Tuesday, March 22, 2016

Familial Risk in Patients With Carcinoma of Unknown Primary

abstract

Importance Carcinoma of unknown primary (CUP) accounts for 3% to 5% of all cancers and is associated with poor prognosis. Familial clustering of different cancer sites with CUP is unknown and may provide information regarding etiology, as well as elevated cancer risks in relatives.
Objective To quantify the risk of cancer by site in first- and second-degree relatives and first cousins of individuals with CUP.
Design, Setting, and Participants Nested case-control study of patients who received a diagnosis of CUP between 1980 and 2010 identified from the Utah Cancer Registry. Population controls with no CUP diagnosis were sex and age matched 10:1 to patients with CUP. Data about relatives were drawn from the Utah Population Database.
Main Outcomes and Measures Familial aggregation of cancer risk in relatives of cases compared with controls using Cox regression analysis.
Results For the 4160 index patients (median [interquartile range] age, 72 [62-81] years; 47.6% male) who had received a diagnosis of CUP, first-degree relatives were at an elevated risk of CUP themselves (hazard ratio [HR], 1.35 [95% CI, 1.07-1.70]), as well as lung (HR, 1.37 [95% CI, 1.22-1.54]), pancreatic (HR, 1.28 [95% CI, 1.06-1.54]), myeloma (HR, 1.28 [95% CI, 1.01-1.62]), and non-Hodgkin lymphoma (HR, 1.16 [95% CI, >1.00-1.35]) cancers compared with controls without CUP. When the analysis was restricted to relatives of cancer-free controls, additional increased risks for colon (HR, 1.19 [95% CI, 1.06-1.33]) and bladder (HR, 1.18 [95% CI, >1.00-1.38]) cancers were observed. Second-degree relatives of patients with CUP were at a slight increased risk of lung (HR, 1.14 [95% CI, 1.03-1.26]), pancreatic (HR, 1.17 [95% CI, 1.01-1.37]), breast (HR, 1.09 [95% CI, 1.02-1.16]), melanoma (HR, 1.09 [95% CI, >1.00-1.19]), and ovarian (HR, 1.19 [95% CI, 1.02-1.39]) cancers.
Conclusions and Relevance Relatives of patients with CUP are at increased risk of CUP and several other malignant neoplasms, including lung, pancreatic, and colon cancer. The present data may suggest sites of origin for CUP and provide cancer risk information for relatives of patients with CUP that can lead to effective intervention. Relatives of patients with CUP should be aware of the elevated risks for lung, pancreatic, and colon cancer and encouraged to modify risk factors and adhere to site-specific population cancer screening.

Chinese herbal medicine for menopausal symptoms. Cochrane Database Syst Rev. 2016

abstract

(blogger's note: 2 sources - see Cochrane plain english version below; not specific to surgical menopause)

BACKGROUND: Chinese herbal medicine (CHM) usage is expected to increase as women suffering from menopausal symptoms are seeking alternative therapy due to concerns from the adverse effects (AEs) associated with hormone therapy (HT). Scientific evidence for their effectiveness and safety is needed.

OBJECTIVES: To evaluate the effectiveness and safety of CHM in the treatment of menopausal symptoms.

SEARCH METHODS: We searched the Gynaecology and Fertility Group's Specialised Register of controlled trials, Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 3), MEDLINE, Embase, CINAHL, AMED, and PsycINFO (from inception to March 2015). Others included Current Control Trials, Citation Indexes, conference abstracts in the ISI Web of Knowledge, LILACS database, PubMed, OpenSIGLE database, and China National Knowledge Infrastructure database (CNKI, 1999 to 2015). Other resources included reference lists of articles as well as direct contact with authors.

SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing the effectiveness of CHM with placebo, HT, pharmaceutical drugs, acupuncture, or another CHM formula in women over 18 years of age, and suffering from menopausal symptoms.

DATA COLLECTION AND ANALYSIS: Two review authors independently assessed 864 studies for eligibility. Data extractions were performed by them with disagreements resolved through group discussion and clarification of data or direct contact with the study authors. Data analyses were performed in accordance with Cochrane Collaboration guidelines.

MAIN RESULTS: We included 22 RCTs (2902 women). Participants were from different ethnic backgrounds with the majority of Chinese origin. When CHM was compared with placebo (eight RCTs), there was little or no evidence of a difference between the groups for the following pooled outcomes: hot flushes per day (MD 0.00, 95% CI -0.88 to 0.89; 2 trials, 199 women; moderate quality evidence); hot flushes per day assessed by an overall hot flush score in which a difference of one point equates to one mild hot flush per day (MD -0.81 points, 95% CI -2.08 to 0.45; 3 RCTs, 263 women; low quality evidence); and overall vasomotor symptoms per month measured by the Menopause-Specific Quality of Life questionnaire (MENQOL, scale 0 to 6) (MD -0.42 points; 95% CI -1.52 to 0.68; 3 RCTs, 256 women; low quality evidence).In addition, results from individual studies suggested there was no evidence of a difference between the groups for daily hot flushes assessed by severity (MD -0.70 points, 95% CI -1.00, -0.40; 1 RCT, 108 women; moderate quality evidence); or overall monthly hot flushes scores (MD -2.80 points, 95% CI -8.93 to 3.33; 1 RCT, 84 women; very low quality evidence); or overall daily night sweats scores (MD 0.07 points, 95% CI -0.19 to 0.33, 1 RCT, 64 women; low quality evidence); or overall monthly night sweats scores (MD 1.30 points, 95% CI -1.76 to 4.36, 1 RCT, 84 women; very low quality evidence). However one study using the Kupperman Index reported that overall monthly vasomotor symptom scores were lower in the CHM group (MD -4.79 points, 95% CI -5.52 to -4.06; 1 RCT, 69 women; low quality evidence).When CHM was compared with hormone therapy (HT) (10 RCTs), only two RCTs reported monthly vasomotor symptoms using MENQOL. It was uncertain whether CHM reduces vasomotor symptoms (MD 0.47 points, 95% CI -0.50 to 1.44; 2 RCTs, 127 women; very low quality evidence).Adverse effects were not fully reported in the included studies. Adverse events reported by women taking CHM included mild diarrhoea, breast tenderness, gastric discomfort and an unpleasant taste. Effects were inconclusive because of imprecise estimates of effects: CHM versus placebo (RR 1.51; 95% CI 0.69 to 3.33; 7 trials, 705 women; I² = 40%); CHM versus HT (RR 0.96; 95% CI 0.66 to 1.39; 2 RCTs, 864 women; I² = 0%); and CHM versus specific conventional medications (such as Fluoxetine and Estazolam) (RR 0.20; 95% CI 0.03 to 1.17; 2 RCTs, 139 women; I² = 61%).

AUTHORS' CONCLUSIONS: We found insufficient evidence that Chinese herbal medicines were any more or less effective than placebo or HT for the relief of vasomotor symptoms. Effects on safety were inconclusive. The quality of the evidence ranged from very low to moderate; there is a need for well-designed randomised controlled studies.

Plain language summary

Title: Chinese herbal medicines for menopausal symptoms

Review Question: Are Chinese herbal medicines effective and safe for relieving menopausal symptoms?
Background: Menopause usually takes place when a woman is around 51 years of age. Women can experience symptoms such as hot flushes, sweats, poor sleep, joint pains, anxiousness, dry skin and vagina when the organs which produce female hormones slow down. Usually hormone therapy (HT) is prescribed to reduce the symptoms.
Due to concerns on long term use of HT resulting in adverse effects, women have been looking for alternative treatments to relieve their symptoms. Chinese herbal medicines (CHM) is one of the popular choices. Although CHM has been used for a very long time clinically, its effectiveness and long-term safety remained unanswered from a scientific perspective.
Study characteristics: This review examined 22 randomised clinical trials where 2902 women took part in the studies; 1499 in the CHM group and 1403 in the control group which might include a placebo (non-active compound made to look, taste and smell the same as the study compound) or a drug or HT or another CHM formula (different from the one being tested). Most of the studies had a trial period for 12 weeks. The data are current to March 2015.
Key results: We found insufficient evidence that CHM were any more or less effective than placebo or HT for the relief of vasomotor symptoms. Adverse effects were not well reported, some women taking CHM reported mild diarrhoea, breast tenderness, gastric discomfort and an unpleasant taste. Effects on safety were inconclusive.
Quality of the evidence: The quality of the evidence ranged from very low to moderate. The studies did not produce good quality evidence to allow the authors to draw a conclusive statement regarding the effectiveness or safety of CHM.

The value of surrogate endpoints for predicting real-world survival across five cancer types

abstract

breast, colorectal, lung, ovarian, and pancreatic cancer
72,600 SEER-Medicare patients similar to RCT participants

Objective It is unclear how well different outcome measures in randomized controlled trials (RCTs) perform in predicting real-world cancer survival. We assess the ability of RCT overall survival (OS) and surrogate endpoints – progression-free survival (PFS) and time to progression (TTP) – to predict real-world OS across five cancers.

Conclusions Among the five tumor types investigated, trial OS and surrogates were each independently valuable in predicting real-world OS outcomes for patients similar to trial participants. In broader real-world populations, however, trial OS added little incremental value over surrogates alone.

Rajavithi-ovarian cancer predictive score (R-OPS): A new scoring system for predicting ovarian malignancy in women presenting with a pelvic mass

abstract

OBJECTIVE:

To develop a new scoring system based on menopausal status, ultrasound (US) findings, serum cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) to predict ovarian cancer (OC) in women presenting with a pelvic or adnexal mass.

CONCLUSIONS:

The new R-OPS scoring system showed good discrimination between non-cancerous lesions and OC. However, a prospective study in a different setting is required to confirm these preliminary data.

Safety of bevacizumab in clinical practice for recurrent ovarian cancer: A retrospective cohort study

open access

The primary aim of the present study was to describe the safety profile of bevacizumab in routine practice. The most common AEs observed were hypertension, proteinuria and epistaxis (open access), which are known side effects of bevacizumab treatment. The risk of the occurrence of such events may be dose-associated, as indicated by the multivariate Cox regression analysis and by previously published data (35–37).

Endpoints assessment (n=156)

The safety profile of bevacizumab was the primary endpoint of the study. Secondary endpoints included the usage conditions of bevacizumab (e.g., dose schedule, concurrent chemotherapy) and survival rates. During bevacizumab therapy, AEs potentially attributable to the monoclonal antibody were described according to the Common Terminology Criteria for Adverse Events, Version 3.0 (31). The AEs of particular interest in the present study were defined prior to data collection, and focused on the following: Hypertension, proteinuria, epistaxis, bleeding or hemorrhage, venous thromboembolic event, arterial thromboembolic event, wound healing complication, intestinal perforation, gastrointestinal (GI) fistula, reversible posterior leak-encephalopathy syndrome and pulmonary hypertension.
Overall survival (OS) was determined from the time of bevacizumab introduction to the time of the mortality of the patients (due to any cause). Progression-free survival (PFS) was determined from the time of bevacizumab introduction to disease progression or patient mortality. The data for patients who were alive without undergoing disease progression were censored at the date of their last assessment.
During bevacizumab treatment, disease progression was evaluated by each treating physician through clinical examination and/or carbohydrate antigen 125 (CA125) levels and/or radiological examination. Biological progression was defined, according to the Gynecological Cancer Intergroup criteria (32), as an increase of CA125 levels. Determination of radiological and clinical progression relied on physician judgement.

Phase III RCT comparing primary surgery vs neoadjuvant chemotherapy in advanced epithelial ovarian cancer...

abstract

Phase III randomised clinical trial comparing primary surgery versus neoadjuvant chemotherapy in advanced epithelial ovarian cancer with high tumour load (SCORPION trial): Final analysis of peri-operative outcome.

OBJECTIVE:

To establishing whether neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) is superior primary debulking surgery (PDS) in terms of clinical outcome as well as peri-operative morbidity in advanced epithelial ovarian cancer (AEOC) endowed with high tumour load (HTL).

CONCLUSIONS:

Perioperative moderate/severe morbidity as well as QoL scores were shown to be more favourable in NACT/IDS (neo-interval) arm than PDS (primary) in AEOC patients with very HTL (high tumuor load) . Completion of patient enrolment and analysis of survival data will clarify whether PDS with such a high rate of severe complications is an acceptable treatment in AEOC women with HTL.

Chemotherapy is of Value in Second Line and Beyond, Relapsed High-grade, Serous Epithelial Ovarian Cancer (Oral Etoposide)

abstract

Chemotherapy is of Value in Second Line and Beyond, Relapsed High-grade, Serous Epithelial Ovarian Cancer: An Analysis of Outcomes Obtained With Oral Etoposide

Background: Epithelial ovarian cancer is chemotherapy responsive, and multiple lines of chemotherapy are often given. However, there are few data with regard to its effectiveness in later lines. Our aim was to assess its benefit in the high-grade, serous subtype relative to the line of therapy, using etoposide as the example. Methods: Women treated with oral etoposide at the British Columbia Cancer Agency upon recurrence/progression in the years 2000 to 2010 were reviewed. Kaplan-Meier and Cox regression methods were used to correlate line of therapy with overall survival, progression-free survival, and interval between etoposide initiation and next progression or death (EPFS).
Results: A total of 219 women, median age 61, received etoposide as second (17%), third (30%), fourth (26%), fifth (17%), and sixth to eighth (11%) lines of therapy. The median number of cycles was 2 to 4. Patients who received etoposide as fourth-line to eighth-line treatment had a significantly longer median overall survival and initial progression-free survival (from diagnosis to first relapse) when compared with those who received it as second-line to third-line treatment (47.8 vs. 25.8 mo, P<0.0001; and 16.1 vs. 12.1 mo, P<0.0001, respectively); that is, a selected population of survivors received it later in the course of their disease. On univariate analysis, there was no significant difference in median EPFS (range, 2 to 2.9 mo) on the basis of line of therapy. On multivariate analysis, the hazard ratios improved through the third, fourth, and fifth lines (hazard ratios: 0.82, 0.77, and 0.34, respectively), and was statistically significant in the fifth line. The a priori-defined endpoint of clinical benefit was the "percentage not progressing at 3 months," and this was achieved in 32% to 48%.
Conclusions: In this retrospective study, a similar degree of benefit from etoposide, as defined by the percentage remaining progression free at 3 months, was seen in all lines of therapy.

Monday, March 21, 2016

Frozen Section Helps Diagnose Early Ovarian Cancer (Cochrane/Reuters/Medscape)

(Medscape) Reuters Health
March 20, 2016:
NEW YORK (Reuters Health) - Intraoperative frozen section analysis can help distinguish early ovarian cancer from a benign mass, though it is less accurate for borderline tumors, according to a Cochrane review.
Dr. Nithya D.G. Ratnavelu, from Northern Gynaecological Oncology Centre, Gateshead, UK, and colleagues used data from 38 studies to assess the accuracy of frozen section for diagnosing suspicious pelvic masses. Overall, 3200 women had invasive cancer, 1055 had borderline tumors and 6926 had benign tumors, as determined by paraffin section. The cohort included 3953 participants with a frozen section result of either borderline or invasive cancer.
"Studies with small numbers of disease-negative cases (borderline cases) had more variation in estimates of specificity," the authors wrote in the Cochrane Database of Systematic Reviews.
A frozen section diagnosis of benign mass would be right 94% of the time, and a frozen section diagnosis of malignancy would be right 99% of the time, according to the March 1 report.
In contrast, a frozen section diagnosis of borderline tumor would turn out to be cancer only 21% of the time.....

Diagnostic Test Accuracy Review

Intraoperative frozen section analysis for the diagnosis of early stage ovarian cancer in suspicious pelvic masses

Objectives

To assess the diagnostic test accuracy of frozen section (index test) to diagnose histopathological ovarian cancer in women with suspicious pelvic masses as verified by paraffin section (reference standard).....

Author Response: re - adjuvant hormone therapy in epithelial ovarian cancer

Reply to S. Kilickap et al, Y. Karakas et al, and I.A. Voutsadakis

+ Author Affiliations

The Institute of Cancer Research, Sutton, London, United Kingdom

Corresponding author: James P. Morden, MSc, Clinical Trials and Statistics Unit, Division of Clinical Studies, The Institute of Cancer Research, 15 Cotswold Rd, Sutton, London, United Kingdom

We thank Kilickap and Tural,¹ Karakas et al,² and Voutsadakis³ for their correspondence regarding the Adjuvant Hormone Therapy (AHT) trial results in our recent article in Journal of Clinical Oncology,⁴ and we would like to respond to the comments raised.

Although the correspondents are correct in their assertion that a more marked numerical difference between randomly assigned treatment groups was seen with respect to nonovarian cancer deaths (AHT, three of 75 [4%]; control, 12 of 75 [16%]) than to ovarian cancer deaths (AHT, 50 of 75 [67%]; control, 56 of 75 [75%]), we do not feel that this invalidates the most important finding of our study (ie, that if ovarian cancer treatment results in debilitating menopausal symptoms, then we do not have evidence that hormone-replacement therapy [HRT] should be withheld). We recognize that in any study of this size there is a risk of anomalous findings, but we have observed no evidence of an increase in the risk of death with HRT.

The AHT trial was initiated in 1990; as acknowledged in our discussion, there were a number of data items that would now be collected as standard in a newly initiated trial, which were not collected at the time......

REFERENCES

Better Evidence About Older Adults With Cancer Will Not Improve Survival Rates Alone; Clinicians Need More Support

Letter to the Editor

To the Editor:

Macmillan Cancer Support welcomes the call by Hurria et al¹ to improve the evidence base for treating older adults with cancer. Cancer is primarily a disease of age, so it is essential that clinicians, researchers, and patients work together to develop our understanding of the suitability of cancer treatments for older people.

However, evidence alone will not be enough to improve survival rates. It is also essential that clinicians have access to tools that allow them to use this evidence appropriately in their day-to-day decision making.

Much like in the United States, older adults (age ≥ 65 years) in the United Kingdom comprise a significant proportion (63%) of the cancer population.^2,3....

March 21st: On Adjuvant Hormone Therapy in Epithelial Ovarian Cancer

On Adjuvant Hormone Therapy in Epithelial Ovarian Cancer

(Norgestrel (INN, USAN, BAN, JAN) (brand names Logynon, Nordette, Eugynon, Microgynon, Ovran, Ovranette, Trinordiol, numerous others) is a steroidal progestin that has been used in hormonal contraceptives. It is a mixture of two stereoisomers, dextronorgestrel (CAS# 797-64-8 ) and levonorgestrel (CAS# 797-63-7 ).)

To the Editor:

In their recent article in Journal of Clinical Oncology, Eeles et al¹ discuss the adjuvant hormone-replacement therapy (AHT) trial, a randomized trial of 150 patients with ovarian cancer, which included patients across different epithelial cancer histologies and stages who, as a result, were expected to have significantly different outcomes, independent of AHT intervention. The planned duration of replacement as per the protocol was 5 years, but patients stayed on treatment for an average of 1.14 years. Most women were postmenopausal or perimenopausal. Fifty-three of the 72 patients who received therapy in the treatment arm had an estrogen-only preparation, whereas 19 patients received estrogens combined with norgestrel. Doses actually received are not given (suggested doses are listed in the protocol presented in the appendix), which is a significant shortcoming for a study that examines the effect of a pharmacologic intervention.......

REFERENCES

Oncolytics Biotech® Inc. Reports Data from Randomized Phase 2 Study of REOLYSIN® in Ovarian Cancer (measured by CA125)

press release

Intent-to-Treat Analysis Shows Statistically Significant Reduction in Tumour Burden as Measured by CA-125

Update Highlights
Response Using CA-125 Measurements by Treatment Among all Patients

CA-125 Response	Treatment
	Paclitaxel	Paclitaxel+REOLYSIN^®	Total
Full Response	1 (1.85%)	5 (9.26%)	6
Partial Response	9 (16.67%)	7 (12.96%)	16
Stable Disease	3 (5.56%)	12 (22.22%)	15
Progressive Disease	0 (0.00%)	2 (3.70%)	2
Indeterminate	16 (29.63%)	13 (24.07%)	29
Not Evaluable	25 (46.30%)	15 (27.78%)	40
Total	54	54	108

Tipping the balance (unreported serious adverse drug reactions)

open access
Tipping the balance - Cover-Story - January-February-2016 Issue 70 - Cancer World - Shaping the future of cancer care

Almost four in ten serious adverse drug reactions now listed in the labels of 12 targeted cancer therapies were not mentioned in the studies that led to their approval. Half the serious reactions that were missed are potentially fatal. How can we improve the way we investigate and report the side effects of new drugs?

Questions are being raised about the accuracy and integrity of reports from pivotal clinical trials that provide the evidence for licensing cancer drugs. There is increasing concern that reports overstate the effectiveness of innovative drugs in a real world setting, because patients on trials are healthier and fitter than most of the people it will be used in, and understate side effects. This distorts the information used by clinicians to define the recommended dose, by regulators to assess the risk–benefit profile, and by patients to choose between treatment options.....

SGO (meeting): Studies Hone Prediction of Ovarian Ca Outcomes

Medpage Today

Action Points

Note that these studies were published as abstracts and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
A study examining mutations in homologous recombination genes (which include the BRCA-family) found that they were protective in terms of survival in women with treated ovarian cancer.

SGO: Abstract and late-breaking abstract titles now available

SGO

Session times, abstract titles, authors and institutions and late-breaking abstracts are now available online for the SGO Annual Meeting in San Diego. Full abstracts will become available on the day of the session on which they will be presented.

An Immunohistochemical Algorithm for Ovarian Carcinoma Typing-funded in part by Terry Fox Foundation

Abstract - open access (pdf)

There are 5 major histotypes of ovarian carcinomas. Diagnostic typing criteria have evolved over time, and past cohorts may be misclassified by current standards. Our objective was to reclassify the recently assembled Canadian Ovarian Experimental Unified Resource and the Alberta Ovarian Tumor Type cohorts using immunohistochemical (IHC) biomarkers and to develop an IHC algorithm for ovarian carcinoma histotyping. A total of 1626 ovarian carcinoma samples from the Canadian Ovarian Experimental Unified Resource and the Alberta Ovarian Tumor Type were subjected to a reclassification by comparing the original with the predicted histotype. Histotype prediction was derived from a nominal logistic regression modeling using a previously reclassified cohort (N=784) with the binary input of 8 IHC markers. Cases with discordant original or predicted histotypes were subjected to arbitration.

After reclassification, 1762 cases from all cohorts were subjected to prediction models (χ Automatic Interaction Detection, recursive partitioning, and nominal logistic regression) with a variable IHC marker input. The histologic type was confirmed in 1521/1626 (93.5%) cases of the Canadian Ovarian Experimental Unified Resource and the Alberta Ovarian Tumor Type cohorts. The highest misclassification occurred in the endometrioid type, where most of the changes involved reclassification from endometrioid to high-grade serous carcinoma, which was additionally supported by mutational data and outcome. Using the reclassified histotype as the endpoint, a 4-marker prediction model correctly classified 88%, a 6-marker 91%, and an 8-marker 93% of the 1762 cases. This study provides statistically validated, inexpensive IHC algorithms, which have versatile applications in research, clinical practice, and clinical trials.

Saturday, March 19, 2016

The health-related quality of life journey of gynecologic oncology surgical patients...

abstract
The health-related quality of life journey of gynecologic oncology surgical patients: Implications for the incorporation of patient-reported outcomes into surgical quality metrics

Highlights

•: Temporary declines in functional QOL are balanced by improvements in emotional QOL and anxiety.
•: Commonly used HRQOL instruments may not best reflect the perioperative surgical experience.

Abstract

Objective

To report the changes in patient-reported quality of life for women undergoing gynecologic oncology surgeries.

Methods

In a prospective cohort study from 10/2013–10/2014, women were enrolled pre-operatively and completed comprehensive interviews at baseline, 1, 3, and 6 months post-operatively. Measures included the disease-specific Functional Assessment of Cancer Therapy-General (FACT-GP), general Patient Reported Outcome Measure Information System (PROMIS) global health and validated measures of anxiety and depression. Bivariate statistics were used to analyze demographic groups and changes in mean scores over time.

Results

Of 231 patients completing baseline interviews, 185 (80%) completed 1-month, 170 (74%) 3-month, and 174 (75%) 6-month interviews. Minimally invasive (n = 115, 63%) and laparotomy (n = 60, 32%) procedures were performed. Functional wellbeing (20 → 17.6, p < 0.0001) decreased at 1-month, and recovered by 3 and 6 months. Emotional wellbeing increased (16.3 → 20.1, p < 0.0001) and anxiety decreased (54.2 → 49.0, p < 0.0001) at 1-month, and were stable at 3 and 6 months. Physical wellbeing scales were not sensitive to surgery. These patterns were consistent across procedure type, cancer diagnosis, and adjuvant therapy administration. In an exploratory analysis of the interaction of QOL and quality, patients with increased postoperative healthcare resource use were noted to have higher baseline levels of anxiety.

Conclusions

For women undergoing gynecologic oncology procedures, temporary declines in functional wellbeing are balanced by improvements in emotional wellbeing and decreased anxiety symptoms after surgery. Not all commonly used QOL surveys are sensitive to changes during the perioperative period and may not be suitable for use in surgical quality metrics.

The influence of clinical and genetic factors on patient outcome in small cell carcinoma of the ovary, hypercalcemic type

abstract

Highlights

•: All SCCOHT patients should undergo genetic testing for germline SMARCA4 mutations.
•: HDC-aSCR may offer SCCOHT patients the best outcome, and should be studied further.

Abstract

Objective

Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is an aggressive tumor, with long term survival at ~ 30% in early stage disease. SCCOHT is caused by germline and somatic SMARCA4 mutations, but the effect of the mutation type on patients remains unknown. Furthermore, the rarity of SCCOHT has resulted in varied treatment, with no standardized protocols. We analyzed 293 cases to determine the effect of treatment modalities and SMARCA4 mutations on patient diagnosis and outcome.

Methods

In 293 SCCOHT patients we collected information on age and stage at diagnosis, treatment modality (surgery, chemotherapy, radiotherapy, and/or high-dose chemotherapy with autologous stem cell rescue (HDC-aSCR)), SMARCA4 mutation origin (germline/somatic), and overall survival. Cox analysis and log-rank tests were performed on 257 cases with available survival data.

Ovarian Cancer and Us blog: top page views (spoiler alert) #1 - Avastin #2 - 23andMe

http://ovariancancerandus.blogspot.com/feeds/posts/default


Bevacizumab helped resolve pericardial and pleural... Mar 17, 2016
23andMe Opens Up About Direct-to-Consumer Genetic ... Mar 11, 2016
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Ovarian Cancer and Us blog: top page views this week - by country

http://ovariancancerandus.blogspot.com/feeds/posts/default


#1 United States
#2 Germany
#3 Canada
#4 Poland
#5 Spain

open access: Risks of Less Common Cancers in Proven Mutation Carriers With Lynch Syndrome

(2012) Risks of Less Common Cancers in Proven Mutation Carriers With Lynch Syndrome

Among the seven less common cancer types considered in our analysis, small bowel and ovarian cancer showed the earliest mean ages at diagnosis (mean, 46 years for small bowel and 44 years for ovarian cancer).

Figures 1 and 2 show the age-dependent cumulative risks for the seven cancer types compared by gene and sex (univariate comparison). Table 2 gives information about mean ages at diagnosis, cumulative lifetime risks at 70 years, and SIRs with regard to the general population. Table 3 summarizes the results of multivariate modeling of sex and mutated gene, adjusted for registry and year of birth.

Introduction
In this retrospective cohort study, we investigated the risks of less common cancers in patients with LS. We were particularly interested in describing risk differences by sex and mutated MMR gene (MLH1, MSH2, and MSH6). Colorectal cancer and endometrial cancer were not included in this analysis because patients were preferentially ascertained on the basis of the presence of these cancers in their families. Therefore, in retrospective studies, the risks for these cancers are likely to be largely overestimated if the analysis does not account for ascertainment bias.^21....

Pathologists identify new potential target in ovarian serous cancer: HER4 expression.....

medical news
HER4 expression may be linked to chemotherapy resistance, lower survival rate

Moffitt pathologists looked at the levels of HER4 expression in 100 ovarian serous carcinoma specimens. They found that the samples that contained the HER4 expression were linked to chemotherapy resistance and a shortened life span. This means HER4 may be a prognostic and potentially a predictive marker in ovarian serous cancer, but more studies are needed. In addition HER4 could potentially become a target for therapy.

reprinted from materials provided by H. Lee Moffitt Cancer Center & Research Institute. Note: Materials may be edited for content and length.

Adjunct histamine blockers as premedications to prevent carboplatin hypersensitivity reactions

Abstract

OBJECTIVE:

The objective of this study is to evaluate the impact of premedications given as an adjunct to carboplatin on the incidence of hypersensitivity reactions in women with ovarian cancer. Medications of interest include a histamine₁ (H₁ ) and histamine₂ (H₂ ) blocker in addition to dexamethasone.

METHODS:

This was a retrospective chart review evaluating the addition of an H₁ and H₂ blocker in addition to dexamethasone as standard premedications on the incidence of carboplatin hypersensitivity reactions (CHR) in women with ovarian cancer.

MAIN RESULTS:

The odds ratio for premedication use was 0.46 with a 95% confidence interval (0.17-1.27), suggesting that patients with premedication use had approximately one-half of the risk of CHR compared to patients without premedication. The overall incidence of CHR decreased from 7.9% at baseline to 3.2% after the addition of premedications. The incidence of CHR was 5.2% in patients with recurrent or progressive disease (N=58) compared to 2.1% in the newly diagnosed patients (N=96). Lifetime dose greater than 3377 milligrams, number of cycles greater than six, and progressive or recurrent disease were predictive factors of CHR in women with ovarian cancer.

PRINCIPAL CONCLUSIONS:

Total lifetime exposure to carboplatin remains the greatest predictive factor of CHR in women with ovarian cancer. While data analysis indicates the addition of premedications for all ovarian cancer patients receiving carboplatin did not result in a statistically significant reduction in CHR, a patient benefit in CHR reduction was observed. A prospective study is needed to confirm these findings.

Primary Glial and Neuronal Tumors of the Ovary or Peritoneum: A Clinicopathologic Study of 11 Cases

abstract

Primary glial and neuronal tumors of the ovary or peritoneum are rare neuroectodermal-type tumors similar to their counterparts in the central nervous system. We retrospectively reviewed 11 cases. These cases included 4 ependymomas, 6 astrocytic tumors, and 1 neurocytoma. Patients' age ranged from 9 to 50 years (mean, 26 y; median, 24 y). All ependymal tumors with detailed clinical history (n=3) were not associated with any other ovarian neoplasm. In contrast, all astrocytic tumors were associated with immature teratoma (n=4), mature cystic teratoma (n=1), or mixed germ cell tumor (n=1). The neurocytoma arose in association with mature teratomatous components in a patient with a history of treated mixed germ cell tumor. Immunohistochemical staining showed that 7 of 7 ependymal and astrocytic tumors (100%) were positive for glial fibrillary acidic protein, and 2 of 2 ependymomas (100%) were positive for both estrogen and progesterone receptors. The neurocytoma was positive for synaptophysin and negative for S100 protein, glial fibrillary acidic protein, and SALL4. No IDH1-R132H mutation was detected in 2 of 2 (0%) astrocytomas by immunohistochemistry. Next-generation sequencing was performed on additional 2 ependymomas and 2 astrocytomas but detected no mutations in a panel of 50 genes that included IDH1, IDH2, TP53, PIK3CA, EGFR, BRAF, and PTEN. Follow-up information was available for 8 patients, with the follow-up period ranging from 4 to 59 months (mean, 15 mo; median, 8.5 mo), of which 3 had no evidence of disease and 5 were alive with disease. In conclusion, primary glial and neuronal tumors of the ovary can arise independently or in association with other ovarian germ cell tumor components. Pathologists should be aware of these rare tumors and differentiate them from other ovarian neoplasms. Even though an IDH1 or IDH2 mutation is found in the majority of WHO grade II and III astrocytomas, and in secondary glioblastomas arising from them, such mutations were not identified in our series, suggesting that these tumors are molecularly different from their central nervous system counterparts despite their morphologic and immunophenotypic similarities.

Caregiver Reaction Scale

Caregiver Burden in End-Stage Ovarian Cancer(MSK Cancer Center/Nursing Rockefeller)

Caregiver Burden

Memorial Sloan Kettering Cancer Center.
²Heilbrunn Family Center for Research Nursing at Rockefeller University.

Abstract

BACKGROUND:

Caregiver burden associated with caring for women with ovarian cancer has received limited focus. However, these patients often have complex needs, requiring a high level of care at home and imposing substantial burdens on caregivers.

OBJECTIVES:

This pilot study assessed the level of caregiver burden experienced by the primary caregivers of patients with end-stage ovarian cancer and identified variables associated with caregiver burden.

METHODS:

Caregiver burden was assessed using the Caregiver Reaction Assessment. Fifty caregivers completed an anonymous and voluntary survey. Pearson correlations and independent samples t tests were used to analyze data.

FINDINGS:

Most participants were Caucasian, married or living with a partner, and college graduates, with an annual household income of less than $90,000. Caregiver ages ranged from 29-81 years. Participants agreed most with the self-esteem scale, indicating they had pride in caring for their loved ones. Disrupted schedules and financial problems were the most burdensome factors in providing care. Because financial issues affected caregiver burden, nurses should facilitate interdisciplinary support. Future research is needed to determine the impact of nurse-led interventions to reduce caregiver burden.

Genetic anticipation in BRCA1/BRCA2 families after controlling for ascertainment bias and cohort effect. - PubMed - NCBI

abstract

BACKGROUND:

Genetic anticipation, the earlier onset of disease in successive generations, has been reported in hereditary breast and ovarian cancer syndrome (HBOC), but little is known about its underlying mechanisms. Ascertainment bias has been suggested as a reason in previous studies. Likewise, cohort effect, which may be caused by environmental factors, can be misinterpreted as genetic anticipation.

METHODS:

The authors reviewed the pedigrees of 176 kindreds, segregating those with deleterious mutations in breast cancer genes 1 and 2 (BRCA1/BRCA2) who had at least 2 consecutive generations of the same cancer (breast or ovarian). By using mutation probabilities as analytical weights in weighted random-effect models, generational differences in the age at onset of breast/ovarian cancer were calculated. The analyses were further controlled for ascertainment bias by excluding probands and adjusting for birth-cohort effect in the anticipation models.

RESULTS:

The mean age at the onset of breast cancer for the probands' generation was 41.9 years, which was 6.8 years and 9.8 years earlier than the parents' and grandparents' generations, respectively. The anticipation effect for breast cancer remained significant after excluding the probands. There was a birth-cohort effect: patients who were born in 1930s and 1940s had breast cancer 5.0 years and 7.6 years earlier than patients who were born before 1920. The difference in breast cancer age of onset across generations was no longer significant after adjusting for birth-cohort effect.

CONCLUSIONS:

The observed anticipation effect was driven mainly by a decrease in age of onset across birth cohorts, underscoring the need for risk-reducing interventions that target changing environmental/lifestyle factors in BRCA1/BRCA2 carriers.

HNPCC/Lynch syndrome in three dimensions

abstract

BACKGROUND:

Hereditary non-polyposis colorectal cancer (HNPCC) is defined by family history, and Lynch syndrome (LS) is defined genetically. However, universal tumour testing is now increasingly used to screen for patients with defective mismatch repair. This mixing of the results of family history, tumour testing and germline testing produces multiple permutations and combinations that can foster confusion. We wanted to clarify hereditary colorectal cancer using the three dimensions of classification: family history, tumour testing and germline testing.

METHODS:

Family history (Amsterdam I or II criteria versus not Amsterdam criteria) was used to define patients and families with HNPCC. Tumour testing and germline testing were then performed to sub-classify patients and families. The permutations of these classifications are applied to our registry.

RESULTS:

There were 234 HNPCC families: 129 had LS of which 55 were three-dimensional Lynch (family history, tumour testing and germline testing), 66 were two-dimensional Lynch and eight were one-dimensional Lynch. A total of 10 families had tumour Lynch (tumours with microsatellite instability or loss of expression of a mismatch repair protein but an Amsterdam-negative family and negative germline testing), five were Lynch like (Amsterdam-positive family, tumours with microsatellite instability or loss of expression of a mismatch repair protein on immunohistochemistry but negative germline testing), 26 were familial colorectal cancer type X and 95 were HNPCC.

CONCLUSION:

Hereditary colorectal cancer can be confusing. Sorting families in three dimensions can clarify the confusion and may direct further testing and, ultimately, surveillance.

Friday, March 18, 2016

American Medical Association Joins AllTrials Campaign for Clinical Trial Transparency

AllTrials

The incidence of leukaemia in women with BRCA1 and BRCA2 mutations: an International Prospective Cohort Study

Abstract
The incidence of leukaemia in women with BRCA1 and BRCA2 mutations: an International Prospective Cohort Study

Background:

Germline mutations in BRCA1 and BRCA2 increase the susceptibility to develop breast and ovarian cancers as well as increase the risk of some other cancers. Primary objective was to estimate the risk of leukaemia in BRCA1 and BRCA2 mutation carriers.

Methods:

We followed 7243 women with a BRCA1 or a BRCA2 mutation for incident cases of leukaemia. We used the standardised incidence ratio (SIR) to estimate the relative risk of leukaemia, according to mutation and history of breast cancer.

Results:

We identified five incident cases of leukaemia (two BRCA1, three BRCA2). All five women had a prior history of breast cancer and four had received chemotherapy. The mean time from breast cancer diagnosis to the development of leukaemia was 10.2 years (range 3–18 years). The SIR for BRCA1 carriers was 0.66 (95% CI: 0.11–2.19, P=0.61) and the SIR for BRCA2 carriers was 2.42 (95% CI: 0.61–6.58, P=0.17). The SIR was significantly higher than expected for women with a BRCA2 mutation and breast cancer (SIR=4.76, 95% CI:1.21–12.96, P=0.03), in particular for women who received chemotherapy (SIR=8.11, 2.06–22.07, P=0.007).

Conclusions:

We observed an increased risk of leukaemia in women with a BRCA2 mutation who receive chemotherapy for breast cancer.

Does the Presence of Endometriosis Affect Prognosis of Ovarian Cancer?

abstract

Ovarian cancers diagnosed between 2000 and 2013 were examined and cases with and without endometriosis compared. Among 139 epithelial ovarian, there were 49 (35%) with endometriosis and 90 (65%) without endometriosis. Endometriosis associated ovarian cancers were more likely to be confined to the pelvis (54% vs. 9%, p < 0.0001) and lower grade (51% vs. 29%, p = 0.014). Younger age and earlier stage independently predicted the presence of endometriosis (p = 0.0011 and p < 0.0001, respectively). Ovarian cancer patients with endometriosis had improved PFS and OS [(HR = 0.20; 95% CI, 0.09–0.43), (HR = 0.18; 95% CI, 0.04–0.81)], compared to patients without endometriosis; however, endometriosis had no independent prognostic significance.

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Title: Chinese herbal medicines for menopausal symptoms

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Monday, March 21, 2016

Objectives

Reply to S. Kilickap et al, Y. Karakas et al, and I.A. Voutsadakis

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To the Editor:

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Saturday, March 19, 2016

Highlights

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Methods

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Highlights

Abstract

Objective

Methods

OBJECTIVE:

METHODS:

MAIN RESULTS:

PRINCIPAL CONCLUSIONS:

Abstract

BACKGROUND:

OBJECTIVES:

METHODS:

FINDINGS:

BACKGROUND:

METHODS:

RESULTS:

CONCLUSIONS:

The observed anticipation effect was driven mainly by a decrease in age of onset across birth cohorts, underscoring the need for risk-reducing interventions that target changing environmental/lifestyle factors in BRCA1/BRCA2 carriers.

BACKGROUND:

METHODS:

RESULTS:

CONCLUSION:

Friday, March 18, 2016

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