Platinum-based adjuvant chemotherapy on moderate - and high-risk stage I and II epithelian ovarian cancer patients. Long-term single institution exper

Background Although the optimal management of women with FIGO stages I and II epithelial ovarian cancer (EOC) is still controversial, platinum-based adjuvant chemotherapy (CT) is the mainstay of treatment. Suboptimal survival results have led to major efforts to identify prognostic factors, improve surgical staging and develop adjuvant therapies to improve patients' outcomes.

Patients and methods We evaluate in a retrospective study clinical efficacy and the toxicity profile of a platinum-based adjuvant CT in FIGO stages I and II EOC treated at our institution from March 1984 to December 2006. Grade I FIGO stages IA-IB were excluded from the analysis. In the first period (1984-1997), patients received a platinum-based regimen without taxanes. In the second period from 1997 onwards, patients were treated with carboplatin and paclitaxel. Four to six cycles of adjuvant CT were administered. Potential predictive factors of efficacy and the role of paclitaxel addition were also analysed.

Results One hundred and fifty-eight patients (60 treated with paclitaxel) met inclusion criteria and were evaluable. Median age at diagnosis was 53.7 years (range 19-81) and most patients had an Eastern Cooperative Oncology Group performance status score (ECOG) of 0-1 (91.8%); 82.9% patients had pathological stage I and 17.1% pathological stage II. With a median follow up of 8.34 years (range 4.4-11.6), 103 patients (74.1%) were free of disease and 110 of them were alive (79.1%). Median relapse-free survival (RFS) and median overall survival (OS) had not been reached at the time of the analysis. No survival difference was found between paclitaxel and carboplatin combination or non-paclitaxel-containing regimens. Statistically significant prognostic factors for better RFS in the multivariate analysis were: ECOG 0 (p=0.023; HR 0.32; 95% CI 0.17-0.57); FIGO I stage (p<0.001; HR 0.30; 95% CI 0.15-0.58); I-II histological grade (p=0.005; HR 0.38; 95% CI 0.19-0.75); mucinous histology (p=0.013; HR 0.28; 95% CI 0.13-0.53); non-surgical adherences (p<0.002, HR 0.32; 95% CI 0.15-0.54); paracolic gutters inspection (p=0.033; HR 0.50; 95% CI 0.26-0.95) and liver surface biopsies (p=0.048; HR 0.64; 95% CI 0.41-0.98).Toxicity was generally mild and non-haematologic events were the most commonly found (62.9% of the total). The most frequent haematologic toxicities were neutropenia (41.7% in all grades, 9.5% grade 3-4) and anaemia (29.1% in all grades, 3.2% grade 3-4).

Conclusions The long-term outcome of this series is comparable to the published evidence and reflects the limited activity of platinum-based CT in the adjuvant setting. The potential survival advantage of the addition of paclitaxel to carboplatin cannot be definitively answered due to the small number of patients, the limited follow-up and the retrospective nature of the study. More effective and specific treatments are clearly required, in particular for those patients with stage II and undifferentiated tumours. Quality of surgery entails prognostic value.

Lynch Syndrome and MYH-Associated Polyposis: Review and Testing Strategy. Goodenberger M, Lindor NM.

Abstract

Individuals with Lynch syndrome have an increased risk for colorectal cancer, endometrial cancer, and other associated cancers such as gastric cancer, ovarian cancer, urothelial cancers, hepatobiliary tract cancer, brain cancer, cancer of the small intestine, pancreatic cancer, and particular skin cancers.
Lynch syndrome caused by defects in DNA mismatch repair genes, and diagnostic testing for Lynch syndrome begins with microsatellite instability and immunohistochemical analysis on the tumor specimen followed by germline genetic testing and possibly further studies on the tumor. MYH-associated polyposis syndrome is a recently characterized, autosomal recessive, polyposis syndrome caused by biallelic mutations in the MYH gene. Individuals carrying 2 copies of the mutation have a significantly increased risk of polyposis, colorectal cancer, upper gastrointestinal polyps and additional features commonly seen in familial adenomatous polyposis syndrome. Genetic testing for MYH mutation is complicated by the phenotypic overlap of MYH-associated polyposis with other colorectal cancer syndromes. This study serves to clarify the best testing approach.

Surgical management of bowel obstruction in gynaecological malignancies.

Abstract

PURPOSE OF REVIEW: Bowel obstruction in gynaecological malignancies continues to present clinical challenges and a multidisciplinary approach to discuss management is crucial. Surgery, usually with palliative intent, is associated with significant morbidity and mortality. There is an absence of level 1 evidence and national guidelines, and only limited quality-of-life data.
RECENT FINDINGS: Acute bowel obstruction in gynaecological cancer patients is rare and surgery is associated with a higher morbidity and mortality rate. Less commonly, emergency bowel obstruction cases will have had radiotherapy or recent chemotherapy, which also increases surgical morbidity and mortality. However, most often, bowel obstruction in irradiated gynaecological cancer patients is not due to cancer. Ovarian cancer is the most common malignancy. Caution is needed in those EOC patients with ascites, short treatment-free interval, acute abdomen and chemoresistance. Comorbidities are frequent. The decision for surgery should be made on an individual basis. Palliative care input is important early in patient management as for most patients the surgical goal is palliation and not cure. There is still a paucity of published data on quality-of-life assessments.
SUMMARY: There is a need to identify those patients who may benefit from palliative surgical intervention and those who will not. Ideally, agreed national guidelines should be produced and regularly reviewed.

Undetectable antimüllerian hormone levels and recovery of chemotherapy-induced ovarian failure in women with breast cancer on an oral aromatase inhibitors

Abstract

OBJECTIVE: Knowledge of the menopause status of a woman with breast cancer is important for good clinical practice. Long-lasting amenorrhea is frequent in this population, often for reasons other than definitive menopause. Antiestrogens like tamoxifen or oral aromatase inhibitors (AIs) may reactivate the ovary causing vaginal bleeding, menstruation, pregnancy, and unopposed endometrial stimulation. In contrast to tamoxifen, AIs are not active against breast cancer in the presence of functional ovaries. Antimüllerian hormone (AMH) is a potential marker of residual ovarian function that can predict not only the onset of menopause but also chemotherapy-induced amenorrhea (CIA) and fertility. We assess the value of AMH in women who recovered from CIA on an AI.

Retrospective study of the impact of pharmacogenetic variants on paclitaxel toxicity and survival in patients with ovarian cancer.

PURPOSE: Paclitaxel has a broad spectrum of anti-tumor activity and is useful in the treatment of ovarian, breast, and lung cancer. Paclitaxel is metabolized in the liver by CYP2C8 and CYP3A4 and transported by P-glycoprotein. The dose-limiting toxicities are neuropathy and neutropenia, but the interindividual variability in toxicity and also survival is large. The main purpose of this study was to investigate the impact of genetic variants in CYP2C8 and ABCB1 on toxicity and survival.
METHODS: The 182 patients previously treated for ovarian cancer with carboplatin and paclitaxel in either the AGO-OVAR-9 or the NSGO-OC9804 trial in Denmark or Sweden were eligible for this study. Genotyping was carried out on formalin-fixed tissue. The patients' toxicity profiles and survival data were derived from retrospective data. CYP2C8*3, ABCB1 C1236T, G2677T/A, and C3435T were chosen a priori for primary analysis; a host of other variants were entered into an exploratory analysis.
RESULTS: Clinical data and tissue were available from a total of 119 patients. Twenty-two single nucleotide polymorphisms (SNPs) in 10 genes were determined. Toxicity registration was available from 710 treatment cycles. In the primary analysis, no statistically significant correlation was found between CYP2C8*3, ABCB1 C1236T, G2677T/A, and C3435T and neutropenia, sensoric neuropathy, and overall survival.
CONCLUSION: CYP2C8*3 and the ABCB1 SNPs C1236T, G2677T/A, and C3435T were not statistically significantly correlated to overall survival, sensoric neuropathy, and neutropenia in 119 patients treated for ovarian cancer with paclitaxel/carboplatin.

Sugars in diet and risk of cancer in the NIH-AARP diet and health study

Abstract

Prospective epidemiologic data on the effects of different types of dietary sugars on cancer incidence have been limited. In this report, we investigated the association of total sugars, sucrose, fructose, added sugars, added sucrose and added fructose in the diet with risk of 24 malignancies.
Participants (n = 435,674) aged 50-71 years from the NIH-AARP Diet and Health Study were followed for 7.2 years. The intake of individual sugars was assessed using a 124-item food frequency questionnaire (FFQ)......... We identified 29,099 cancer cases in men and 13,355 cases in women. In gender-combined analyses, added sugars were positively associated with risk of esophageal adenocarcinoma ; added fructose was associated with risk of small intestine cancer ; and all investigated sugars were associated with increased risk of pleural cancer. In women, all investigated sugars were inversely associated with ovarian cancer. We found no association between dietary sugars and risk of colorectal or any other major cancer.
Measurement error in FFQ-reported dietary sugars may have limited our ability to obtain more conclusive findings. Statistically significant associations observed for the rare cancers are of interest and warrant further investigation.

Long-term clinical and immunological effects of p53-SLP® vaccine in ovarian cancer patients

Abstract

Vaccine-induced p53-specific immune responses were previously reported to be associated with improved response to secondary chemotherapy in small cell lung cancer patients. We investigated longterm clinical and immunological effects of the p53-SLP® vaccine in recurrent ovarian cancer patients. Twenty patients were immunized with the p53-SLP® vaccine between July 2006 and August 2007.
Follow-up information on patients was obtained. Clinical responses to secondary chemotherapy after p53-SLP® immunizations was determined by computerized tomography and/or tumour marker levels (CA125). Disease-specific survival was compared with a matched historical control group. Immune responses were analysed by flow cytometry, proliferation assay, IFN-γ ELISPOT and/or cytokine bead array. Lymphocytes cultered from skin biopsy were analysed by flow cytometry and proliferation assay.
Of twenty patients treated with the p53-SLP® vaccine, seventeen were subsequently treated with chemotherapy. Eight of these volunteered another blood sample. No differences in clinical response rates to secondary chemotherapy or disease-specific survival were observed between immunized patients and historical controls (p=0.925, resp. p=0.601). P53-specific proliferative responses were observed in 5/8 patients and IFN-γ production in 2/7 patients. Lymphocytes cultured from a prior injection site showing inflammation during chemotherapy did not recognise p53-SLP®. Thus treatment with the p53- SLP® vaccine does not affect responses to secondary chemotherapy or survival, although p53-specific T-cells do survive chemotherapy.

Phase II Clinical Study of the Combination Chemotherapy Regimen of Irinotecan Plus Oral Etoposide for the Treatment of Recurrent Ovarian Cancer

OBJECTIVE: To evaluate the efficacy and safety of the combination chemotherapy regimen of irinotecan plus oral etoposide for the treatment of patients with recurrent ovarian cancer after previous treatment with platinum and taxane agents.
PATIENTS AND METHODS: A total of 42 patients with recurrent ovarian cancer who had an evaluable lesion and provided informed consent for participation in the present study were analyzed. Irinotecan was administered intravenously at a dose of 60 mg/m on days 1 and 15. Etoposide was administered orally at a daily dose of 50 mg/body weight from days 1 to 21. A 28-day period comprised one cycle. The tumor response, adverse events, progression-free survival, and overall survival were examined. Tumor response was evaluated based on the Response Evaluation Criteria in Solid Tumors and the serum CA125 levels (Gynecologic Cancer Intergroup criteria). Adverse events were assessed according to the NCI-CTCAE (version 3.0).
RESULTS: Partial response was observed in 21 patients, stable disease in 14 patients, and progressive disease in 7 patients. The response rate was 50.0%, and the clinical benefit (partial response + stable disease) rate was 83.3%. Hematological toxicities of at least grade 3 severity included leukopenia in 21 patients (50.0%), neutropenia in 22 patients (52.4%), thrombocytopenia in 1 patient (2.4%), anemia in 9 patients (21.4%), and febrile neutropenia in 3 patients (7.1%). Nonhematological toxicities of at least grade 3 severity included queasy feeling in 5 patients (11.9%), vomiting in 3 patients (7.1%), and diarrhea in 2 patients (4.8%). Acute myeloid leukemia occurred in one patient (2.4%).
CONCLUSIONS: It is suggested that combination chemotherapy with irinotecan plus oral etoposide offers significant clinical benefit to patients with recurrent ovarian cancer previously treated with platinum and taxane agents.

Diagnostic performance of urgent referrals for suspected gynaecological malignancies.

PURPOSE: The objective of this study was to investigate the outcome of the urgent referrals with suspected gynaecological malignancy.
CONCLUSION: The overall predictive value of two-week wait referrals for suspected gynaecological malignancies is low. Refinement of the current referral guidelines is required with particular emphasis in the premenopausal women where the diagnostic performance of the urgent referrals is significantly poorer.

Studying Therapy Response and Resistance in Mouse Models for BRCA1-Deficient Breast Cancer

Gynecological Cancers. [Methods Mol Biol. 2011]

Abstract

The clinical problems raised in patients presenting with all forms of gynecological malignancy are currently addressed using conventional cross-sectional imaging, usually MRI. In general, F-18 FDG PET-CT has not been shown to have a clinical role in any of these cancers at presentation, although studies are under way to use this form of metabolic imaging to predict prognosis and the response to treatment. Although F-18 FDG PET-CT is superior to conventional imaging techniques, it is only moderately sensitive in demonstrating lymph node metastasis preoperatively, and is inadequate for local staging of patients with endometrial cancer. In ovarian cancer, F-18 FDG PET-CT provides an accurate assessment of the extent of disease, particularly in areas difficult to assess for metastases by CT and MRI such as the abdomen and pelvis, mediastinum, and supraclavicular region. F-18 FDG PET-CT is a sensitive method of detecting pelvic and para-aortic lymph nodal disease in cervical cancer, and appears to be superior to MRI and CT despite the limitations in identifying small foci of disease. In the main, as elsewhere in patients with cancer, the value of PET-CT is in identifying and defining the extent of recurrent disease, in distinguishing between posttreatment fibrosis and recurrence, and possibly in monitoring response to therapy.

Non-Curable Tumours of the Female Genital Tract: Therapeutic Options in Bowel Stenosis and Bleeding

BACKGROUND: ......  Ovarian cancer is in particular associated with peritoneal carcinomatosis or local tumour progression entailing different intestinal complications.
.

most recent top 5 popular blog views (just curious?)

Inequity in access to cancer care: a review of the... Jan 18, 2011 OXiGENE Inc. (OXGN) Enters into Collaborative Agre... Feb 14, 2011 abstract: Phase II study evaluating consolidation ... Feb 5, 2011 A Fighting Spirit Won’t Save Your Life - NYTimes.c... Jan 30, 2011 Cancer Epigenetics - 2010 - CA (includes discussio... Jan 17, 2011

full free access: Quality in Cancer Diagnosis (table 1 gyn)

Table 1. Diagnostic Steps for Gynecologic and Nongynecologic Specimens

Ovarian Cancer Surgery, Why Should A Woman Have A Gynecologic Oncologist...

full free access: Lessons From the Adjuvant Bevacizumab Trial on Colon Cancer: What Next?

"........Finally, how should we consider the use of antiangiogenic therapy in general in the adjuvant setting? Will VEGF blockade ever suffice when administered as single antiangiogenic agent in combination with chemotherapy, or will we need to combine bevacizumab with other antiangiogenic agents? Although an easy solution at this stage would be to lose interest in the therapeutic potential of antiangiogenic therapy in the adjuvant setting because of these initial disappointing results, the more challenging way forward will require a better understanding of the underlying mechanisms of why bevacizumab treatment differs so much in the adjuvant setting versus the macrometastatic setting. Only by achieving this goal will it be possible to make a more informed decision on this important matter"

abstract: Disease course patterns after discontinuation of bevacizumab (Avastin): pooled analysis of randomized phase III trials

also note: secondary link source including professional commentary

 http://plus.mcmaster.ca/EvidenceUpdates/NewArticles.aspx?Page=1&ArticleID=38192#ArticleComments

Abstract:

Purpose:     Preclinical studies have suggested accelerated tumor growth, local invasion, and distant metastasis after withdrawal of treatment with some antiangiogenic agents. To investigate whether discontinuation of bevacizumab treatment is associated with accelerated disease progression or increased mortality, we retrospectively analyzed five randomized, placebo-controlled phase III studies in 4,205 patients with breast, colorectal, renal, and pancreatic cancer.

Conclusion This retrospective analysis of five placebo-controlled clinical trials does not support a decreased time to disease progression, increased mortality, or altered disease progression pattern after cessation of bevacizumab therapy.

Footnotes

• Supported in part by F. Hoffmann-La Roche, Basel, Switzerland.
• Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.
• Clinical trial information can be found for the following: NCT00738530.

CRD Summary/Commentary: Increased ovarian cancer risk associated with menopausal estrogen therapy is reduced by adding a progestin

original link source: http://www.crd.york.ac.uk/CRDWeb/ShowRecord.asp?ID=12009104538

Reference: Cancer 2009; 115(3): 531-539

Source: DARE

 

Date published: 15/02/2011 14:53

Summary

by: Hazel Burnham
 

CRD Summary: The authors concluded that oestrogen therapy use increased ovarian cancer in a duration-dependent manner; adding progestins appeared to reduce this effect to some extent. The conclusions appeared to be supported by the evidence but the limited search, lack of reporting of review methods and study quality, and reliance upon predominantly observational studies mean that findings should be interpreted with caution.
CRD Commentary: The review question was stated and appropriate inclusion criteria were defined. Limiting the search to English language published studies identified in one database plus references and linked articles may have resulted in the omission of other relevant studies and raised the potential for publication and language bias. However, no evidence of publication bias was found. Methods used to select studies and extract data were not described, so it is not known whether efforts were made to reduce reviewer errors and bias. Study validity was not assessed, so results from these studies and any synthesis may not be reliable.
Other than duration of oestrogen-only therapy/oestrogen plus progestin therapy use, no information was provided about participants. No information was provided about which potential confounders were adjusted for in individual studies. Data were pooled using meta-analysis and heterogeneity was assessed. Studies were predominantly observational and adjustments were made for potential confounders. The authors’ conclusions appeared to be supported by the evidence, but the limited search, lack of reporting of review methods and study quality, and reliance upon predominantly observational studies mean that findings should be interpreted with caution.

About this library entry

Category: 6.4.1 Female sex hormones | Cancer: gynaecological | Menopause / hormone replacement therapy (HRT)

NeLM area: Evidence > Medication Safety

DARE abstract

Randomized Phase III Clinical Trial Evaluating Weekly Cisplatin for Advanced Epithelial Ovarian Cancer — J. Natl. Cancer Inst.

Thus, increasing dose intensity of cisplatin does not improve PFS or OS compared with standard chemotherapy.

full free access: How Research Influences Policy Makers: Still Hazy After All These Years — J. Natl. Cancer Inst. Steven Lewis (author)

"Libraries have been written about the theory and practice of public policy making. Yet, this enormous scholarship has proved insufficient to lift the veil of mystery and idiosyncrasy that shrouds the art of decision making. The heady ambition to turn both clinical practice and health policy into evidence-based bastions of rationalist decision making has been downgraded; the vocabulary is now “evidence-informed,” and the realm of admissible evidence has been greatly expanded to include preferences, political contingencies, and psychology (1). This newfound conceptual modesty and nuance does not suggest that we should abandon efforts to understand decision-making processes and to enhance the role of research-based evidence in policy. It merely confirms the complexity, contingency, and messiness of the terrain............This leads to a second issue: the definition of “use.” The questionnaires simply asked whether the respondents intended to use the brief. We do not know what “use” means.." cont'd

abstract: Indication for oophorectomy during cytoreduction for intraperitoneal metastatic spread of colorectal or appendiceal origin(cytoreductive surgery/HIPEC)

BACKGROUND: The incidence of ovarian metastases at the time of peritoneal carcinomatosis, and the influence of such metastases on survival after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), are unknown.
METHODS: This retrospective analysis included 194 women subjected to CRS and HIPEC since 2001. The incidence of ovarian metastases, disease-free survival and disease-specific survival were analysed.
RESULTS: The histological diagnosis was colorectal cancer carcinomatosis in 108 patients, peritoneal mucinous carcinomatosis (PMCA) in 23 and disseminated peritoneal adenomucinosis (DPAM) in 63. Ninety-nine patients underwent oophorectomy during the HIPEC procedure. Ovarian metastases were confirmed in at least 52 per cent of the patients. There was a significant difference in disease-free survival between women with or without ovarian metastases in both PMCA and DPAM groups (P = 0·044 and P = 0·010 respectively). No significant differences in survival were found in the group with colorectal cancer carcinomatosis.
CONCLUSION: When peritoneal carcinomatosis of colorectal or appendiceal origin is confirmed, at least 52 per cent of ovaries will have synchronous metastases. Disease-free survival after a HIPEC procedure for PMCA or DPAM is significantly lower in women with ovarian metastases. Oophorectomy during CRS for peritoneal carcinomatosis should be strongly considered.

(full free pdf file access) Endometriosis-Associated Ovarian Carcinomas — NEJM

abstract: Metastatic neoplasms of the ovaries: a clinicopathological study of 97 cases (metastatic breast, GI neoplasms....)

OBJECTIVE: To present the clinicopathological features of metastatic ovarian neoplasms with emphasis in the diagnostic challenge.
METHODS: This is a retrospective study including 97 patients with pathological diagnosis of metastatic ovarian neoplasms, examined during the decade 2000-2009. The gross, microscopical and immunohistochemical characteristics as well as the clinical data (age of the patients, origin of the neoplasm, symptoms, treatment options) and 5-year survival rates were examined.
RESULTS: The mean age of the patients is 55 years (range 26-78 years). 62.89% of the tumors were metastatic from extragenital organs (from stomach 21.65%, breast 15.46%, colon 15.46%, appendix 3.09%, pancreas 2.06%, lung 1.03% and kidney 1.03%, sarcoma 1.03% melanoma 1.03%) and 37.11% tumors originated from the genital tract. The 3-year survival rates ranged from 25.39% for metastatic ovarian neoplasms originating outside the genital tract up to 29.41% for those originating from the genital tract. Tumor immunohistochemistry is a helpful aid in the differential diagnosis mainly between primary mucinous ovarian tumors and metastatic colon cancers and in the recognition of metastatic breast cancers and other neoplasms of the GI tract.
CONCLUSION: The management of metastatic ovarian neoplasms should include specific immunohistochemical methods in order to identify the primary neoplasm site. The differential diagnosis of a pelvic mass should always include metastatic neoplasms of the ovaries.

abstract: The spread pattern of right and left epithelial ovarian cancers

OBJECTIVE: No attention has been paid in the past to the spread pattern of right and left epithelial carcinomas of the ovaries. We aimed to investigate the incidence, spread pattern and distribution of lymph node metastasis in epithelial ovarian cancer (EOC), comparing right versus left EOC of any stage, where the contralateral ovary is apparently and histologically tumor-free.

full access: Assessing the information desire of patients with advanced cancer by providing information with a decision aid, which is evaluated in a randomized trial: a study protocol

Discussion

This study attempts to settle the debate on the desirability of informing patients with cancer. In contrast to several earlier studies, we will actually deliver information on treatment options to patients at the point of decision making.
Trial registration: NTR1113

Bisphosphonates in Oncology. [Bone. 2011]

abstract: Clinical characteristics of borderline ovarian tumors and stage I epithelial ovarian cancer: an analysis of 143 cases

abstract: Tubal ligation and the risk of ovarian cancer: review and meta-analysis — Hum Reprod Update (serous/mucinous/endometrioid)

BACKGROUND The reduction of ovarian cancer (OC) risk in women with a history of tubal ligation (TL) has been reported repeatedly, mostly on small populations. We have aimed to provide a critical overview of the studies available to date and to conduct a meta-analysis.

METHODS There were 40 relevant studies identified. The studies were divided into two groups for strict and extended meta-analysis, respectively. Subgroup analysis was performed for age, time dependency since TL, histological types of OC and BReast CAncer (BRCA) mutation.

RESULTS Meta-analysis of 13 strictly selected studies showed a reduced risk of epithelial OC by 34%. The protective effect of TL was confirmed even in a subgroup of women 10–14 years after the procedure. The risk reduction was confirmed for the endometrioid (RR = 0.40) and serous (RR = 0.73) cancers but not for mucinous.

CONCLUSIONS The review of relevant articles, as well as the meta-analysis of selected studies, yields consistent data on a significant reduction of OC risk in women who had undergone TL. The results of this meta-analysis should provide an impulse for further research on the etiology of ovarian epithelial cancers, focusing particularly on the importance of retrograde transport of endometrial cells.

summary: Abagovomab: an anti-idiotypic CA-125 targeted immunotherapeutic agent for ovarian cancer phase 111 MIMOSA trial

Abagovomab: an anti-idiotypic CA-125 targeted immunotherapeutic agent for ovarian cancer

Rachel N Grisham​‌¹, Jonathan Berek​‌², Jacobus Pfisterer​‌³ & Paul Sabbatini​‌^†1

Ovarian cancer remains the leading cause of death due to gynecologic malignancies. Most patients present with advanced disease at the time of diagnosis. Although many have a good initial response to surgical debulking and platinum-based chemotherapy, relapse is common, with the eventual development of chemotherapy resistance. Innovative treatments are needed in the remission setting to prolong the disease-free interval or prevent recurrence. Abagovomab is a murine monoclonal anti-idiotypic antibody (molecular wieght: 165–175 kDa) that functionally imitates the tumor-associated antigen, CA-125. It has been shown to be well tolerated and to induce a sustained immune response in initial Phase I and II clinical trials. An ongoing, double-blind, placebo-controlled, multicenter, Phase III trial (MIMOSA) completed its double-blind period in December 2010 and will compare abagovomab maintenance therapy to placebo, which will definitively determine the efficacy of this immunotherapeutic approach in patients with ovarian cancer.

full free access: Effect of preventive messages tailored to family history on health behaviors: the Family Healthware Impact Trial. Ann Fam Med. 2011 (includes ovarian cancer)

PURPOSE: We wanted to determine the impact of automated family history assessment and tailored messages for coronary heart disease, stroke, diabetes, colorectal, breast, and ovarian cancer on preventive behaviors compared with a standard preventive message. ....cont'd for full free access

OXiGENE Inc. (OXGN) Enters into Collaborative Agreement with NCI for Cancer Drug - Intl Business Times (Zybrestat/Avastin))

OXiGENE Inc., a clinical-stage biopharmaceutical company focused on developing novel therapeutics to treat cancer and eye diseases, has entered into a cooperative research and development agreement with the National Cancer Institute’s (NCI) Cancer Therapy Evaluation Program (CTEP) to collaborate on the conduct of a randomized phase 2 trial of OXiGENE’s ZYBRESTAT in combination with bevacizumab in patients with relapsed ovarian cancer.....cton'd

Questioning Need for Routine Pelvic Exam - WSJ.com

full free text: The safety implications of missed test results for hospitalised patients: a systematic review -- BMJ Quality and Safety (references World Alliance for Patient Safety)

Introduction

The World Alliance for Patient Safety recently identified poor test follow-up as one of the major processes contributing to unsafe patient care.1 Failure to follow up test results increases the risk of missed or delayed diagnoses. This may produce suboptimal clinical outcomes2–8 with potential medicolegal implications.9–12......

.........All seven studies explored the impact on patient outcomes31–33 35–38 which included no negative effects,31 a delayed diagnosis from a missed x-ray report,37 one case of missed positive Chlamydia where the patient subsequently developed pelvic inflammatory disease,36 inappropriate or unnecessary antibiotics prescribed,35 missed cancer diagnoses33 and death.38.....cont'd

What Is A Patient? A Doctor’s Perspective - Better Health

full free access: Effect of tamoxifen and radiotherapy in women with locally excised ductal carcinoma in situ: long-term results from the UK/ANZ DCIS trial

Effect of Occult Metastases on Survival in Node-Negative Breast Cancer — NEJM

Conclusions

Occult metastases were an independent prognostic variable in patients with sentinel nodes that were negative on initial examination; however, the magnitude of the difference in outcome at 5 years was small (1.2 percentage points). These data do not indicate a clinical benefit of additional evaluation, including immunohistochemical analysis, of initially negative sentinel nodes in patients with breast cancer. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00003830.)

European Journal of Human Genetics - Abstract of article: On the origin and diffusion of BRCA1 c.5266dupC (5382insC) in European populations

"The BRCA1 mutation c.5266dupC was originally described as a founder mutation in the Ashkenazi Jewish (AJ) population. However, this mutation is also present at appreciable frequency in several European countries, which raises intriguing questions about the origins of the mutation. We genotyped 245 carrier families from 14 different population groups (Russian, Latvian, Ukrainian, Czech, Slovak, Polish, Danish, Dutch, French, German, Italian, Greek, Brazilian and AJ) for seven microsatellite markers and confirmed that all mutation carriers share a common haplotype from a single founder individual.............Our results illustrate that (1) BRCA1 c.5266dupC originated from a single common ancestor and was a common European mutation long before becoming an AJ founder mutation and (2) the mutation is likely present in many additional European countries where genetic screening of BRCA1 may not yet be common practice."

The rise of the genome bloggers : Nature News (not amateurs)

“They are not amateurs. They are far from being amateurs.”

full free access: Genomics and the Continuum of Cancer Care — NEJM (long article covering differing concerns)

abstract only: Update in Hormone Therapy Use in Menopause -- Journal of Clinical Endocrinology & Metabolism

abstract: HE4 and CA125 as a diagnostic test in ovarian cancer: prospective validation of the Risk of Ovarian Malignancy Algorithm

Conclusion:
This independent validation study demonstrated similar performance indices to those recently published. However, in this study, HE4 and ROMA did not increase the detection of malignant disease compared with CA125 alone. Although the initial reports were promising, measurement of HE4 serum levels does not contribute to the diagnosis of ovarian cancer

abstract: High prevalence of symptoms associated with ovarian cancer among Australian women

Background:  Symptoms associated with ovarian cancer are often vague and non-specific, such as abdominal bloating and pain. Presently, nothing is known about the prevalence of these symptoms among women in the community.
Aims:  To identify the prevalence and correlates of symptoms associated with ovarian cancer in a nationally representative sample of Australian women. Methods:  Women answered questions about symptoms associated with ovarian cancer via computer-assisted telephone interviews. Binomial regression was used to assess the association between reporting symptoms, demographic characteristics and sexual problems.
Results:  Data on 2235 women aged 18-70 who had not had an oophorectomy or hysterectomy were analysed. Prevalences of symptoms were abdominal bloating 52%, abdominal pain 37%, increased abdominal size 30%, pelvic pain 29%, feeling full quickly 18% and unable to eat normally 15%. One-third of women (32%) reported three or more symptoms, 2% reported all six and 32% of women reported none. Severe symptoms were generally reported by <10% of women reporting symptoms, and symptoms usually persisted for 5 days or less a month. Older women were less likely to report symptoms, as were women who had been pregnant. There was an association between symptoms and sexual difficulties whereby women who reported multiple ovarian cancer symptoms were more likely to report sexual problems.
Conclusions:  There is a high prevalence of ovarian cancer symptoms in the Australian community. Because of this, awareness campaigns will likely impact a large number of women who do not have ovarian cancer.

(no abstract) Peritoneal fibrosis leading to small bowel obstruction two years after first-line intraperitoneal chemotherapy for optimally debulked ovarian cancer Australian

DOI: 10.1111/j.1479-828X.2010.01230.x

Issue

Australian and New Zealand Journal of Obstetrics and Gynaecology

Volume 51, Issue 1, pages 91–92, February 2011

abstract: Changes in pre-diagnostic serum C-reactive protein concentrations and ovarian cancer risk: a longitudinal study

Define: C-reactive protein (CRP) is a protein found in the blood, the levels of which rise in response to inflammation (an acute-phase protein). ...
en.wikipedia.org/wiki/C-reactive_protein
Abstract

BACKGROUND: Evidence suggests that inflammation may be associated with increased risk of ovarian cancer but there is paucity of studies investigating this association, especially using over-time changes in inflammatory biomarkers.

MATERIALS AND METHODS: We conducted a prospective population-based case-control study nested within the Finnish Maternity Cohort (FMC). Within the FMC, 170 women with ovarian cancer who had donated serum samples to the cohort twice, ≥1 year apart, before cancer diagnoses were identified. One control per case was matched for age, parity and sampling date.

RESULTS: Comparing the highest with lowest tertiles, the odds ratio (OR) of ovarian cancer using the first set of serum samples (mean lag time to cancer diagnosis 9.0 years) was 1.62 [95% confidence interval (CI) 0.93-2.83]. However, analysis conducted using the second set of serum samples donated closer to cancer diagnosis (mean lag time 6.4 years) revealed a significantly increased risk of ovarian cancer comparing extreme tertiles of C-reactive protein (CRP) concentrations; OR 1.96 (95% CI 1.11-3.4). Over time, increases in individuals' CRP concentrations were also associated with increased risk; OR 1.90 (95% CI 1.12-3.23).

CONCLUSION: The results suggest that inflammation may precede ovarian cancer since increasing CRP concentrations, both across tertiles and longitudinally at the individual level, were associated with increased risk.

Table of Contents — January 2011, 22 (suppl 1) — Hereditary Breast and Ovarian Cancer: Risks and Challenges 10–12 September 2009: Bari, Italy

Note: numerous papers, full free access

abstract: Centralized treatment of advanced stages of ovarian cancer improves survival: a nationwide Danish survey

"...Treatment in a referral center was an independent prognostic factor for overall survival hazard ratio, 0.83 (confidence interval 0.70-0.98).  
Conclusion. Patients with stage IIIC and IV ovarian cancer benefit from treatment in a tertiary referral center."

abstract: Centralized treatment of advanced stages of ovarian cancer improves survival: a nationwide Danish survey

abstract: Trends in incidence of borderline ovarian tumors in Denmark 1978-2006

Note: other research is of the same opinions (see prior blog posts) that incident rates of ovarian cancer are in fact not reducing (eg. population...)


Conclusions. The incidence rate of borderline ovarian tumors increased significantly in Denmark in 1978-2006. In line with results from ovarian cancer, Denmark had a higher incidence rate of borderline ovarian tumors compared with the other Nordic countries in 1978-2006.

abstract: A systematic review of gynecological cancer surveillance in women belonging to Hereditary Nonpolyposis Colorectal Cancer (Lynch syndrome) fa

Conclusions.
Currently available published studies on gynecological cancer surveillance in women with HNPCC do not adequately allow for evidence-based clinical decisions. Detection of endometrial cancer or hyperplasia in nonsymptomatic women belonging to a HNPCC family is improved by adding routine endometrial sampling along with transvaginal ultrasound for surveillance visits. No benefit was shown for ovarian cancer surveillance.

abstract: A patient presenting nasal septum perforation during bevacizumab-containing chemotherapy for advanced breast cancer (and colorectal/ovarian) see Blogger's note

Blogger's note:  

nasal perforations (while rare) has been widely reported in patient social networks and vastly under-reported by institutions, as evidenced by the incidence rates per this abstract; this is not a new issue/concern

Abstract: 

Nasal septum perforation is a rare but described complication of the anti-angiogenetic agent bevacizumab. ........ The patient denied use of cocaine or other intranasal irritants. ........ Thus far 8 other cases of bevacizumab-related nasal septum perforation have been published: 5 patients with colorectal cancer, 2 patients with breast cancer and 1 with ovarian cancer.....cont'd

abstract: Recreational physical activity and ovarian cancer

CONCLUSIONS: Our data provide weak evidence in support of beneficial effects of physical activity on ovarian cancer risk and survival, but results should be interpreted cautiously because of the lack of a clear dose response relation with higher levels of exercise and the likely misclassification of self-reported activity.

abstract: Morbidity of diaphragmatic surgery for advanced ovariannext term cancer: Retrospective study of 148 cases

Conclusions

Diaphragmatic surgery achieved complete removal of the tumour but resulted in pulmonary complications in addition to complications of radical surgery.

full free access: Histotype predicts the curative potential of radiotherapy: the example of ovarian cancers — Ann Oncol (stage/cell type)

Note: tables for survival data (longterm) eg. cell types

"....The Gynecology Tumour Group of our institution has elected to continue to advise the use of CRT in women with stage Ic and II endometrioid and mucinous lesions, and all stage I and II clear cell disease, on the basis of these data and a recently published analysis of histotype-specific outcomes [32]. However, RT will be targeted to the pelvis, with consideration of extending the field to include paraaortic nodes if stage IIc (given the higher rate of occult nodal involvement reported for this stage [26]). RT will be dropped from our prescription for those with serous tumors.

Our findings also bring into question the nonselective surgical and CT approaches that have characterized ovarian cancer care and are of potential clinical importance for those with other tumors, which have been collectively defined by presumed organ of origin rather than underlying biological features"

full free access abstract + full paper: Social and ethical implications of BRCA testing — Ann Oncol

Abstract:
"Oncologists are asked with increasing frequency to counsel their patients with respect to the medical, psychological and social repercussions of genetic testing for cancer susceptibility that may have been prescribed by physicians or carried out through direct-to-consumer tests. This article critically reviews the main ethical and social implications of BRCA testing, focusing on genetic responsibility and genetic discrimination. Genetic responsibility toward oneself and others is a highly debated implication of genetic testing for cancer predisposition that requires broad considerations of the boundaries between individual and community rights and a reappraisal of the notion of autonomy as relational. Physicians’ duty to warn ‘at risk’ relatives can be an ethical quandary, yet confidentiality is key to the patient–doctor relationship. Mutation carriers may be subject to different forms and degrees of genetic discrimination and many individuals at risk have forgone BRCA testing to avoid potential discrimination. The scientific and medical community, together with patients and the public, has actively engaged against genetic discrimination. The legislation in many countries now protects against genetic discrimination by insurance companies and employers. Legal and regulatory issues are not the final answer to discrimination and profound cultural changes are required to create understanding and acceptance of all differences...."

media - Light sentence would spare sex doc’s victims (unconcious female patients)

videotaped a naked and unconscious patient after removing her hospital gown

abstract: Analysis of postoperative complications associated with the use of anti-adhesion sodium hyaluronate-carboxymethylcellulose (HA-CMC) barrier after cytoreductive surgery for ovarian, fallopian tube and peritoneal cancers

Conclusions

HA-CMC adhesion barrier placement at the time of optimal cytoreductive surgery for ovarian, fallopian tube, and peritoneal cancer is not associated with major postoperative complications but may be associated with increased risk of pelvic abscess

abstract: A new index of priority symptoms in advanced ovarian cancer

Note: advanced ovarian cancer study

Ovarian cancer patient surveillance after curative-intent initial treatment

Nearly 25% of Women With Early Ovarian Cancer Not Given Recommended Biopsies - US News and World Report

"The Lab - Avoiding Research Misconduct: (video) Office of Research Integrity: The Lab. An Interactive Video on Avoiding Misconduct

"To participate in this interactive experience, go to:

http://ori.hhs.gov/TheLab

This interactive film is an extremely rich and substantively educational resource for teaching/learning research integrity and ethics. It deals with the issue of research misconduct. Filmed in a university research environment, it makes excellent use of the best knowledge and science regarding ethical decision-making and the responsible conduct of research. The video simulation allows users to assume the role of a graduate student, post-doc, research administrator, or PI and make decisions that affect the integrity of research."

Medscape: 'Unrealistic Optimism' Plagues Early-Phase Oncology Trials

Patients' Association of Canada

Patient Led, Patient Governed Promoting and enhancing the patient voice in health care

NCI Cancer Bulletin: Coming Home to Roost: The Self-Seeding Hypothesis of Tumor Growth

The ROMA (Risk of Ovarian Malignancy Algorithm) for estimating the risk of epithelial ovarian cancer in women presenting with pelvic mass: is it really useful? (HE4/CA125/pre-post menopausal)

Conclusions: The ROMA is a simple scoring system which shows excellent diagnostic performance for the detection of EOC in post-menopausal women, but not in pre-menopausal women. Moreover, the dual marker combination of HE4 and CA125 (ROMA) does not show better performance than HE4 alone.

European cancer mortality predictions for the year 2011 — Ann Oncol

Note: see Tables for differing countries within EU

Global cancer statistics - 2011 - A Cancer Journal for Clinicians - Wiley Online Library

CORRECT(2/4): Roche CEO Defends Avastin Cancer Drug, Despite Scrutiny - WSJ.com

Less is Better in Early Stage Breast Cancer Care - ABC News

full free access: Journal of Oncology — Review Article: Potential Markers for Detection & Monitoring of Ovarian Cancer Feb 8, 2011

  Note:  pdf file


Conclusions and Emerging Trends in Biomarkers for Ovarian Cancer

"The ultimate aim of effective screening techniques is to bring about a reduction in mortality form ovarian cancer. As early detection continues to be vital in ovarian cancer patients, biomarkers may hold the key to unlocking effective screening strategies for the general population. It is also important to identify screening techniques with low false positive rates and high positive predictive value so that the number of negative surgical interventions can be minimized. Since our currently available single markers are not highly sensitive or specific, a combination of markers may be utilized as a profile for risk assessment. The current problem with screening panels is that the improvement in sensitivity usually correlates with a decrease in specificity, making the target positive predictive value hard to obtain. The multimodal screening profiles of the genetic markers could be utilized in the future for risk assessment, early diagnosis, prognosis and response to therapeutic treatment. Recent literature reports state that the screening is only recommended for the high risk population identified as those with a family history of the disease, women with BRCA1 and BRCA2 mutations, or with hereditary non polyposis colorectal cancer. Recent literature reports also emphasize that the different subtypes of ovarian cancer may have different genetic biomarker expression profiles. Current randomized controlled screening trials are directed towards finding the best molecular and genetic markers for the specific histology of the ovarian tumor with the most impact on reduction in morbidity and mortality. The tumor markers identified in these trials may also lead to novel targets for antitumor therapy."

full free access: Review Article: Cancer Stem Cells and Epithelial Ovarian Cancer

"This paper highlights the current experimental approaches that have been used in the field and discusses their limitations, with specific emphasis on the identification and characterisation of the CSC population in epithelial ovarian cancer."

UPDATE 2-Avastin helps ovarian cancer patients live longer | Reuters

Abstract: Peutz-Jeghers syndrome: a study of long-term surgical morbidity and causes of mortality

"Patients with Peutz-Jeghers syndrome (PJS) require lifelong multidisciplinary care for gastrointestinal polyposis and increased risk of cancer.

...The cause of death was unknown in 4 patients, but was due exclusively to malignancies in all other patients, most commonly due to metastatic gynecologic cancer (5)...."

abstract - BRCA1 mutations and colorectal cancer in Poland

"This study suggests that BRCA1 mutations may be associated with early-onset of colorectal cancer."

abstract: Treatment-Related Mortality With (Avastin) Bevacizumab in Cancer Patients JAMA (alone vs combo)

Data Synthesis "A total of 10 217 patients with a variety of advanced solid tumors from 16 RCTs were included in the analysis...."

January 5, 2011 Gynecologic Oncology Group Survival - White Paper

January 5, 2011 Gynecologic Oncology Group Survival In 2010


cancerletter.com/downloads/20110203/download

"In 2010, the Institute of Medicine (IOM) produced a report recommending wide-ranging changes in the Cooperative Group program and, in response the National Cancer Institute (NCI) has proposed a reorganization of the nation’s cancer Clinical Trials program that would significantly change the program’s current structure....."

Abstract/full free access: An evaluation of access to health care services along the rural-urban continuum in Canada

Conclusion

Inequities in access to care along the rural-urban continuum exist and can be masked when evaluation is done at a very large scale with gross indicators of rural-urban. Understanding the relationship between rural-urban and other determinants will help policy makers to target interventions appropriately: to specific demographic, provincial, community, or rural categories.

Why a journal (Emergency Medicine Australasia) decided to stop taking pharma ads - Gary Schwitzer's HealthNewsReview Blog

By Gary Schwitzer on February 4, 2011 2:26 PM

The journal, Emergency Medicine Australasia, announced it will no longer accept advertising from drug companies.
The full editorial making the announcement is available online.

Australia: eMJA: Editorial - Managing patients with advanced cancer: the benefits of early referral for palliative care

If early referral for specialist palliative care were an expensive new drug, it would quite appropriately be marketed as a major advance in improving the care of patients with incurable cancer.

Happiness: Do we have a choice? » Scienceline

full free access: Gynaecological malignancies from palliative care perspective Mishra K Indian J Palliat Care (focus on symptoms/complications)

Hormone Therapy At Menopause May Pose Breast Cancer Risk — J. Natl. Cancer Inst.

abstract: Surgical-site infections and postoperative complications: agreement between the Danish Gynecological Cancer Database and a randomized clinical trial (patient safety)

Conclusions. The randomized trial reported significantly more surgical-site infections than the clinical database. The DGCD reported only 50% of the deep and organ-space infections, and hence, the low-overall agreement indicates a need for more careful database registration.

abstract: Phase II study evaluating consolidation whole abdominal intensity-modulated radiotherapy (IMRT) in patients with advanced ovarian cancer stage FIGO III - The OVAR-IMRT-02 Study

BACKGROUND:
".... Recurrences of the disease occur mostly intraperitoneally. Ovarian cancer is a radiosensitive tumor, so that the use of whole abdominal radiotherapy (WAR) as a consolidation therapy would appear to be a logical strategy. WAR used to be the standard treatment after surgery before the chemotherapy era; however, it has been almost totally excluded from the treatment of ovarian cancer during the past decade because of its high toxicity. Modern intensity-modulated radiation therapy (IMRT) has the potential of sparing organs at risk like kidneys, liver, and bone marrow while still adequately covering the peritoneal cavity with a homogenous dose. Our previous phase I study showed for the first time the clinical feasibility of intensity-modulated WAR and pointed out promising results concerning treatment tolerance. The current phase-II study succeeds to the phase-I study to further evaluate the toxicity of this new treatment. Methods / design: The OVAR-IMRT-02 study is a single-center one arm phase-II trial. Thirty seven patients with optimally debulked ovarian cancer stage FIGO III having a complete remission after chemotherapy will be treated with intensity-modulated WAR as a consolidation therapy. A total dose of 30 Gy in 20 fractions of 1.5 Gy will be applied to the entire peritoneal cavity including the liver surface and the pelvic and para-aortic node regions. Organ at risk are kidneys, liver (except the 1cm-outer border), heart, vertebral bodies and pelvic bones. Primary endpoint is tolerability; secondary objectives are toxicity, quality of life, progression-free and overall survival.

DISCUSSION: Intensity-modulated WAR provides a new promising option in the consolidation treatment of ovarian carcinoma in patients with a complete pathologic remission after adjuvant chemotherapy. Further consequent studies will be needed to enable firm conclusions regarding the value of consolidation radiotherapy within the multimodal treatment of advanced ovarian cancer. Trial registration: NCT01180504.

abstract: Phase II trial of combretastatin A4 phosphate, carboplatin, and paclitaxel in patients with platinum-resistant ovarian cancer

Note: searching blog for A4 will provide further research specific to  clear cell/A4


CONCLUSIONS: The addition of CA4P to paclitaxel and carboplatin is well tolerated and appears to produce a higher response rate in this patient population than if the chemotherapy was given without CA4P. A planned randomised trial will test this hypothesis.

abstract: Indication for oophorectomy during cytoreduction for intraperitoneal metastatic spread of colorectal or appendiceal origin

BACKGROUND: The incidence of ovarian metastases at the time of peritoneal carcinomatosis, and the influence of such metastases on survival after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), are unknown.
CONCLUSION: When peritoneal carcinomatosis of colorectal or appendiceal origin is confirmed, at least 52 per cent of ovaries will have synchronous metastases. Disease-free survival after a HIPEC procedure for PMCA or DPAM is significantly lower in women with ovarian metastases. Oophorectomy during CRS for peritoneal carcinomatosis should be strongly considered.

abstract: Whole abdominopelvic radiotherapy using intensity-modulated arc therapy in the palliative treatment of chemotherapy-resistant ovarian cancer with bulky peritoneal disease

CONCLUSION: WAPRT delivered using intensity-modulated arc therapy offers important palliation in the case of peritoneal metastatic ovarian cancer. WAPRT resolved intestinal obstruction for a substantial period.

abstract: Role of adjuvant radiotherapy in granulosa cell tumors of the ovary

PURPOSE: To review the role of adjuvant radiotherapy (RT) in the outcome and recurrence patterns of granulosa cell tumors (GCTs) of the ovary.

CONCLUSION: Ovarian GCTs can be indolent, with patients achieving long-term survival. In our series, adjuvant RT resulted in a significantly longer DFS. Ideally, randomized trials with long-term follow-up are needed to define the role of adjuvant RT for ovarian GCTs.

abstract: The perils of a vanishing cohort: a study of social comparisons by women with advanced ovarian cancer

Note: plain english language version??

Programs - INCTR – International Network for Cancer Treatment and Research

(no abstract) How Surgeon Age Affects Surveillance After Curative-Intent Primary Treatment for Ovarian Carcinoma

How Surgeon Age Affects Surveillance After Curative-Intent Primary Treatment for Ovarian Carcinoma

A.Y. Patel1, F. Gao2, D.G. Mutch2, R.K. Gibb2, K.S. Virgo3, F.E. Johnson1

18.2

No abstract is available. To read the body of this article, please view the Full Text online.

1 Saint Louis University, Saint Louis, MO

2 Washington University, Saint Louis, MO

3 American Cancer Society, Atlanta, GA

PII: S0022-4804(10)01509-X

doi:10.1016/j.jss.2010.11.585

Scientists peer into the future of stem cell biology (microRNAs)

Biological diversity of ovarian cancer lessens value of screening

abstract: Laparoscopic Excision of Ovarian Remnants: Retrospective Cohort Study with Long-term Follow-up

media: Letter to the Editor (Darlene Gray/OCATS) Refreshing leadership

Promoting genetic literacy: cancer control in the BRCA era - Cutting Edge - Cancer World (including Lynch Syndrome/spectrum of cancers)

Note: worth reading; covers a variety of concerns
 
IN BRIEF

• Accounting for around 5%–10% of all breast cancers, harmful mutations in BRCA1 or BRCA2 increase a woman’s chance of developing breast cancer over their lifetime by approximately five times compared to the normal population.
• Carriers of the harmful BRCA1/2 mutations are also approximately 10–30 times more likely to develop ovarian cancer, with these mutations accounting for around 10% of all ovarian cancers.
• There is no single BRCA mutation, but a wide variety of mutations on these two genes, many of which have yet to be recorded. Only some have been demonstrated to be harmful.
• BRCA mutations can also raise the risk of other cancers, including gastric, pancreatic, colon and prostate cancer, as well as melanoma and male breast cancer.
• Other ‘cancer genes’ include mutated APC genes, responsible for familial adenomatous polyposis, which lead to colon cancer, and mutated MLH1, MSH2 MSH6, or PMS2 genes, which are associated with hereditary non-polyposis colon cancer (HNPCC) (Lynch Syndrome), a syndrome that also raises the risk of endometrial (uterine), stomach, ovarian, small bowel (intestinal), urinary tract, liver, and bile duct cancers.

(2010) Slipstream - When Patients Meet Online, Are There Side Effects? - NYTimes.com (patient exploitation)

"...raises important questions about the trade-off between the benefits of information sharing and the risk of patient exploitation."

Seth's Blog: Pleasing

Ovariancancerandus Blog: top 5 most recently read articles

A Fighting Spirit Won’t Save Your Life - NYTimes.c...

abstract: Validation of a Self-Concept Scale for L...

Lancet (abstract) Retraction: validation of gene s...

Medical News: Implant Focus Shifts to Rarity of Im...

abstract: Is surgical restaging indicated in appar...

MSKCC (Memorial Sloan Kettering) Winter 2011 newsletter Molecular Medicine for Ovarian and Endometrial Cancer - Douglas A Levine

Note: includes reference to PARP inhibitors

Download Article - Update in Gynecologic Oncology, Winter 2011

Using Quality of Life Measures in Breast Cancer Clinical Trials — J. Natl. Cancer Inst. (and all cancers)

"Both the World Health Organization and the U.S. Food and Drug Administration have endorsed quality of life, but they are not always incorporated into trials because of the additional resources needed for data collection."

Cancer Awareness A Must For Women February is Ovarian Cancer month in Australia

abstract: Cancer survival among Latinos and the Hispanic Paradox.

CONCLUSIONS: No evidence of a Hispanic advantage was found in cancer survival. Improvement in mortality follow-up procedures for Latinos, especially for those without a valid social security number, is critical. By considering Hispanics as a whole rather than by subgroup, existing survival disparities are being missed.

abstract: Healthy eating index and ovarian cancer risk. [Cancer Causes Control. 2011] - PubMed result

The evidence for a role of diet on ovarian cancer prevention remains inconclusive.
While many studies have evaluated individual foods and food groups, the evaluation of a comprehensive dietary quality index for predicting cancer risk has received little attention.
This study investigates the association between the Healthy Eating Index (HEI), which reflects adherence to the current USDA Dietary Guidelines for Americans and ovarian cancer risk in a population-based case-control study in New Jersey. A total of 205 cases and 390 controls completed the Block 98.2 food frequency questionnaire (FFQ) in addition to reporting on potential risk factors for ovarian cancer. FFQ data were then utilized to calculate the HEI score, and cup, ounce, gram, or caloric equivalents for the 12 different food groups comprising the index. In multivariate models, the OR for the highest tertile of the HEI score compared with the lowest (reflecting a better diet compared with a worse diet) was 0.90 (95% CI: 0.55-1.47).
There was limited evidence for a statistically significant association between any of the 12 individual food components and ovarian cancer risk. Based on this study's results, neither individual food groups nor dietary quality showed potential for preventing ovarian cancer.

abstract: A non-BRCA1/2 hereditary breast cancer sub-group defined by aCGH profiling of genetically related patients (BRCAx)

Germline mutations in BRCA1 and BRCA2 explain approximately 25% of all familial breast cancers.

Despite intense efforts to find additional high-risk breast cancer genes (BRCAx) using linkage analysis, none have been reported thus far.

Here we explore the hypothesis that BRCAx breast tumors from genetically related patients share a somatic genetic etiology that might be revealed by array comparative genomic hybridization (aCGH) profiling.

As BRCA1 and BRCA2 tumors can be identified on the basis of specific genomic profiles, the same may be true for a subset of BRCAx families. Analyses used aCGH to compare 58 non-BRCA1/2 familial breast tumors (designated BRCAx) to sporadic (non-familiar) controls, BRCA1 and BRCA2 tumors. The selection criteria for BRCAx families included at least three cases of breast cancer diagnosed before the age of 60 in the family, and the absence of ovarian or male breast cancer.

Hierarchical cluster analysis was performed to determine sub-groups within the BRCAx tumor class and family heterogeneity. Analysis of aCGH profiles of BRCAx tumors indicated that they constitute a heterogeneous class, but are distinct from both sporadic and BRCA1/2 tumors. The BRCAx class could be divided into sub-groups. One subgroup was characterized by a gain of chromosome 22. Tumors from family members were classified within the same sub-group in agreement with the hypothesis that tumors from the same family would harbor a similar genetic background. This approach provides a method to target a sub-group of BRCAx families for further linkage analysis studies.

full free acPhase II Trial of Trastuzumab in Women with Advanced or Recurrent, HER2-Positive Endometrial Carcinoma: a Gynecologic Oncology Group Study

abstract: Clear cell carcinoma of the ovary: A report from the first Ovarian Clear Cell Symposium, June 24th, 2010 (plus blogger's commentary)

Blogger's Notes: with the exception of the 2 mutations mentioned, there is nothing new in this abstract;  social media can overcome past issues with patient accrual


OBJECTIVES: Recent literature has highlighted histological types of ovarian carcinoma as distinct diseases, each with unique clinical and molecular features. Historically, the diagnosis of ovarian clear cell carcinoma (CCC) has been of concern to both patients and physicians due to reports that CCC is associated with a worse prognosis than the more common serous type of ovarian carcinoma (HGSC). This review discusses the unique features of ovarian CCC.

METHODS: In June of 2010, a group of researchers and clinicians convened in Vancouver to review and discuss the clinical, pathological, molecular, and treatment-related features of CCC.

RESULTS: CCC is the second most common type of ovarian epithelial cancer, representing 5-25% of ovarian carcinomas. It is characterised by its association with endometriosis, and frequent mutations of ARID1A and PIK3CA. Low-stage CCC appears to have a better outcome than stage matched HGSC, while the opposite is true for high-stage disease, suggesting that the current standard treatments applied to HGSC (high grade serous) are ineffective for CCC.

CONCLUSIONS: Ovarian CCC is highly distinct from HGSC, and a clearer understanding of the basic biology of this disease is needed. Alternative therapies should be explored: irradiation and targeting disease-specific molecular markers should be examined in greater detail. Finally, novel approaches to clinical trial design are needed due to the smaller numbers of patients affected.

abstract: Surgical staging of early stage epithelial ovarian... [Gynecol Oncol. 2011] - PubMed result

Note: positive lymph node findings upgrade staging from early stage to advanced stage; full access is by subscription ($$$)


OBJECTIVES: The objectives of this study were to determine the adequacy of surgical staging performed on surgically treated epithelial ovarian cancer (EOC) patients with apparent early stage disease and to determine if receipt of surgical staging had an influence on survival.
METHODS: Detailed surgical staging information was collected from medical records for 721 patients diagnosed between 1998 and 2000 with EOC. Patients resided in California or New York and were identified through population-based cancer registries.
RESULTS:  Nearly 90% of patients had removal of the omentum and evaluation of bowel serosa and mesentery but only 72% had assessment of retroperitoneal lymph nodes and the majority of patients did not receive biopsies of other peritoneal locations. Only lymph node assessment (as well as node assessment combined with washings and omentectomy) had a statistically significant association with improved survival. The 5-year survival for women with node sampling was 84.2% versus 69.6% for those without this surgical procedure, and patients who did not have lymph node assessment had nearly twice the risk of death as those who did. When patients were stratified by receipt of chemotherapy, lack of node sampling had an effect only on patients who also had no chemotherapy (adjusted HR=2.2, CI=1.0-4.5).
CONCLUSIONS: The results of this population-based study confirm the prognostic importance of surgical staging for women with EOC, and the important role of gynecologic oncologists in treating these patients. Adjuvant chemotherapy does not appear to further improve survival for those women who receive adequate surgical staging.

sanibel island photo (testing android app)

Published with Blogger-droid v1.6.7

abstract: Ovarian serous surface papillary borderline tumors form sea anemone-like masses

PURPOSE: To clarify the imaging characteristics of ovarian serous surface papillary borderline tumor (SSPBT), whose prognosis is far better than that of serous surface papillary adenocarcinoma (SSPC).

in research: (miR-335) Running A Cancer Roadblock - Science News breast/ovarian

"The function of miR-335 in controlling whether escaped cancer cells can form a new tumor may also be important in ovarian cancer. Women with ovarian cancer who later had a relapse were more likely to be missing a copy of miR-335 in their original tumors than women who did not relapse, the team found."

in research: (miR-429) Discovery may lead to turning back the clock on ovarian cancer | Science Blog

Imedex: Great Debates & Updates in Gynecologic Malignancies April 9, 2011 New York, New York conference notice

New study alters long-held beliefs about shingles (herpes zoster virus)

in research: Generic drug (Losartan) may improve the effectiveness of cancer nanotherapies

"Low doses of an inexpensive, FDA-approved hypertension medication may improve the results of nanotherapeutic approaches to cancer treatment. In a report in the early edition of Proceedings of the National Academy of Sciences, Massachusetts General Hospital (MGH) investigators describe experiments showing that the generic drug losartan, by modifying the network of collagen fibers that characterizes most solid tumors, improved the effectiveness of two nanotherapeutics against several types of cancer....."

"....Experiments with two nanotherapeutics – liposomes containing the chemotherapy drug doxorubicin and a virus designed to infect and destroy cancer cells – showed that combining each treatment with losartan significantly reduced the size or delayed the growth of implanted tumors...."

Podcasts (numerous) - the Art of Oncology (ASCO)

ASCO Expert Corner: Young Adults With Cancer Q & A (+ most common types of cancers in YA)

Q: What are the most common types of cancer that are diagnosed in young adults?
A: Among young adults (defined here as those ages 15 to 39), the ten most common types of cancer, in order of frequency, are breast cancer, lymphoma (non-Hodgkin and Hodgkin), melanoma, sarcoma, gynecologic cancers of the ovary and cervix, thyroid cancer, testicular cancer, colorectal cancer, leukemia, and brain tumors. These types account for 90% of the cancers in this age group.

abstract: Anthropometric factors and ovarian cancer risk in the Malmö Diet and Cancer Study

define: anthropometry - The field that involves the measurement of the dimensions and other physical characteristics of people and the application of this information to the design of things they use.
www.fda.gov/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm095024.htm

"....Neither height, weight, BMI, body fat percentage, waist- or hip circumference were associated with overall risk, nor with risk for different subtypes, differentiation grade or stage.
Conclusions: These results demonstrate that a high WHR (waist hip ratio) is associated with a decreased risk of EOC. Other anthropometric factors were not associated with EOC risk."

abstract: Racial disparities in ovarian cancer surgical care: A population-based analysis

Conclusions Among women undergoing initial surgery for ovarian cancer, African-American patients are significantly less likely to be operated on by a high-volume surgeon and to undergo important ovarian cancer-specific surgical procedures compared to White patients.

case report: Simultaneous breast and ovarian metastasis from gallbladder carcinoma

CONCLUSION: This is an unusual case of carcinoma of the gallbladder with metastasis to the breast and ovary, which has not been documented before.

abstract: The PREMM(1,2,6) model predicts risk of MLH1, MSH2, and MSH6 germline mutations based on cancer history (Lynch Syndrome)

full free access: Effect of Direct-to-Consumer Genomewide Profiling to Assess Disease Risk — NEJM

CPSI (Canadian Patient Safety Institute) Bulletin

Improving Care Bulletin

This report is written about you – our partners, stakeholders, policy makers and advocates.
We want this document to speak to you and value any feedback you have as we work together to make a patient safety ripple in our healthcare system.
If you would like paper copies of this report please contact Jody White at jwhite@cpsi-icsp.ca.

• Improving Care Bulletin - January 2011
• Quarterly Update - December 2010
• Quarterly Update - August 2010
• Quarterly Update - January to April 2010

NIH summit to focus on management of radiation dose in computerized tomography, Tuesday, February 1, 2011 News Release - National Institutes of Health (NIH)

Cancer - Volume 117, Issue 3 - 1 February 2011 - Wiley Online Library (subscription required to view full text)

Note: this is the index of the most current volume with abstracts only without a subscription; numerous references to ovarian cancer

Commentary: Early versus delayed treatment of relapsed ovarian cancer : The Lancet (re: Rustin trial early vs delayed treatments/survival)

Polymorphism in the GALNT1 Gene and Epithelial Ovarian Cancer in Non-Hispanic White Women: The Ovarian Cancer Association Consortium

"In summary, the present analysis fails to replicate an earlier reported association of a GALNT1 variant with risk of ovarian cancer. This study highlights the need to replicate putative findings in genetic association studies."

Ovarian Metastases of Pancreaticobiliary Tract Adenocarcinomas: Analysis of 35 Cases, With Emphasis on the Ability of Metastases to Simulate Primary Ovarian Mucinous Tumors

New clinical trial to determine ovarian cancer risks in African-American women

Loss of protein could contribute to early breast and ovarian cancer deaths (protein MCPH1)

FDA review indicates possible association between breast implants and a rare cancer anaplastic large cell lymphoma (ALCL) - lymphoma

Advance Directive Language and Laws May Interfere With Patient Wishes - RWJF

The guidelines created to protect patients making end-of-life decisions may have the opposite effect. A Robert Wood Johnson Foundation Physician Faculty Scholar identifies problems and offers solutions

A Fighting Spirit Won’t Save Your Life - NYTimes.com (plus public comments)

plus public comments

Medical News: Implant Focus Shifts to Rarity of Implant-Related Cancer - in Product Alert, Devices and Vaccines from MedPage Today

Lancet (abstract) Retraction: validation of gene signatures that predict the response of breast cancer to neoadjuvant chemotherapy: a substudy of the EORTC 10994/BIG 00-01 clinical trial

Note: full details available to subscribers ($$$)

 Comment

Retraction—validation of gene signatures that predict the response of breast cancer to neoadjuvant chemotherapy: a substudy of the EORTC 10994/BIG 00-01 clinical trial

abstract: Is surgical restaging indicated in apparent stage IA pure ovarian dysgerminoma?

Objective

Conservative surgery followed by platinum-based chemotherapy is considered the standard approach for pure ovarian dysgerminoma (POD), except for correctly staged IA patients. The aim of study was to evaluate the outcome of IA POD patients with incomplete surgical staging in order to define the proper management.

abstract: Validation of a Self-Concept Scale for Lynch Syndrome in Different Nationalities (multinational study) Denmark, Sweden, Canada

J Genet Couns. 2011 Jan 26. [Epub ahead of print]

"Learning about hereditary cancer may influence an individual's self-concept, which otherwise represents a complex but stable cognitive structure. Recently, a 20-statement self-concept scale, with subscales related to stigma-vulnerability and bowel symptom-related anxiety, was developed for Lynch syndrome. We compared the performance of this scale in 591 mutation carriers from Denmark, Sweden and Canada. Principal component analysis identified two sets of linked statements-the first related to feeling different, isolated and labeled, and the second to concern and worry about bowel changes. The scale performed consistently in the three countries. Minor differences were identified, with guilt about passing on a defective gene and feelings of losing one's privacy being more pronounced among Canadians, whereas Danes more often expressed worries about cancer. Validation of the Lynch syndrome self-concept scale supports its basic structure, identifies dependence between the statements in the subscales and demonstrates its applicability in different Western populations."

CIHI report 2011: Multiple chronic conditions, not age, main driver of health system use by seniors - debunking the myth

abstract: Hormone replacement therapy and breast cancer

Hormone replacement therapy and breast cancer.

Howell A, Evans GD.

Genesis Prevention Centre, University Hospital of South Manchester, Manchester, M23 9LT, UK, anthony.howell@christie.nhs.uk.

Abstract

There is evidence that hormone replacement therapy (HRT) may both stimulate and inhibit breast cancers, giving rise to a spectrum of activities, which are frequently hard to understand. Here we summarise the evidence for these paradoxical effects and, given the current data, attempt to give an indication where it may or may not be appropriate to prescribe HRT.It is clear that administration of oestrogen-progestin (E-P) and oestrogen alone (E) HRT is sufficient to stimulate the growth of overt breast tumours in women since withdrawal of HRT results in reduction of proliferation of primary tumours and withdrawal responses in metastatic tumours. E-P, E including tibolone are associated with increased local and distant relapse when given after surgery for breast cancer. For women given HRT who do not have breast cancer the only large randomised trial (WHI) of E-P or E versus placebo has produced some expected and also paradoxical results. E-P increases breast cancer risk as previously shown in observational studies. Risk is increased, particularly in women known to be compliant. Conversely, E either has no effect or reduces breast cancer risk consistent with some but not all observational studies. Two observational studies report a decrease or at least no increase in risk when E-P or E are given after oophorectomy in young women with BRCA1/2 mutations. Early oophorectomy increases death rates from cardiovascular and other conditions and there is evidence that this may be reversed by the use of E post-oophorectomy. HRT may thus reduce the risk of breast cancer and other diseases (e.g., cardiovascular) in young women and increase or decrease them in older women.