Lynch Syndrome and Cervical Cancer Intl Jnl of Cancer

abstract

 Carriers of germline mutations in DNA mismatch repair (MMR) genes are at increased risk of several cancers including colorectal and gynecologic cancers (Lynch syndrome). There is no substantial evidence that these mutations are associated with an increased risk of cervical cancer. A total of 369 families with at least one carrier of a mutation in a MMR gene (133 MLH1, 174 MSH2, 35 MSH6, and 27 PMS2) were ascertained via population cancer registries or via family cancer clinics in Australia, New Zealand, Canada, and USA. Personal and family histories of cancer were obtained from participant interviews. Modified segregation analysis was used to estimate the hazard ratio (incidence rates for carriers relative to those for the general population), and age-specific cumulative risks of cervical cancer for carriers. A total of 65 cases of cervical cancer were reported (including 10 verified by pathology reports). The estimated incidence was 5.6–fold (95% CI: 2.3–13.8; p=0.001) higher for carriers than for the general population with a corresponding cumulative risk to 80 years of 4.5% (95% CI: 1.9–10.7%) compared with 0.8% for the general population. The mean age at diagnosis was 43.1 years (95% CI: 40.0–46.2), 3.9 years younger than the reported USA population mean of 47.0 years (p=0.02). Women with MMR gene mutations were found to have an increased risk of cervical cancer. Due to limited pathology verification we cannot be certain that a proportion of these cases were not lower uterine segment endometrial cancers involving the endocervix, a recognized cancer of Lynch syndrome.

Difficult Patients (nurse/PhD commentary)

ASCO Connection

 We all have our fair share of so-called “difficult” patients. And, I would suggest that how we define “difficult” is as diverse as we are as health care providers and as individuals. Some patients come to us with that reputation—perhaps, a vague descriptor in a referral letter or a note in the patient’s chart. Maybe the receptionist or nurse makes a side comment that the next patient is “challenging” or “uptight,” and we accept their assessment......

Have we given up on a cure for ovarian cancer? - Narod

Current Oncology

Commentary

Have we given up on a cure for ovarian cancer?

---

A Countercurrents Series^a
S.A. Narod , MD ^*
* Women’s College Research Institute, Women’s College Hospital, Toronto, ON.


doi: http://dx.doi.org/10.3747/co.22.2517

In December 2014, on the force Web site, executive director Sue Friedman, heralded a game-changing holiday gift for people with BRCA mutations: “Today is a landmark for the hboc [hereditary breast and ovarian cancer] community”1. In an accompanying article 2, Lisa Rezende wrote about the U.S. Food and Drug Administration ( fda ) decision to approve olaparib for the treatment of recurrent ovarian cancer in women with a BRCA1 or BRCA2 mutation:.......

REFERENCES

1. Friedman S. A Game-Changing Holiday Gift for People with BRCA Mutations [blog post]. Tampa, FL: Facing Our Risk of Cancer Empowered (force); 2014. [Available at: http://www.facingourrisk.org/get-involved/HBOC-community/BRCAHBOC-blogs/FORCE/uncategorized/a-game-changing-holiday-gift-for-people-with-brca-mutations/; cited 17 April 2015]

Osteoporosis Risk and Management in BRCA 1/ 2 carriers who undergo Risk-Reducing Salpingo-oophorectomy

abstract

Highlights:

• •Only 44% of BRCA carriers had a DXA scan after risk-reducing salpingo-oophorectomy, at median of 41 months from testing
• •68% of DXA scans in BRCA carriers who had undergone risk-reducing salpingo-oophorectomy were abnormal
• •There was a 4% rate of a traumatic fracture in BRCA carriers following RRSO

Conclusions

 Women with BRCA mutations who undergo RRSO have many risk factors for bone loss. The majority of these women are not being screened for bone loss. A clear guideline for screening needs to be established to improve detection of post-RRSO bone disease.

(new) see comments: Cochrane Review: Antidepressants for the treatment of depression

Cochrane Review: Antidepressants for the treatment of depression in people with cancer (see comments)

(new) see comments: Cochrane Review: Antidepressants for the treatment of depression

Cochrane Review: Antidepressants for the treatment of depression in people with cancer (see comments)

Why Have Ovarian Cancer Mortality Rates Declined? Part III. Prospects for the Future

abstract

Highlights

• •Up to 17% of ovarian cancers are potentially preventable through population-based genetic testing of known ovarian cancer susceptibility genes
• •Primary debulking surgery leaving no residual disease followed by intraperitoneal chemotherapy appears to hold the greatest potential for cure

Abstract

Over the last 40 years, the age-adjusted ovarian cancer mortality rate in the USA declined by 23%. The decline in mortality paralleled a decline in incidence, which was largely due to changes in reproductive risk factors. There was no reduction in ovarian cancer case-fatality at 12 years, indicating that improvements in early detection or in treatment did not contribute to the decline in mortality. Here, we discuss potential strategies to further reduce ovarian cancer mortality through prevention, early detection and treatment. The first approach is to increase genetic testing, in order to identify women who are at a high risk of developing ovarian cancer and offer them preventive bilateral salpingo-oophorectomy. At present, up to 17% of ovarian cancers are potentially preventable through population-based genetic testing of known ovarian cancer susceptibility genes. The second approach is to increase the proportion of ovarian cancer patients who achieve a status of no residual disease through primary debulking surgery and subsequently receive adjuvant intraperitoneal chemotherapy. We believe that through a combination of screening to better identify low-volume advanced stage ovarian cancer, aggressive surgery to leave no residual disease and adjuvant intraperitoneal chemotherapy, the cure rate of ovarian cancer might be improved significantly.

Immunohistochemical Comparison of Ovarian and Uterine Endometrioid Carcinoma, Endometrioid Carcinoma With Clear Cell Change, and Clear Cell Carcinoma

abstract

 Accurate distinction of clear cell carcinoma (CCC) from endometrioid carcinoma (EC) has important clinical implications, but, not infrequently, EC demonstrates clear cell change (EC-CC), mimicking CCC. We examined whether a panel of immunomarkers can help distinguish between these tumors. Sixty-four CCCs (40 ovarian and 24 uterine), 34 ECs (21 ovarian and 13 uterine), and 34 EC-CCs (6 ovarian and 28 uterine) were stained for HNF1[beta], BAF250a, Napsin A, ER, and PR. Intensity and extent of immunoreactivity was assessed. Fifty-seven of 64 (89%) CCCs, 14/34 (41%) EC-CCs, and 16/34 (47%) ECs expressed HNF1[beta], and 56/64 (88%) CCCs, 4/34 (12%) EC-CCs, and 1/34 (3%) ECs stained for Napsin A. Most CCCs demonstrated at least moderate and diffuse staining for both markers, whereas only focal and weak expression was identified in most EC-CC/EC. Compared to HNF1[beta], Napsin A showed increased specificity (93.0% vs. 55.9%, P<0.0001) and similar sensitivity (87.5% vs. 89.1%) in distinguishing CCC from EC-CC/EC. Thirteen of 64 (20%) CCCs, 6/34 (18%) EC-CCs, and 2/34 (6%) ECs showed loss of BAF250a. ER was expressed by 10/64 (16%) CCCs, 30/34 (88%) EC-CCs, and 33/34 (97%) ECs, whereas PR positivity was identified in 9/64 (14%) CCCs, 26/34 (77%) EC-CCs, and 33/34 (97%) ECs. The majority of EC and EC-CC demonstrated diffuse staining for ER/PR, whereas most CCCs showed very focal positivity. There is a statistically significant difference in HNF1[beta], Napsin A, ER, and PR immunoexpression between CCC and EC/EC-CC, with Napsin A being a more specific marker for CCC than HNF1[beta]. Overall, the immunoprofile of EC-CC is more comparable to that of EC than CCC. The use of a panel of immunostains can help distinguish EC-CC from CCC.

Ovarian Seromucinous Carcinoma: Report of a Series of a Newly Categorized and Uncommon Neoplasm

abstract

 Seromucinous neoplasms are a new category of ovarian epithelial tumor in the revised World Health Organization Classification of Tumours of the Female Reproductive Organs. Borderline variants are well described, but there have been few reports of seromucinous carcinomas. We report the clinicopathologic features in 19 cases of ovarian seromucinous carcinoma in patients aged 16 to 79 years (mean 47). In 16 cases, the neoplasm was unilateral and in 3 cases bilateral. The tumors ranged in size from 1.8 to 18 cm (mean 10.5 cm). The tumors were stage I (n=15), stage II (n=1), and stage III (n=3). The histologic features were highly variable both within and between individual tumors. The majority of neoplasms (12 cases) exhibited a predominant papillary architecture with lesser components of glandular, microglandular, and solid growth. A predominant glandular architecture was present in 6 cases, whereas 1 had a predominantly solid growth. A characteristic feature was an admixture of cell types. Most of the tumors (15 cases) were mainly composed of endocervical-like mucinous cells, whereas in 4 cases there was predominant endometrioid differentiation. Other cell types, present in varying proportions, included hobnail cells, eosinophilic cells, squamous cells, clear cells, and signet-ring cells. An infiltrate of neutrophil polymorphs was a prominent feature in most cases. Most cases also exhibited areas of microglandular architecture with cytoplasmic clearing and intraluminal polymorphs, the features closely resembling cervical microglandular hyperplasia. Areas of stromal hyalinization, adenofibromatous growth, and psammoma bodies were present in a minority of cases. Endometriosis was identified in the same ovary in 10 cases, and in 10 there was a component of seromucinous borderline tumor. Thirteen, 5, and 1 tumor were of grades 1, 2, and 3, respectively (using the FIGO grading system for endometrioid adenocarcinomas of the uterine corpus). A synchronous uterine endometrioid adenocarcinoma was present in 1 case. Immunohistochemically, there was positive staining with CK7 (17/17 cases), estrogen receptor (16/16 cases), progesterone receptor (6/7 cases), CA125 (15/15 cases), PAX8 (8/8 cases), CEA (8/13 cases), CA19.9 (8/9 cases), and WT1 (2/13 cases). CK20 and CDX2 were negative in all cases tested (16 and 14, respectively). p53 showed “wild-type” staining in 4/4 cases, and p16 was focally positive in 5/5 cases. Follow-up information was available in 8 patients. Seven were alive with no evidence of disease (follow-up 3 to 74 mo), whereas 1 patient who initially presented with a stage IIB tumor died of disease at 192 months. Given the characteristic admixture of cell types and the overlapping morphologic features with low-grade serous, mucinous, and endometrioid neoplasms, the most appropriate categorization of seromucinous carcinomas is uncertain, but we believe they are best regarded as a distinct type of ovarian epithelial malignancy and are most similar to endometrioid adenocarcinomas. We recommend grading them in an analogous manner to ovarian endometrioid adenocarcinomas.

OCNA - URGENT: Protect Ovarian Cancer Research at the DOD

Ask your Senator to Oppose the McCain Amendment to the Defense Bill

Senator John McCain has an amendment to the Defense Authorization bill to wipe out many of the research programs run by the Department of Defense, including the Ovarian Cancer Research Program (OCRP). The OCRP funds $20 million in innovative, high-risk, high-reward research each year. Please call or write your Senators TODAY and ask them to oppose this dangerous amendment.

 

Evolving paradigms in the treatment of opioid-induced bowel dysfunction

abstract

 In recent years prescription of opioids has increased significantly. Although effective in pain management, bothersome gastrointestinal adverse effects are experienced by a substantial proportion of opioid-treated patients. This can lead to difficulties with therapy and subsequently inadequate pain relief. Collectively referred to as opioid-induced bowel dysfunction, these adverse effects are the result of binding of exogenous opioids to opioid receptors in the gastrointestinal tract. This leads to disturbance of three important gastrointestinal functions: motility, coordination of sphincter function and secretion. In the clinic this manifests in a wide range of symptoms such as reflux, bloating, abdominal cramping, hard, dry stools, and incomplete evacuation, although the most known adverse effect is opioid-induced constipation. Traditional treatment with laxatives is often insufficient, but in recent years a number of novel pharmacological approaches have been introduced. In this review the pathophysiology, symptomatology and prevalence of opioid-induced bowel dysfunction is presented along with the benefits and caveats of a suggested consensus definition for opioid-induced constipation. Finally, traditional treatment is appraised and compared with the latest pharmacological developments. In conclusion, opioid antagonists restricted to the periphery show promising results, but use of different definitions and outcome measures complicate comparison. However, an international working group has recently suggested a consensus definition for opioid-induced constipation and relevant outcome measures have also been proposed. If investigators within this field adapt the suggested consensus and include symptoms related to dysfunction of the upper gut, it will ease comparison and be a step forward in future research.

Eudaimonic well-being and tumor norepinephrine in patients with epithelial ovarian cancer

abstract

BACKGROUND

The impact of psychological well-being on the physiologic processes involved in cancer progression remains unclear. Prior research has implicated adrenergic signaling in tumor growth and metastasis. Given that adrenergic signaling is influenced by both positive and negative factors, the authors examined how 2 different aspects of well-being (eudaimonic and positive affect) and psychological distress were associated with tumor norepinephrine (NE) in patients with ovarian cancer.

(definition: epinephrine and norepinephrine,  also called adrenaline and noradrenaline,  two separate but related hormones secreted by the medulla of the adrenal glands.)

METHODS

A total of 365 women with suspected ovarian cancer completed psychosocial assessments before surgery and clinical information was obtained from medical records.

Ovarian cancer treatment: The end of empiricism? open access

Open access

Abstract

The diagnosis, investigation, and management of ovarian cancer are in a state of flux—balancing ever rapid advances in our understanding of its biology with 3 decades of clinical trials. Clinical trials that started with empirically driven selections have evolved in an evidence-informed manner to gradually improve outcome. Has this improved understanding of the biology and associated calls to action led to appropriate changes in therapy? In this review, the authors discuss incorporating emerging data on biology, combinations, dose, and scheduling of new and existing agents with patient preferences in the management of women with ovarian cancer.

Table 1. Prioritization Questions in the Management of Ovarian Cancer and Current Proposed Strategies

Conclusion

The treatment of ovarian cancer is on the verge of a major change that will propel improvement in outcomes.[87] Recent developments emphasize that a multipronged approach is warranted, integrating genomics, subtype-specific maintenance therapy, and other directions that will be used alongside increasingly sensitive disease-detection tools. Better definition of treatment timing may further allow exploitation of additional benefits of surgery as the role of surgery remains central to OC treatment. Taken together, this will allow us to build on our understanding of the heterogeneity of OC to tailor treatment. Future therapeutic strategy should target genetics, microenvironment, and sequence schedule to keep cancer cells from developing resistance. To move forward, we have to take some bold steps based on biology, require objective evidence of benefit, and reflect on experience from other cancers and diseases. It is important to constantly re-evaluate data and expect that, for therapy to be considered “standard,” it has to demonstrate objective, clinically meaningful, as well as statistically significant benefit. The timing is right for a paradigm shift that will require clinicians to have the courage and confidence to not prescribe treatments without evidence of benefit. This will necessitate optimizing surgery and appropriate evidence-based recommendations for each subtype of ovarian cancer. This therapeutic direction has to be supported by excellence and precision in pathology, molecular profiling, and imaging. In equal measure, it will require open dialogue with patients and being honest about treatments that have evidence of benefit and, especially, those that do not.

Use of common analgesics is not associated with ovarian cancer survival

abstract



Background: Use of analgesics has been associated with lower risk of ovarian cancer, but to date, very few studies have explored the association between analgesics and ovarian cancer survival.
Methods: We examined the relationship between self-reported pre-diagnostic use of aspirin, ibuprofen, and acetaminophen and overall survival (OS), progression-free survival (PFS), ascites at the time of primary treatment, and persistence of disease after primary treatment among 699 women diagnosed with epithelial ovarian carcinoma. The associations between use of these medications and OS and PFS were estimated using Cox-proportional hazards models. We utilized unconditional logistic regression models to estimate associations between medication use and presence of ascites and persistence of disease.
Results: Pre-diagnostic intake of aspirin, both low-dose and regular-dose, ibuprofen, and acetaminophen were not associated with any of the outcomes of interest.
Conclusions: Our results indicate a lack of association between pre-diagnostic intake of selected analgesics and OS, PFS, presence of ascites at the time of primary treatment, and persistence of disease after primary treatment.

Impact:  Pre-diagnostic intake of analgesics may not be associated with ovarian cancer outcomes.

Who should decide how much and what information is important in person-centred health care?

open access

.... We do not need the concept of an ‘informed decision’, only that of a good, better or best possible decision. For none of these will there be a definition that is not multi-dimensional and therefore preference-sensitive. The question is to whose preferences should the definition be sensitive? There can only be one answer: the patient’s – or the person’s if they are not a patient.

Cost Effectiveness of Chemotherapeutic Agents and Targeted Biologics in Ovarian Cancer

abstract
 

Cost Effectiveness of Chemotherapeutic Agents and Targeted Biologics in Ovarian Cancer: A Systematic Review

.....Future research incorporating real-world data is essential to corroborate findings from trial-based economic evaluations. In addition, for improving consistency in reporting and quality of studies, incorporating QALYs in this population is important, especially since chemotherapy is administered for lengthy periods of time.

Why Have Ovarian Cancer Mortality Rates Declined? Part II. Case-fatality

abstract
  
Highlights

•

The decline in ovarian cancer mortality cannot be explained by a reduction in case-fatality

•

New treatments improve short-term survival and median survival, but not long-term survival or cure

---

In the United States, the age-adjusted mortality rate from ovarian cancer declined by 8% from 1975 to 1991 and by 18% from 1992 to 2011. A decline in the incidence rate of ovarian cancer paralleled the decline in mortality (described in Part I). The decline in mortality might also be due to a reduced proportion of ovarian cancer patients who die from their cancer (case-fatality). Here, we examine rates of ovarian cancer case-fatality from the Surveillance Epidemiology and End Results (SEER) registry database, and we consider to what extent advances in treatment also contribute to the observed decline in mortality. From 1973 to 1999, the five-year case-fatality rate for women with ovarian cancer fell by 7.5%, whereas the 12-year case-fatality rate fell by only 1.2%. The declines in five-year case-fatality corresponded in time with the introduction and expansion in use of cis-platinum and paclitaxel in clinical practice. However, modest declines in 12-year case-fatality indicate that the introduction of chemotherapy has not contributed to the decline in mortality. Developments in the last two decades include targeted therapies, aggressive surgical techniques, the use of neoadjuvant chemotherapy and intraperitoneal chemotherapy. The impact of these treatment modalities on ovarian cancer mortality still needs to be evaluated.

Why Have Ovarian Cancer Mortality Rates Declined? Part I. Incidence

abstract

 The age-adjusted mortality rate from ovarian cancer in the United States has declined over the past several decades. The decline in mortality might be the consequence of a reduced number of cases (incidence) or a reduction in the proportion of patients who die from their cancer (case-fatality). In Part I of this three-part series, we examine rates of ovarian cancer incidence and mortality from the Surveillance Epidemiology and End Results (SEER) registry database and we explore to what extent the observed decline in mortality can be explained by a downward shift in the stage distribution of ovarian cancer (i.e. due to early detection) or by fewer cases of ovarian cancer (i.e. due to a change in risk factors). The proportion of localized ovarian cancers did not increase, suggesting that a stage-shift did not contribute to the decline in mortality. The observed decline in mortality paralleled a decline in incidence. The trends in ovarian cancer incidence coincided with temporal changes in the exposure of women from different birth cohorts to various reproductive risk factors, in particular, to changes in the use of the oral contraceptive pill and to declining parity. Based on recent changes in risk factor propensity, we predict the trend of the declining age-adjusted incidence rate of ovarian cancer in the United States will reverse and rates will increase in coming years.

Alterations in the mitochondrial responses to PENAO (ovarian cancer cell lines)

Abstract
  
Alterations in the mitochondrial responses to PENAO as a mechanism of resistance in ovarian cancer cells

Highlights

•

PENAO has promising anti-proliferative activity on cells established from four histological subtypes of ovarian cancer.

•

SKOV-3 endometrioid ovarian carcinoma resistance towards PENAO results from a strong heme oxygenase induction and a shift towards glycolytic metabolism.

•

PENAO and mTOR pathway inhibition synergizes to reverse SKOV-3 endometrioid ovarian carcinoma drug resistance.

---

Objective

The purpose of this study was to test PENAO, a promising new organoarsenical that is in phase 1 testing in patients with solid tumors, on a range of ovarian cancer cell lines with different histotypes, and to understand the molecular basis of drug resistance exhibited by the endometrioid ovarian cancer cell line, SKOV-3.

Disease-free ovarian cancer patients report severe pain and fatigue over time: prospective

abstract

OBJECTIVE: Among ovarian cancer patients, cancer treatment is aggressive and yet survival is often so limited; hence, this study sought to measure quality of life with the ultimate goal of identifying ways of improving it over the duration of these patients' lives. 

MATERIALS AND METHODS: The medical records of all ovarian cancer patients who received some/all of their initial chemotherapy at the Mayo Clinic in Rochester, Minnesota from late 2010 through 2012 were reviewed. Patient-reported quality of life was derived from the following ten-point linear analogue scale questions which had been administered to all patients: 1) How would you describe your degree of pain, on average ? 2) How would you describe your level of fatigue, on average ? 3) How would you describe your overall quality of life ? Quality of life data were censored upon cancer recurrence.

RESULTS: Among 59 eligible patients, the median cumulative interval during which quality of life was serially assessed was 1.15 years (range: three months, 3.2 years). Area under the curve for pain, fatigue, and global quality of life showed no statistically significant differences between patients treated with dose-dense chemotherapy with carboplatin/paclitaxel (n = 10) versus three-week chemotherapy with carboplatin/paclitaxel (n = 36) versus other (n = 13). Although pain, fatigue, and global quality of life improved over time, 35 of 59 (59%) patients reported grade 4 or worse pain during follow up, and 47 of 59 (80%) reported grade 4 or worse fatigue (higher scores denote worse pain or fatigue). After completion of cancer treatment, 30 (51%) described grade 4 or worse pain or fatigue. The most common pain site was the abdomen/pelvis, followed by the back, followed by the hands, feet, fingers, and toes.

CONCLUSION: In ovarian cancer patients who remain cancer-free, severe pain and fatigue occur years after cancer treatment. Further research should focus on how best to address these symptoms. 

Cochrane Revidew: Antidepressants for the treatment of depression in people with cancer

Abstract

 AUTHORS' CONCLUSIONS:
Despite the impact of depression on people with cancer, available studies were very few and of low quality. This review found very low quality evidence for the effects of these drugs compared with placebo. On the basis of these results clear implications for practice cannot be made. The use of antidepressants in people with cancer should be considered on an individual basis and, considering the lack of head-to-head data, the choice of which agent should be prescribed may be based on the data on antidepressant efficacy in the general population of individuals with major depression, also taking into account that data on medically ill patients suggest a positive safety profile for the SSRIs. Large, simple, randomised, pragmatic trials comparing commonly used antidepressants versus placebo in people with cancer with depressive symptoms, with or without a formal diagnosis of a depressive disorder, are urgently needed to better inform clinical practice.

Despite warnings, mesh use for prolapse on the rise

Urology Times

Despite the FDA’s warnings about health risks associated with the use of surgical mesh for transvaginal repair of pelvic organ prolapse (POP), use of the device is increasing, according to a study of POP patients in New York state.

At the same time, risks of reinterventions within 1 year and post-surgery urinary retention continue, said the authors of the study, which was published online in BMJ (June 2, 2015).

 Researchers at Weill Medical College of Cornell University in New York analyzed a statewide database of nearly 28,000 women who had prolapse repair procedures in the state from 2008 to 2011....

Advances and prospects in adoptive cell transfer therapy for ovarian cancer - Immunotherapy

open access

Tyrosine Kinase Inhibitors as Potential Therapeutic Agents in the Treatment of GCTof the Ovary

abstract

OBJECTIVE:

Granulosa cell tumors of the ovary (GCTs) represent a specific subset of malignant ovarian tumors, of which there are 2 distinct subtypes, the juvenile and the adult form. Aside from surgery, no reliable therapeutic options currently exist for patients with GCT. This study sought to investigate the potential role of small molecule tyrosine kinase inhibitors (TKIs) as novel therapeutics in the clinical management of GCT.

MATERIALS AND METHODS:

Using TKI with distinct but overlapping multitargeted specificities, cellular proliferation, viability, and apoptosis were evaluated in 2 human GCT-derived cell lines, COV434 and KGN.

RESULTS:

Sunitinib, which targets the imatinib-inhibited tyrosine kinases of VEGFR, KIT, PDGFR, and FLT-3, was without effect in COV434 and KGN cell lines. Sorafenib, which has a high affinity for RAF1 and BRAF, dose dependently inhibited cellular proliferation and viability in both cell lines at concentrations equivalent to that seen in other systems. A RAF1 kinase inhibitor was without effect, suggesting that sorafenib is acting via inhibition of BRAF, or that aberrant signaling originates upstream of BRAF in the MAPK pathway. In the presence of a selective Src family inhibitor (SU6656), cell proliferation and cell viability responses dissociated; that is, although SU6656 dose dependently inhibited cell viability, it had limited effect on proliferation and apoptosis.

CONCLUSIONS:

These findings implicate BRAF in the activated signaling responsible for the growth and viability of GCT and suggest that TKI already in clinical use may be a therapeutic option in the treatment of GCT.

Evaluation of the Hematologic Safety of Same Day Vs Standard Administration of Pegfilgrastim in Gynecology Oncology Patients

abstract

CONCLUSIONS:
The incidence of hematologic toxicities and dose modification in patients receiving same-day pegfilgrastim were not as low as in those undergoing standard administration. However, treatment delays were found to be no more frequent in those receiving same-day pegfilgrastim versus standard administration. Same-day administration of pegfilgrastim is a reasonable option.

Epithelial Ovarian Cancer Metastatic to the CNS and a Family History Concerning for HBOC

abstract (edited stats for ease of reading)

Epithelial Ovarian Cancer Metastatic to the Central Nervous System and a Family History Concerning for Hereditary Breast and Ovarian Cancer-A Potential Relationship.

OBJECTIVES:

To estimate the frequency of hereditary breast and ovarian cancer (HBOC) in women with central nervous system (CNS) metastasis from epithelial ovarian cancer (EOC) and to evaluate for a potential relationship between HBOC status and survival.

METHODS AND MATERIALS:

A total of 1240 cases of EOC treated between 1995 and 2014 were reviewed to identify CNS metastasis. Demographics, treatment, family history, genetic testing, and survival outcomes were recorded. Women were then classified as HBOC+ or HBOC- based on histories and genetic testing results....

RESULTS:

Of 1240 cases, 32 cases of EOC with CNS metastasis were identified (2.58%). Median age was 52  years, and 87% had stage III to IV disease. Among those with documented personal and family history, 66.7% (20/30) were suspicious for HBOC syndrome. Among those who underwent germline testing, 71.43% (5/7) had a pathogenic BRCA mutation. The median time from diagnosis to CNS metastasis was 29 months. At a median survival of 5.97 months from the time of CNS metastasis and 43 months from the time of EOC diagnosis, 29 women died of disease. Univariate Cox proportional hazard models were used to compare HBOC- to HBOC+ women and did not reveal a significant difference for survival outcomes.

CONCLUSIONS:

Confirmed BRCA mutations and histories concerning for HBOC syndrome are common in women with EOC metastatic to the CNS. We did not demonstrate a relationship between HBOC status and survival outcomes, but were not powered to do so.

Rectal Cancer Diagnosed after Cesarean Section in Which MSI-H Indicated Lynch Syndrome

 Rectal Cancer Diagnosed after Cesarean Section in Which High Microsatellite Instability Indicated the Presence of Lynch Syndrome

abstract
 
We report a case of rectal cancer with microsatellite instability (MSI) that probably resulted from Lynch syndrome and that was diagnosed after Cesarean section. The patient was a 28-year-old woman (gravid 1, para 1) without a significant medical history. At 35 gestational weeks, vaginal ultrasonography revealed a 5 cm tumor behind the uterine cervix, which was diagnosed as a uterine myoma. The tumor gradually increased in size and blocked the birth canal, resulting in the patient undergoing an emergency Cesarean section. Postoperatively, the tumor was diagnosed as rectal cancer with MSI. After concurrent chemoradiation therapy, a lower anterior resection was performed. The patient's family history revealed she met the criteria of the revised Bethesda guidelines for testing the colorectal tumor for MSI. Testing revealed that the tumor did indeed show high MSI and, combined with the family history, suggested this could be a case of Lynch syndrome. Our findings emphasize the importance of considering the possibility of Lynch syndrome in pregnant women with colorectal cancer, particularly those with a family history of this condition. We suggest that the presence of Lynch syndrome should also be considered for any young woman with endometrial, ovarian, or colorectal cancer. 

Gynecologic Oncology | Vol 138, Iss 1, Pgs 1-220, (July 2015)

 Blogger's Note: edited index for ovarian cancer related items

Index (subscriber based)
 

Meeting Reports

1. • Highlights from the Society of Gynecologic Oncology 2015 Annual Meeting on Women's Cancer

   • Pages 3-6
   • Camille C. Gunderson, Jeff Boyd, David M. O'Malley
   • •  Purchase PDF - $39.95
   •  Not entitled to full text
2. • Summary of the 2015 American Association for Cancer Research (AACR) Annual Meeting

   • Pages 7-10
   • Jeremy Chien, Charles N. Landen Jr.
   • •  Purchase PDF - $39.95
   •  Not entitled to full text

Original Research Reports

Lead Article

3. • A phase 2 study of cediranib in recurrent or persistent ovarian, peritoneal or fallopian tube cancer: A trial of the Princess Margaret, Chicago and California Phase II Consortia

     Original Research Article
   • Pages 55-61
   • H. Hirte, S. Lheureux, G.F. Fleming, A. Sugimoto, R. Morgan, J. Biagi, L. Wang, S. McGill, S.P. Ivy, A.M. Oza
   • • Abstract
     • Close research highlights
     •  Purchase PDF - $39.95

     Highlights

     •

     Cediranib has activity in recurrent ovarian cancer.

     •

     Expected toxicities were manageable with a dose reduction of cediranib (30 mg daily).

   •  Not entitled to full text
4. • Risk stratification and outcomes of women undergoing surgery for ovarian cancer

     Original Research Article
   • Pages 62-69
   • Sonali Patankar, William M. Burke, June Y. Hou, Ana I. Tergas, Yongmei Huang, Cande V. Ananth, Alfred I. Neugut, Dawn L. Hershman, Jason D. Wright
   • • Abstract
     • Close research highlights
     •  Purchase PDF - $39.95
     • Supplementary content

     Highlights

     •

     Surgery for ovarian cancer is associated with substantial morbidity.

     •

     Performance of extended cytoreductive procedures is the strongest risk factor for complications.

     •

     Alternative treatment strategies may be considered in women with ovarian cancer at high risk for complications.

   •  Not entitled to full text
5. • Development of a prediction model for residual disease in newly diagnosed advanced ovarian cancer

     Original Research Article
   • Pages 70-77
   • Jo Marie Tran Janco, Gretchen Glaser, Bohyun Kim, Michaela E. McGree, Amy L. Weaver, William A. Cliby, Sean C. Dowdy, Jamie N. Bakkum-Gamez
   • • Abstract
     • Close research highlights
     •  Purchase PDF - $39.95
     • Supplementary content

     Highlights

     •

     Preoperative factors may predict cytoreduction for advanced ovarian cancer.

     •

     Age, ECOG status, CT findings may predict complete or suboptimal cytoreduction.

   •  Not entitled to full text
6. • Long-term safety of fertility sparing surgery in early stage ovarian cancer: Comparison to standard radical surgical procedures

     Original Research Article
   • Pages 78-82
   • Antonino Ditto, Fabio Martinelli, Giorgio Bogani, Domenica Lorusso, Marialuisa Carcangiu, Valentina Chiappa, Claudio Reato, Cristina Donfrancesco, Karla Jeanette Amaya De Carrillo, Francesco Raspagliesi
   • • Abstract
     • Close research highlights
     •  Purchase PDF - $39.95

     Highlights

     •

     Conservative treatment of early stage ovarian cancer does not impact on survival outcomes.

     •

     High-risk ovarian cancer patients undergoing conservative surgery experience similar outcomes than those undergoing non-conservative approach.

   •  Not entitled to full text

Health Services Research

7. • Adherence patterns to National Comprehensive Cancer Network (NCCN) guidelines for referral to cancer genetic professionals

     Original Research Article
   • Pages 109-114
   • Terri Febbraro, Katina Robison, Jennifer Scalia Wilbur, Jessica Laprise, Amy Bregar, Vrishali Lopes, Robert Legare, Ashley Stuckey
   • • Abstract
     • Close research highlights
     •  Purchase PDF - $39.95

     Highlights

     •

     Genetic counseling and testing is being underutilized.

     •

     Breast cancer patients are more likely to be referred for genetic counseling.

     •

     Referred patients are likely to follow up with counseling and testing.

   •  Not entitled to full text
8. • Geographic access to gynecologic cancer care in the United States

     Original Research Article
   • Pages 115-120
   • David I. Shalowitz, Alexandra M. Vinograd, Robert L. Giuntoli II
   • • Abstract
     • Close research highlights
     •  Purchase PDF - $39.95

     Highlights

     •

     A total of 36% of US counties are > 50 miles from the closest gynecologic oncologist.

     •

     A total of 14.8 million women live in these low access counties.

     •

     Outreach is needed to ensure these women have access to gynecologic cancer care.

   •  Not entitled to full text
9. • Socioeconomic status as a predictor of adherence to treatment guidelines for early-stage ovarian cancer

     Original Research Article
   • Pages 121-127
   • Melissa Hodeib, Jenny Chang, Fong Liu, Argyrios Ziogas, Sarah Dilley, Leslie M. Randall, Hoda Anton-Culver, Robert E. Bristow
   • • Abstract
     • Close research highlights
     •  Purchase PDF - $39.95

     Highlights

     •

     Disadvantaged populations experience substandard ovarian cancer care.

     •

     Specifically, lower socioeconomic status is an independent predictor of receiving sub-optimal ovarian cancer treatment that deviates from the NCCN guidelines.

     •

     Adherence to the NCCN guidelines has the potential to improve ovarian cancer survival rates among all populations of women.

   •  Not entitled to full text
10. • 
      

Cancer Epidemiology and Prevention

11. • The effect of weight-based chemotherapy dosing in a cohort of gynecologic oncology patients

      Original Research Article
    • Pages 154-158
    • Jean Hansen, Jean-Marie Stephan, Michele Freesmeier, David Bender, Anna Button, Michael J. Goodheart
    • • Abstract
      • Close research highlights
      •  Purchase PDF - $39.95

      Highlights

      •

      No serous effects were noted in obese patients who received full weight- based dosing

      •

      Heme toxicities were not seen in obese patients with capped vs weight-based dosing

      •

      Weight-based dosing in gynecologic oncology patients appears to be well tolerated

    •  Not entitled to full text

Translational Science

12. • TP53 hot spot mutations in ovarian cancer: Selective resistance to microtubule stabilizers in vitro and differential survival outcomes from The Cancer Genome Atlas

      Original Research Article
    • Pages 159-164
    • Brandon-Luke L. Seagle, Chia-Ping Huang Yang, Kevin H. Eng, Monica Dandapani, Oluwatosin Odunsi-Akanji, Gary L. Goldberg, Kunle Odunsi, Susan Band Horwitz, Shohreh Shahabi
    • • Abstract
      • Close research highlights
      •  Purchase PDF - $39.95
      • Supplementary content

      Highlights

      •

      Mutant TP53 ovarian cancer cells show selective microtubule stabilizer resistance.

      •

      R248 mutant ovarian cancer cells have reduced epothilone B induced cell death.

      •

      Patients with different TP53 mutations may have different overall survival.

    •  Not entitled to full text

13. • Formation of stable small cell number three-dimensional ovarian cancer spheroids using hanging drop arrays for preclinical drug sensitivity assays

      Original Research Article
    • Pages 181-189
    • Shreya Raghavan, Maria R. Ward, Katelyn R. Rowley, Rachel M. Wold, Shuichi Takayama, Ronald J. Buckanovich, Geeta Mehta
    • • Abstract
      • Close research highlights
      •  Purchase PDF - $39.95
      • Supplementary content

      Highlights

      •

      We describe stable incorporation of low cell numbers into ovarian cancer spheroids.

      •

      Spheroids have uniform geometry and three-dimensional presence.

      •

      Spheroids contain viable cells that can be utilized for high throughput drug screens.

      •

      Spheroids are chemoresistant to cisplatin compared to conventional monolayer cultures.

      •

      Spheroids generated on hanging drop platforms are high throughput amenable.

    •  Not entitled to full text

Reviews

14. • The vaginal and gastrointestinal microbiomes in gynecologic cancers: A review of applications in etiology, symptoms and treatment

      Review Article
    • Pages 190-200
    • Dana Chase, Alison Goulder, Frederic Zenhausern, Bradley Monk, Melissa Herbst-Kralovetz
    • • Abstract
      • Close research highlights
      •  Purchase PDF - $39.95

      Highlights

      •

      Dysbiotic gut and vaginal microbiota may be implicated in carcinogenesis, therapy-related side effects and treatment outcomes in gynecologic cancers.

      •

      Changes in the microbiome following chemotherapy and radiation may impact patient quality of life and/or treatment outcomes.

      •

      Further research is needed to determine optimal composition, function and efficacy of probiotics in reinstating mucosal homeostasis and barrier function.

    •  Not entitled to full text
15. • Impact of obesity on chemotherapy management and outcomes in women with gynecologic malignancies

      Review Article
    • Pages 201-206
    • Neil S. Horowitz, Alexi A. Wright
    • • Abstract
      • Close research highlights
      •  Purchase PDF - $39.95

      Highlights

      •

      Obesity is associated with an increased risk of developing cancer and worse outcomes.

      •

      Up to 40% of obese patients receive inappropriate low doses of chemotherapy.

      •

      Full dose chemotherapy in obese patients does not lead to increased toxicities.

      •

      Guidelines exist that outline appropriate chemotherapy dosing in obese patients.

    •  Not entitled to full text
16. • Seeing is saving: The benefit of 3D imaging in gynecologic brachytherapy

      Review Article
    • Pages 207-215
    • Akila N. Viswanathan, Beth A. Erickson
    • • Abstract
      • Close research highlights
      •  Purchase PDF - $39.95

      Highlights

      •

      Gynecologic brachytherapy utilizing 3D imaging improves outcomes.

      •

      Clinical atlas based contouring is recommended.

    •  Not entitled to full text
17. • The impact of pleural disease on the management of advanced ovarian cancer

      Review Article
    • Pages 216-220
    • Cecilia Escayola, Gwénael Ferron, Marga Romeo, Juan Jose Torrent, Denis Querleu
    • • Abstract
      • Close research highlights
      •  Purchase PDF - $39.95

      Highlights

      •

      Malignant pleural effusion is the most common site of stage IV EOC.

      •

      PET/CT is able to identify stage IV EOC patients.

      •

      VATS can alter the therapeutic management.

Bilateral Salpingo-oophorectomy and Pelvic Organ Prolapse

Medscape

 Objective. This study aims to estimate the effects of bilateral salpingo-oophorectomy (BSO) at the time of hysterectomy and estrogen therapy on vaginal prolapse.

Evaluation of Wellness Determinants and Interventions by Citizen Scientists

JAMA Network

Most medical research focuses on disease rather than health. Yet people are interested predominantly in health and wellness. Wellness refers to diverse and interconnected dimensions of physical, mental, and social well-being that extend beyond the traditional definition of health. It includes choices and activities aimed at achieving physical vitality, mental alacrity, social satisfaction, a sense of accomplishment, and personal fulfillment. Equally healthy people may differ vastly in terms of their wellness, eg, whether their life is filled with creativity, altruism, friendship, and physical and intellectual achievement. Disease is incompatible with health, but not with wellness.....

 .....For too long, the research enterprise has not adequately reflected the preferences and values of people, widening the gap between the interests of researchers and study participants. Encouraging motivated people participating in high-quality cohorts to contribute to the design and conduct of simple trials could align the interests of investigators and citizen scientists interested in wellness.

Patient-Reported Outcomes in Cancer Drug Development/US Regulatory Review

JAMA Oncology 

 Patient-Reported Outcomes in Cancer Drug Development and US Regulatory ReviewPerspectives From Industry, the Food and Drug

 Data reported directly by patients about how they feel and function are rarely included in oncology drug labeling in the United States, in contrast to Europe and to nononcology labeling in the United States, where this practice is more common. Multiple barriers exist, including challenges unique to oncology trials, and industry’s concerns regarding cost, logistical complexities.....

Multigene Panel Testing in Oncology Practice: How Should We Respond?

JAMA Oncology

 A great success of modern human genetics is the identification of specific genes that, when altered, confer clinically recognized traits, such as cancer susceptibility, and enable predictive genetic testing. In past decades, cost and turn-around time limited cancer genetic risk assessment, and it was rarely feasible to test a patient for more than 1 well-defined condition (eg, hereditary breast ovarian cancer [HBOC] or Lynch syndrome)......

Using Somatic Mutations to Guide Treatment Decisions: Context Matters

JAMA Oncology 

Addressing the Financial Burden of Cancer Treatment: From Copay to Can’t Pay

JAMA Oncology open access

Safety evaluation of olaparib for treating ovarian cancer

abstract

Expert opinion: Oral olaparib 400 mg twice daily has acceptable tolerability when administered as maintenance monochemotherapy in women with relapsed OC. The common toxicities – nausea/vomiting, fatigue and anemia – are mild or moderate in severity and appear consistent across subgroups (BRCA carriers/wild-type). Though the risk is low, long-term monitoring of patients is warranted to determine the potential risk for hematological complications such as anemia, myelodysplastic syndrome or acute myeloid leukemia.