abstract
Sunday, April 26, 2015
Removal of Ovaries associated with decrease in breast cancer death in women with cancer, BRCA1 mutation
Science
Story Source:
The above story is based on materials provided by The JAMA Network Journals. Note: Materials may be edited for content and length.
The above story is based on materials provided by The JAMA Network Journals. Note: Materials may be edited for content and length.
Journal Reference:
- Kelly Metcalfe, Henry T. Lynch, William D. Foulkes, Nadine Tung, Charmaine Kim-Sing, Olufunmilayo I. Olopade, Andrea Eisen, Barry Rosen, Carrie Snyder, Shelley Gershman, Ping Sun, Steven A. Narod. Effect of Oophorectomy on Survival After Breast Cancer inBRCA1andBRCA2Mutation Carriers. JAMA Oncology, 2015; DOI: 10.1001/jamaoncol.2015.0658
The ARID1A pathway in ovarian clear cell and endometrioid carcinoma, contiguous endometriosis, and benign endometriosis
Abstract
Objective
To assess ARID1A-encoded protein (BAF250a) and phosphorylated AKT (pAKT) expression, apoptosis, and the DNA damage response pathway in endometrioid and clear cell ovarian cancers (endometriosis-associated ovarian cancers [EAOCs]), and benign endometriotic ovarian cysts.Methods
In a retrospective study, tissue samples were reviewed from patients who had undergone surgery for EAOC or endometriotic ovarian cysts at a center in Montreal, QC, Canada, between 2000 and 2012. A tissue microarray including cases of endometrioid carcinoma, clear cell carcinoma, contiguous endometriosis (i.e. apparently benign endometriosis near the EAOC), and benign endometriotic ovarian cysts, was analyzed for the expression of various proteins.Results
Loss of BAF250a expression was seen in 13 (22%) of 59 endometrioid cancers, 17 (47%) of 36 clear cell cases, 8 (44%) of 18 contiguous endometriosis cases, and 3 (8%) of 66 benign endometriotic ovarian cysts. In tissues showing loss of BAF250a, expression of pAKT, γH2AX, BIM, and BAX was higher in EAOC and contiguous endometriosis than in benign endometriosis (P < 0.05), whereas expression of pATM, pCHK2, and Bcl2 was low. All proteins except for Bcl2 showed low expression in benign endometriosis.Conclusion
Loss of ARID1A-encoded protein seems to be an early event in EOAC, along with pAKT activation, alteration of γH2AX, and concomitant activation of the apoptosis pathway.ARID1A Expression in Ovarian Clear Cell Carcinoma with an Adenofibromatous Component
Abstract
Aims
The
carcinogenesis of ovarian clear cell carcinoma (CCC) has been
hypothesized to comprise two different pathways: an adenofibroma-carcinoma sequence and an endometriosis-carcinoma sequence.
However, the difference in the genetic basis of these two pathways
remains unclear. Recent studies have suggested that an ARID1A mutation
and the loss of the corresponding protein, BAF250a, are frequent events
in CCC. Herein, we investigated the difference in the loss of BAF250a
expression in adenofibroma-related CCC and endometriosis-related CCC.
Methods and Results
In
total, 93 cases of surgically treated CCC were evaluated. The presence
of adenofibroma and endometriosis associated with carcinoma was
determined by reviewing hematoxylin and eosin-stained slides for each
case. BAF250a expression in carcinoma was examined
immunohistochemically. The loss of BAF250a expression was detected in
carcinomas in 50 of 93 (54%) cases, including 5/18 (28%) with adenofibroma alone, 30/45 (67%) with endometriosis alone, 8/18 (44%) with both conditions, and 7/12 (58%)
with neither condition. The loss of BAF250a expression was
significantly less frequent in CCC cases with adenofibroma than in cases
with endometriosis (p = 0.01, Fisher's exact test).
Conclusions
The action of ARID1A in carcinogenesis differs between adenofibroma-related CCC and endometriosis-related CCC.
Assessment of a new system for primary site assignment in high-grade serous carcinoma of the fallopian tube, ovary, and peritoneum
Abstract
Aims
The
available evidence indicates that most non-uterine high-grade serous
carcinomas (HGSCs) arise from the fallopian tube (FT), but approaches to
primary site assignment have not evolved to reflect this. The aim of
this study was to assess the application of recently proposed criteria
for site assignment.
Methods and results
One
hundred and fifty-one HGSCs from four centres were reviewed
retrospectively. Sixty-three of 80 (79%) chemonaive (CN) and 45 of 71
(68%) post-neoadjuvant chemotherapy (NACT) cases were assigned as FT
primaries with the new criteria, whereas 58 of 80 (73%) and 45 of 71
(63%) were assigned as ovarian primaries with traditional criteria (P < 0.0001).
Of 111 prospectively collected HGSCs, with consistent detailed fimbrial
examination, 44 of 53 (83%) CN and 44 of 58 (76%) NACT cases were
assigned as FT primaries. The reproducibility of site assignment was
tested in a subset of 50 cases: all four reviewing pathologists agreed
on the primary site in 48 of 50 (96%) cases, and three of four agreed in
49 of 50 (98%) cases. Of the 53 prospectively studied CN cases,
bilateral ovarian involvement (62%) was significantly more frequent than
bilateral tubal involvement (12%, P < 0.0001), further supporting a tubal origin and ovarian metastasis in most cases.
Conclusions
With
currently accepted protocols, the proposed guidelines are easy to apply
and result in consistent site assignment in non-uterine HGSCs. Most
cases of non-uterine HGSC were considered to be primary FT neoplasms.
Clear cell carcinoma of the ovary: evaluation of prognostic parameters based on a clinicopathological analysis of 100 cases
abstract
AIMS:
The aim of this study was to evaluate the clinicopathological features of ovarian
clear cell carcinomas in order to identify which, if any, are
prognostically significant, and to determine whether there is value in
grading these tumours.
METHODS AND RESULTS:
One hundred tumours with clinical follow-up were reviewed. Features evaluated included age, preoperative/intraoperative rupture, size, architectural pattern(s), presence of oxyphilic cells, degree of cytological atypia, nucleolar grade, mitoses, background precursor and stage. Survival differences were analysed using the log-rank test and Kaplan-Meier estimator. Stage and lymph node status were the only parameters that were statistically significant (P < 0.0001). Patients with stage I disease (71%) had a 92% 5-year survival compared to a 31% 5-year survival in advanced stage disease (29%). Those with negative lymph nodes (92%) had an 80% 5-year survival compared to a 22% 5-year survival for those with positive nodes (8%).CONCLUSIONS:
This study shows that stage and lymph node status are the only prognostically significant parameters in patients with ovarian clear cell carcinoma. It also confirms that most patients with clear cell carcinoma present with disease confined to the ovary, and have an excellent prognosis. Grading ovarian clear cell carcinomas based on morphological features is not recommended, as none are of prognostic significance.Saturday, April 25, 2015
Ca-125 in diagnosis and monitoring of patients with ovarian cancer - Bulgaria
abstract
The carbohydrated antigen Ca-125 is identified by Bast et al. in 1981. The cut off value of 35 KU/l for serum levels of the marker covers in fact 98-99% of the healthy women. There are some variations in the levels of pre- and post menopausal women, and also some race- dependent and cycle-dependent differences. Although Ca-125 is the only one accepted tumor marker for ovarian cancer, its screening usage is controversial, because of the high percentage of false positive results. Ca-125 and HE4 are both validated serum markers for differential diagnose of pelvic masses. The Ca-125 main role is monitoring patients, having ovarian cancer in their chemotherapy, early recurrence finding and progression. Ca-125 rising values in monitoring patients are predictor of image or clinical recurrence in 59-96% of the cases. FDG PET/CT gave a new standard in ovarian cancer staging, especially in patients, having high levels of Ca-125, but negative conventional imaging examinations.
Histological subtypes of ovarian carcinoma and their importance for clinical prognosis - Bulgaria
abstract
[Histological subtypes of ovarian carcinoma and their importance for clinical prognosis].
[Article in Bulgarian]
[No authors listed]
Abstract
Ovarian
cancer is one of the most common and most lethal cancers. For Bulgaria
(2012) it occupies third place in the structure of gynecological
malignancies with a share of 22.6 percent, while regarding mortality is
at first place with 35.7 percent. New cases are 838 with crude incidence
22.3 x 10(5), and the deaths are 463 with crude mortality 12.3 x 10(5).
Ovarian tumors, even when they are of the same histological type
clearly differ in their cellular differentiation, molecular
characteristiques and subsequently in their biological behavior. In this
review, we discuss the frequency origin, morphology and molecular
characteristiques of the five major subtypes of ovarian cancer--serous
low and high grade, mucinous, endometroid and and clear cell. The role
of different risk and prognostic factors for the efficiency of the
treatment and control of disease been discussed.
FDA Alert: Injectable Products by Mylan: Recall - includes Gemcitabine, Carbo, Methotrexate
FDA Alert:
Including certain lots of:
- Gemcitabine for Injection
- Carboplatin Injection
- Methotrexate Injection
- Cytarabine Injection
BACKGROUND: Gemcitabine for Injection, USP 200mg is an intravenously administered product indicated for the treatment of ovarian cancer, breast cancer, non-small cell lung cancer and pancreatic cancer. These lots were distributed in the U.S. between Feb. 18, 2014, and Dec. 19, 2014, and were manufactured and packaged by Agila Onco Therapies Limited, a Mylan company. Lot 7801089 is packaged with a Pfizer Injectable label.
Carboplatin Injection 10mg/mL is an intravenously administered product indicated for the treatment of advanced ovarian carcinoma. The lot was distributed in the U.S. between Aug. 11, 2014, and Oct. 7, 2014, and was packaged by Agila Onco Therapies Limited, a Mylan company, with a Mylan Institutional label.
Methotrexate Injection, USP 25mg/mL can be administered intramuscularly, intravenously, intra-arterially, or intrathecally and is indicated for certain neoplastic diseases, severe psoriasis and adult rheumatoid arthritis. The lot was distributed in the U.S. between Jan. 16, 2014, and March 25, 2014, and was packaged by Agila Onco Therapies Limited, a Mylan company, with a Pfizer Injectables label.
Cytarabine Injection can be administered intravenously or intrathecally and in combination with other approved anti-cancer drugs is indicated for remission induction in acute non-lymphocytic leukemia of adults and pediatric patients. The lot was distributed in the U.S. between May 02, 2014, and July 24, 2014, and was manufactured and packaged by Agila Onco Therapies Limited, a Mylan company located in Bangalore, India and is packaged with a Pfizer Injectables label......
Friday, April 24, 2015
Earlier ovarian cancer detection (in research)
ScienceDaily
Successful ovarian cancer treatment often relies on catching it early. A study at The University of Texas MD Anderson Cancer Center may help point to a new method for women at risk.....
.....The study looked at antibodies produced by patients against the tumor gene TP53 which is mutated and overexpressed in the majority of ovarian cancers to see whether their presence would improve the ability of CA125 to detect ovarian cancer in an earlier stage.
"Anti-TP53 autoantibodies were detected an average of 13 months prior to rising CA125 levels and 33 months prior to diagnosis in patients who did not have a rising CA125," said Bast. "While only a quarter of cases are associated with anti-TP53 autoantibodies, when present, these antibodies promise to detect ovarian cancer at an earlier interval than CA125.". The data was presented on April 20 at the 2015 American Association for Cancer Research (AACR) Annual Meeting in Philadelphia.
PLOS ONE: Disease Specific Productivity of American Cancer Hospitals
American Cancer Hospitals open access
Conclusion
Research productivity varies considerably among the sample. Overall cancer productivity conceals great variation between diseases. Disease specific rankings identify sites of high academic productivity, which may be of interest to physicians, patients and researchers.
Cancer specific rankings
Different cancers are treated and studied by different physicians in different departments using a variety of techniques. To capture this diversity, we generated ranked lists over 25 different conditions. The 10 institutions with the highest score in each category, including ties, are presented as Table 2. M.D. Anderson Cancer center appeared on the most top-10 lists, 24/25, as well as having the highest score in 13/25. However, 43 of the 50 institutions make at least 1 appearance on a top 10 list, and 6 different organization were top ranked in at least one area. A full accounting of these appearances is presented as Table 3.
Prevalence, Classification, and Risk Factors for Postoperative Lower Extremity Lymphedema in Women With Gynecologic Malignancies: A Retrospective Study
abstract
Objective: Lower extremity lymphedema (LEL) is a major
long-term complication of radical surgery. We aimed to estimate the
incidence and grading of LEL in women who underwent lymphadenectomy and
to evaluate risk factors associated with LEL.
Materials and Methods: We retrospectively reviewed 358
patients with cervical, endometrial, and ovarian cancer who underwent
transabdominal complete systematic pelvic and para-aortic
lymphadenectomy between 1997 and 2011. Lower extremity lymphedema was
graded according to criteria of the International Society of Lymphology.
Incidence of LEL and its correlation with various clinical
characteristics were investigated using Kaplan-Meier survival and Cox
proportional hazards methods.
Results: Overall incidence of LEL was 21.8% (stage 1,
60%; stage 2, 32%; and stage 3, 8%). Cumulative incidence increased with
observation period: 12.9% at 1 year, 20.3% at 5 years, and 25.4% at 10
years. Age, cancer type, stage (International Federation of Gynecology
and Obstetrics), body mass index, hysterectomy type, lymphocyst
formation, lymph node metastasis, and chemotherapy were not associated
with LEL. Multivariate analysis confirmed that removal of circumflex
iliac lymph nodes (hazard ratio [HR], 4.28; 95% confidence interval
[CI], 2.09–8.77; P < 0.0001), cellulitis (HR, 3.48; 95% CI, 2.03–5.98; P < 0.0001), and number of removed lymph nodes (HR, 0.99; 95% CI, 0.98–0.99; P = 0.038) were independent risk factors for LEL.
Conclusions: Postoperative LEL incidence increased
over time. The results of the present study showed a significant
correlation with removal of circumflex iliac lymph nodes and cellulitis
with the incidence of LEL. Multicenter or prospective studies are
required to clarify treatment efficacies.
Gynecologic Cancer InterGroup (GCIG) Consensus Review for Clear Cell Carcinoma of the Ovary
abstract
Clear cell carcinoma of the ovary (CCC) is a histologic subtype of epithelial ovarian cancer with a distinct clinical behavior. There are marked geographic differences in the prevalence of CCC. The CCC is more likely to be detected at an early stage than high-grade serous cancers, and when confined within the ovary, the prognosis is good. However, advanced disease is associated with a very poor prognosis and resistance to standard treatment. Cytoreductive surgery should be performed for patients with stage II, III, or IV disease. An international phase III study to compare irinotecan/cisplatin and paclitaxel/carboplatin as adjuvant chemotherapy for stage IIV CCC has completed
enrollment (GCIG/JGOG3017). Considering the frequent PIK3CA mutation in CCC, dual inhibitors targeting PI3K, AKT in the mTOR pathway, are promising. Performing these trials and generating the evidence will require considerable international collaboration.
Endometrial Cancers in Mutation Carriers From Hereditary Breast Ovarian Cancer Syndrome Kindreds:
abstract
Endometrial Cancers in Mutation Carriers From Hereditary Breast Ovarian Cancer Syndrome Kindreds: Report From the Creighton University Hereditary Cancer Registry With Review of the Implications
Objective: The aim of this study was to categorize and
report endometrial cancers in mutation carriers from hereditary breast
ovarian cancer families.
Methods: Our Hereditary Cancer Registry was searched for gynecologic and peritoneal cancers linked to mutations in BRCA1 or BRCA2.
Invasive cancers were registered in 101 mutation carriers with complete
pathology reports. Efforts were made to secure diagnostic surgical
pathology tissues for review. All records and available diagnostic
slides were meticulously studied, and primary cancers were classified.
Findings: Eight malignancies were classified as
primary endometrial cancers. Five of these were low- or
intermediate-grade endometrioid carcinomas, and 3 were pure serous
carcinomas or contained serous carcinoma elements mixed with high-grade
endometrioid carcinoma. Breast cancers were diagnosed in 5 patients
before and in 1 patient after endometrial carcinoma. Three endometrioid
carcinomas were preceded by estrogen treatment, 2 for many years and the
other for only 2 months, and 2 of the patients with serous carcinoma
had been treated with tamoxifen.
Conclusions: The finding that 8 of gynecologic and
peritoneal cancers in 101 mutation carriers were endometrial cancers
with a smaller proportion of endometrioid carcinomas than reported in
general populations is added to the current controversial literature on
endometrial cancer, particularly regarding serous carcinomas, in
hereditary breast ovarian cancer syndrome. Well-designed prospective
programs for standardized surgical and pathologic handling, processing,
and reporting are essential for working out the pathogenesis, true
risks, and best management of this disease in carriers of deleterious BRCA1 and BRCA2 germline mutations.
Does Omentectomy in Epithelial Ovarian Cancer Affect Surviva... : International Journal of Gynecological Cancer
abstract
Objective: Although omentectomy is part of the staging
and treatment of epithelial ovarian cancer (EOC), its performance in a
patient with a grossly normal omentum—acknowledging its role in
debulking gross tumor deposits—has never been definitively shown to
improve survival.
Methods/Materials: Using Surveillance, Epidemiology,
and End Results data from 1998 to 2010, we identified patients with EOC
and assessed their age, race, year of diagnosis, tumor grade, histologic
subtype, International Federation of Gynecology and Obstetrics stage,
lymph node dissection, nodal findings, and performance of omentectomy.
We compared disease-specific survival (DSS) based on the presence or
absence of omentectomy using log-rank univariate analysis, Cox
multivariate analysis, and Kaplan-Meier survival curves.
Results: A total of 20,975 patients with invasive EOC
underwent surgical treatment. Initial univariate analysis indicated a
lower mean DSS with performance of omentectomy. However, multivariate
analysis demonstrated no significant association between DSS and
performance of omentectomy (hazard ratio, 0.978; P = 0.506). The DSS was improved if lymphadenectomy was performed (hazard ratio, 0.60; P < 0.001). In recent years, there was a trend toward decreased performance of omentectomy.
To look specifically at patients without bulky omental
disease, a subset analysis was done looking at patients with stage
I-IIIA disease who had had lymphadenectomy performed. There were 5454
patients in the group who underwent an omentectomy and 2404 patients in
the group who did not. No difference in DSS was seen between the groups
based on performance of omentectomy (P = 0.89). However, the
analysis was limited by the lack of Surveillance, Epidemiology, and End
Results data on the extent of omentectomy, amount of residual disease,
and adjuvant chemotherapy.
Conclusions: In this analysis, performance of
omentectomy in patients with EOC without bulky disease (≤stage IIIA) did
not seem to confer improvement in survival. A randomized control trial
would be needed to fully address this question.
Prognostic Significance of the Number of Postoperative Intraperitoneal Chemotherapy Cycles for Patients With Advanced Epithelial Ovarian Cance
abstract
|
|
Feelings of Women With Strong Family Histories Who Subsequent to Their Breast Cancer Diagnosis Tested BRCA Positive (Canada)
abstract
Objective: Family physicians in Canada as reported in
several studies do not recognize the importance of family history in
relation to breast/ovarian cancer and thus Canadian women with strong
family histories continue to develop early-onset breast cancer without
the knowledge of or ability to make choices regarding increased
surveillance or preventative strategies. This study explored the
feelings of women who learned about their hereditary risk only after
their diagnosis younger than 52 years and who eventually tested positive
for a BRCA gene mutation.
Methods: Thirty-four such women were mailed an
invitation to participate in this research including a letter of
information, consent form, and discussion prompts for their written
narrative response. Rigorous mixed method analyses were performed using
Charmaz-based qualitative analyses as well as quantitative analyses.
Results: Thirteen women (38.2%) responded with
narratives for qualitative analysis from which 4 themes were
coconstructed as follows: I, types of emotions; II, emotional response;
III, coping with emotions; and IV, advice to women at similar risk.
Women felt they should have learned about their hereditary risk from
their family physician and through public education before their
diagnosis. Although not experienced at the time of diagnosis, anger,
frustration, and regret were experienced after receiving their BRCA
results. These emotions arose from our research participants’ lack of
opportunity for prior genetic counseling and testing opportunity for
genetic counseling and testing.
Conclusions: With increased public and physician
education, it is hoped that women with significant family histories of
breast/ovarian cancer will be identified before diagnosis and given
options regarding cancer surveillance and risk reduction strategies.
Quantifying Physical Activity and the Associated Barriers for Women With Ovarian Cancer
abstract
Objective: The purpose of this study was to quantify
physical activity levels and determine the barriers to physical activity
for women with ovarian cancer.
Materials and Methods: Women with ovarian cancer from 3
oncology clinics enrolled in the cross-sectional study. Physical
activity and barriers to physical activity were measured using the
International Physical Activity Questionnaire and Perceived Physical
Activity Barriers scale, respectively. Demographic, medical, and
anthropometric data were obtained from medical records.
Results: Ninety-five women (response rate, 41%), with a mean (SD) age of 61 (10.6) years, a body mass index of 26.5 (6.8) kg/m2,
and 36.6 (28.2) months since diagnosis, participated in the study. The
majority of the participants had stage III (32%) or IV (32%) ovarian
cancer, were undergoing chemotherapy (41%), and had a history of
chemotherapy (93%). The majority of the participants reduced their
physical activity after diagnosis, with 19% meeting recommended physical
activity guidelines. The participants undergoing treatment reported
lower moderate-vigorous physical activity compared with those not
undergoing active treatment (mean [SD], 42 [57] vs 104 [119] min/wk; P < 0.001) and less total physical activity barriers (mean [SD], 49 vs 47; P
> 0.4). The greatest barriers to physical activity included fatigue
(37.8%), exercise not in routine (34.7%), lack of self-discipline
(32.6%), and procrastination (27.4%).
Conclusions: Women with ovarian cancer have low levels
of physical activity. There are disease-specific general barriers to
physical activity participation. The majority of the participants
reduced their physical activity after diagnosis, with these patients
reporting a higher number of total barriers. Behavioral strategies are
required to increase physical activity adherence in this population to
ensure that recommended guidelines are met to achieve the emerging known
benefits of exercise oncology.
Fibroblast Growth Factor Receptor 2 Is Associated With Poor Overall Survival in Clear Cell Carcinoma of the Ovary and May Be a Novel Therapeutic Approach
abstract
|
|
An Organizational Guideline for Gynecologic Oncology Service (Canada)
Abstract
Objectives: Documented variations in practice
compelled the need to establish a network that would facilitate the flow
of patients through the care continuum of a provincial health care
system in accordance with best practices. Therefore, a guideline was
developed to provide recommendations for the optimal organization of
gynecologic oncology services in this higher resource location to
improve access to multidisciplinary care and appropriate treatment.
Methods: A systematic review was conducted of Web
sites of international guideline developers, relevant cancer agencies,
and Medline and EMBASE from 1996 to 2011 using search terms related to
gynecologic malignancies, combined with organization of services,
patterns of care, and various facility and physician characteristics.
The results of the review were combined with expert consensus and
stakeholder consultation to develop a gynecologic oncology services
organizational guideline.
Results: The evidence review yielded a lower quality
evidence base; therefore, recommendations were determined through
consensus, including guidance for physician and hospital specialization,
and other domains including human and physical resources. Definitive
surgical treatment of most invasive cancers by subspecialist gynecologic
oncologists is recommended. In addition, it is recommended that these
subspecialists provide care within designated gynecologic oncology
centers. The recommendations also outline which services, such as
radiation therapy, may be provided in other affiliated centers.
Multidisciplinary team management is also endorsed.
Conclusions: These recommendations are intended to
allow a collaborative community of practice, supported by formal
interorganizational processes, to evolve to facilitate adherence to
guidelines and best practices at a system-wide level.
The New Cancer Survivors | Psychology Today
The New Cancer Survivors
.....All these developments are factors in the increasing number of people whose cancer can be considered cured, a nebulous term that generally describes those who are cancer-free five years after their diagnosis. But at the same time, they’re enabling more and more people like Brad Slocum to live longer with active or persistent cancer, including tumors that are controlled without being eliminated or tumors that go through continuous cycles of remission and recurrence.
“It’s very different from being cured,” says Michael Fisch, chair of general oncology at the MD Anderson Cancer Center in Houston. “Being cured becomes a story like, ‘Back in 2002, I had a small breast tumor, and they took care of it,’ or ‘I had a small melanoma removed five years ago, and I live a normal life now.’ It’s a line item on a medical history that maybe isn’t too important. But taking Sutent, or periodically having surgeries, or having a lot of CT scans, or having a fear of recurrence or progression, or being on maintenance chemotherapy—that’s a different experience.”.....
.... But there are other days where I feel a great trepidation. It’s not like chronic asthma or chronic diabetes. The term chronic is not commensurate. With cancer, there’s always this extraordinary dread of recurrence, of tumor growth, and incredible fear and uncertainty about what the future holds.”.....
Thursday, April 23, 2015
Wednesday, April 22, 2015
Practical guidance for applying the ADNEX model from the IOTA group to discriminate between different subtypes of adnexal tumors
Practical guidance
All gynecologists are faced with ovarian tumors on a regular basis, and the accurate preoperative diagnosis of these masses is important because appropriate management depends on the type of tumor. Recently, the International Ovarian Tumor Analysis (IOTA) consortium published the Assessment of Different NEoplasias in the adneXa (ADNEX) model, the first risk model that differentiates between benign and four types of malignant ovarian tumors: borderline, stage I cancer, stage II-IV cancer, and secondary metastatic cancer. This approach is novel compared to existing tools that only differentiate between benign and malignant tumors, and therefore questions may arise on how ADNEX can be used in clinical practice. In the present paper, we first provide an in-depth discussion about the predictors used in ADNEX and the ability for risk prediction with different tumor histologies. Furthermore, we formulate suggestions about the selection and interpretation of risk cut-offs for patient stratification and choice of appropriate clinical management. This is illustrated with a few example patients. We cannot propose a generally applicable algorithm with fixed cut-offs, because (as with any risk model) this depends on the specific clinical setting in which the model will be used. Nevertheless, this paper provides a guidance on how the ADNEX model may be adopted into clinical practice.
IOTA - ADNEX model (ovarian cancer)
IOTA
(ovarian c
Objectives
To develop a risk prediction model to preoperatively discriminate between benign, borderline, stage I invasive, stage II-IV invasive, and secondary metastatic ovarian tumours.Towards an evidence-based approach for diagnosis and management of adnexal masses: findings of the International Ovarian Tumour Analysis (IOTA) studies
abstract
Whilst the outcomes for patients with ovarian cancer clearly benefit from centralised, comprehensive care in dedicated cancer centres, unfortunately the majority of patients still do not receive appropriate specialist treatment. Any improvement in the accuracy of current triaging and referral pathways whether using new imaging tests or biomarkers would therefore be of value in order to optimise the appropriate selection of patients for such care. An analysis of current evidence shows that such tests are now available, but still await recognition, acceptance and widespread adoption. It is therefore to be hoped that present guidance relating to the classification of ovarian masses will soon become more "evidence-based". These promising tests include the International Ovarian Tumour Analysis (IOTA) LR2 model and ultrasound-based Simple Rules (SR). Based on a comprehensive recent meta-analysis both currently offer the optimal "evidence-based" approach to discriminating between cancer and benign conditions in women with adnexal tumours needing surgery. LR2 and SR are reliable tests having been shown to maintain a high sensitivity for cancer after independent external and temporal validation by the IOTA group in the hands of examiners with various levels of ultrasound expertise. They also offer more accurate triage compared to the existing Risk of Malignancy Index (RMI). The development of the IOTA ADNEX model represents an important step forward towards more individualised patient care in this area. ADNEX is a novel test that enables the more specific subtyping of adnexal cancers (i.e. borderline, stage 1 invasive, stage II-IV invasive, and secondary metastatic malignant tumours) and shares similar levels of accuracy to IOTA LR2 and SR for basic discrimination between cancer and benign disease. The IOTA study has made significant progress in relation to the classification of adnexal masses, however what is now needed is to see if these or new diagnostic tools can assist clinicians to select patients with adnexal masses that are suitable for expectant management, and that will work in all health care settings (i.e. primary vs secondary vs tertiary care). These important themes will likely control the future agenda of the IOTA project.
JCO Correspondence: Good…but Bad News - Quality of cancer pain management
Good…but Bad News
To the Editor:
We read with interest the paper by Greco et al.1
The authors conclude that that cancer pain management is improving.
After analyzing the literature in two different periods,
they have found a better quality of cancer pain
management reported in the last 6 years. While all researchers and
clinicians
would be happy with better quality of cancer pain
management, the bad news is that this conclusion is not accurate based
on
the parameters compared by the authors.
The Pain Management Index (PMI) score continues to be used inappropriately as an indirect measure of quality of pain management.2
The achievement of an appropriate analgesic treatment cannot be based
on this score, calculated by drug class and pain intensity.
This index was originally developed by Cleeland et
al3
to measure physicians' response to patients' pain, which is a generic
attitude in prescription, including for example drugs
prescribed but not necessary administered. Thus,
PMI does not provide any measure of adequacy of a pain treatment. With
this
score any patient receiving the class of strong
opioids is considered adequately treated and there is no consideration
of
pain intensity, opioid type, or even opioid dose.4.......Authors' Response
We appreciate the interest of Mercadante and Bruera1 in our article.2 They raise two important issues: first, the Pain Management Index (PMI) as a tool to measure the appropriateness of cancer
pain management, and second, the role of early palliative care in the management of patients with cancer.
We knew that the PMI, exclusively calculated
on pain intensity and class of drug given, would create discussion and
we expected
that our work would have raised interest because in
the last few years an increased attention in the role of opioids for
cancer
pain treatment was detected.....REFERENCES
- (2014) Quality of cancer pain management: An update of a systematic review of under treatment of patients with cancer. J Clin Oncol 32:4149–4154.
Tuesday, April 21, 2015
New Genetic Tests for Breast Cancer Hold Promise
NYTimes.com
A Silicon Valley start-up with some big-name backers is threatening to upend genetic screening for breast and ovarian cancer by offering a test on a sample of saliva that is so inexpensive that most women could get it.
At the same time, the nation’s two largest clinical laboratories, Quest Diagnostics and LabCorp, normally bitter rivals, are joining with French researchers to pool their data to better interpret mutations in the two main breast cancer risk genes, known as BRCA1 and BRCA2. Other companies and laboratories are being invited to join the effort, called BRCA Share.
The
announcements being made on Tuesday, although coincidental in their
timing, speak to the surge in competition in genetic risk screening for cancer since 2013, when the Supreme Court invalidated the gene patents that gave Myriad Genetics a monopoly on BRCA testing......
TEDMED - video - There is no genome for the human spirit
TEDMED
Amy McGuire, an Associate Professor of Medicine and Biomedical Ethics and Director of the Center for Medical Ethics and Health Policy at Baylor College of Medicine, provides a cautionary framework for genomic sequencing that takes into account personal, social and policy consequences.
Transfusions of blood products and cancer outcomes (solid tumors)
abstract
Approximately half of cancer patients scheduled for major surgery are anemic. Also, a significant number of patients will present to the operating room with low platelet counts and coagulopathic disorders. Unfortunately, administration of red blood cells, platelets concentrates and fresh-frozen plasma is associated with unwanted adverse effects including fever, hemolytic reactions and transfusion-related immunomodulation (TRIM). TRIM is a multifactorial immunologic phenomenon in the recipient mediated by donor leukocytes, microparticles such as ectosomes, and growth factors. As some of these molecules are secreted in a time-dependent manner, blood storage time may play an important in TRIM, although the evidence is limited. Perioperative administration of red blood cells and associated TRIM has also been associated with increased recurrence of certain solid tumors, such as colorectal, lung, and hepatobiliary tumors. In this continuing education article, we review the available evidence on how perioperative blood product transfusions can affect oncological outcomes, such as cancer recurrence.
A Phase 2 study of cediranib in recurrent or persistent ovarian, peritoneal or fallopian tube cancer
Abstract
A Trial of the Princess Margaret, Chicago and California Phase II Consortia
Highlights
- •Cediranib has activity in recurrent ovarian cancer
- •Expected toxicities were manageable with a dose reduction of cediranib (30 mg daily)
Cediranib is a potent multitargeted inhibitor of vascular endothelial growth factor receptor (VEGFR) 1, 2 and 3. The study was initiated to evaluate the activity of cediranib in patients (pts) with recurrent ovarian, peritoneal or fallopian tube cancer (OC).
Methods
Eligible pts had persistent/recurrent OC following one prior platinum-based chemotherapy with measurable disease or progression based on Gynecologic Cancer Inter Group CA-125 criteria. Because of toxicities observed in the first 23 pts, the initial starting dose of oral daily (od) cediranib was reduced from 45 mg to 30 mg. The primary endpoint was objective response rate at 16 weeks. This study was stratified into two arms: platinum-sensitive (PL-S) and platinum-resistant (PL-R).Results
74 pts were enrolled; 39 were PL-S and 35 PL-R, with a median age of 58 years [31–87]. In PL-S group, 10 partial responses (PR) and stable disease (SD) in 20 (51%) were confirmed while in the PL-R arm there were no confirmed PR and 23 pts (66%) had SD. The main grade 3/4 toxicities were hypertension (24%), fatigue (17%) and diarrhea (9%). The median progression-free survival for all patients was 4.9 months [3.9-7.0], 7.2 months [4.3-9] for PL-S and 3.7 months [2.6-4.5] for PL-R group. The median overall survival was 18.9 months (95% CI: 13.5-31.5); 27.7 months [17.8-43.3] for PL-S and 11.9 months [8.1-18.9] for PL-R group.Conclusion
Cediranib shows significant activity in recurrent platinum sensitive OC. The toxicities were expected and manageable at the dose of 30 mg od.Ovarian Cancer Community Joins Forces to Fund Ovarian Cancer Dream Team
Dream Team
OCRF has teamed up with Stand Up To Cancer, Ovarian Cancer National Alliance (OCNA), and the National Ovarian Cancer Coalition (NOCC) to fund an Ovarian Cancer “Dream Team,” which will conduct a large-scale research project to help change the future of ovarian cancer. The project will be spearheaded by Alan D’Andrea, MD (Dana-Farber Cancer Institute) and Elizabeth Swisher, MD (University of Washington), who is a member of the OCRF Scientific Advisory Committee and also an OCRF grantee.
The SU2C-OCRF-OCNA-NOCC Ovarian Cancer Dream Team, which was announced on April 20, 2015, will focus on “DNA Repair Therapies for Ovarian Cancer,” building on recent advances that have identified DNA repair as a common weakness in ovarian cancer. Researchers will also explore the prevention and early detection of ovarian cancer by developing a web-based approach to genetic testing and counseling. Dream Team researchers hope to offer women identified as genetically high-risk a choice of surgical options, including one that removes the fallopian tubes but spares the ovaries. The Dream Team grant will provide funding over a three-year period, starting in July 2015..........
Monday, April 20, 2015
CT Contrast in Radiation Oncology Simulation - Journal of Cancer Review
open access
Abstract
Objectives: With IMRT and advanced radiation planning, anatomy and contouring is becoming increasingly important in the field of radiation oncology. The use of iodinated computed tomography (CT) contrast for radiation simulation CT scans can help define anatomy more precisely and thus improve contouring. The major risks of CT contrast (which at least partly accounts for the aversion by some departments to its routine use) are contrast induced nephropathy and allergic-like reactions.
Results: The evidence of complications attributable to standard doses of contrast for diagnostic CT examinations is weak. The preponderance of data on contrast induced nephropathy has been compiled from interventional cardiology procedures, and the current guidelines regarding diagnostic CT contrast require extrapolation on mostly retrospective data. The evidence available suggests that CT contrast related adverse events are rare, and contrast related nephropathy most often spontaneously resolves without further decline in baseline renal function.
Conclusion: The current data regarding safety of CT contrast provides a limited foundation on which to make evidence-based recommendations. We have reviewed the literature on CT contrast. By following some simple algorithms CT contrast can be safely utilized.
Full Text: PDF
Sunday, April 19, 2015
A Reappraisal of WHI Estrogen-Alone Trial: Long-Term Outcomes in Women 50–59 Years of Age
open access
7. Conclusions
Women 50–59 years of age at time of randomization to CEE or placebo in the WHI Estrogen-Alone Trial were similar in median age to women initiating hormone replacement therapy in clinical practice. In the intervention phase, for women 50–59 years of age with CEE, there was an increased risk of DVT, gall bladder disease, and stroke, while the reduction in MI, invasive breast cancer, and global index of events was not statistically significant. With cumulative 13-year long-term follow-up, women 50–59 years of age with CEE showed a reduction in MI, as well as a reduced global index of events. The increased risk of stroke and DVT in the intervention phase for women 50–79 years of age, which did not show significant trends with age, declined with cessation of CEE. Long-term follow-up including at least 5 years of follow-up after completion of hormone therapy is necessary to optimally evaluate effects of hormone replacement therapy on cardiovascular, cancer, and mortality outcomes. Though a subgroup analysis does not provide an adequate basis for making guideline recommendations for primary prevention, the preponderance of evidence in the WHI Estrogen-Alone Trial strongly suggests an overall benefit with CEE with cumulative long-term follow-up in women 50–59 years of age. These potential benefits only apply to women with prior hysterectomy and for duration of CEE use similar to what was used in the trial. The WHI Estrogen-Alone Trial data does not provide information on longer durations of use and strongly suggests that initiation of hormone therapy at significantly later ages is harmful.
Friday, April 17, 2015
Ovarian cancer - Genetic testing should be available to all women with the disease (media item)
Note: study does not discuss Lynch Syndrome
Ovarian cancer
"...These findings rationalize genetic testing for all women with ovarian cancer, which is currently not the standard of care. We need to inform women of the benefits of this option." "
Research partners
The study "A targeted analysis identifies a high frequency of BRCA1 and BRCA2 mutation carriers in women with ovarian cancer from a founder population" was co-authored by Moria H. Belanger and Lena Dolman of McGill University; Suzanna L. Arcand of the RI-MUHC; Zhen Shen and George Chong of the Jewish General Hospital; Anne-Marie Mes-Masson and Diane Provencher of Centre de recherche du Centre Hospitalier de l'Université de Montréal and Institut du cancer de Montréal; and Patricia N Tonin of the RI-MUHC and McGill University.
The Lancet: The history and fate of the gold standard
open access
.....The past several years have seen increasing calls for an ecumenical approach to clinical research, with more flexible standards for what counts as acceptable study designs. Physicians have developed new methods to extract robust analyses from patient registries and from the ever-growing databases provided by electronic medical records. Will this erode the status of RCTs as a gold standard? The rise of personalised medicine, meanwhile, might make it more difficult to defend gold standards in diagnostic and therapeutic practice. Personalised medicine refocuses clinical attention away from the “typical” patients analysed by RCTs and onto the idiosyncrasies, genetic or otherwise, of individual patients. Has the phrase outlived its usefulness in medicine? It is too soon to tell. Yet even as some physicians turn away from their commitment to medical gold standards, some politicians, newly wary about global financial turbulence, talk of restoring the financial gold standard. Gold standards, whether actual or figurative, represent structures of exchange and aspirations toward stability, despite developments that threaten both.
Subscribe to:
Posts
(
Atom
)
