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.

• 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).

- See more at: http://www.cancerresearch.org/cancer-immunotherapy/impacting-all-cancers/ovarian-cancer#sthash.oremPX4Q.dpuf

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).

- See more at: http://www.cancerresearch.org/cancer-immunotherapy/impacting-all-cancers/ovarian-cancer#sthash.oremPX4Q.dpuf

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.

Symptom Clusters in Ovarian Cancer Patients With Chemotherapy After Surgery

abstract

 BACKGROUND:

Ovarian cancer is 1 of the most common malignancies in the female reproductive system. Identification of symptom clusters in ovarian cancer patients may improve management of symptoms.

OBJECTIVE:
The objective of this article is to explore the changes in symptom clusters in ovarian cancer patients with adjuvant chemotherapy after surgery at different time points.

METHODS:
Basic details of the patients were documented and a longitudinal investigation was carried out. We used the Memorial Symptom Assessment Scale to examine 115 Chinese ovarian cancer patients' symptom experience at 4 time points: days before chemotherapy (T1), chemotherapy cycle 1 (T2), chemotherapy cycle 3 (T3), and chemotherapy cycle 6 (T4). The exploratory factor analysis was performed to determine the numbers and components of symptom clusters.

RESULTS:
Symptom clusters varied at different time points, which were classified as pain-related symptom cluster, psychological symptom cluster, menopausal symptom cluster, gastrointestinal symptom cluster, body image symptom cluster, and peripheral neurologic symptom cluster. The gastrointestinal symptom cluster and body image symptom cluster appeared at T1 and remained consistent at T3 and T4, whereas the peripheral neurologic symptom cluster was noted at T3 and T4.

CONCLUSIONS:
Clinicians should prioritize symptom management interventions with ovarian cancer patients to focus on the most severe symptom cluster: psychological symptom cluster at T1, gastrointestinal symptom cluster at T2, and body image symptom cluster at T3 and T4.

IMPLICATIONS FOR PRACTICE:
The ability to predict symptom clusters in ovarian cancer patients receiving chemotherapy may help to make optimized clinical decision in advance to alleviate patients' symptoms and improve their life quality.

Risk factors for endometrial cancer among women with a BRCA1 or BRCA2 mutation: a case control study

Rabstract

Abstract

BRCA mutation carriers may use tamoxifen for breast cancer prevention or treatment. Hormone replacement therapy is often prescribed after surgical menopause and oral contraceptives are recommended for ovarian cancer prevention.

The objective of this study was to assess the impact of these medications and other risk factors on endometrial cancer risk in BRCA carriers. Women with a BRCA1 or BRCA2 mutation were identified from a registry of mutation carriers. Cases were 83 women who had a diagnosis of endometrial cancer. Controls were 1027 matched women who did not develop endometrial cancer and who had an intact uterus. All women completed a baseline questionnaire, which included questions about ages at menarche and menopause, oral contraceptive use, hormone replacement therapy use, hysterectomy, oophorectomy, breast cancer history and tamoxifen use. We estimated the odds ratio associated with each risk factor in a multivariate analysis. No differences were found between cases and controls in terms of age at menarche, BMI, smoking, or oral contraceptive use. In a multivariate analysis, for women taking estrogen-only hormone replacement therapy, the odds ratio was 0.23 (95 % CI 0.03-1.78, p = 0.16), and for women taking progesterone-only hormone replacement therapy the odds ratio was 6.91 (95 % CI 0.99-98.1, p = 0.05). The adjusted odds ratio for endometrial cancer associated with a history of tamoxifen use was 3.50 (95 % CI 1.51-8.10, p = 0.003). The observed increased risk of endometrial cancer associated with progesterone-only therapy merits further study.

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.

Specialist Surgery for Ovarian Cancer in England

abstract

OBJECTIVE:

To evaluate the impact of the 1999 national recommendations for ovarian cancer surgery in England to be performed by specialist surgeons in specialist centres.


METHODS:

A retrospective analysis of English cancer registry records, Hospital Episode Statistics (HES) data for all English NHS providers and General Medical Council (GMC) sub-specialty accreditation, to consider changes to the annual proportion of ovarian cancer (ICD10 C56-C57) patients undergoing major gynaecological surgery in gynaecological cancer centres (GCCs) or by specialist gynaecological oncologists (GOs).


RESULTS:

From 2000 to 2009, 2,428 consultants were responsible for surgery on 30,753 patients. There were significant increases in the proportions of patients undergoing surgery at GCCs (43% to 76%, P<0.001), by GMC accredited GOs (5% to 36%, P<0.001), and by high ovarian cancer caseload (≥18 cases) surgeons (22% to 56%, P<0.001).


CONCLUSION:

There has been increased centralisation and specialisation of surgery for ovarian cancer patients since the NHS Cancer Plan (2000) and there has also been improved survival. However, by 2009, many ovarian cancer patients were still not receiving specialist surgery; the majority of patients were not operated on by GMC accredited gynaecological oncologists and there was considerable regional variation. Systems of accreditation should be reviewed and trusts should ensure HES data accurately records clinical activity.

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.

Surgeon, CT Discord Sways Ovarian Cancer Outcome

medpage

 Primary Source

• Society of Gynecologic Oncology

  Source Reference: Eskander RN, et al "Correlation between surgeon's assessment of residual disease and findings on postoperative pretreatment computed tomography scan in women with advanced stage ovarian cancer reported to have undergone optimal cytoreduction: An NRG Oncology/GOG study" SGO 2015; Abstract 5.

Cancer Patients Should Avoid Fish, Fish Oil During Chemo, Researchers Warn

Medpage

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.

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.

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”.

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."

More than what the eye can see: the emotional journey and experience of powerlessness of integrated care service users and their carers

Blogger's Note: not specific to cancer but common themes

open access

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

Women with ovarian cancer gain extra months with addition of drug to standard chemotherapy SGO press release

press release

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

open access: Correspondence - IP Long-Term Outcomes Revive a Long-Running Debate

open access

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

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

#SGO2015 - Twitter

#SGO2015 

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......

Ovarian Cancer: Interactive CT Case Study

Medscape (pre-operative/post-operative/3D slides)

15 Cancer Milestones (slides)

Medscape slides

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.

Genomics - CDC.gov

Genomics|Home

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.”

Intraperitoneal Chemo Ups 10-Year Ovarian Cancer Survival

Cancer Network

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.

Menopausal Hormone Therapy and Risk for Ovarian Cancer

Medscape

OPEN ACCESS: Hereditary predisposition to ovarian cancer, looking beyond BRCA1/BRCA2

full text - open access published Jan 2015


 

Gynecologic Oncology April 2015 index of articles

issue index



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

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; TAM

Considerations 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

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.

breaking news: Canadians have right to doctor-assisted suicide, Supreme Court rules

breaking news - The Globe and Mail

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• Palliative care Despite impending ruling on assisted death, we need better palliative care
• Health care Canadian doctors drafting new rules in case doors open to assisted suicide

Infertility in reproductive-age female cancer survivors

abstract

 Improved survival rates among reproductive-age females diagnosed with cancer have increased the focus on long-term quality of life, including maintenance of the ability to conceive biological children. Cancer-directed therapies such as high-dose alkylating agents and radiation to the pelvis, which deplete ovarian reserve, radiation to the brain, which affects the hypothalamic-pituitary-gonadal axis, and surgical resection of reproductive structures can decrease the likelihood of having biological children. Standard fertility preservation strategies such as embryo and oocyte cryopreservation before the onset of therapy offer the opportunity to conserve fertility, but they may not be feasible because of the urgency to start cancer therapy, financial limitations, and a lack of access to reproductive endocrinologists. Ovarian tissue freezing is considered experimental, with limited data related to pregnancies, but it minimizes treatment delay. Studies evaluating gonadotropin-releasing hormone analogues have had mixed results, although a recent randomized, prospective study in women with breast cancer demonstrated a protective effect. Fertility preservation programs are increasingly being developed within cancer programs. In this article, we describe risks to infertility and options for preservation, raise psychosocial and ethical issues, and propose elements for establishing an effective fertility preservation program.

(AICR): CRU: New Survey: Low Awareness of Key Cancer Risk Factors

 

New Survey

Current unmet needs of cancer survivors: Analysis of open-ended responses to the ACS Study of Cancer Survivors II

abstract

BACKGROUND

Cancer survivors may continue to experience psychosocial and physical needs related to their cancer experience for many years after treatment. The specification of these needs across cancer types and by survivor characteristics may lead to better prevention approaches and clinical responses. Mixed methods were used to examine responses to an open-ended question about current unmet needs from a survey of 2-, 5-, and 10-year cancer survivors.

METHODS

Qualitative techniques were used to code themes of unmet needs from open-ended responses. These themes were then examined with quantitative techniques to describe the frequency of unmet needs across disease subgroups and demographic subgroups of survivors.

RESULTS

There were 1514 responses to the open-ended question on unmet needs. Respondents ranged in age from 24 to 97 years and included proportionately more women, and 18% were minorities (black and Hispanic). Sixteen themes of unmet needs were identified. The number and type of unmet needs were not associated with the time since cancer treatment. Breast cancer survivors identified more unmet needs than other survivors. Male survivors and especially prostate cancer survivors identified personal control problems as current needs. Older cancer survivors identified fewer unmet needs on average than younger survivors.

CONCLUSIONS

This analysis of an open-ended question on unmet needs extends our understanding of how cancer survivors perceive problems related to cancer. How cancer-related needs change over time and differ by sex, race, and ethnicity and how problems with personal control become manifest are areas of inquiry requiring further research. 

Comparison of oncology drug approval between Health Canada and the US Food and Drug Administration

abstract

BACKGROUND

The drug approval timeline is a lengthy process that often varies between countries. The objective of this study was to delineate the Canadian drug approval timeline for oncology drugs and to compare the time to drug approval between Health Canada (HC) and the US Food and Drug Administration (FDA).

METHODS

In total, 54 antineoplastic drugs that were approved by the FDA between 1989 and 2012 were reviewed. For each drug, the following milestones were determined: the dates of submission and approval for both the FDA and HC (Health Canada) and the dates of availability on provincial drug formularies in Canadian provinces and territories. The time intervals between the aforementioned milestones were calculated.

RESULTS

Of 54 FDA-approved drugs, 49 drugs were approved by HC at the time of the current study. The median time from submission to approval was 9 months (interquartile range [IQR], 6-14.5 months) for the FDA and 12 months (IQR, 10-21.1 months) for HC (P < .0006). The time from HC approval to the placement of a drug on a provincial drug formulary was a median of 16.7 months (IQR, 5.9-27.2 months), and there was no interprovincial variability among the 5 Canadian provinces that were analyzed (P = .5).

CONCLUSIONS

The time from HC submission to HC approval takes 3 months longer than the same time interval for the FDA. To the authors' knowledge, this is the first documentation of the time required to bring an oncology drug from HC submission to placement on a provincial drug formulary.

Trends in gynaecological cancers in the largest obstetrics and gynaecology hospital in China from 2003 to 2013I

abstract

The incidence and the trend of gynaecological cancers have been suggested to vary by ethnicity and geographical regions. Whether the incidence and type of gynaecological cancers in China is different have not been fully investigated. In this study, we reported the trend of gynaecological cancers in China. Data on 13,518 women with gynaecological cancers were collected from the largest obstetrics and gynaecology hospital in China from 2003 to 2013. Data included age at diagnosis and the annual number of women with diagnosed endometrial, ovarian, cervical cancer and other gynaecological cancers. The number of women with diagnosed gynaecological cancers increased by almost sixfold in 2013 compared to that in 2003. It was largely due to the increase of women with newly diagnosed cervical cancer. The percentage of women with endometrial and ovarian cancer within total gynaecological cancers was decreased, whilst the percentage of cervical cancer significantly increased between 2003 and 2013. The mean age of women with endometrial or ovarian cancer at diagnosis was 53 or 48 years, respectively, which was no difference over 11 years. However, the mean age of women with cervical cancer at diagnosis was significantly delayed from 42 years in 2003 to 46 years since 2011. This was also confirmed by the age-specific distribution of gynaecological cancers over 11 years. Our study found that the age onset of endometrial and ovarian cancer has not changed over 11 years. But the age onset of cervical cancer is delayed since 2011 in China.

Microbiology of Pelvic Lymphocyst Infection after Lymphadenectomy for Malignant Gynecologic Tumors

abstract

 Background: Pelvic lymphocyst infection is a rare complication after lymphadenectomy for malignant gynecologic tumors. Although medical therapy is a useful addition to surgical drainage, the appropriate antibiotic regimen is unknown because few studies have examined the causative organisms. The purpose of this case series was to identify the micro-organisms infecting pelvic lymphocysts.

Methods: This was a single-center, retrospective, case-series review conducted at a tertiary-care cancer center between October 2002 and March 2013. The participants included all patients who experienced their first pelvic lymphocyst infection after undergoing pelvic lymphadenectomy for cervical, endometrial, or ovarian cancer and exhibited positive lymphocyst fluid culture. Computed tomography- or sonography-guided percutaneous aspiration procedures were performed to obtain lymphocyst fluid for culture.

Results: During the study period, 878 patients underwent lymphadenectomy for gynecologic malignant tumors, and 13 developed a pelvic lymphocyst infection documented microbiologically. Cultures identified Staphylococcus aureus (three patients), S. epidermidis (one patient), Streptococcus agalactiae (three patients), Enterococcus (two patients), Escherichia coli (one patient), and anaerobic bacteria (three patients). They were all monomicrobial infections.

Conclusions: Our study and other smaller ones suggest that lymphocyst infections following pelvic lymphadenectomy for malignant gynecologic tumors usually are monomicrobial and caused by gram-positive cocci, including Staphylococcus, Streptococcus, and Enterococcus, and anaerobes such as Bacteroides fragilis. These bacteria should be considered when selecting empiric antibiotic therapy.

Immunotherapy for Ovarian Cancer (paywalled)

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OPINION STATEMENT:

All work referenced herein relates to treatment of epithelial ovarian carcinomas, as their treatment differs from ovarian germ cell cancers and other rare ovarian cancers, the treatments of which are addressed elsewhere. Fallopian tube cancers and primary peritoneal adenocarcinomatosis are also generally treated as epithelial ovarian cancers. The standard of care initial treatment of advanced stage epithelial ovarian cancer is optimal debulking surgery as feasible plus chemotherapy with a platinum plus a taxane agent. If this front-line approach fails, as it too often the case, several FDA-approved agents are available for salvage therapy. However, because no second-line therapy for advanced-stage epithelial ovarian cancer is typically curative, we prefer referral to clinical trials as logistically feasible, even if it means referring patients outside our system. Immune therapy has a sound theoretical basis for treating carcinomas generally, and for treating ovarian cancer in particular. Advances in understanding the immunopathogenic basis of ovarian cancer, and the immunopathologic basis for prior failures of immunotherapy for it and other carcinomas promises to afford novel treatment approaches with potential for significant efficacy, and reduced toxicities compared with cytotoxic agents. Thus, referral to early phase immunotherapy trials for ovarian cancer patients that fail conventional treatment merits consideration.

Are we winning the war on cancer? The old suffer more than they should

Commentary


In 1971 Richard Nixon declared “War on Cancer” with the signing of the National Cancer Act. Significant progress has been made in the intervening 44 years – and Europe has been at the forefront of many of the advances.
But on February 4, World Cancer Day, it is worth asking whether we are winning the war on a disease which affects more than 22m people annually?......

Spatial Analysis of Advanced-Stage Ovarian Cancer Mortality in California

abstract

def: spatial

OBJECTIVE:

To determine the impact of geographic location on advanced-stage ovarian cancer mortality in relation to adherence to National Comprehensive Cancer Network (NCCN) treatment guidelines and hospital case volume.

STUDY DESIGN:

Retrospective observational cohort study of patients diagnosed with stage IIIC/IV epithelial ovarian cancer (1/1/96-12/31/06) identified from the California Cancer Registry. Generalized additive models were created to assess the effect of spatial distributions of geographic location, demographic characteristics, disease-related variables, adherence to NCCN guidelines, and hospital case volume, with simultaneous smoothing of geographic location and adjustment for confounding variables.

RESULTS:

A total of 11,765 patients were identified. Twelve of the 378 hospitals (3.2%) were high-volume hospitals (≥20 cases/year, HVH) and cared for 2,112 patients (17.9%). For all patients, the median distance to a HVH was 22.7km/14.1mi and 80% were located within 79.6km/49.5mi of a HVH. Overall, 45.4% of patients were treated according to NCCN guidelines. The global test for location revealed that geographic position within the state was significantly correlated with ovarian cancer mortality after adjusting for other variables (p<0.001). Distance to receive care ≥32km/20mi was protective against mortality (HR=0.86, 95%CI=0.79-0.93), while distance from a HVH ≥80km/50mi was associated with an increased risk of death (HR=1.13, 95%CI=1.03-1.23). The effects of geographic predictors were attenuated when non-adherence to NCCN guidelines (HR=1.25, 95%CI=1.18-1.32) and care at a HVH (HR=0.87, 95%CI=0.81-0.93) were introduced into the model.

CONCLUSIONS:

Geographic location is a significant predictor of advanced-stage ovarian cancer mortality and the effect is primarily related to the likelihood of receiving NCCN guideline adherent care and treatment at a HVH.

Identification of rare germline copy number variations over-represented in five human cancer types

open access

".... Results  We explored the germline CNVs (copy number variations) in five cancer cohorts from the Cancer Genome Atlas (TCGA) consisting of 351 brain, 336 breast, 342 colorectal, 370 renal, and 314 ovarian cancers, genotyped on Affymetrix SNP6.0 arrays.....

 ......Many of these loci are new and in some cases are associated with a substantial increase in disease risk......

Research describes new way of shrinking ovarian cancer tumors, improving drug delivery

medical news

 New research published in the February 2015 issue of The FASEB Journal, may eventually help improve the five-year survival rate of ovarian cancer patients by describing a new way of shrinking ovarian cancer tumors while also simultaneously improving drug delivery. This new method involves the use of a portion of a naturally occurring protein inhibitor of angiogenesis called thrombospondin-1 or TSP-1. The portion, known as 3TSR, interacts with another protein called CD36 causing cells needed for tumors to create new blood vessels (endothelial cells) to stop growing and die. In turn, this reduces the formation of new blood vessels (angiogenesis) needed for tumors to grow......

World Cancer Day 2015 | WCD

World Cancer Day 2015 | WCD

Pediatric ovarian neoplastic tumors: incidence, age at presentation, tumor markers and outcome

abstract

OBJECTIVE:

To investigate the incidence, age of onset and tumor marker levels in benign and malignant pediatric ovarian neoplastic tumors. Design. Retrospective database study.

SETTING:

Single center study.

POPULATION:

Forty-five 0-15 year old patients operated on for ovarian neoplastic tumors from the beginning of 1999 to the end of 2013.

METHODS:

Serum alpha-fetoprotein, human chorionic gonadotropin and cancer antigen-125 levels as well as follow-up data were recorded from patient charts and tumor histology was re-evaluated.

MAIN OUTCOME MEASURES:

Incidence of ovarian neoplastic tumors in the pediatric population. Differences in patient characteristics and tumor marker levels between those with benign and malignant tumors.

RESULTS:

The annual incidence of ovarian tumors was 2.2/100 000 females. Median age at presentation was 13.0 years (range 0.9-15.7), similar in both the 33 (73%) with a benign and the 12 patients (27%) with a malignant tumor. The tumors with the highest propensity to metastase (yolk sac tumors, mixed germ cell tumors, small cell carcinoma) were only found in girls >9 years. Elevated serum alpha-fetoprotein and cancer antigen-125 values associated more often with malignant tumors (p<0.001 and 0.031, respectively). There were no deaths or local recurrences. Four patients with a mature teratoma developed a contralateral benign ovarian tumor during follow-up.

CONCLUSIONS:

Both benign and malignant ovarian tumors are rare in the pediatric population, but the incidence increases with age. High alpha-fetoprotein and cancer antigen-125 levels were associated with malignant tumors. The prognosis of the pediatric ovarian tumors seems to be favorable.

Assessment of a new system for primary site assignment in high-grad... - PubMed - NCBI

Abstract

AIMS: 

Evidence indicates that most non-uterine high-grade serous carcinomas (HGSC) arise from the fallopian tube, but approaches to primary site assignment have not evolved to reflect this. This study aimed to assess application of recently proposed criteria for site assignment.

METHODS AND RESULTS:

151 HGSCs from four centres were reviewed retrospectively. 63/80 (79%) chemo-naïve (CN) and 45/71 (68%) post-neoadjuvant chemotherapy (NACT) cases were assigned as fallopian tube (FT) primaries with the new criteria, while 58/80 (73%) and 45/71 (63%) were considered ovarian primaries using traditional criteria (p<0.0001). In 111 prospectively collected HGSC's, with consistent detailed fimbrial examination, 44/53 (83%) CN and 44/58 (76%) NACT cases were assigned as FT primaries. Reproducibility of site assignment was tested in a subset of 50 cases: 4/4 reviewing pathologists agreed on primary site in 48/50 (96%), and 3/4 in 49/50 (98%) cases. Of the 53 prospectively studied CN cases, bilateral ovarian involvement (62%) was significantly more frequent than bilateral tubal involvement (12%, p<0.0001), further supporting tubal origin and ovarian metastasis in most cases.

CONCLUSIONS:

With currently accepted protocols, the proposed guidelines are easy to apply and result in consistent site assignment in non-uterine HGSC. Most cases of non-uterine HGSC were considered primary FT neoplasms

Survival Advantage Associated with Decrease in Stage at Detection from Stage IIIC to Stage IIIA Epithelial Ovarian Cancer

abstract/open access

Objective.
The aim of this study was to document the survival advantage of lowering stage at detection from Stage IIIC to Stage IIIA epithelial ovarian cancer.

Methods.
Treatment outcomes and survival were evaluated in patients with Stage IIIA and Stage IIIC epithelial ovarian cancer treated from 2000 to 2009 at the University of Kentucky Markey Cancer Center (UKMCC) and SEER institutions.

Results. Cytoreduction to no visible disease  and complete response to platinum-based chemotherapy occurred more frequently in Stage IIIA than in Stage IIIC cases. Time to progression was shorter in patients with Stage IIIC ovarian cancer than in those with Stage II1A disease. Five-year overall survival (OS) improved from 41% in Stage IIIC patients to 60% in Stage IIIA patients treated at UKMCC and from 37% to 56% in patients treated at SEER institutions for a survival advantage of 19% in both data sets. 53% of Stage IIIA and 14% of Stage IIIC patients had NED at last followup.

Conclusions. Decreasing stage at detection from Stage IIIC to stage IIIA epithelial ovarian cancer is associated with a 5-year survival advantage of nearly 20% in patients treated by surgical tumor cytoreduction and platinum-based chemotherapy.

 Table 1: Definitions of Stage IIIA and Stage IIIC ovarian cancer*.

Stage III     
Tumor involves one or both ovaries with cytologically or histologically confirmed spread to the peritoneum outside the pelvis and/or metastasis to the retroperitoneal lymph nodes.     
 
Stage IIIA     
  Microscopic metastasis beyond the pelvis.     
 
Stage IIIC     
  Macroscopic, extrapelvic, peritoneal metastasis >2 cm in the greatest dimension and/or regional lymph node metastasis.
     
From Edge et al. [6].

 1. Introduction

Despite advances in radical surgery, postoperative care, and chemotherapy, ovarian cancer remains the leading cause of gynecologic cancer mortality among women in the United States. This year, over 14,000 deaths from ovarian cancer will be reported in the United States alone [1]. Most women continue to present with advanced disease where the cost of treatment is high and survival is low. Since the 5-year survival of patients with early stage ovarian cancer is excellent, many investigators believe that the most effective way to reduce ovarian cancer mortality is through earlier detection. It has been estimated that if 75% of ovarian cancer cases were detected with early stage disease, the number of women dying of this cancer could be reduced by one half.....

Communicating with Biobank Participants: Preferences for Receiving and Providing Updates to Researchers

abstract

Background Research biobanks collect biological samples and health information. Previous work shows that biobank participants desire study updates, but preferences regarding the method or frequency of these communications have not been explored. Thus, we surveyed participants in a long-standing research biobank.

Methods Eligible participants were drawn from a study of patients with personal/family history suggestive of Cowden syndrome, a poorly-recognized inherited cancer syndrome. Participants gave blood samples and access to medical records and received individual results but had no other study interactions. The biobank had 3618 participants at sampling. Survey eligibility included age >18 years, enrollment within the biobank's first five years, normal PTEN analysis, and contiguous United States address. Multivariate logistic regression analyses identified predictors of participant interest in internet-based vs. offline methods and methods allowing participant-researcher interaction vs. one-way communication. Independent variables were narrowed by independent Pearson correlations by cutoff p<0.2, with p<0.02 considered significant.

Results Surveys were returned from 840/1267 (66%) eligible subjects. Most (97%) wanted study updates with 92% wanting updates at least once a year. Participants preferred paper (66%) or emailed (62%) newsletter methods with 95% selecting one of these. Older, less-educated, and lower-income respondents strongly preferred offline approaches (p<0.001). Most (93%) had no concerns about receiving updates and 97% were willing to provide health updates to researchers.

Conclusion Most participants were comfortable receiving and providing updated information. Demographic factors predicted communication preferences. Impact Researchers should make plans for ongoing communication early in study development and funders should support the necessary infrastructure for these efforts.

Utah Ovarian Cancer Alliance | Not all Cancers are Pink

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World Health Organization’s advice based on weak evidence

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Scientific mysteries we could solve in the 21st century (cancer and luck)

Business Insider

 6. Genes, cancer and luck

You might have read recently that most cancer is caused by bad luck, as a study published in Science supposedly concluded. (Actually, the study concluded that the disparity in prevalence of cancer of various types was largely due to luck.) A firestorm of protest followed, essentially based on the belief that such a study must be wrong because it would “send the wrong message” to the public. Proving the illogic of that syllogism should be left as an exercise for the reader.
Other responses revealed that experts do not agree on how random mutations (bad luck) compare with heredity (parent’s fault) plus lifestyle (your fault) and environmental exposure to bad things (somebody else’s fault) in causing cancer. Sorting all that out, and in the process solving cancer’s other mysteries, should be a high-priority exercise for 21st century science. And yes, there is a considerable amount of research relating game theory to cancer.

Read more: https://www.sciencenews.org/blog/context/top-10-scientific-mysteries-21st-century#ixzz3QahPDw3B

A Unique Subset of Epithelial Ovarian Cancers with Platinum Sensitivity and PARP Inhibitor Resistance

Abstract


Platinum and PARP inhibitor (PARPi) sensitivity commonly coexist in epithelial ovarian cancer (EOC) due to the high prevalence of alterations in the homologous recombination (HR) DNA repair pathway that confer sensitivity to both drugs. In this report, we describe a unique subset of EOC with alterations in another DNA repair pathway, the nucleotide excision repair (NER) pathway, which may exhibit a discordance in sensitivities to these drugs. Specifically, 8% of high-grade serous EOC from The Cancer Genome Atlas dataset exhibited NER alterations, including nonsynonymous or splice site mutations and homozygous deletions of NER genes. Tumors with NER alterations were associated with improved overall survival (OS) and progression-free survival (PFS), compared with patients without NER alterations or BRCA1/2 mutations. Furthermore, patients with tumors with NER alterations had similar OS and PFS as BRCA1/2-mutated patients, suggesting that NER pathway inactivation in EOC conferred enhanced platinum sensitivity, similar to BRCA1/2-mutated tumors. Moreover, two NER mutations (ERCC6-Q524* and ERCC4-A583T), identified in the two most platinum-sensitive tumors, were functionally associated with platinum sensitivity in vitro. Importantly, neither NER alteration affected HR or conferred sensitivity to PARPi or other double-strand break-inducing agents. Overall, our findings reveal a new mechanism of platinum sensitivity in EOC that, unlike defective HR, may lead to a discordance in sensitivity to platinum and PARPi, with potential implications for previously reported and ongoing PARPi trials in this disease.

Cancer Res; 75(4); 1-7. ©2014 AACR.
©2014 American Association for Cancer Research

Gynecologic Cancer Imaging with MRI, FDG PET-CT and PET-MRI

abstract

Abstract

MRI and FDG PET-CT play central and complementary roles in gynecologic cancer care. Because treatment often requires combinations of surgery, radio- and chemotherapy, imaging is central to triage and to determine prognosis. This article reviews the use of the two imaging modalities in the initial evaluation of the common cancers --- uterine cervical, uterine endometrial and epithelial ovarian cancers. Imaging features that impact on management and the relative strengths and weaknesses of the two modalities are highlighted. Use of imaging after initial therapy to assess for recurrence and to plan salvage therapy is described. Newer functional and molecular techniques in MRI and PET are evaluated. Finally, we describe our initial experience with PET-MRI, an emerging technology that may prove to be a mainstay in personalized gynecologic cancer care and adaptive therapy.

Copyright © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.