Background and Aims

Microsatellite instability (MSI) in colorectal cancer (CRC) cells results from deficient mismatch repair (MMR) protein function, either acquired or from germline alterations, such as in patients with Lynch Syndrome. Universal screening initiatives for Lynch Syndrome have been encouraged. However, little is known about the true prevalence of MMR deficiency and MSI in colorectal tumors among individuals from different racial and ethnic subgroups or their clinical effects in these populations.

Methods

We performed a retrospective analysis of 253 surgically resected, primary colorectal adenocarcinoma specimens identified from the University of Miami tumor registry from 2005 through 2010. We collected clinical data, including overall survival (OS), the proportion of patients alive at specific intervals, from non-Hispanic White, Hispanic, and Black patients matched by stage. We performed immunohistochemical staining to detect MMR proteins in all specimens and PCR analysis of 51 tumors to detect MSI.

Results

We detected MMR deficiency in 28/253 cases (11.1%), evenly distributed among Blacks (9.6%), non-Hispanic Whites (10.4%), and Hispanics (12.6%) (P=.79). Combined deficiencies in MLH1 and PMS2 were found in 23/28 of MMR deficient samples (82.1%); MSH2 and MSH6 were most frequently absent in tumor samples from Hispanics (P=.03). Eleven of 51 tumor samples (21.6%) had high levels of MSI, and we observed a high level of concordance between MMR and MSI (k=.81). OS was significantly better in patients whose tumors had deficient MMR (hazard ratio for patients with MMR deficient tumors vs MMR proteins intact=0.37; 95% confidence interval, 0.15–0.91; P=.03). Race and ethnicity were not significant predictors of OS.

Conclusions

MMR deficiency in colorectal tumors occurs with similar rates among patients of different racial and ethnic groups, based on an immunohistochemical analysis of 253 primary tumor specimens. This finding indicates the potential value of universal testing of CRC by immunohistochemistry in minority populations and confirms the benefit of MMR deficiency to OS.

Advances in Hereditary Colorectal and Pancreatic Cancers (Lynch syndrome)

Abstract

Purpose

Innovations in genetic medicine have led to improvements in the early detection, prevention, and treatment of cancer for patients with inherited risks of gastrointestinal cancer, particularly hereditary colorectal cancer and hereditary pancreatic cancer.

Methods

This review provides an update on recent data and key advances that have improved the identification, understanding, and management of patients with hereditary colorectal cancer and hereditary pancreatic cancer.

Findings

This review details recent and emerging data that highlight the developing landscape of genetics in hereditary colorectal and pancreatic cancer risk. A summary is provided of the current state-of-the-art practices for identifying, evaluating, and managing patients with suspected hereditary colorectal cancer and pancreatic cancer risk. The impact of next-generation sequencing technologies in the clinical diagnosis of hereditary gastrointestinal cancer and also in discovery efforts of new genes linked to familial cancer risk are discussed. Emerging targeted therapies that may play a particularly important role in the treatment of patients with hereditary forms of colorectal cancer and pancreatic cancer are also reviewed. Current approaches for pancreatic cancer screening and the psychosocial impact of such procedures are also detailed.

Implications

Given the availability of new diagnostic, risk-reducing, and therapeutic strategies that exist for patients with hereditary risk of colorectal or pancreatic cancer, it is imperative that clinicians be vigilant about evaluating patients for hereditary cancer syndromes. Continuing to advance genetics research in hereditary gastrointestinal cancers will allow for more progress to be made in personalized medicine and prevention.

Key words:

familial gastrointestinal cancer, genetic testing, Lynch syndrome, multigene panel testing

Genetic Testing in Pancreatic Ductal Adenocarcinoma: Implications for Prevention and Treatment (note: Lynch Syndrome)

abstract

 For example, PDAC (Pancreatic Ductal Adenocarcinoma)
is not included in the Amsterdam or Bethesda guidelines that define Lynch syndrome even though these individuals have a higher PDAC risk than the general population. ... MLH1, MSH2, MSH6, PMS2,and EPCAMGenes (Lynch syndrome).

Purpose

This article reviews the progress to date and future directions for investigation of germline and somatic genetic testing to inform pancreatic adenocarcinoma (PDAC) treatment, screening, and prevention strategies.

Methods

We searched PubMed to identify recent articles regarding genetic testing in pancreatic cancer, including both germline and somatic testing, and recent genome-wide association studies. References were specifically hand searched as relevant. Guidelines for testing and screening high-risk individuals were included. We searched clinicaltrials.gov to review the current landscape of active clinical trials.

Findings

Approximately 10% of PDACs are associated with an identified germline mutation. Although germline mutations may inform treatment options and identify high-risk individuals for screening in other cancers, the data on PDAC are only now emerging. For example, poly adenosine diphosphate ribose polymerase (PARP) inhibitors are under investigation for BRCA-associated PDAC. Somatic mutations have also been identified in PDAC. However, current data are limited regarding treatment for potential PDAC somatic driver mutations. Although erlotinib is used in PDAC, its use is not targeted based on a tumor marker. Many tyrosine kinase inhibitors targeted toward potential driver mutations and critical pathways are in development, including BRAF/MEK, ALK, and CDK4/6. A consensus on screening strategies for individuals at high risk for PDAC is still evolving because of the relatively low prevalence of the disease, the relative invasiveness of endoscopic procedures often used as part of screening, and the lack of a clear survival benefit.

Implications

Pancreatic cancer has been slower to move toward genomic testing, partially because of a lower prevalence of mutations and partially because of a limited effect of results on treatment choices outside a clinical trial. This is an area of active investigation, and we anticipate that there will be both preventive and therapeutic implications of driver mutations in the coming decade.

Short-Term Impact of Surgical Menopause on Cognitive Function in Women at Elevated Risk for Ovarian Cancer

study

 Summary
The purpose of this study is to identify changes in memory and cognition that may result from surgical menopause in women at high risk of ovarian cancer who choose to reduce their risk of cancer by having their tubes and ovaries removed. The study will examine whether hormone replacement therapy has an effect on memory and cognition.
Researchers will collect information about personal and family history of cancer, along with personal demographics, lifestyle habits and medical history. A cognitive assessment tool will be utilized to better understand individuals at high risk for ovarian cancer.

Study Coordinator and Contact

Daniella Kamara, MS, LCGC
Phone: 310-423-9966
daniella.kamara@cshs.org

Inclusion Criteria

• Planning to have surgery to remove both ovaries or remaining ovary if only one ovary is intact
• No personal history of ovarian, peritoneal, or tubal cancer
• Menstrual cycles in the past six months or is not yet menopausal
• Currently has at least one ovary intact
• High risk for ovarian cancer as defined by standard criteria to include:
• Positive for breast cancer susceptibility gene (BRCA)
• Positive for Lynch Syndrome
• First degree relative with ovary cancer
• Ashkenazi Jewish with a personal history of breast cancer
• Two relatives with ovary cancer regardless of age of onset
• Any relative diagnosed breast cancer with age of diagnosis less than 50
• Family history of BRCA (patient not tested)
• Family history of Lynch Syndrome (patient not tested)
• At least 18 years old
  

Exclusion Criteria

• Pregnant women
• Children

Opinion: As hospitals go digital, human stories get left behind

 Blogger's Note: not specific to cancer but relative to EHRs

opinion

  The software is made by Epic Systems, based in Verona, Wis. It is the most widely used electronic health record in America, employed by more than half of large hospitals as well as many outpatient clinics.

But the problem-list format that Epic uses to organize medical information is, in itself, fragmented. The risk of this format, as physician and medical informatics expert Dr. Robert Wachter points out in a blog post, is that we may forget that “patients are more than the sum of their problems.”

The importance of importance (prognostic factors/survival)

abstract (not open access requires $$)

 We define the notion of importance of prognostic factors in studies of survival, and suggest quantifying it by the Schemper-Henderson measure of explained variation. Conceptual differences to the standard approach for the statistical analysis of oncologic studies of survival are discussed and exemplified by means of a study of ovarian cancer. Explained variation permits to establish a ranking of the importance of factors, also if measured on different scales, or of different types (dichotomous, qualitative or continuous), and permits to compare groups of related factors. In practice the importance of prognostic factors often is disappointingly low. From this it follows that even strong and highly significant prognostic factors often do not translate into close determination of individual survival of patients.

BRCA somatic mutations and epigenetic BRCA modifications in serous ovarian cancer

1) abstract 

2) open access - pdf 

 Key Message: "This article summarises the evolving role and challenges of somatic BRCA mutations and BRCA methylation in ovarian cancer"

Conclusion

The activity of PARP inhibitors is now beyond germline BRCA mutation-associated ovarian cancer and more widely applicable to HRD. The therapeutic implications of BRCA epigenetic modifications are not clear...... 

 

 (HRD: homologous combination deficiency)

Pfizer: Pragmatic RCT's: A Proposal to Enhance Evaluation of New Cancer Therapies with Early Signs of Exceptional Activity

abstract

Author Affiliations

1. ¹Pfizer Oncology, New York, NY, USA
2. ²Pfizer Oncology, Cambridge, MA, USA
3. ³Pfizer Oncology, Regional Medical Affairs, Berlin, Germany
4. ⁴Pfizer, Worldwide Safety and Regulatory, Groton, CT, USA

An analysis of oncology regulatory approvals since 2011 reveals that several new drugs demonstrate exceptional clinical activity in Phase 1 or Phase 2 trials. This has led to increased use of regulatory mechanisms that allow initial approval based on these early data. However, full regulatory approval is contingent upon subsequent verification of clinical benefit in confirmatory Phase 3 randomized controlled trials.

There has been a growing interest in the systematic collection of real-world data to gain further insight into the impact of new drugs as they are introduced into clinical practice. Furthermore, payers, physicians, and patients increasingly require more data on alternative comparators, specific subgroups, patient-reported outcomes, and long-term toxicities - data that may be more appropriately collected in real-world studies than in separate confirmatory trials.

We propose that for oncology drugs that demonstrate “exceptional activity” in early trials and receive accelerated/conditional approval and/or Breakthrough Therapy Designation, and for certain expanded indications, regulatory authorities should consider accepting data from prospectively agreed pragmatic randomized clinical trials (pRCTs) to grant full regulatory approval. The “exceptional activity” would be defined as (1) an objective response rate ≥50% to a single agent or (2) a hazard ratio of <0.5 in an early randomized study. In pRCTs, patients would be randomized to two or more interventions and then treated and followed up according to the investigators' usual practice. Patients participating in pRCTs would be representative of the real-world population. pRCTs would provide data necessary for full regulatory approval and would address questions of the new drug's value for reimbursement purposes.

The truth about WebMD, a hypochondriac's nightmare and Big Pharma's dream

media

World Ovarian Cancer Day - May 8th (note that the genetics section includes only BRCA)

World Ovarian Cancer Day
 

Ovarian Cancer

Ovarian cancer is diagnosed annually in nearly a quarter of a million women globally, and is responsible for 140,000 deaths each year. Statistics show that just 45% of women with ovarian cancer are likely to survive for five years compared to up to 89% of women with breast cancer.

 

Prevention & Diagnosis

There is currently no reliable screening test for ovarian cancer.
If you have signs and symptoms of ovarian cancer, your doctor should perform, or refer you for, a: • Complete pelvic exam
• Transvaginal or pelvic ultrasound
• CA-125 blood test

Risk Factors

It is important to talk to your doctor to determine what your own personal risk may be. If you have a family history of breast or ovarian cancer as described above, you may wish to seek genetic counseling.

 

Genetic Testing

Genetic testing will indicate whether you have a change in your gene structure in either the BRCA1 or BRCA2 genes, which may make you more susceptible to breast or ovarian cancer.

 

 

Inversion of exons 1–7 (8) of the MSH2 gene is a frequent cause of unexplained Lynch syndrome in one local population

open access (technical)

Fig. 3

Pedigrees of patients who are carriers of the MSH2 gene inversion. Cancer history is illustrated as reported by the probands. Only Lynch syndrome-related cancers are shown. Inconsistencies in cancer incidence and ages of onset were found when comparing ...

Table 1

Clinical characteristics of unexplained MSH2-type Lynch syndrome patients

 In our analysis, we used allelic drop out in long PCR analysis as a method to find regions of possible inversions. This method could be further developed to look for other inversion in the MSH2 gene, as well as in other genes where current methods of testing fail to find a causative mutation. In the meantime, clinical testing services should add an analysis for the 10 Mb inversion to their clinical testing repertoire. This study also demonstrates the importance of enrolling patients with suspected Lynch syndrome, but negative germline testing results, into research registries where their DNA can be tested until an answer is found.

Hot Topics in Cancer Risk: Your Most Frequently Asked Questions (AICR)

AICR

New Genetic Mutations for Hereditary Women's Cancers

New Genetic Mutations
 
....The recent discovery that the genetic mutation PALB2 is associated with an aggressive form of breast cancer, as well as the realization that the newer ovarian cancer genes RAD51C, RAD51D, and BRIP1 pose an added lifetime risk for ovarian cancer, should prompt physicians to discuss possible prophylactic procedures with patients who are found to carry these mutations, Tuya Pal, MD, from the Moffitt Cancer Center, Tampa, Florida, said here at the NCCN 21st Annual Conference.
"Within the past year, more data have emerged regarding these new genes for ovarian cancer risk. In the past, the NCCN recommendation to either recommend or consider risk-reducing salpingo-oophorectomy was limited to the presence of BRCA1, BRCA2 and Lynch syndrome," Dr Pal told Medscape Medical News.
"With BRCA1, the lifetime risk for ovarian cancer is up to 44%, with BRCA2, it is up to 27%, and for Lynch syndrome, our guess is around 10%. Now, based on multiple studies, we are saying there is a similar level of evidence, if not even more, to indicate a higher risk of ovarian cancer with BRIP1, RAD51C and RAD51D," she said.
Dr Pal noted that the NCCN guidelines are not recommending salpingo-oophorectomy when these genetic mutations are present, only that the possibility of the procedure should be discussed.....

PubMed Asked to Add Conflict-of-Interest Info to Abstracts

PubMed

Eliminating the Term Primary Care “Provider”: Consequences of Language for the Future of Primary Care

JAMA Network

Chinese suppliers flood US and Canada with deadly fentanyl

medical news

.... When it comes to the illegal sale of fentanyl, most of the attention has focused on Mexican cartels that are adding the drug to heroin smuggled into the United States. But Chinese suppliers are providing both raw fentanyl and the machinery necessary for the assembly-line production of the drug powering a terrifying and rapid rise of fatal overdoses across the United States and Canada, according to drug investigators and court documents.....

Genetic Testing Underused for GI Cancers (eg. BRCA vs Lynch syndrome)

Clinical Oncology News
  Drs. Idos and Yurgelun reported a financial relationship with Myriad.

The new findings come from a subanalysis of an ongoing multicenter, prospective clinical trial that is evaluating the clinical utility of multigene panels. The trial recruited 2,000 patients who had been referred for a 25-gene multigene panel test at three medical centers in California between August 2014 and June 2015. Patients with a 2.5% or greater probability of an identifiable mutation were invited to participate in the study. The panel tested 25 genes including BRCA1/2, EPCAM and MLH1 (Table).
Observing that there were few referrals for GI cancers during the interim analysis of this study, the researchers set out to quantify the extent of the problem. In an analysis of 500 patients, almost twice as many patients received genetic testing for a primary workup of HBOC as for a workup of GI cancer syndromes (66.4% vs. 28.8%)....

OXiGENE Receives Fast Track Designation for CA4P (fosbretabulin)

oncologynews
 

Status: Granted fast track designation for the treatment of platinum-resistant ovarian cancer

Significant Data:

• The company plans to conduct a randomized, double-blind, placebo-controlled study divided into two parts to maximize the speed of data collection.
• Stage 1 (n=up to 80 patients), serial interim analyses will be conducted to initially assess the efficacy and safety of the combination regimen when compared with standard of care.
• Stage 2 (n=approximately 356 patients) is a confirmatory Phase III study that would begin immediately after evidence of safety and efficacy is initially demonstrated in stage 1.
• The study is designed to build upon data from the GOG-0186I study, which demonstrated that CA4P improves progression-free survival in women with recurrent ovarian cancer when combined with bevacizumab (Avastin, Genentech) compared with bevacizumab alone.

Online comment sections may influence readers' opinions on health issues

sciencenews

Preclinical Investigations of PM01183 (Lurbinectedin) as a Single Agent or in Combination with Other Anticancer Agents for Clear Cell Carcinoma of the Ovary

open access
 

Introduction

Clear cell carcinoma (CCC) of the ovary is known to be less sensitive to platinum-based first-line chemotherapy and to be associated with a worse prognosis than serous adenocarcinoma (SAC), a more common histological subtype of ovarian cancer [1–4]. On the basis of previous preclinical and clinical studies suggested that irinotecan is more effective in CCC cells than other anticancer agents [5,6], a phase III study comparing the activity of irinotecan plus cisplatin versus carboplatin plus paclitaxel as a first-line treatment for CCC was conducted by the Japanese Gynecologic Oncology Group (JGOG) (protocol JGOG3017). However, this study failed to demonstrate the superiority of irinotecan plus cisplatin over carboplatin plus paclitaxel [7]. The lack of an effective chemotherapy for recurrent CCC is another important clinical problem [8]. Therefore, novel treatment strategies for CCC (for both first-line treatment and salvage treatment for recurrent disease) are required.
Trabectedin, an anticancer agent, has recently become the focus of attention for researchers investigating the treatment of CCC. On the basis of the results of a phase III clinical study (the OVA301 study) [9], the use of trabectedin in combination with pegylated liposomal doxorubicin was approved by the European Union in 2009 as a treatment for relapsed platinum-sensitive ovarian cancer. Trabectedin interacts with the nucleotide excision repair (NER) machinery, a versatile DNA repair system that acts against DNA damage induced by platinum-based agents [10], in an unusual manner. An elegant study demonstrated that NER-deficient cells (deficient in NER-related genes) exhibited resistance to trabectedin and that their sensitivity to trabectedin was restored by the transfection of the corresponding genes [11]. These findings are in clear contrast with the results obtained for platinum-based agents [12]. Thus, CCC that display increased NER activity [11], might be the candidates for trabectedin treatment. Consistent with the promising results obtained in preclinical studies of ovarian CCC [13,14], a phase II study involving recurrent ovarian CCC patients showed that combination therapy with trabectedin and temsirolimus exhibited significant activity, with a response rate of 14.3% and a clinical benefit rate of 42.9% [15....

AmbryShare - Ambry Genetics

About AmbryShare

 WHAT IS AMBRYSHARE? (patient section)

It’s a chance to help stop data hoarding and unlock the promise of the human genome project.

AmbryShare is a program based on Ambry’s commitment to sequence and share collective exome data of all consenting patients to understand the genetic basis of all human disease. It is comprised of three key pieces: The AmbryShare database, scientific community, and patients. Like an ecosystem, we need all these pieces to work together to help bring understanding to the relationships between genetics and human disease.

(AmbryShare) Genetics Company Makes Available Cancer Sequencing Database | Science and Enterprise

Science and Enterprise

  8 March 2016. A genetic testing company is making freely available a database of genomic sequencing data from patients with breast and ovarian cancer. The database, from 10,000 human genomes but with personal identity removed, is offered by Ambry Genetics in Aliso Viejo, California....

 AmbryShare, the database being made available to the public, will first offer data from its test archives, with the consent of the individuals and personal identifies removed. The data will contain exome sequences from breast and ovarian cancer patients. The company plans to continuously add data to AmbryShare, with up to 200,000 new entries added each year.

 

The AmbryShare service is now designed for bioinformatics specialists, but Ambry says it plans to add features for medical professionals and individuals. Eventually says the company, AmbryShare will be compatible with other open-source databases, including ClinVar from National Center for Biotechnology Information, to which Ambry already contributes data. To support AmbryShare, Dunlop is asking clinicians to provide as much family history information as possible through its online questionnaire.
Dunlop and Ambry are known as aggressive opponents of intellectual property restrictions on genetic data. The company fought efforts by genetic test competitor Myriad Genetics to block Ambry’s use of DNA-based tests for BRCA1 and BRCA2 genes associated with hereditary breast and ovarian cancer. In February 2015, Ambry settled a patent-infringement suit brought by Myriad Genetics, University of Utah Research Foundation, and others after a Federal appeals court in December 2014 ruled that claims from three of their patents covering DNA-based BRCA1 and BRCA2 tests did not contain subject matter eligible for patent protection.

Opinion: Early integration of palliative care in the care of women with advanced epithelial ovarian cancer: the time is now

open access

......Despite tremendous advances in surgery, primary chemotherapy and novel treatments for recurrent disease, the diagnosis of advanced epithelial ovarian cancer in 2016 remains ultimately fatal in the majority of cases. Additionally, both the disease and the associated adjuvant treatment are not without substantial effect on overall quality of life. The cancer causes symptoms, but the treatment can cause even more significant problems, including neuropathy, nausea, fatigue, anorexia, and pain, among others. As oncology providers, we have a natural tendency to focus on the cancer and response to treatment rather than on the suffering of our patients related to treatment. Our patients in turn are reluctant to report their symptoms for fear that we will stop or change their treatment. As a result, though the cancer may be temporarily beaten into submission by aggressive surgery and adjuvant therapy, the patient may be simultaneously suffering from treatment related symptoms that in some cases are permanent.
The early integration of palliative care in the treatment of women with advanced epithelial ovarian cancer allows us to address this quandary and not only improve quality of life, but in some cases also prolong life.....