Blogger's Note: 1 reference to ovarian cancer - "Genetic determinants of human health and disease (including breast, endometrial, prostate, ovarian and melanoma cancers)."
Report Card
Tuesday, April 07, 2015
Report Card - Reflections on 2014 (Canada) Cancer Advocacy Coalition
Blogger's Note: 1 reference to ovarian cancer - "Genetic determinants of human health and disease (including breast, endometrial, prostate, ovarian and melanoma cancers)."
Report Card
Ovarian Sex Cord-Stromal Tumors in Patients With Probable or Confirmed Germline DICER1 Mutations
Oabstract
....The present small series suggests that some ovarian Sertoli-Leydig cell tumor associated with germline DICER1 mutations may show distinctive histologic features in particular admixed Sertoli cell and juvenile granulosa cell tumor-like features. Larger studies are required to establish whether heterologous elements are also a more common feature of these tumors.
Cediranib Aims for a Comeback
extract JNCI
Women with advanced ovarian or cervical cancer are living longer, with fewer disease symptoms, and that reflects advances
across clinical and supportive therapies.
Bevacizumab, for instance—a
recently approved monoclonal antibody that targets vascular endothelial
growth factor (VEGF)—improves
overall survival (OS) and progression-free survival
(PFS) in both diseases. In August 2014, the U.S. Food and Drug
Administration
approved bevacizumab in combination with
chemotherapy to treat platinum-resistant recurrent ovarian cancer. And
the following
November, FDA approved the drug to treat
persistent, recurrent, or metastatic cervical cancer, also with
chemotherapy. Those
were the first new approvals in ovarian and
cervical cancer treatment since 2006.
Interest Revived
Now a different VEGF-directed compound,
cediranib, a tyrosine kinase inhibitor, is making steady gains in
ovarian and cervical
cancer treatment. Cediranib’s manufacturer,
AstraZeneca, abandoned its own sponsored development of the drug in 2011
after
it failed to meet phase III goals in lung and
colorectal cancers. But investigator-initiated studies in gynecological
cancers
gave cediranib another chance. These studies
show improved OS and PFS, but also with side effects that seem worse
than those
associated with bevacizumab, according to David
Hyman, M.D., a gynecological medical oncologist and assistant professor
at
New York’s Memorial Sloan–Kettering Cancer
Center.
“We don’t really know if bevacizumab and cediranib are interchangeable,” he said. “We still need to define the approval setting
…
Breast Cancer Patients Concerned About Genetic Risk, Survey Finds
Drugs.com
MONDAY April 6, 2015, 2015 -- Although many women with breast cancer are concerned about their genetic risk for other cancers -- as well as their relatives' risk for breast cancer -- almost half of these patients don't get information about genetic testing, a new study finds.
Researchers surveyed more than 1,500 breast cancer patients in Detroit and Los Angeles and found that 35 percent had a strong interest in genetic testing.......Many of those interested in genetic testing were also concerned about their own future risk of other types of cancer, according to the study in the current issue of the Journal of Clinical Oncology....
Platinum-Induced Neurotoxicity and Preventive Strategies: Past, Present, and Future
abstract
Neurotoxicity is a burdensome side effect of platinum-based chemotherapy that prevents administration of the full efficacious dosage and often leads to treatment withdrawal. Peripheral sensory neurotoxicity varies from paresthesia in fingers to ataxic gait, which might be transient or irreversible. Because the number of patients being treated with these neurotoxic agents is still increasing, the need for understanding the pathogenesis of this dramatic side effect is critical. Platinum derivatives, such as cisplatin and carboplatin, harm mainly peripheral nerves and dorsal root ganglia neurons, possibly because of progressive DNA-adduct accumulation and inhibition of DNA repair pathways (e.g., extracellular signal-regulated kinase 1/2, c-Jun N-terminal kinase/stress-activated protein kinase, and p38 mitogen-activated protein kinass), which finally mediate apoptosis. Oxaliplatin, with a completely different pharmacokinetic profile, may also alter calcium-sensitive voltage-gated sodium channel kinetics through a calcium ion immobilization by oxalate residue as a calcium chelator and cause acute neurotoxicity. Polymorphisms in several genes, such as voltage-gated sodium channel genes or genes affecting the activity of pivotal metal transporters (e.g., organic cation transporters, organic cation/carnitine transporters, and some metal transporters, such as the copper transporters, and multidrug resistance-associated proteins), can also influence drug neurotoxicity and treatment response. However, most pharmacogenetics studies need to be elucidated by robust evidence. There are supportive reports about the effectiveness of several neuroprotective agents (e.g., vitamin E, glutathione, amifostine, xaliproden, and venlafaxine), but dose adjustment and/or drug withdrawal seem to be the most frequently used methods in the management of platinum-induced peripheral neurotoxicity. To develop alternative options in the treatment of platinum-induced neuropathy, studies on in vitro models and appropriate trials planning should be integrated into the future design of neuroprotective strategies to find the best patient-oriented solution.
BRCA1 and BRCA2 Mutations in Ethnic Lebanese Arab Women With High Hereditary Risk Breast Cancer
abstract
Conclusion. Prevalence of deleterious BRCA mutations is lower than expected and does not support the hypothesis that BRCA mutations alone cause the observed high percentage of breast cancer in young women of Lebanese and Arab descent. Studies to search for other genetic mutations are recommended.
Monday, April 06, 2015
A targeted analysis identifies a high frequency of BRCA1 & 2 mutation carriers in women with ovarian cancer from a founder population
Journal of Ovarian Research | Full text | A targeted analysis identifies a high frequency of BRCA1 and BRCA2 mutation carriers in women with ovarian cancer from a founder population
Background
The frequency of BRCA1 and BRCA2 mutations in ovarian cancer patients varies depending on histological subtype and population investigated. The six most commonly recurring BRCA1 and BRCA2 mutations previously identified in a founder French Canadian population were investigated in 439 histologically defined ovarian, fallopian tube and primary peritoneal cancer cases that were ascertained at one hospital servicing French Canadians. To further assess the frequency of BRCA1/BRCA2 mutations, a defined subgroup of 116 cases were investigated for all mutations previously reported in this population.....
http://ovariancancerandus.blogspot.com/feeds/posts/default
Ovarian, fallopian tube and peritoneal cancer staging: rationale and explanation of new FIGO staging 2013
abstract
Ovarian, fallopian tube, and peritoneal cancers have a similar clinical presentation and are treated similarly, and current evidence supports staging all 3 cancers in a single system. The primary site (i.e. ovary, fallopian tube, or peritoneum) should be designated where possible. The histologic type should be recorded. Intraoperative rupture (“surgical spill”) is IC1; capsule ruptured before surgery or tumor on ovarian or fallopian tube surface is IC2; and positive peritoneal cytology with or without rupture is IC3. The new staging includes a revision of stage III patients; assignment to stage IIIA1 is based on spread to the retroperitoneal lymph nodes without intraperitoneal dissemination. Extension of tumor from omentum to spleen or liver (stage IIIC) should be differentiated from isolated parenchymal metastases (stage IVB).
Relationship of tumor marker CA125 and ovarian tumor stem cells
Full text: Relationship of tumor marker CA125 and ovarian tumor stem cells: preliminary identification
....In 1981, Robert et al. [18] found antigen CA125 in the ovarian cancer cells by using monoclonal antibody OC125. Since then, CA125 has been an auxiliary diagnostic marker for ovarian cancer, and research about immunological treatment of ovarian cancer using the antibody’s specificity for CA125 is also emerging. Our experiments showed that CA125 may be one of the surface markers of tumor stem cells, and further studies are needed to investigate the existence of other markers, which is the direction of our future studies. Finding the markers of ovarian cancer stem cells and targeting killing these “seed cells”, making the prevention and treatment of ovarian cancer possible.
Evidence for induction of a tumor metastasis-receptive microenvironment for ovarian cancer cells in bone marrow and other organs as an unwanted and underestimated side effect of chemotherapy/radiotherapy
Journal of Ovarian Research - open access
Background One of side effects of chemotherapy and radiotherapy is the induction of
several factors in various tissues and organs that create a pro-metastatic microenvironment
for cancer cells that survive initial treatment. Methods In the present study, we
employed human ovarian cancer cell line A2780 and immunodeficient mice xenogrfat model
to test effect of both ibuprofen and dexamethasone to ameliorate the therapy-induced
pro-metastatic microenvironment in bone marrow, liver, and lung. Results In our studies,
we found that total body irradiation or administration of cisplatin increases the
metastatic spread of human ovarian cancer cells transplanted into immunodeficient
mice compared with animals unexposed to irradiation or cisplatin. Moreover, conditioned
media harvested from irradiated murine bone marrow, lung, and liver chemoattracted
human ovarian cancer cells, and this chemotactic activity was inactivated by heat,
suggesting a major involvement of peptide or peptide-bound chemoattractants. We also
observed that human ovarian cancer cells proliferate better if exposed to cell debris
harvested from irradiated murine bone marrow. Finally, the pro-metastatic microenvironment
in mice induced by radio- or chemotherapy was significantly ameliorated if animals
were treated at the time of radiochemotherapy administration with non-steroid (ibuprofen)
or steroid (prednisone) anti-inflammatory drugs. Conclusions In summary, we propose
that a radiochemotherapy-induced, pro-metastatic microenvironment plays an important
role in the metastasis of cancer cells that are resistant to treatment. Such cells
have characteristics of cancer stem cells and are highly migratory, and simple, intensive,
anti-inflammatory treatment by non-steroid agents to suppress induction of pro-metastatic
factors after radiochemotherapy would be an interesting anti-metastatic treatment
alternative.
The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.
open access: Development and analytical validation of a 25-gene next generation sequencing panel that includes the BRCA1 & 2 genes to assess hereditary cancer risk
open access - authors Myriad
Background Germline DNA mutations that increase the susceptibility of a patient to certain cancers have been identified in various genes, and patients can be screened for mutations in these genes to assess their level of risk for developing cancer. Traditional methods using Sanger sequencing focus on small groups of genes and therefore are unable to screen for numerous genes from several patients simultaneously. The goal of the present study was to validate a 25-gene panel to assess genetic risk for cancer in 8 different tissues using next generation sequencing (NGS) techniques. Methods Twenty-five genes associated with hereditary cancer syndromes were selected for development of a panel to screen for risk of these cancers using NGS. In an initial technical assessment, NGS results for BRCA1 and BRCA2 were compared with Sanger sequencing in 1864 anonymized DNA samples from patients who had undergone previous clinical testing. Next, the entire gene panel was validated using parallel NGS and Sanger sequencing in 100 anonymized DNA samples. Large rearrangement analysis was validated using NGS, microarray comparative genomic hybridization (CGH), and multiplex ligation-dependent probe amplification analyses (MLPA). Results NGS identified 15,877 sequence variants, while Sanger sequencing identified 15,878 in the BRCA1 and BRCA2 comparison study of the same regions. Based on these results, the NGS process was refined prior to the validation of the full gene panel. In the validation study, NGS and Sanger sequencing were 100% concordant for the 3,923 collective variants across all genes for an analytical sensitivity of the NGS assay of >99.92% (lower limit of 95% confidence interval). NGS, microarray CGH and MLPA correctly identified all expected positive and negative large rearrangement results for the 25-gene panel. Conclusion This study provides a thorough validation of the 25-gene NGS panel and indicates that this analysis tool can be used to collect clinically significant information related to risk of developing hereditary cancers.
The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.
Tackling the cancer epidemic - Editorial
The Lancet Oncology
Editorial
Tackling the cancer epidemic
Cancer
is the primary cause of death in many countries, now exceeding heart
disease. In lower income countries, incidence is rising fast, creating
unprecedented challenges for health systems, many of which were designed
in an era that did not foresee, were simply incapable of pre-empting,
or knowingly ignored the future. For lower-to-middle income countries,
these challenges are multiplied by the double burden of disease—the
long-running battle against infection complicated by the rising burden
of chronic diseases.
Advances in care are allowing
patients to live longer, better quality lives. Survival has improved
substantially as knowledge of the biology and aetiology of cancer has
increased, offering the promise of precision oncology. However, these
remarkable achievements come at a price—the cost of care is outpacing
national budgets, the numbers of cancer patients and survivors are
putting greater pressures on health-care systems, and increasing numbers
of vulnerable patients from less traditional demographics, such as
children and younger adults, require different clinical solutions that
have yet to be fully conceived.
This month, The Lancet Oncology launches a campaign
focused on tackling the cancer epidemic at a systems level. This
campaign will provide a comprehensive assessment of the necessary
changes in patient services and outcomes. We will document, via monthly
updates, the evolution of four Commissions intended for publication
later this year that aim to define the scale of the challenge, the
underlying drivers, and the improvements needed to cancer-care systems.
These special reports will cover global access to radiotherapy, surgical
resource availability and its fundamental role in cancer treatment, the
intersection of primary care in a comprehensive cancer service fit for
the 21st century, and the ongoing oncology requirements in the
low-to-middle income countries of Latin America. When published, we hope
these Commissions will offer practical advice and specific
recommendations to help overcome this tremendous health-care challenge.
Ovarian Cancer National Alliance - 2015 report SGO conference
American Gastroenterological Association technical review on diagnosis and management of Lynch syndrome
pdf (81 pages)
reference:
16.National Comprehensive Cancer Network, About the NCCN Clinical Practice Guidelines in Oncology. 2014. (Accessed Januaty 2015, at https://www.nccn.org/store/login/login.aspx?ReturnURL=http://www.nccn.org/professionals/physician_gls/pdf/colon.pdf.)
Ovarian Cancer - CRI
CRI
.... A number of immune-based therapies are being investigated in early-phase clinical trials for patients with ovarian cancer. Go to our Cancer Immunotherapy Clinical Trial Finder to find clinical trials of immunotherapies for ovarian cancer that are currently enrolling patients.....
A
number of immune-based therapies are being investigated in early-phase
clinical trials for patients with ovarian cancer. Go to our Cancer
Immunotherapy Clinical Trial Finder to find clinical trials of
immunotherapies for ovarian cancer that are currently enrolling
patients. - See more at:
http://www.cancerresearch.org/cancer-immunotherapy/impacting-all-cancers/ovarian-cancer#sthash.oremPX4Q.dpuf
A
number of immune-based therapies are being investigated in early-phase
clinical trials for patients with ovarian cancer. Go to our Cancer
Immunotherapy Clinical Trial Finder to find clinical trials of
immunotherapies for ovarian cancer that are currently enrolling
patients. - See more at:
http://www.cancerresearch.org/cancer-immunotherapy/impacting-all-cancers/ovarian-cancer#sthash.oremPX4Q.dpuf
IMMUNOTHERAPy
Immunotherapy for Ovarian Cancer - CRI
Immunotherapy for Ovarian Cancer - CRI
Checkpoint Inhibitors and Immune Modulators
Another promising avenue of clinical research in ovarian cancer is the use of checkpoint inhibitors and immune modulators. These treatments work by targeting molecules that serve as checks and balances in the regulation of immune responses. By blocking inhibitory molecules or, alternatively, activating stimulatory molecules, these treatments are designed to unleash or enhance pre-existing anti-cancer immune responses.
Ipilimumab (Yervoy®), which targets the CTLA-4 checkpoint molecule on activated immune cells, is being tested in a variety of cancer types, including ovarian cancer, for which a phase II study (NCT01611558) is currently under way.
MEDI4736, an anti-PD-L1 checkpoint inhibitor made by MedImmune/AstraZeneca, is being tested in a number of trials:
A phase I/II trial of MEDI4736 for patients with solid tumors (NCT01693562).
A phase I/II trial of MEDI6469, an anti-OX40 agonist antibody, alone or with tremelimumab, an anti-CTLA-4 antibody, and/or MEDI4736 (NCT02205333).
A phase I trial of MEDI0680 (AMP-514), an anti-PD-1 antibody, and MEDI4736 in patients with advanced cancers (NCT02118337).
MEDI4736 and tremelimumab are being tested in two trials. One is a phase I trial sponsored by MedImmune for patients with solid tumors (NCT02261220). The other is a phase I trial, sponsored by Ludwig Cancer Research in collaboration with CRI and MedImmune, in patients with advanced solid tumors, including ovarian cancer (NCT01975831).
A phase Ib trial to test pembrolizumab (Keytruda®, MK-3475), an anti-PD-1 antibody being developed by Merck, in patients with advanced, biomarker-positive solid tumors (NCT02054806).
Two phase I trials to test MPDL3280A, an anti-PD-L1 antibody being developed by Roche/Genentech, in patients with several cancers (NCT01375842, NCT01633970).
A phase I trial testing urelumab (BMS-663513), an anti-4-1BB/CD137 antibody made by Bristol-Myers Squibb, in patients with advanced cancers (NCT01471210). Another phase I/II trial of urelumab given along with nivolumab (anti-PD-1) in patients with solid tumors (NCT02253992).
A phase I trial to test PF-05082566, an anti-4-1BB/CD137 antibody developed by Pfizer, in patients with solid tumors (NCT01307267).
A phase I study of lirilumab, an anti-KIR antibody being developed by Bristol-Myers Squibb, in combination with nivolumab (anti-PD-1) in patients with advanced solid tumors (NCT01714739).
A phase I trial to test BMS-986016, a LAG-3 antibody, with or without nivolumab (anti-PD-1) in patients with solid tumors (NCT01968109).
A pilot study to test INCB024360, an IDO1 inhibitor, in patients with newly diagnosed ovarian, fallopian tube, or primary peritoneal cancer (NCT02042430).
Checkpoint Inhibitors and Immune Modulators
Another promising avenue of clinical research in ovarian cancer is the use of checkpoint inhibitors and immune modulators. These treatments work by targeting molecules that serve as checks and balances in the regulation of immune responses. By blocking inhibitory molecules or, alternatively, activating stimulatory molecules, these treatments are designed to unleash or enhance pre-existing anti-cancer immune responses.
Another promising avenue of clinical research in ovarian cancer is the use of checkpoint inhibitors and immune modulators. These treatments work by targeting molecules that serve as checks and balances in the regulation of immune responses. By blocking inhibitory molecules or, alternatively, activating stimulatory molecules, these treatments are designed to unleash or enhance pre-existing anti-cancer immune responses.
- Ipilimumab (Yervoy®), which targets the CTLA-4 checkpoint molecule on activated immune cells, is being tested in a variety of cancer types, including ovarian cancer, for which a phase II study (NCT01611558) is currently under way.
-
MEDI4736, an anti-PD-L1 checkpoint inhibitor made by MedImmune/AstraZeneca, is being tested in a number of trials:
- A phase I/II trial of MEDI4736 for patients with solid tumors (NCT01693562).
- A phase I/II trial of MEDI6469, an anti-OX40 agonist antibody, alone or with tremelimumab, an anti-CTLA-4 antibody, and/or MEDI4736 (NCT02205333).
- A phase I trial of MEDI0680 (AMP-514), an anti-PD-1 antibody, and MEDI4736 in patients with advanced cancers (NCT02118337).
- MEDI4736 and tremelimumab are being tested in two trials. One is a phase I trial sponsored by MedImmune for patients with solid tumors (NCT02261220). The other is a phase I trial, sponsored by Ludwig Cancer Research in collaboration with CRI and MedImmune, in patients with advanced solid tumors, including ovarian cancer (NCT01975831).
- A phase Ib trial to test pembrolizumab (Keytruda®, MK-3475), an anti-PD-1 antibody being developed by Merck, in patients with advanced, biomarker-positive solid tumors (NCT02054806).
- Two phase I trials to test MPDL3280A, an anti-PD-L1 antibody being developed by Roche/Genentech, in patients with several cancers (NCT01375842, NCT01633970).
- A phase I trial testing urelumab (BMS-663513), an anti-4-1BB/CD137 antibody made by Bristol-Myers Squibb, in patients with advanced cancers (NCT01471210). Another phase I/II trial of urelumab given along with nivolumab (anti-PD-1) in patients with solid tumors (NCT02253992).
- A phase I trial to test PF-05082566, an anti-4-1BB/CD137 antibody developed by Pfizer, in patients with solid tumors (NCT01307267).
- A phase I study of lirilumab, an anti-KIR antibody being developed by Bristol-Myers Squibb, in combination with nivolumab (anti-PD-1) in patients with advanced solid tumors (NCT01714739).
- A phase I trial to test BMS-986016, a LAG-3 antibody, with or without nivolumab (anti-PD-1) in patients with solid tumors (NCT01968109).
- A pilot study to test INCB024360, an IDO1 inhibitor, in patients with newly diagnosed ovarian, fallopian tube, or primary peritoneal cancer (NCT02042430).
Checkpoint Inhibitors and Immune Modulators
Another promising avenue of clinical research in ovarian cancer is the use of checkpoint inhibitors and immune modulators. These treatments work by targeting molecules that serve as checks and balances in the regulation of immune responses. By blocking inhibitory molecules or, alternatively, activating stimulatory molecules, these treatments are designed to unleash or enhance pre-existing anti-cancer immune responses.
Another promising avenue of clinical research in ovarian cancer is the use of checkpoint inhibitors and immune modulators. These treatments work by targeting molecules that serve as checks and balances in the regulation of immune responses. By blocking inhibitory molecules or, alternatively, activating stimulatory molecules, these treatments are designed to unleash or enhance pre-existing anti-cancer immune responses.
- Ipilimumab (Yervoy®), which targets the CTLA-4 checkpoint molecule on activated immune cells, is being tested in a variety of cancer types, including ovarian cancer, for which a phase II study (NCT01611558) is currently under way.
-
MEDI4736, an anti-PD-L1 checkpoint inhibitor made by MedImmune/AstraZeneca, is being tested in a number of trials:
- A phase I/II trial of MEDI4736 for patients with solid tumors (NCT01693562).
- A phase I/II trial of MEDI6469, an anti-OX40 agonist antibody, alone or with tremelimumab, an anti-CTLA-4 antibody, and/or MEDI4736 (NCT02205333).
- A phase I trial of MEDI0680 (AMP-514), an anti-PD-1 antibody, and MEDI4736 in patients with advanced cancers (NCT02118337).
- MEDI4736 and tremelimumab are being tested in two trials. One is a phase I trial sponsored by MedImmune for patients with solid tumors (NCT02261220). The other is a phase I trial, sponsored by Ludwig Cancer Research in collaboration with CRI and MedImmune, in patients with advanced solid tumors, including ovarian cancer (NCT01975831).
- A phase Ib trial to test pembrolizumab (Keytruda®, MK-3475), an anti-PD-1 antibody being developed by Merck, in patients with advanced, biomarker-positive solid tumors (NCT02054806).
- Two phase I trials to test MPDL3280A, an anti-PD-L1 antibody being developed by Roche/Genentech, in patients with several cancers (NCT01375842, NCT01633970).
- A phase I trial testing urelumab (BMS-663513), an anti-4-1BB/CD137 antibody made by Bristol-Myers Squibb, in patients with advanced cancers (NCT01471210). Another phase I/II trial of urelumab given along with nivolumab (anti-PD-1) in patients with solid tumors (NCT02253992).
- A phase I trial to test PF-05082566, an anti-4-1BB/CD137 antibody developed by Pfizer, in patients with solid tumors (NCT01307267).
- A phase I study of lirilumab, an anti-KIR antibody being developed by Bristol-Myers Squibb, in combination with nivolumab (anti-PD-1) in patients with advanced solid tumors (NCT01714739).
- A phase I trial to test BMS-986016, a LAG-3 antibody, with or without nivolumab (anti-PD-1) in patients with solid tumors (NCT01968109).
- A pilot study to test INCB024360, an IDO1 inhibitor, in patients with newly diagnosed ovarian, fallopian tube, or primary peritoneal cancer (NCT02042430).
Cyst fluid iron-related compounds as useful markers to distinguish malignant transformation from benign endometriotic cysts
abstact
OBJECTIVE:
The purpose of this study was to investigate cyst fluid levels of total iron, heme iron and free iron in benign endometriotic cysts and endometriosis-associated ovarian cancer (EAOC) and to demonstrate the significance of these biomarkers in differential diagnosis between EAOC and endometriotic cysts.METHODS:
Cyst fluid samples were obtained from eleven patients with EAOC and thirty-six women with benign endometriotic cysts at the time of surgery.RESULTS:
The median (± SD) total iron levels for endometriotic cysts and EAOC cysts were 244.4 ± 204.9 mg/L and 14.2 ± 36.6 mg/L, respectively. EAOC patients had much lower levels of iron-related compounds compared with endometriotic cyst samples (p< 0.001). When the total iron results were analyzed using the receiver operating characteristics (ROC) curve method, the optimum diagnostic cut-off point was 64.8 mg/L, sensitivity was 90.9%, specificity was 100%, positive predictive value (PPV) was 100%, and negative predictive value (NPV) was 97.3%. Patient demographic characteristics such as tumor size, age at operation, parity and menopause were not correlated with cyst fluid iron levels.CONCLUSIONS:
We conclude for the first time that iron-related compounds are important biomarkers that can predict malignant transformation with high sensitivity and specificity for women with endometriosis.Participation of Korean families at high risk for hereditary breast and ovarian cancer in BRCA1/2 genetic testing
abstract
OBJECTIVE:
The aim of our study was to determine the rate of participation in genetic testing, to determine the reasons for non-participation and to identify the factors affecting participation in BRCA genetic testing for high-risk patients.METHODS:
This study was performed through a retrospective review of 804 individuals who underwent genetic counseling for BRCA1/2 gene mutations at Seoul National University Bundang Hospital between July 2003 and September 2012.RESULTS:
In total, 728 (90.5%) individuals underwent BRCA1/2 mutation screening after the initial genetic counseling; 88.2% of 647 probands and 100% of 157 family members were screened. In multivariate analysis, family history of breast cancer and younger age were independent variables affecting participation in genetic testing. Of the 132 people who initially declined genetic testing, 58 (43.9%) postponed the decision, 30 (22.7%) needed time to discuss the issue with family members, 22 (16.7%) did not want to know if they had a BRCA1/2 mutation, and 22 (16.7%) declined the test because of financial problems. When analyzing refusal of testing according to the time period before and after the implementation of national health insurance coverage for BRCA1/2 genetic testing, the critical reason given for refusal was different. After insurance coverage, refusal for financial reason was decreased from 61.1 to 9.6%.CONCLUSIONS:
A family history of breast cancer and a younger age were important factors associated with participation in genetic testing. National health insurance decreased the proportion of individuals who did not participate in testing owing to a financial reason. In genetic counseling, we have to understand these issues and consider several factors that may influence an individual's decision to be tested.Delay in Chemotherapy Administration Impacts Survival in Elderly Patients with Epithelial Ovarian Cancer. - PubMed - NCBI
abstract
OBJECTIVES:
The objective of this study was to characterize chemotherapy treatment patterns in elderly patients with epithelial ovarian cancer (EOC) and their impact on overall survival (OS).METHODS:
We identified patients age ≥ 65 years with stage II-IV EOC who underwent cytoreduction from 2003 - 2011. Relevant clinical variables were extracted and correlated with OS. Statistical analyses were performed using logistic regression, Kaplan-Meier methods, and multivariable Cox proportional hazard models.RESULTS:
One hundred and eighty-four patients were included in the analysis. The average age was 73 years with American Society of Anesthesiology Physical Status Class 2 or 3. Approximately 78% underwent primary debulking surgery (PDS). OS for the entire cohort was 3.3 years. One hundred and fifty-seven patients received adjuvant chemotherapy, of which 70% received initial platinum-based doublet therapy; 67.5% of patients were able to complete the intended six cycles of chemotherapy; of these, 34% experienced a dose reduction and 45% experienced one or more dose delays. Any dose delay was associated with a decrease in overall survival (p = 0.02) and remained significant even after controlling for age, stage, and residual disease and number of chemotherapy cycles received (p=0.029).CONCLUSIONS:
Elderly EOC patients frequently required chemotherapy dose reductions and delays in chemotherapy administration. Multivariate analysis confirmed that dose delays are an independent factor associated with decreased OS.Awareness of symptoms and risk factors of ovarian cancer in a population of women and healthcare providers
Abstract
BACKGROUND:
Awareness of ovarian cancer among women and healthcare providers is understudied. (Blogger's Note - understudied ???) An early awareness of ovarian cancer may lead to early detection and treatment of ovarian cancer.
OBJECTIVES:
The purpose of this study was to determine the level of that awareness among a sample of women and providers.
METHODS:
Written surveys were developed by the authors based on available literature and were administered to women (n = 857) and healthcare providers (n = 188) attending or volunteering at a community health fair. Chi-square tests for independence and z tests were used for analysis.
FINDINGS:
Healthcare providers were significantly more likely to identify the symptoms and risk factors for ovarian cancer. Forty percent of women reported being at least slightly familiar with the symptoms of ovarian cancer. Women who were familiar with symptoms were significantly more likely to identify symptoms and risk factors correctly and to report symptoms immediately to a provider. Identification of symptoms among healthcare providers ranged from 59%-93%. Identification of ovarian cancer symptoms and risk factors is poor among women, and knowledge deficits are present in providers. Increasing familiarity and awareness could lead to improvements in early diagnosis.
Impact of NCIC Cancer Centers on Ovarian Cancer Treatment and Survival
abstract
BACKGROUND:
The regional impact of care at a National Cancer Institute Comprehensive Cancer Center (NCI-CCC) on adherence to National Comprehensive Cancer Network (NCCN) ovarian cancer treatment guidelines and survival is unclear.
STUDY DESIGN:
We performed a retrospective population-based study of consecutive patients diagnosed with epithelial ovarian cancer between January 1, 1996 and December 31, 2006 in southern California. Patients were stratified according to care at an NCI-CCC (n = 5), non-NCI high-volume hospital (≥10 cases/year, HVH, n = 29), or low-volume hospital (<10 cases/year, LVH, n = 158). Multivariable logistic regression and Cox-proportional hazards models were used to examine the effect of NCI-CCC status on treatment guideline adherence and ovarian cancer-specific survival.
RESULTS:
A total of 9,933 patients were identified (stage I, 22.8%; stage II, 7.9%; stage III, 45.1%; stage IV, 24.2%), and 8.1% of patients were treated at NCI-CCCs. Overall, 35.7% of patients received NCCN guideline adherent care, and NCI-CCC status (odds ratio [OR] 1.00) was an independent predictor of adherence to treatment guidelines compared with HVHs (OR 0.83, 95% CI 0.70 to 0.99) and LVHs (OR 0.56, 95% CI 0.47 to 0.67). The median ovarian cancer-specific survivals according to hospital type were: NCI-CCC 77.9 (95% CI 61.4 to 92.9) months, HVH 51.9 (95% CI 49.2 to 55.7) months, and LVH 43.4 (95% CI 39.9 to 47.2) months (p < 0.0001). National Cancer Institute Comprehensive Cancer Center status (hazard ratio [HR] 1.00) was a statistically significant and independent predictor of improved survival compared with HVH (HR 1.18, 95% CI 1.04 to 1.33) and LVH (HR 1.30, 95% CI 1.15 to 1.47).
CONCLUSIONS:
National Cancer Institute Comprehensive Cancer Center status is an independent predictor of adherence to ovarian cancer treatment guidelines and improved ovarian cancer-specific survival. These data validate NCI-CCC status as a structural health care characteristic correlated with superior ovarian cancer quality measure performance. Increased access to NCI-CCCs through regional concentration of care may be a mechanism to improve clinical outcomes.
Thursday, April 02, 2015
Decision Making about Contralateral Prophylactic Mastectomy Among BRCA1/2 Noncarriers with Newly-diagnosed Breast Cancer
abstract
Decision Making about Contralateral Prophylactic Mastectomy Among BRCA1/2 Noncarriers with Newly-diagnosed Breast Cancer: Examining Cognitive, Emotional, and Sociodemographic Influences
Pre-surgical BRCA1/2 genetic testing provides valuable risk information to guide a newly-diagnosed breast cancer patient's decision about whether to have a contralateral prophylactic mastectomy (CPM) to reduce her future risk of cancer in her unaffected breast. Although BRCA1/2 mutation noncarriers face a much lower objective ten-year risk of developing contralateral disease (approximately 3–10%) as compared to the risk of BRCA1/2 mutation carriers (27–37%), some noncarriers still choose to undergo a CPM.
The psychosocial factors that motivate this decision are not well understood and warrant investigation. Thus, as part of a prospective study of pre-surgical BRCA1/2 testing, we examined the frequency and psychosocial correlates of the decision to undergo a CPM among newly-diagnosed breast cancer patients who were identified as BRCA1/2 mutation noncarriers. Self-report questionnaire data from 90 BRCA1/2 noncarriers (median age = 43 years, range = 29–59) were analyzed. A sizeable minority of the BRCA1/2 noncarriers (24.4%) chose to undergo a CPM after learning their mutation status (compared to 88% of the 8 BRCA1/2 carriers in the sample). Both bivariate and multivariable analyses indicated that perceiving that one's physician had recommended CPM (OR = 11.17, P = 0.007), perceiving greater risk for contralateral breast cancer (OR = 6.46, P = 0.02), and perceiving greater pros of CPM (OR = 1.37, P = 0.004) were all significantly associated with noncarriers' decision to undergo CPM. However, factors including age, Ashkenazi Jewish ethnicity, breast cancer-related distress, perceived cons of CPM, and decisional conflict regarding CPM were not related to the CPM decision (all ps > 0.05).
Results demonstrate that although noncarriers' decision making regarding CPM was unrelated to sociodemographic and emotional factors, their cognitive perceptions of contralateral disease risk, surgical benefits, and physician recommendations were particularly important. Future studies should examine the content of patient-physician communication regarding CPM and hereditary risk in greater detail, and explore how these conversations shape and interact with women's past experiences, emotions, and beliefs to influence their cancer prevention decisions.
Population Distribution of Lifetime Risk of Ovarian Cancer in the United States
abstract
Background: In U.S. women, lifetime risk of ovarian cancer is 1.37%, but some women are at a substantially lower or higher risk than
this average.
Methods: We have
characterized the distribution of lifetime risk in the general
population. Published data on the relative risks and
their variances for five well-accepted risk and
protective factors for ovarian cancer, oral contraceptive use, parity,
tubal
ligation, endometriosis, and first-degree family
history of ovarian cancer in conjunction with a genetic risk score using
genome-wide significant common, low penetrance
variants were used. The joint distribution of these factors (i.e.,
risk/protective
factor profiles) was derived using control data
from four U.S. population–based studies, providing a broad
representation
of women in the United States.
Results: A total of 214
combinations of risk/protective factors were observed, and the lifetime
risk estimates ranged from 0.35% [95%
confidence interval (CI), 0.29–0.42] to 8.78% (95%
CI, 7.10–10.9). Among women with lifetime risk ranging from 4% to 9%,
73%
had no family history of ovarian cancer; most of
these women had a self-reported history of endometriosis.
Conclusions: Profiles
including the known modifiable protective factors of oral contraceptive
use and tubal ligation were associated with
a lower lifetime risk of ovarian cancer. Oral
contraceptive use and tubal ligation were essentially absent among the
women
at 4% to 9% lifetime risk.
Impact: This work
demonstrates that there are women in the general population who have a
much higher than average lifetime risk of
ovarian cancer. Preventive strategies are
available. Should effective screening become available, higher than
average risk
women can be identified. Cancer Epidemiol Biomarkers Prev; 24(4); 671–6. ©2015 AACR.
Tuesday, March 31, 2015
Cancer specialist warns of potentially fatal dangers of 'miracle cure' fad diets - media
ABC News (Australian Broadcasting Corporation) http://ovariancancerandus.blogspot.com/feeds/posts/default
Patient Survey: Ontario (Canada) Value in the Patient-Doctor Relationship Survey
Blogger's Note: a somewhat odd survey (structure) but worth having your view
Patient Survey
"We're
the Association of Family Health Teams of Ontario, and we're working
with Patients Canada to find out what matters most to YOU in your
relationship with your family doctor and clinic. Your input is just one
way to help influence how family doctors work with patients and how
family health teams develop programs. We hope you will participate.
ABOUT THIS SURVEY:
Family Health Teams or Care Teams are already collecting information that measures how well doctors are doing in relation to “best practices” (ie Medications are reviewed yearly, patients with diabetes have blood tests done at the recommended times, etc). However, this doesn’t tell us how important EACH of these measures is to YOU (the patient) in your relationship with your doctor. This is the purpose of this survey.
Your input will help us understand what matters, how much it matters, and what part of your relationship is affected by these areas. We’re not asking you if your doctor is currently doing everything, but rather, how you would feel if they did do what we are asking.
There are 2 parts to the questions you will see. The first part will ask you about how important an area is to your relationship with your doctor. Sometimes we will ask you how much the previous question matters to different aspects of your relationship. The different categories you will be asked about are explained below. If the question has nothing to do with a category, simply check “not applicable”.
ABOUT THIS SURVEY:
Family Health Teams or Care Teams are already collecting information that measures how well doctors are doing in relation to “best practices” (ie Medications are reviewed yearly, patients with diabetes have blood tests done at the recommended times, etc). However, this doesn’t tell us how important EACH of these measures is to YOU (the patient) in your relationship with your doctor. This is the purpose of this survey.
Your input will help us understand what matters, how much it matters, and what part of your relationship is affected by these areas. We’re not asking you if your doctor is currently doing everything, but rather, how you would feel if they did do what we are asking.
There are 2 parts to the questions you will see. The first part will ask you about how important an area is to your relationship with your doctor. Sometimes we will ask you how much the previous question matters to different aspects of your relationship. The different categories you will be asked about are explained below. If the question has nothing to do with a category, simply check “not applicable”.
We
have set up the survey so your responses are anonymous; no one can find
out if you completed the survey, or how you responded.
This survey is voluntary. It should take about 15-20 minutes to complete. Please allow yourself enough time to finish as answers cannot be saved.
The survey will be available online for you to complete until Friday, April 10th at 11:59pm."
This survey is voluntary. It should take about 15-20 minutes to complete. Please allow yourself enough time to finish as answers cannot be saved.
The survey will be available online for you to complete until Friday, April 10th at 11:59pm."
Canadian and American health-care professionals - news - integrative oncology advanced cancers
News
Announced March 31, 2015 – Canadian and American health-care professionals will work together to study the effectiveness of advanced integrative oncology (AIO) treatment for patients with late stage cancer. AIO treatment includes elements of conventional and naturopathic medicine.
The funding was announced today by the Ottawa Integrative Cancer Centre (OICC) in Ottawa, Canada, an arm of the Canadian College of Naturopathic Medicine (CCNM), and the Bastyr University Research Institute in Washington State, USA.
The $3 million grant, provided by a private Canadian foundation that wishes to remain anonymous, will fund the Canadian/US Integrative Oncology Study (CUSIOS). This is the largest-ever North American observational study to assess integrative oncology for people with late stage cancer.
Read the news release
Sunday, March 29, 2015
SGO recommendations for the prevention of ovarian cancer - abstract
abstract
Mortality from ovarian cancer may be dramatically reduced with the implementation of attainable prevention strategies. The new understanding of the cells of origin and the molecular etiology of ovarian cancer warrants a strong recommendation to the public and health care providers. This document discusses potential prevention strategies, which include 1) oral contraceptive use, 2) tubal sterilization, 3) risk-reducing salpingo-oophorectomy in women at high hereditary risk of breast and ovarian cancer, 4) genetic counseling and testing for women with ovarian cancer and other high-risk families, and 5) salpingectomy after childbearing is complete (at the time of elective pelvic surgeries, at the time of hysterectomy, and as an alternative to tubal ligation). The Society of Gynecologic Oncology has determined that recent scientific breakthroughs warrant a new summary of the progress toward the prevention of ovarian cancer. This review is intended to emphasize the importance of the fallopian tubes as a potential source of high-grade serous cancer in women with and without known genetic mutations in addition to the use of oral contraceptive pills to reduce the risk of ovarian cancer
Long-Term Survival Advantage & Prognostic Factors Associated With IP Treatment in Advanced Ovarian Cancer
abstract
Purpose To determine long-term survival and associated prognostic factors after intraperitoneal (IP) chemotherapy in patients with
advanced ovarian cancer.
Patients and Methods Data from Gynecologic Oncology Group protocols 114 and 172 were retrospectively analyzed. Cox proportional hazards regression
models were used for statistical analyses.
Results In 876
patients, median follow-up was 10.7 years. Median survival with IP
therapy was 61.8 months (95% CI, 55.5 to 69.5),
compared with 51.4 months (95% CI, 46.0 to 58.2)
for intravenous therapy. IP therapy was associated with a 23% decreased
risk
of death (adjusted hazard ratio [AHR], 0.77; 95%
CI, 0.65 to 0.90; P = .002). IP therapy improved survival of those with gross residual (≤ 1 cm) disease (AHR, 0.75; 95% CI, 0.62 to 0.92; P = .006). Risk of death decreased by 12% for each cycle of IP chemotherapy completed (AHR, 0.88; 95% CI, 0.83 to 0.94; P < .001). Factors associated with poorer survival included: clear/mucinous versus serous histology (AHR, 2.79; 95% CI, 1.83
to 4.24; P < .001), gross residual versus no visible disease (AHR, 1.89; 95% CI, 1.48 to 2.43; P < .001), and fewer versus more cycles of IP chemotherapy (AHR, 0.88; 95% CI, 0.83 to 0.94; P < .001). Younger patients were more likely to complete the IP regimen, with a 5% decrease in probability of completion with
each year of age (odds ratio, 0.95; 95% CI, 0.93 to 0.96; P < .001).
Conclusion The advantage of IP over intravenous chemotherapy extends beyond 10 years. IP therapy enhanced survival of those with gross
residual disease. Survival improved with increasing number of IP cycles.
Footnotes
-
See accompanying editorial doi: 10.1200/JCO.2014.60.2797
Local estrogen metabolism in epithelial ovarian cancer suggests novel targets for therapy
open access (technical/in research)
.....Thus EOC is likely estrogen-responsive. Paradoxically, ovarian cancer generally occurs in post-menopausal women when the ovary no longer actively secretes estrogen. This raises the question: if estrogen is involved, how is it produced?......
FANG Vaccine Markedly Decreases Disease Recurrence in Phase II Ovarian Cancer Trial
SGO conference report
A
2:1 open-label phase II trial of the FANG vaccine achieved a marked
delay in time to progression, in all 14 of 21 patients with stage III/IV
ovarian cancer who participated. The other 7 patients did not receive
the vaccine. The data were presented March 28 in Chicago, at the 2015
Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.
- See more at: http://www.targetedonc.com/conference/sgo-2015/FANG-Vaccine-Markedly-Decreases-Disease-Recurrence-in-Phase-II-Ovarian-Cancer-Trial#sthash.WJglSoeW.dpuf
- See more at: http://www.targetedonc.com/conference/sgo-2015/FANG-Vaccine-Markedly-Decreases-Disease-Recurrence-in-Phase-II-Ovarian-Cancer-Trial#sthash.WJglSoeW.dpuf
The Utility of Vascular Disrupting Agent in Ovarian Cancer - youtube video
video - Dr Monk (SGO)
Bradley J. Monk, MD, FACOG, FACS, Director, Division of Gynecologic Oncology, Vice Chair, Department of Obstetrics and Gynecology, University of Arizona Cancer Center-Phoenix, discusses a phase II trial presented at the 2015 SGO meeting. The trial evaluated bevacizumab in combination with the vascular disrupting agent fosbretabulin for the treatment of patients with recurrent ovarian, tubal, or peritoneal carcinoma.
Bradley
J. Monk, MD, FACOG, FACS, Director, Division of Gynecologic Oncology,
Vice Chair, Department of Obstetrics and Gynecology, University of
Arizona Cancer Center-Phoenix, discusses a phase II trial presented at
the 2015 SGO meeting. The trial evaluated bevacizumab in combination
with the vascular disrupting agent fosbretabulin for the treatment of
patients with recurrent ovarian, tubal, or peritoneal carcinoma.
- See more at:
http://www.targetedonc.com/conference/sgo-2015/The-Utility-of-Vascular-Disrupting-Agent-in-Ovarian-Cancer#sthash.kvCvgnkw.dpuf
Bradley
J. Monk, MD, FACOG, FACS, Director, Division of Gynecologic Oncology,
Vice Chair, Department of Obstetrics and Gynecology, University of
Arizona Cancer Center-Phoenix, discusses a phase II trial presented at
the 2015 SGO meeting. The trial evaluated bevacizumab in combination
with the vascular disrupting agent fosbretabulin for the treatment of
patients with recurrent ovarian, tubal, or peritoneal carcinoma.
- See more at:
http://www.targetedonc.com/conference/sgo-2015/The-Utility-of-Vascular-Disrupting-Agent-in-Ovarian-Cancer#sthash.kvCvgnkw.dpuf
Broadcast Schedule — N.E.D. (No Evidence of Disease)
nedthemovie
Television Broadcast Schedule
No Evidence of Disease premiered on March 4th, 2015 on WORLD and will continue to be broadcast nationally by American Public Television, and in Spanish by Vme TV. Over the next few months, catch this award-winning documentary in the comfort of your home, and tell your friends! We will continue to add stations and broadcast times as they are confirmed, so check back here often.
Find your local station below:
Please note: Public television schedules vary from region to region and can sometimes change.
If you can't find a broadcast in your area, please check your local public television listings.....
Experts Support Jolie's Prophylactic Surgery Decision
Medscape
Experts in gynecologic oncology have spoken in support of Angelina Jolie's decision to have her ovaries and fallopian tubes removed as a move against ovarian cancer.
Such surgery is the "cornerstone of management" in these cases, said Karen Lu, MD, professor of gynecologic oncology, codirector for clinical cancer genetics, and director of the High Risk Ovarian Cancer Screening Clinic at the University of Texas M.D. Anderson Cancer Center in Houston.
In an interview with Medscape Medical News, Dr Lu said that the star is representative of a growing number of women who are making decisions about cancer before they get cancer; they are described as "previvors" (in contrast to survivors who are living after cancer).
These previvors represent a new wave of patients that has never been seen before. These are women who have been genetically tested and found to have a very high risk for cancer, but have not yet been touched by cancer. "This is something new," she emphasized, "as previously we have been dealing with patients who first had cancer and then were tested and found to be at high risk."
Dr Lu also observed that these previvors have a different approach to the choices that are available to them than the average woman, or a woman with some family history of cancer, as they have very specific information about their risk as a result of the genetic testing......
Friday, March 27, 2015
The National Organization for Rare Disorders (NORD) 2014 Review: Short Bowel Syndrome
General Discussion
Summary
Short bowel syndrome is a complex disease that occurs due to the physical loss or the loss of function of a portion of the small and/or large intestine. Consequently, individuals with short bowel syndrome often have a reduced ability to absorb nutrients such as fats, carbohydrates (sugars) vitamins, minerals, trace elements and fluids (malabsorption). The specific symptoms and severity of short bowel syndrome vary from one person to another. Diarrhea is common, often severe and can cause dehydration, which can even be life threatening. Short bowel syndrome can lead to malnutrition, unintended weight loss and additional symptoms may be due to the loss of essential vitamins and minerals. There is no cure, but the disorder usually can be treated effectively. However, in severe cases, short bowel syndrome can lead to severe, disabling and life-threatening complications. Short bowel syndrome is most commonly associated with the surgical removal (resection) of half or more of the small intestine. Such surgery is performed to treat intestinal diseases such as Crohn's disease, injury or trauma to the small bowel, or congenital birth defects. The presence or absence of the large intestine (colon) also plays an important role in the genesis and/or treatment of the short bowel syndrome.
Thursday, March 26, 2015
A non-randomized confirmatory study regarding selection of fertility-sparing surgery for patients with epithelial ovarian cancer: Japan Clinical Oncology Group
Abstract
Fertility-sparing treatment has been accepted as a standard treatment for epithelial ovarian cancer in stage IA non-clear cell histology grade 1/grade 2. In order to expand an indication of fertility-sparing treatment, we have started a non-randomized confirmatory trial for stage IA clear cell histology and stage IC unilateral non-clear cell histology grade 1/grade 2. The protocol-defined fertility-sparing surgery is optimal staging laparotomy including unilateral salpingo-oophorectomy, omentectomy, peritoneal cytology and pelvic and para-aortic lymph node dissection or biopsy. After fertility-sparing surgery, four to six cycles of adjuvant chemotherapy with paclitaxel and carboplatin are administered. We plan to enroll 250 patients with an indication of fertility-sparing surgery, and then the primary analysis is to be conducted for 63 operated patients with pathologically confirmed stage IA clear cell histology and stage IC unilateral non-clear cell histology grade 1/grade 2. The primary endpoint is 5-year overall survival. Secondary endpoints are other survival endpoints and factors related to reproduction. This trial has been registered at the UMIN Clinical Trials Registry as UMIN000013380.
Early Alopecia May Signal Chemo Response in Ovarian Cancer
Cancer Network
......When adjusting for the common clinicopathologic features such as postoperative tumor residuals, histology, and FIGO stage, early-onset—up to cycle 4—grade 2 alopecia appeared to significantly correlate with a more favorable OS,” the researchers wrote. “It needs to be further elucidated whether early-onset alopecia is just a surrogate marker for higher sensitivity to chemotherapy and hence associated with a longer survival or if other unidentified biological pathways are underlying that correlate alopecia with cytotoxicity and survival.”
Epidemiology and risk factors of bladder and urothelial tumors
Blogger's Note: not included in this abstract is the risk for Lynch syndrome mutation carriers (MSH2)
Epidemiology and risk factors of bladder and urothelial tumors - Abstract
Published: 25 March 2015
Bladder cancer is the 5th most commonly diagnosed cancer in France, and most of cases occur in men and patients aged more than 65 years.
The incidence and mortality are declining except in women in whom the incidence is increasing in recent years. Urothelial tumors of the upper urinary tract are less common but have similar aetiology to the bladder tumours. The recurrent aspect of superficial tumors and the morbidity of invasive tumors are an economic burden in the Western health systems. The two main risk factors for urothelial tumors are tobacco smoking and occupational exposure to chemicals carcinogens such as polycyclic aromatic hydrocarbons, nitrosamines, aromatic amines and arsenic. Other risk factors include urinary schistosomiasis, pelvic radiation therapy, the use of cyclophosphamide and probably diet and lifestyle factors. Prevention of bladder tumors is based on the control of these risk factors and individual screening in high-risk patients. Recognition as an occupational disease is an important part of the social management of patient, which is today inadequately performed.
A phase II evaluation of the potent, highly selective PARP inhibitor veliparib in the treatment of persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients who carry a germline BRCA 1/2
Abstract
Highlights
•
Veliparib demonstrated single agent activity among recurrent ovarian cancer patients carrying a germline BRCA1/2 mutation
•
Adverse events were observed but generally mild and managed conservatively
•
Clinical responses were observed among enrolled with platinum-sensitive and -resistant recurrent disease
Background
Veliparib is a potent small molecule inhibitor of PARP-1/2, which is cytotoxic in tumor cells with deficiencies in BRCA1 or BRCA2. We studied the clinical activity and toxicity of veliparib in ovarian cancer patients carrying a germline BRCA1 or BRCA2 mutation (gBRCA).
Methods
Eligibility included three or fewer prior chemotherapy regimens, measurable disease and no prior use of a PARP inhibitor. Veliparib was administered at 400 mg orally BID with one cycle being 28 days. The two-stage Simon design was capable of detecting a 25% response probability with 90% power while controlling alpha=10% (at a 10% assumed null response probability).
Results
The median age of the 50 eligible patients was 57 years (range 37–94) and 14, 18, and 18 patients had 1, 2, and 3 prior therapies respectively. Thirty patients (60%) were platinum-resistant. The median number of cycles administered was 6 (1-27). There was one grade 4 thrombocytopenia. Grade 3 adverse events were: fatigue (n=3), nausea (2), leukopenia (1), neutropenia (1), dehydration (1), and ALT (1). Grade 2 events > 10% were: nausea (46%), fatigue (26%), vomiting (18%), and anemia (14%). The proportion responding was 26% (90% CI: 16%-38%, CR:2, PR:11); for platinum-resistant and platinum-sensitive patients the proportion responding was 20% and 35%, respectively. The most common reason for treatment discontinuation was progression (62%). Twenty-nine patients are alive; two with SD remain on veliparib. The median PFS is 8.18 months.
Conclusions
The single agent efficacy and tolerability of veliparib for BRCA mutation-associated recurrent ovarian cancer warrants further investigation.
Keywords
veliparib;
ovarian cancer;
PARP inhibitor;
toxicity;
Phase II trial;
BRCA1, BRCA2 mutation
Immunotherapeutic approaches to ovarian cancer treatment
Abstract
J Immunother Cancer. 2015 Mar 24;3:7. doi: 10.1186/s40425-015-0051-7. eCollection 2015.
Immunotherapeutic approaches to ovarian cancer treatment.
Chester C1, Dorigo O2, Berek JS2, Kohrt H1.
Author information
1Department of Medicine, Division of Oncology, Stanford University School of Medicine, Stanford, CA USA.
2Stanford Women's Cancer Center, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA 94305 U.S.A.
Abstract
Despite advances in combinatorial chemotherapy regimens and the advent of intraperitoneal chemotherapy administration, current therapeutic options for ovarian cancer patients are inadequate. Immunotherapy offers a novel and promising therapeutic strategy for treating ovarian tumors. Following the demonstration of the immunogenicity of ovarian tumors, multiple immunotherapeutic modalities have been developed. Antibody-based therapies, immune checkpoint blockade, cancer vaccines, and chimeric antigen receptor-modified T cells have demonstrated preclinical success and entered clinical testing. In this review, we discuss these promising immunotherapeutic approaches and emphasize the importance of combinatorial treatment strategies and biomarker discovery.
KEYWORDS:
ACT; Antibody; Cancer vaccine; ID8; IDO; Immune checkpoint blockade; Ovarian cancer; TAMConsiderations and management of a patient with three metachronous cancers in association with Lynch syndrome and ileal Crohn's disease: A case report
abstract
INTRODUCTION:
Lynch syndrome and Crohn's disease are two entirely separate conditions but each have major gastrointestinal characteristics and carry a substantial increase in the risk of intestinal malignancy. Their co-existence in the patient who is the subject of this report dictated the need for an individualised treatment plan to deal with both conditions adequately.
PRESENTATION OF CASE:
We report a case of a 51 year old female with a past medical history that includes Lynch syndrome and small bowel Crohn's disease. Over a period of fifteen months, she developed three separate primary metachronous tumors in her endometrium, colon and duodenum.
DISCUSSION:
A patient with a combination of Lynch syndrome and ileal Crohn's disease presents significant therapeutic implications that are not usually present when these conditions are treated in isolation.
CONCLUSION:
The surgical treatment of patients with Lynch syndrome requires a sound knowledge of the possible neoplastic conditions that can arise in the syndrome. Early detection is paramount, either by implementation of evidence based surveillance programs or at least by a heightened clinical awareness of the features of this disease. Ideally this will result in both reduced surgical morbidity and improved oncologic outcome. Furthermore, the medical treatment of Crohn's disease in a patient with tumors arising from Lynch syndrome must be undertaken with at least a consideration of the possibility that the use of immunosuppressive medication might increase the risk of cancer recurrence.
Decisions about prophylactic gynecologic surgery: a qualitative study of the experience of female Lynch syndrome mutation carriers
Abstract
BACKGROUND:
Women who carry a mutation for Lynch syndrome face complex decisions regarding strategies for managing their increased cancer risks. At present, there is limited understanding of the factors influencing women's prophylactic surgery decisions.
METHODS:
As part of an exploratory pilot project, semi-structured interviews were conducted with 10 women who were Lynch syndrome mutation carriers and had made prophylactic surgery decisions. Nine of 10 women had chosen to undergo prophylactic hysterectomy and/or oophorectomy as a means of managing their increased gynecological cancer risks.
RESULTS:
Study findings revealed that surgery decisions were influenced by multiple factors, including demographic variables such as age and parity, as well as psychosocial factors such as cancer worry, in addition to personal and social knowledge of gynecological cancer. While all women were satisfied with their surgery decision, some reported they were not fully informed about the negative impact on their quality of life post-surgery (e.g., complications of surgically-induced menopause), nor about the potential for, or risks and benefits of, hormone replacement therapy.
CONCLUSIONS:
Study findings highlight some of the factors associated with prophylactic surgery decisions and women's perceptions about pre-surgical information provision and needs. Suggestions are made for improving the information and support provided to female carriers of a Lynch syndrome mutation
Friday, February 13, 2015
Menopausal hormone use and ovarian cancer risk: individual participant meta-analysis of 52 epidemiological studies - The Lancet
open access (click on pdf)
Abstract/Full text
Summary
Background
Half the epidemiological studies with information about menopausal hormone therapy and ovarian cancer risk remain unpublished, and some retrospective studies could have been biased by selective participation or recall. We aimed to assess with minimal bias the effects of hormone therapy on ovarian cancer risk.Methods
Individual participant datasets from 52 epidemiological studies were analysed centrally. The principal analyses involved the prospective studies (with last hormone therapy use extrapolated forwards for up to 4 years). Sensitivity analyses included the retrospective studies. Adjusted Poisson regressions yielded relative risks (RRs) versus never-use.Findings
During prospective follow-up, 12 110 postmenopausal women, 55% (6601) of whom had used hormone therapy, developed ovarian cancer. Among women last recorded as current users, risk was increased even with <5 years of use (RR 1·43, 95% CI 1·31–1·56; p<0·0001). Combining current-or-recent use (any duration, but stopped <5 years before diagnosis) resulted in an RR of 1·37 (95% CI 1·29–1·46; p<0·0001); this risk was similar in European and American prospective studies and for oestrogen-only and oestrogen-progestagen preparations, but differed across the four main tumour types (heterogeneity p<0·0001), being definitely increased only for the two most common types, serous (RR 1·53, 95% CI 1·40–1·66; p<0·0001) and endometrioid (1·42, 1·20–1·67; p<0·0001). Risk declined the longer ago use had ceased, although about 10 years after stopping long-duration hormone therapy use there was still an excess of serous or endometrioid tumours (RR 1·25, 95% CI 1·07–1·46, p=0·005).Interpretation
The increased risk may well be largely or wholly causal; if it is, women who use hormone therapy for 5 years from around age 50 years have about one extra ovarian cancer per 1000 users and, if its prognosis is typical, about one extra ovarian cancer death per 1700 users.
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