- •We defined the MTD of IV docetaxel and IP oxaliplatin in recurrent ovarian cancer.
- •Most patients had PR or SD, with patient-reported outcomes showing temporary but tolerable decrements in QoL.
- •IP oxaliplatin provides a significant peritoneal PK advantage.
Sunday, June 28, 2015
Value in Cancer Care | ASCO.org - online survey
Value in Cancer Care
Please let us know what you think by taking our online survey.
ASCO Releases Value Framework
ASCO has released a conceptual framework for assessing the value of new cancer therapies based on treatment benefits, toxicities, and costs. The initial version of the ASCO Value Framework was published on June 22, 2015 in the Journal of Clinical Oncology.
Developed by the ASCO Value in Cancer Care Task Force, the framework will ultimately serve as the basis for user-friendly, standardized tools that physicians can use with their patients to discuss the relative value of new cancer therapies as compared with established treatments.
Seeking comment from all stakeholders
ASCO will be soliciting comments from all interested stakeholders on the value framework through August 21, 2015. Comments will inform the evolution of the value framework, which will be modified in response to feedback and updated as new data are developed about the utility and impact of new treatments in different clinical scenarios. Please let us know what you think by taking our online survey.
Saturday, June 27, 2015
Top 5 viewed items week of June 20-27, 2015 https://ovariancancerandus.blogspot.com
Top 5 viewed items week of June 20-27, 2015
June 2015 - top 5 read articles: https://ovariancancerandus.blogspot.com
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Estrogen pathway mutations and cancer (MMR/Lynch Syndrome/estrogen)
open access
Estrogen pathway mutations and cancer
Abstract
Cancer is caused by an accumulation of mutations in a stem
cell. A defective mismatch repair (MMR) system can lead to such an
accumulation of mutations. MMR defects are found in a cancer syndrome
called Lynch Syndrome, and tumors of this syndrome are indeed
characterized by such an accumulation of mutations, particularly in
short repetitive DNA sequences, called microsatellites. When such
mutated microsatellites are located in the coding sequences of genes
with essential roles for tumorigenesis, we speak of ‘target genes’. Many
such target genes have been found and in this review we focus the
possible involvement of target genes involved in the estrogen-receptor
pathway (ER).
We recently identified NRIP1, encoding the nuclear receptor-interacting protein 1, as the most frequently mutated gene in microsatellite instable (MSI) endometrial cancer (EC). NRIP1 is a known corepressor of the ER pathway, the pathway essential in regulating the concentrations of estrogens, a hormone for which the endometrium is highly responsive. This in combination with the fact that high exposure to estrogens is currently considered the major risk factor for EC - approximately 80% of all sporadic EC tumors are estrogen dependent carcinomas - make NRIP1 the perfect target gene for EC.
Interestingly, mutations in NRIP1 were also detected in MSI colorectal carcinoma (CRC) samples. Finding mutations in an estrogen receptor signaling protein in colorectal tissue might not be that expected, as colon is not typically associated with being responsive to estrogens. However, evidence is accumulating to better understand this finding. For instance, it was shown that NRIP1, in colon tissue, stimulates APC gene transcription and inhibits β-catenin activation. Moreover, some studies suggested that estrogens can increase the expression of MLH1 in colon cancer cells, highlighting the implications of estrogen protecting against colon cancer, by regulating the MMR system.
All in all we conclude that genes involved in the estrogen pathway are the perfect candidates to be studied in MMR-deficient tumors, especially those developing in hormonal responsive tissues.
We recently identified NRIP1, encoding the nuclear receptor-interacting protein 1, as the most frequently mutated gene in microsatellite instable (MSI) endometrial cancer (EC). NRIP1 is a known corepressor of the ER pathway, the pathway essential in regulating the concentrations of estrogens, a hormone for which the endometrium is highly responsive. This in combination with the fact that high exposure to estrogens is currently considered the major risk factor for EC - approximately 80% of all sporadic EC tumors are estrogen dependent carcinomas - make NRIP1 the perfect target gene for EC.
Interestingly, mutations in NRIP1 were also detected in MSI colorectal carcinoma (CRC) samples. Finding mutations in an estrogen receptor signaling protein in colorectal tissue might not be that expected, as colon is not typically associated with being responsive to estrogens. However, evidence is accumulating to better understand this finding. For instance, it was shown that NRIP1, in colon tissue, stimulates APC gene transcription and inhibits β-catenin activation. Moreover, some studies suggested that estrogens can increase the expression of MLH1 in colon cancer cells, highlighting the implications of estrogen protecting against colon cancer, by regulating the MMR system.
All in all we conclude that genes involved in the estrogen pathway are the perfect candidates to be studied in MMR-deficient tumors, especially those developing in hormonal responsive tissues.
Full Text:
PDFDOI: http://dx.doi.org/10.14800/rci.635
Friday, June 26, 2015
Development of biosimilars in an era of oncologic drug shortages
biosimilars
..... Preclinical and clinical characterization is ongoing for potential biosimilars of trastuzumab, rituximab, and bevacizumab, with promising results.
Keywords: biologics, monoclonal antibody, cancer, rituximab, safety, trastuzumab
Download Article [PDF]
British Journal of Cancer - Comment on: /`Evaluation of chemoresponse assays as predictive markers/'
Comment open access
DJS received compensation for consulting work from Helomics Corporation. MJG, SLB and CT are paid employees of Helomics Corporation.
.....We agree with Korn and Freidlin (2015) that evaluating the predictive value of chemoresponse assays is challenging. As with any observational study, it is impossible to entirely exclude bias, and a definitive answer relies on randomised clinical trials. However, randomised trials to evaluate predictive markers are highly challenging in rare tumour types such as recurrent ovarian cancer, particularly when a large number of treatment options are available. The length of time for patient accrual alone is likely to obfuscate clinical utility. Thus, observational studies and other non-randomised prospective studies must continue to have an important role in evaluating chemoresponse assays in this cancer type. We feel that in the appropriate circumstance, our proposed match/mismatch analysis can provide helpful information regarding an assay’s potential prognostic and/or predictive value.
References
Wednesday, June 24, 2015
Standard chemotherapy with/without bevacizumab for women with newly diagnosed ovarian cancer (ICON7).....
open access
Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7): overall survival results of a phase 3 randomised trial
Background
The ICON7 trial previously reported improved progression-free survival in women with ovarian cancer with the addition of bevacizumab to standard chemotherapy, with the greatest effect in patients at high risk of disease progression. We report the final overall survival results of the trial.Panel
Research in context
Bevacizumab in newly diagnosed ovarian cancer - The Lancet Oncology + references
Comment - open access
Several studies have assessed the activity of bevacizumab
when added to chemotherapy in ovarian cancer. In Europe, bevacizumab is
approved by the European Medicines Agency in combination with
carboplatin and paclitaxel in newly diagnosed ovarian cancer, with
carboplatin and gemcitabine in platinum-sensitive relapse ovarian
cancer, and with chemotherapy in platinum-resistant relapse ovarian
cancer. In the USA, bevacizumab is approved by the Food and Drug
Administration when combined with chemotherapy for platinum-resistant
relapse ovarian cancer. These approvals were based on progression-free
survival improvements, but so far no overall survival benefit has been
noted with the addition of bevacizumab to chemotherapy in any overall
study population.2, 3, 4, 5
In The Lancet Oncology, Amit Oza and colleagues1
report the mature overall survival data from ICON7, an open-label
randomised phase 3 trial comparing bevacizumab plus six 3-weekly cycles
of carboplatin and paclitaxel chemotherapy followed by bevacizumab
maintenance versus the carboplatin and paclitaxel chemotherapy regimen
alone. The study participants were patients with newly diagnosed ovarian
cancer following cytoreductive surgery or patients with advanced-stage
disease who had no further surgery planned.1 The primary endpoint of this trial, progression-free survival, has been reported previously.2 Concordant with the results of GOG-218,3 another phase 3 trial comparing chemotherapy and bevacizumab versus chemotherapy alone in upfront therapy for ovarian cancer.....References
- Oza, AM, Cook, AD, Pfisterer, J et al. Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7): overall survival results of a phase 3 randomised trial. Lancet Oncol. 2015; (published online June 23.)http://dx.doi.org/10.1016/S1470-2045(15)00086-8.
- Perren, TJ, Swart, AM, Pfisterer, J et al. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med. 2011; 365: 2484–2496
- Burger, RA, Brady, MF, Bookman, MA et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 2011; 365: 2473–2483
- Aghajanian, C, Blank, SV, Goff, BA et al. OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J Clin Oncol. 2012; 30: 2039–2045
- Pujade-Lauraine, E, Hilpert, F, Weber, B et al. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: the AURELIA open-label randomized phase III trial. J Clin Oncol. 2014; 32: 1302–1308
- Coleman, R, Burger, RA, Brady, MF et al. Analysis of survivorship in high-risk patients on treated on GOG-218. Gynecol Oncol. 2013; 130: e112–e113
- Katsumata, N, Yasuda, M, Isonishi, S et al. Long-term results of dose-dense paclitaxel and carboplatin versus conventional paclitaxel and carboplatin for treatment of advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer (JGOG 3016): a randomised, controlled, open-label trial. Lancet Oncol. 2013; 14: 1020–1026
- Chan, J, Brady, MF, Penson, RT et al. Phase III trial of every-3-weeks paclitaxel versus dose dense weekly paclitaxel with carboplatin +/- bevacizumab in epithelial ovarian, peritoneal, fallopian tube cancer: GOG 262 (NCT0116712). Int J Gynecol Cancer. 2013; 23: 9–10
- Kehoe, S, Hook, J, Nankivell, M et al. Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS): an open-label, randomised, controlled, non-inferiority trial. Lancet. 2015; (published online May 19.)http://dx.doi.org/10.1016/S0140-6736(14)62223-6.
- Vergote, I, Trope, CG, Amant, F et al. Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med. 2010; 363: 943–953
Tuesday, June 23, 2015
Prediction of Optimal Cytoreductive Surgery of Serous Ovarian Cancer With Gene Expression Data
abstract
OBJECTIVES:
Cytoreductive surgery is the cornerstone of ovarian cancer (OVCA) treatment. Detractors of initial maximal surgical effort argue that aggressive tumor biology will dictate survival, not the surgical effort. We investigated the role of biology in achieving optimal cytoreduction in serous OVCA using microarray gene expression analysis.METHODS:
For the initial model, we used a gene expression signature from a microarray expression analysis of 124 women with serous OVCA, defining optimal cytoreduction as removal of all disease greater than 1 cm (with 64 women having optimal and 60 suboptimal cytoreduction). We then applied this model to 2 independent data sets: the Australian Ovarian Cancer Study (AOCS; 190 samples) and The Cancer Genome Atlas (TCGA; 468 samples). We performed a second analysis, defining optimal cytoreduction as removal of all disease to microscopic residual, using data from AOCS to create the gene signature and validating results in TCGA data set.RESULTS:
Of the 12,718 genes included in the initial analysis, 58 predicted accuracy of cytoreductive surgery 69% of the time (P = 0.005). The performance of this classifier, measured by the area under the receiver operating characteristic curve, was 73%. When applied to TCGA and AOCS, accuracy was 56% (P = 0.16) and 62% (P = 0.01), respectively, with performance at 57% and 65%, respectively. In the second analysis, 220 genes predicted accuracy of cytoreductive surgery in the AOCS set 74% of the time, with performance of 73%. When these results were validated in TCGA set, accuracy was 57% (P = 0.31) and performance was at 62%.CONCLUSION:
Gene expression data, used as a proxy of tumor biology, do not predict accurately nor consistently the ability to perform optimal cytoreductive surgery. Other factors, including surgical effort, may also explain part of the model. Additional studies integrating more biological and clinical data may improve the prediction model.Tumour spectrum in non-BRCA hereditary breast cancer families in Sweden
open access
Results
We found that endometrial cancer was overrepresented in the non-BRCA families with
a 6.36 % proportion (CI 4.67–8.2) compared to the proportion in the general population
in the reference years 1970 (3.07 %) and 2010 (2.64 %). Moreover tumours of the ovary,
liver, pancreas and prostate were overrepresented.
Conclusions
To summarise, we found an overrepresentation of endometrial cancer in our cohort of
hereditary non-BRCA families, which supports earlier findings that breast and endometrial
cancer may constitute a breast cancer syndrome. Since results from studies are divergent
this issue needs to be resolved by further studies preferably on cohorts with two
close relatives or more affected by breast cancer or bilateral breast cancer. The
conflicting results could be due to methodology since the association may only be
evident in families with a strong pattern of breast cancer susceptibility. Identifying
new breast cancer syndromes is of importance to reach more women at increased risk
of cancer with preventive programmes. It is also a first step towards detection of
new susceptibility genes.
Prognostic Value of Circulating Tumor Cells in Ovarian Cancer: A Meta-Analysis
open access
Introduction
Ovarian cancer is the second leading cause of death among gynecologic malignancies in the world [1] owing to the fact that a majority of patients are diagnosed in late stages of the disease [2]. In such a setting, identifying prognostic indicators for patients with ovarian cancer is crucial. CA-125 is a frequently used biomarker in ovarian cancer, but some non-malignant conditions also cause elevated serum CA-125 concentrations [3]. Thus additional prognostic markers are urgently needed for ovarian cancer.
Discussion
Many studies have reported the prognostic value of CTCs in patients with ovarian cancer, and this is the first meta-analysis evaluating the value of CTCs in these patients. Overall, our results demonstrated that patients in CTC-positive group had a worse OS and PFS/DFS compared with CTC- negative group; moreover, the presence of CTCs was associated with elevated CA-125.Morphologic and Molecular Characteristics of Mixed Epithelial Ovarian Cancers
abstract
Epithelial ovarian cancer (EOC) consists of 5 major histotypes: high-grade serous carcinoma (HGSC), endometrioid carcinoma (EC), clear cell carcinoma (CCC), mucinous carcinoma (MC), and low-grade serous carcinoma (LGSC). Each can have a broad spectrum of morphologic appearances, and 1 histotype can closely mimic histopathologic features more typical of another. Historically, there has been a relatively high frequency of mixed, defined by 2 or more distinct histotypes present on the basis of routine histopathologic assessment, histotype carcinoma diagnoses (3% to 11%); however, recent immunohistochemical (IHC) studies identifying histotype-specific markers and allowing more refined histotype diagnoses suggest a much lower incidence. We reviewed hematoxylin and eosin-stained slides from 871 cases of EOC and found the frequency of mixed carcinomas to be 1.7% when modern diagnostic criteria are applied. Through international collaboration, we established a cohort totaling 22 mixed EOCs, consisting of 9 EC/CCC, 4 EC/LGSC, 3 HGSC/CCC, 2 CCC/MC, and 4 other combinations. We interrogated the molecular differences between the different components of each case using IHC, gene expression, and hotspot sequencing analyses. IHC data alone suggested that 9 of the 22 cases were not mixed tumors, as they presented a uniform immuno-phenotype throughout, and these cases most probably represent morphologic mimicry and variation within tumors of a single histotype. Synthesis of molecular data further reduces the incidence of mixed carcinomas. On the basis of these results, true mixed carcinomas with both morphologic and molecular support for the presence of >1 histotype within a given tumor represent <1% of EOCs.
Monday, June 22, 2015
Phase I Study of IV Docetaxel and IP Oxaliplatin in Recurrent Ovarian and Fallopian Tube Cancer
abstract
Highlights
Sarcoma: A Lynch syndrome (LS)-associated malignancy?
abstract
Conclusions: From a large sample of nearly 1000 LS families, our findings suggest sarcomas may be a rare manifestation of LS, especially MSH2+ LS. More research of genotype-phenotype correlations in LS is needed.
Quality of patient-reported outcome reporting across cancer randomized controlled trials....
Quality of patient-reported outcome reporting across cancer randomized controlled trials according to the CONSORT patient-reported outcome extension: A pooled analysis of 557 trials
Keywords:
- cancer;
- clinical trials;
- Consolidated Standards of Reporting Trials (CONSORT);
- patient-reported outcomes;
- quality of life
BACKGROUND
The
main objectives of this study were to identify the number of randomized
controlled trials (RCTs) including a patient-reported outcome (PRO)
endpoint across a wide range of cancer specialties and to evaluate the
completeness of PRO reporting according to the Consolidated Standards of
Reporting Trials (CONSORT) PRO extension.
METHODS
RCTs
with a PRO endpoint that had been performed across several cancer
specialties and published between 2004 and 2013 were considered. Studies
were evaluated on the basis of previously defined criteria, including
the CONSORT PRO extension and the Cochrane Collaboration's tool for
assessing the risk of bias of RCTs. Analyses were also conducted by the
type of PRO endpoint (primary vs secondary) and by the cancer disease
site.
RESULTS
A
total of 56,696 potentially eligible records were scrutinized, and 557
RCTs with a PRO evaluation, enrolling 254,677 patients overall, were
identified. PROs were most frequently used in RCTs of breast (n = 123),
lung (n = 85), and colorectal cancer (n = 66). Overall, PROs were
secondary endpoints in 421 RCTs (76%). Four of 6 evaluated CONSORT PRO
items were documented in less than 50% of the RCTs. The level of
reporting was higher in RCTs with a PRO as a primary endpoint. The
presence of a supplementary report was the only statistically
significant factor associated with greater completeness of reporting for
both RCTs with PROs as primary endpoints (β = .19, P = .001) and RCTs with PROs as secondary endpoints (β = .30, P < .001).
CONCLUSIONS
Implementation of the CONSORT PRO extension is equally important across all cancer specialties. Its use can also contribute to revealing the robust PRO design of some studies, which might be obscured by poor outcome reporting.
(repost) Risk Algorithm Using Serial Biomarker Measurements Doubles # of Screen-Detected Ovarian Cancers...
open access
Risk Algorithm Using Serial Biomarker Measurements Doubles the Number of Screen-Detected Cancers Compared With a Single-Threshold Rule in the United Kingdom Collaborative Trial of Ovarian Cancer Screening
..... Although HE4 does not improve CA-125 lead time,22,23 it could help confirm ovarian cancer risk and reduce time to surgery. In the presence of an increasing CA-125, HE4 was increased in samples from 27 of 39 women with ovarian cancer in the PLCO trial.21 TVS does not seem to have the resolution to detect iEOC at low CA-125 levels. Twenty-nine (41%) of 70 women with iEOCs in subgroup A had no abnormality on the initial level II scan, and TVS was abnormal in only 17 of the 39 women in the study by Urban et al.21 The potential of newer technology....
In conclusion, our data support use of velocity-based algorithms as opposed to a predefined single-threshold rule in cancer screening strategies that use blood biomarkers.
ASCO Statement: A Conceptual Framework to Assess the Value of Cancer Treatment Options
open access
CALL FOR COMMUNITY COMMENT
We appreciate that developing a method
for establishing value of specific cancer treatment regimens is a
daunting task. ASCO
views this as an iterative process and encourages
comments from all interested parties regarding the elements we have
included
in the value framework and its utility in
facilitating discussion between providers and patients on the value of
available
treatment options. Comments may be submitted
through August 21, 2015, at www.asco.org/value.
Clear cell carcinomas of the gynecologic tract and thromboembolic events: what do we know so far?
open access (2014)
..... specific malignancies that have been found to increase the risk of thromboembolic events (including gliomas, renal, gastric and pancreatic carcinomas) [2,5,6]. In ovarian cancer patients......
...... The occurrence of thromboembolic events has been found to adversely impact survival in several reports, even in patients with localized disease [6–8]......
The observation that cancer patients may have an increased risk for thromboembolic events was originally made by the French internist Armand Trousseau in 1865 [1]. Almost 150 years later, it is now well-recognized that cancer patients have a four- to seven-fold increase in their risk for venous thromboembolic events relative to their counterparts without cancer, and that 1–15% of cancer patients develop clinical thromboembolic events over the course of their care [2–4]. This increased risk has a multifactorial basis, the precise components of which are not entirely clear at the present time. However, in cancer patients, risk factors for increased thrombosis often abound, including the presence of medical comorbidities......
A patient-initiated voluntary online survey of adverse medical events: the perspective of 696 injured patients/families
open access
Adverse event categories and relative frequency
As shown in table 1,
the leading category of error reported by patients was failure in
diagnosis and treatment. Further breakdown of this category
revealed the leading event
(subcategory) was a delay in diagnosis and treatment. Misdiagnosis was
another frequent event,
as was failure to rescue a patient
whose clinical condition was worsening. The second most common category
was surgical or
procedural complications. Wrong site
surgery was surprisingly common in our survey (4.3%), as were foreign
objects left in
the patient (3.6%).
Hospital-associated infections were the third most common category,
sepsis being the most frequently reported
complication, followed by
postoperative infections, Clostridium difficile intestinal
infection and urinary tract infections. Medication errors were the
fourth major category in our survey. It is
of interest that a significant
percentage (12.8%) reported receiving medications that they were known
to have had an allergic
reaction to in the past.
Common Genetic Variation In Cellular Transport Genes and Epithelial Ovarian Cancer (EOC) Risk
eg. SERPINA7 (clear cell) = thyroid
open access (technical)
Results
The most significant evidence of an association for all invasive cancers combined and for the serous subtype was observed for SNP rs17216603 in the iron transporter gene HEPH (invasive: OR = 0.85, P = 0.00026; serous: OR = 0.81, P = 0.00020); this SNP was also associated with the borderline/low malignant potential (LMP) tumors (P = 0.021). Other genes significantly associated with EOC histological subtypes (p<0.05) included the UGT1A (endometrioid), SLC25A45 (mucinous), SLC39A11 (low malignant potential), and SERPINA7 (clear cell carcinoma). In addition, 1785 SNPs in six genes (HEPH, MGST1, SERPINA, SLC25A45, SLC39A11 and UGT1A) were imputed from the 1000 Genomes Project and examined for association with INV EOC in white-European subjects. The most significant imputed SNP was rs117729793 in SLC39A11 (per allele, OR = 2.55, 95% CI = 1.5-4.35, p = 5.66x10-4).Conclusion
These results, generated on a large cohort of women, revealed associations between inherited cellular transport gene variants and risk of EOC histologic subtypes.Family with MSH2 mutation presenting with keratoacanthoma and precancerous skin lesions
abstract
Muir–Torre syndrome (MTS) is a familial cancer syndrome characterized by a predisposition to keratoacanthoma (KA) and sebaceous tumors. Although MTS and hereditary non-polyposis colorectal cancer (HNPCC) share the same genetic alterations in mismatch repair (MMR) genes, the other skin lesions in MTS or HNPCC have been only rarely reported. We report a family with an MSH2 mutation c.1126_1127delTT (p.Leu376Thrfs*12). A 46-year-old male proband developed KA with sebaceous differentiation, colon cancer and gastric cancer, and fulfilled the diagnostic criteria for MTS. His 80-year-old mother, diagnosed with HNPCC, presented with multiple gastrointestinal tract cancers, Bowen's disease and actinic keratosis. Immunostaining revealed attenuated MSH2 protein expression in KA, as well as in Bowen's disease and actinic keratosis lesions. These findings suggest that MMR gene abnormality is also critical in the development of benign or malignant cutaneous tumors such as actinic keratosis and Bowen's disease in MTS/HNPCC patients.
Lynch Syndrome and Cervical Cancer Intl Jnl of Cancer
abstract
Carriers of germline mutations in DNA mismatch repair (MMR) genes are at increased risk of several cancers including colorectal and gynecologic cancers (Lynch syndrome). There is no substantial evidence that these mutations are associated with an increased risk of cervical cancer. A total of 369 families with at least one carrier of a mutation in a MMR gene (133 MLH1, 174 MSH2, 35 MSH6, and 27 PMS2) were ascertained via population cancer registries or via family cancer clinics in Australia, New Zealand, Canada, and USA. Personal and family histories of cancer were obtained from participant interviews. Modified segregation analysis was used to estimate the hazard ratio (incidence rates for carriers relative to those for the general population), and age-specific cumulative risks of cervical cancer for carriers. A total of 65 cases of cervical cancer were reported (including 10 verified by pathology reports). The estimated incidence was 5.6–fold (95% CI: 2.3–13.8; p=0.001) higher for carriers than for the general population with a corresponding cumulative risk to 80 years of 4.5% (95% CI: 1.9–10.7%) compared with 0.8% for the general population. The mean age at diagnosis was 43.1 years (95% CI: 40.0–46.2), 3.9 years younger than the reported USA population mean of 47.0 years (p=0.02). Women with MMR gene mutations were found to have an increased risk of cervical cancer. Due to limited pathology verification we cannot be certain that a proportion of these cases were not lower uterine segment endometrial cancers involving the endocervix, a recognized cancer of Lynch syndrome.
Thursday, June 18, 2015
Difficult Patients (nurse/PhD commentary)
ASCO Connection
We all have our fair share of so-called “difficult” patients. And, I would suggest that how we define “difficult” is as diverse as we are as health care providers and as individuals. Some patients come to us with that reputation—perhaps, a vague descriptor in a referral letter or a note in the patient’s chart. Maybe the receptionist or nurse makes a side comment that the next patient is “challenging” or “uptight,” and we accept their assessment......
Have we given up on a cure for ovarian cancer? - Narod
Current Oncology
Commentary
Have we given up on a cure for ovarian cancer?
A Countercurrents Seriesa
S.A. Narod , MD *
* Women’s College Research Institute, Women’s College Hospital, Toronto, ON.
doi: http://dx.doi.org/10.3747/co.22.2517
In December 2014, on the
force Web site, executive director Sue Friedman, heralded a game-changing holiday gift for people with
BRCA
mutations: “Today is a landmark for the
hboc
[hereditary breast and ovarian cancer] community”1. In an accompanying article 2, Lisa Rezende wrote about the U.S. Food and Drug Administration (
fda
) decision to approve olaparib for the treatment of recurrent ovarian cancer in women with a
BRCA1
or
BRCA2
mutation:.......
REFERENCES
1. Friedman S. A
Game-Changing Holiday Gift for People with BRCA Mutations [blog post].
Tampa, FL: Facing Our Risk of Cancer Empowered (force); 2014. [Available at: http://www.facingourrisk.org/get-involved/HBOC-community/BRCAHBOC-blogs/FORCE/uncategorized/a-game-changing-holiday-gift-for-people-with-brca-mutations/; cited 17 April 2015]
Tuesday, June 16, 2015
Osteoporosis Risk and Management in BRCA 1/ 2 carriers who undergo Risk-Reducing Salpingo-oophorectomy
abstract
Highlights:
- •Only 44% of BRCA carriers had a DXA scan after risk-reducing salpingo-oophorectomy, at median of 41 months from testing
- •68% of DXA scans in BRCA carriers who had undergone risk-reducing salpingo-oophorectomy were abnormal
- •There was a 4% rate of a traumatic fracture in BRCA carriers following RRSO
Conclusions
Women with BRCA mutations who undergo RRSO have many risk factors for bone loss. The majority of these women are not being screened for bone loss. A clear guideline for screening needs to be established to improve detection of post-RRSO bone disease.Why Have Ovarian Cancer Mortality Rates Declined? Part III. Prospects for the Future
abstract
Highlights
- •Up to 17% of ovarian cancers are potentially preventable through population-based genetic testing of known ovarian cancer susceptibility genes
- •Primary debulking surgery leaving no residual disease followed by intraperitoneal chemotherapy appears to hold the greatest potential for cure
Abstract
Over the last 40 years, the age-adjusted ovarian cancer mortality rate in the USA declined by 23%. The decline in mortality paralleled a decline in incidence, which was largely due to changes in reproductive risk factors. There was no reduction in ovarian cancer case-fatality at 12 years, indicating that improvements in early detection or in treatment did not contribute to the decline in mortality. Here, we discuss potential strategies to further reduce ovarian cancer mortality through prevention, early detection and treatment. The first approach is to increase genetic testing, in order to identify women who are at a high risk of developing ovarian cancer and offer them preventive bilateral salpingo-oophorectomy. At present, up to 17% of ovarian cancers are potentially preventable through population-based genetic testing of known ovarian cancer susceptibility genes. The second approach is to increase the proportion of ovarian cancer patients who achieve a status of no residual disease through primary debulking surgery and subsequently receive adjuvant intraperitoneal chemotherapy. We believe that through a combination of screening to better identify low-volume advanced stage ovarian cancer, aggressive surgery to leave no residual disease and adjuvant intraperitoneal chemotherapy, the cure rate of ovarian cancer might be improved significantly.Immunohistochemical Comparison of Ovarian and Uterine Endometrioid Carcinoma, Endometrioid Carcinoma With Clear Cell Change, and Clear Cell Carcinoma
abstract
Accurate distinction of clear cell carcinoma (CCC) from endometrioid carcinoma (EC) has important clinical implications, but, not infrequently, EC demonstrates clear cell change (EC-CC), mimicking CCC. We examined whether a panel of immunomarkers can help distinguish between these tumors. Sixty-four CCCs (40 ovarian and 24 uterine), 34 ECs (21 ovarian and 13 uterine), and 34 EC-CCs (6 ovarian and 28 uterine) were stained for HNF1[beta], BAF250a, Napsin A, ER, and PR. Intensity and extent of immunoreactivity was assessed. Fifty-seven of 64 (89%) CCCs, 14/34 (41%) EC-CCs, and 16/34 (47%) ECs expressed HNF1[beta], and 56/64 (88%) CCCs, 4/34 (12%) EC-CCs, and 1/34 (3%) ECs stained for Napsin A. Most CCCs demonstrated at least moderate and diffuse staining for both markers, whereas only focal and weak expression was identified in most EC-CC/EC. Compared to HNF1[beta], Napsin A showed increased specificity (93.0% vs. 55.9%, P<0.0001) and similar sensitivity (87.5% vs. 89.1%) in distinguishing CCC from EC-CC/EC. Thirteen of 64 (20%) CCCs, 6/34 (18%) EC-CCs, and 2/34 (6%) ECs showed loss of BAF250a. ER was expressed by 10/64 (16%) CCCs, 30/34 (88%) EC-CCs, and 33/34 (97%) ECs, whereas PR positivity was identified in 9/64 (14%) CCCs, 26/34 (77%) EC-CCs, and 33/34 (97%) ECs. The majority of EC and EC-CC demonstrated diffuse staining for ER/PR, whereas most CCCs showed very focal positivity. There is a statistically significant difference in HNF1[beta], Napsin A, ER, and PR immunoexpression between CCC and EC/EC-CC, with Napsin A being a more specific marker for CCC than HNF1[beta]. Overall, the immunoprofile of EC-CC is more comparable to that of EC than CCC. The use of a panel of immunostains can help distinguish EC-CC from CCC.
Ovarian Seromucinous Carcinoma: Report of a Series of a Newly Categorized and Uncommon Neoplasm
abstract
Seromucinous neoplasms are a new category of ovarian epithelial tumor in the revised World Health Organization Classification of Tumours of the Female Reproductive Organs. Borderline variants are well described, but there have been few reports of seromucinous carcinomas. We report the clinicopathologic features in 19 cases of ovarian seromucinous carcinoma in patients aged 16 to 79 years (mean 47). In 16 cases, the neoplasm was unilateral and in 3 cases bilateral. The tumors ranged in size from 1.8 to 18 cm (mean 10.5 cm). The tumors were stage I (n=15), stage II (n=1), and stage III (n=3). The histologic features were highly variable both within and between individual tumors. The majority of neoplasms (12 cases) exhibited a predominant papillary architecture with lesser components of glandular, microglandular, and solid growth. A predominant glandular architecture was present in 6 cases, whereas 1 had a predominantly solid growth. A characteristic feature was an admixture of cell types. Most of the tumors (15 cases) were mainly composed of endocervical-like mucinous cells, whereas in 4 cases there was predominant endometrioid differentiation. Other cell types, present in varying proportions, included hobnail cells, eosinophilic cells, squamous cells, clear cells, and signet-ring cells. An infiltrate of neutrophil polymorphs was a prominent feature in most cases. Most cases also exhibited areas of microglandular architecture with cytoplasmic clearing and intraluminal polymorphs, the features closely resembling cervical microglandular hyperplasia. Areas of stromal hyalinization, adenofibromatous growth, and psammoma bodies were present in a minority of cases. Endometriosis was identified in the same ovary in 10 cases, and in 10 there was a component of seromucinous borderline tumor. Thirteen, 5, and 1 tumor were of grades 1, 2, and 3, respectively (using the FIGO grading system for endometrioid adenocarcinomas of the uterine corpus). A synchronous uterine endometrioid adenocarcinoma was present in 1 case. Immunohistochemically, there was positive staining with CK7 (17/17 cases), estrogen receptor (16/16 cases), progesterone receptor (6/7 cases), CA125 (15/15 cases), PAX8 (8/8 cases), CEA (8/13 cases), CA19.9 (8/9 cases), and WT1 (2/13 cases). CK20 and CDX2 were negative in all cases tested (16 and 14, respectively). p53 showed “wild-type” staining in 4/4 cases, and p16 was focally positive in 5/5 cases. Follow-up information was available in 8 patients. Seven were alive with no evidence of disease (follow-up 3 to 74 mo), whereas 1 patient who initially presented with a stage IIB tumor died of disease at 192 months. Given the characteristic admixture of cell types and the overlapping morphologic features with low-grade serous, mucinous, and endometrioid neoplasms, the most appropriate categorization of seromucinous carcinomas is uncertain, but we believe they are best regarded as a distinct type of ovarian epithelial malignancy and are most similar to endometrioid adenocarcinomas. We recommend grading them in an analogous manner to ovarian endometrioid adenocarcinomas.
OCNA - URGENT: Protect Ovarian Cancer Research at the DOD
Ask your Senator to Oppose the McCain Amendment to the Defense Bill
Senator
John McCain has an amendment to the Defense Authorization bill to wipe
out many of the research programs run by the Department of Defense,
including the Ovarian Cancer Research Program (OCRP). The OCRP funds $20
million in innovative, high-risk, high-reward research each year.
Please call or write your Senators TODAY and ask them to oppose this
dangerous amendment.
Evolving paradigms in the treatment of opioid-induced bowel dysfunction
abstract
In recent years prescription of opioids has increased significantly. Although effective in pain management, bothersome gastrointestinal adverse effects are experienced by a substantial proportion of opioid-treated patients. This can lead to difficulties with therapy and subsequently inadequate pain relief. Collectively referred to as opioid-induced bowel dysfunction, these adverse effects are the result of binding of exogenous opioids to opioid receptors in the gastrointestinal tract. This leads to disturbance of three important gastrointestinal functions: motility, coordination of sphincter function and secretion. In the clinic this manifests in a wide range of symptoms such as reflux, bloating, abdominal cramping, hard, dry stools, and incomplete evacuation, although the most known adverse effect is opioid-induced constipation. Traditional treatment with laxatives is often insufficient, but in recent years a number of novel pharmacological approaches have been introduced. In this review the pathophysiology, symptomatology and prevalence of opioid-induced bowel dysfunction is presented along with the benefits and caveats of a suggested consensus definition for opioid-induced constipation. Finally, traditional treatment is appraised and compared with the latest pharmacological developments. In conclusion, opioid antagonists restricted to the periphery show promising results, but use of different definitions and outcome measures complicate comparison. However, an international working group has recently suggested a consensus definition for opioid-induced constipation and relevant outcome measures have also been proposed. If investigators within this field adapt the suggested consensus and include symptoms related to dysfunction of the upper gut, it will ease comparison and be a step forward in future research.
Eudaimonic well-being and tumor norepinephrine in patients with epithelial ovarian cancer
abstract
BACKGROUND
The
impact of psychological well-being on the physiologic processes
involved in cancer progression remains unclear. Prior research has
implicated adrenergic signaling in tumor growth and metastasis. Given
that adrenergic signaling is influenced by both positive and negative
factors, the authors examined how 2 different aspects of well-being
(eudaimonic and positive affect) and psychological distress were
associated with tumor norepinephrine (NE) in patients with ovarian
cancer.
(definition: epinephrine and norepinephrine, also called adrenaline and noradrenaline, two separate but related hormones secreted by the medulla of the adrenal glands.)
(definition: epinephrine and norepinephrine, also called adrenaline and noradrenaline, two separate but related hormones secreted by the medulla of the adrenal glands.)
METHODS
A
total of 365 women with suspected ovarian cancer completed psychosocial
assessments before surgery and clinical information was obtained from
medical records.
Ovarian cancer treatment: The end of empiricism? open access
Open access
Abstract
The diagnosis, investigation, and management of ovarian cancer are in a state of flux—balancing ever rapid advances in our understanding of its biology with 3 decades of clinical trials. Clinical trials that started with empirically driven selections have evolved in an evidence-informed manner to gradually improve outcome. Has this improved understanding of the biology and associated calls to action led to appropriate changes in therapy? In this review, the authors discuss incorporating emerging data on biology, combinations, dose, and scheduling of new and existing agents with patient preferences in the management of women with ovarian cancer.Table 1. Prioritization Questions in the Management of Ovarian Cancer and Current Proposed Strategies
Conclusion
The treatment of ovarian cancer is on the verge of a major change that will propel improvement in outcomes.[87]
Recent developments emphasize that a multipronged approach is
warranted, integrating genomics, subtype-specific maintenance therapy,
and other directions that will be used alongside increasingly sensitive
disease-detection tools. Better definition of treatment timing may
further allow exploitation of additional benefits of surgery as the role
of surgery remains central to OC treatment. Taken together, this will
allow us to build on our understanding of the heterogeneity of OC to
tailor treatment. Future therapeutic strategy should target genetics,
microenvironment, and sequence schedule to keep cancer cells from
developing resistance. To move forward, we have to take some bold steps
based on biology, require objective evidence of benefit, and reflect on
experience from other cancers and diseases. It is important to
constantly re-evaluate data and expect that, for therapy to be
considered “standard,” it has to demonstrate objective, clinically
meaningful, as well as statistically significant benefit. The timing is
right for a paradigm shift that will require clinicians to have the
courage and confidence to not prescribe treatments without evidence of
benefit. This will necessitate optimizing surgery and appropriate
evidence-based recommendations for each subtype of ovarian cancer. This
therapeutic direction has to be supported by excellence and precision in
pathology, molecular profiling, and imaging. In equal measure, it will
require open dialogue with patients and being honest about treatments
that have evidence of benefit and, especially, those that do not.
Use of common analgesics is not associated with ovarian cancer survival
abstract
Background: Use of analgesics has been associated with lower risk of ovarian cancer, but to date, very few studies have explored the association between analgesics and ovarian cancer survival.
Methods: We examined the relationship between self-reported pre-diagnostic use of aspirin, ibuprofen, and acetaminophen and overall survival (OS), progression-free survival (PFS), ascites at the time of primary treatment, and persistence of disease after primary treatment among 699 women diagnosed with epithelial ovarian carcinoma. The associations between use of these medications and OS and PFS were estimated using Cox-proportional hazards models. We utilized unconditional logistic regression models to estimate associations between medication use and presence of ascites and persistence of disease.
Results: Pre-diagnostic intake of aspirin, both low-dose and regular-dose, ibuprofen, and acetaminophen were not associated with any of the outcomes of interest.
Conclusions: Our results indicate a lack of association between pre-diagnostic intake of selected analgesics and OS, PFS, presence of ascites at the time of primary treatment, and persistence of disease after primary treatment.
Impact: Pre-diagnostic intake of analgesics may not be associated with ovarian cancer outcomes.
Monday, June 15, 2015
Who should decide how much and what information is important in person-centred health care?
open access
.... We do not need the concept of an ‘informed decision’, only that of a good, better or best possible decision. For none of these will there be a definition that is not multi-dimensional and therefore preference-sensitive. The question is to whose preferences should the definition be sensitive? There can only be one answer: the patient’s – or the person’s if they are not a patient.
Cost Effectiveness of Chemotherapeutic Agents and Targeted Biologics in Ovarian Cancer
abstract
Cost Effectiveness of Chemotherapeutic Agents and Targeted Biologics in Ovarian Cancer: A Systematic Review
.....Future research incorporating real-world data is essential to corroborate findings from trial-based economic evaluations. In addition, for improving consistency in reporting and quality of studies, incorporating QALYs in this population is important, especially since chemotherapy is administered for lengthy periods of time.
Sunday, June 14, 2015
Why Have Ovarian Cancer Mortality Rates Declined? Part II. Case-fatality
abstract
Highlights
- •
- The decline in ovarian cancer mortality cannot be explained by a reduction in case-fatality
- •
- New treatments improve short-term survival and median survival, but not long-term survival or cure
In
the United States, the age-adjusted mortality rate from ovarian cancer
declined by 8% from 1975 to 1991 and by 18% from 1992 to 2011. A decline
in the incidence rate of ovarian cancer paralleled the decline in
mortality (described in Part I). The decline in mortality might also be
due to a reduced proportion of ovarian cancer patients who die from
their cancer (case-fatality). Here, we examine rates of ovarian cancer
case-fatality from the Surveillance Epidemiology and End Results (SEER)
registry database, and we consider to what extent advances in treatment
also contribute to the observed decline in mortality. From 1973 to 1999,
the five-year case-fatality rate for women with ovarian cancer fell by
7.5%, whereas the 12-year case-fatality rate fell by only 1.2%. The
declines in five-year case-fatality corresponded in time with the
introduction and expansion in use of cis-platinum and paclitaxel in
clinical practice. However, modest declines in 12-year case-fatality
indicate that the introduction of chemotherapy has not contributed to
the decline in mortality. Developments in the last two decades include
targeted therapies, aggressive surgical techniques, the use of
neoadjuvant chemotherapy and intraperitoneal chemotherapy. The impact of
these treatment modalities on ovarian cancer mortality still needs to
be evaluated.
Why Have Ovarian Cancer Mortality Rates Declined? Part I. Incidence
abstract
The age-adjusted mortality rate from ovarian cancer in the United States has declined over the past several decades. The decline in mortality might be the consequence of a reduced number of cases (incidence) or a reduction in the proportion of patients who die from their cancer (case-fatality). In Part I of this three-part series, we examine rates of ovarian cancer incidence and mortality from the Surveillance Epidemiology and End Results (SEER) registry database and we explore to what extent the observed decline in mortality can be explained by a downward shift in the stage distribution of ovarian cancer (i.e. due to early detection) or by fewer cases of ovarian cancer (i.e. due to a change in risk factors). The proportion of localized ovarian cancers did not increase, suggesting that a stage-shift did not contribute to the decline in mortality. The observed decline in mortality paralleled a decline in incidence. The trends in ovarian cancer incidence coincided with temporal changes in the exposure of women from different birth cohorts to various reproductive risk factors, in particular, to changes in the use of the oral contraceptive pill and to declining parity. Based on recent changes in risk factor propensity, we predict the trend of the declining age-adjusted incidence rate of ovarian cancer in the United States will reverse and rates will increase in coming years.
Alterations in the mitochondrial responses to PENAO (ovarian cancer cell lines)
Abstract
Alterations in the mitochondrial responses to PENAO as a mechanism of resistance in ovarian cancer cells
Highlights
- •
- PENAO has promising anti-proliferative activity on cells established from four histological subtypes of ovarian cancer.
- •
- SKOV-3 endometrioid ovarian carcinoma resistance towards PENAO results from a strong heme oxygenase induction and a shift towards glycolytic metabolism.
- •
- PENAO and mTOR pathway inhibition synergizes to reverse SKOV-3 endometrioid ovarian carcinoma drug resistance.
Objective
The
purpose of this study was to test PENAO, a promising new
organoarsenical that is in phase 1 testing in patients with solid
tumors, on a range of ovarian cancer cell lines with different
histotypes, and to understand the molecular basis of drug resistance
exhibited by the endometrioid ovarian cancer cell line, SKOV-3.
Disease-free ovarian cancer patients report severe pain and fatigue over time: prospective
abstract
OBJECTIVE: Among ovarian cancer patients, cancer treatment is aggressive and yet survival is often so limited; hence, this study sought to measure quality of life with the ultimate goal of identifying ways of improving it over the duration of these patients' lives.
MATERIALS AND METHODS: The medical records of all ovarian cancer patients who received some/all of their initial chemotherapy at the Mayo Clinic in Rochester, Minnesota from late 2010 through 2012 were reviewed. Patient-reported quality of life was derived from the following ten-point linear analogue scale questions which had been administered to all patients: 1) How would you describe your degree of pain, on average ? 2) How would you describe your level of fatigue, on average ? 3) How would you describe your overall quality of life ? Quality of life data were censored upon cancer recurrence.
RESULTS: Among 59 eligible patients, the median cumulative interval during which quality of life was serially assessed was 1.15 years (range: three months, 3.2 years). Area under the curve for pain, fatigue, and global quality of life showed no statistically significant differences between patients treated with dose-dense chemotherapy with carboplatin/paclitaxel (n = 10) versus three-week chemotherapy with carboplatin/paclitaxel (n = 36) versus other (n = 13). Although pain, fatigue, and global quality of life improved over time, 35 of 59 (59%) patients reported grade 4 or worse pain during follow up, and 47 of 59 (80%) reported grade 4 or worse fatigue (higher scores denote worse pain or fatigue). After completion of cancer treatment, 30 (51%) described grade 4 or worse pain or fatigue. The most common pain site was the abdomen/pelvis, followed by the back, followed by the hands, feet, fingers, and toes.
CONCLUSION: In ovarian cancer patients who remain cancer-free, severe pain and fatigue occur years after cancer treatment. Further research should focus on how best to address these symptoms.
Cochrane Revidew: Antidepressants for the treatment of depression in people with cancer
Abstract
AUTHORS' CONCLUSIONS:
Despite the impact of depression on people with cancer, available studies were very few and of low quality. This review found very low quality evidence for the effects of these drugs compared with placebo. On the basis of these results clear implications for practice cannot be made. The use of antidepressants in people with cancer should be considered on an individual basis and, considering the lack of head-to-head data, the choice of which agent should be prescribed may be based on the data on antidepressant efficacy in the general population of individuals with major depression, also taking into account that data on medically ill patients suggest a positive safety profile for the SSRIs. Large, simple, randomised, pragmatic trials comparing commonly used antidepressants versus placebo in people with cancer with depressive symptoms, with or without a formal diagnosis of a depressive disorder, are urgently needed to better inform clinical practice.
Saturday, June 13, 2015
Despite warnings, mesh use for prolapse on the rise
Urology Times
Despite the FDA’s warnings about health risks associated with the use
of surgical mesh for transvaginal repair of pelvic organ prolapse (POP),
use of the device is increasing, according to a study of POP patients in New York state.
At the same time, risks of reinterventions within 1 year and
post-surgery urinary retention continue, said the authors of the study,
which was published online in BMJ (June 2, 2015).
Researchers at Weill Medical College of Cornell University in New York
analyzed a statewide database of nearly 28,000 women who had prolapse
repair procedures in the state from 2008 to 2011....
Tyrosine Kinase Inhibitors as Potential Therapeutic Agents in the Treatment of GCTof the Ovary
abstract
OBJECTIVE:
Granulosa cell tumors of the ovary (GCTs) represent a specific subset of malignant ovarian tumors, of which there are 2 distinct subtypes, the juvenile and the adult form. Aside from surgery, no reliable therapeutic options currently exist for patients with GCT. This study sought to investigate the potential role of small molecule tyrosine kinase inhibitors (TKIs) as novel therapeutics in the clinical management of GCT.MATERIALS AND METHODS:
Using TKI with distinct but overlapping multitargeted specificities, cellular proliferation, viability, and apoptosis were evaluated in 2 human GCT-derived cell lines, COV434 and KGN.RESULTS:
Sunitinib, which targets the imatinib-inhibited tyrosine kinases of VEGFR, KIT, PDGFR, and FLT-3, was without effect in COV434 and KGN cell lines. Sorafenib, which has a high affinity for RAF1 and BRAF, dose dependently inhibited cellular proliferation and viability in both cell lines at concentrations equivalent to that seen in other systems. A RAF1 kinase inhibitor was without effect, suggesting that sorafenib is acting via inhibition of BRAF, or that aberrant signaling originates upstream of BRAF in the MAPK pathway. In the presence of a selective Src family inhibitor (SU6656), cell proliferation and cell viability responses dissociated; that is, although SU6656 dose dependently inhibited cell viability, it had limited effect on proliferation and apoptosis.CONCLUSIONS:
These findings implicate BRAF in the activated signaling responsible for the growth and viability of GCT and suggest that TKI already in clinical use may be a therapeutic option in the treatment of GCT.Evaluation of the Hematologic Safety of Same Day Vs Standard Administration of Pegfilgrastim in Gynecology Oncology Patients
abstract
CONCLUSIONS:
The incidence of hematologic toxicities and dose modification in patients receiving same-day pegfilgrastim were not as low as in those undergoing standard administration. However, treatment delays were found to be no more frequent in those receiving same-day pegfilgrastim versus standard administration. Same-day administration of pegfilgrastim is a reasonable option.
Epithelial Ovarian Cancer Metastatic to the CNS and a Family History Concerning for HBOC
abstract (edited stats for ease of reading)
Epithelial Ovarian Cancer Metastatic to the Central Nervous System and a Family History Concerning for Hereditary Breast and Ovarian Cancer-A Potential Relationship.
OBJECTIVES:
To estimate the frequency of hereditary breast and ovarian cancer (HBOC) in women with central nervous system (CNS) metastasis from epithelial ovarian cancer (EOC) and to evaluate for a potential relationship between HBOC status and survival.METHODS AND MATERIALS:
A total of 1240 cases of EOC treated between 1995 and 2014 were reviewed to identify CNS metastasis. Demographics, treatment, family history, genetic testing, and survival outcomes were recorded. Women were then classified as HBOC+ or HBOC- based on histories and genetic testing results....RESULTS:
Of 1240 cases, 32 cases of EOC with CNS metastasis were identified (2.58%). Median age was 52 years, and 87% had stage III to IV disease. Among those with documented personal and family history, 66.7% (20/30) were suspicious for HBOC syndrome. Among those who underwent germline testing, 71.43% (5/7) had a pathogenic BRCA mutation. The median time from diagnosis to CNS metastasis was 29 months. At a median survival of 5.97 months from the time of CNS metastasis and 43 months from the time of EOC diagnosis, 29 women died of disease. Univariate Cox proportional hazard models were used to compare HBOC- to HBOC+ women and did not reveal a significant difference for survival outcomes.CONCLUSIONS:
Confirmed BRCA mutations and histories concerning for HBOC syndrome are common in women with EOC metastatic to the CNS. We did not demonstrate a relationship between HBOC status and survival outcomes, but were not powered to do so.Rectal Cancer Diagnosed after Cesarean Section in Which MSI-H Indicated Lynch Syndrome
Rectal Cancer Diagnosed after Cesarean Section in Which High Microsatellite Instability Indicated the Presence of Lynch Syndrome
abstract
We report a case of rectal cancer with microsatellite instability (MSI) that probably resulted from Lynch syndrome and that was diagnosed after Cesarean section. The patient was a 28-year-old woman (gravid 1, para 1) without a significant medical history. At 35 gestational weeks, vaginal ultrasonography revealed a 5 cm tumor behind the uterine cervix, which was diagnosed as a uterine myoma. The tumor gradually increased in size and blocked the birth canal, resulting in the patient undergoing an emergency Cesarean section. Postoperatively, the tumor was diagnosed as rectal cancer with MSI. After concurrent chemoradiation therapy, a lower anterior resection was performed. The patient's family history revealed she met the criteria of the revised Bethesda guidelines for testing the colorectal tumor for MSI. Testing revealed that the tumor did indeed show high MSI and, combined with the family history, suggested this could be a case of Lynch syndrome. Our findings emphasize the importance of considering the possibility of Lynch syndrome in pregnant women with colorectal cancer, particularly those with a family history of this condition. We suggest that the presence of Lynch syndrome should also be considered for any young woman with endometrial, ovarian, or colorectal cancer.
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