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Sunday, May 24, 2015

Patients Included | A charter for conferences



A charter for conferences

 

ACOG Issues Guidelines for Hereditary Cancer Screening



ACOG Issues Guidelines 

 The guidelines, published in the June issue of Obstetrics & Gynecology, recommend that clinicians refer patients to a genetic specialist if the initial screening suggests there might be a familial risk.....

Markman on ASCO: Gyn Cancers: New Regimens, Predictive Biomarkers



medscape

 Hello. I'm Dr Maurie Markman from Cancer Treatment Centers of America in Philadelphia. I want to briefly discuss a number of highly provocative abstracts that are going to be presented in the gynecologic cancer arena at the 2015 American Society of Clinical Oncology (ASCO) meeting.....

Search Result "msh2" 2015 ASCO Annual MeetingAbstracts



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Search Result "ovarian" 2015 ASCO Annual Meeting Abstracts



2015 ASCO Annual Meeting

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398 results found.

4 pages of results.

Photochemical activation of MH3-B1/rGel; a HER2-targeted treatment approach for ovarian cancer



abstract

HER2-targeted therapy has been shown to have limited efficacy in ovarian cancer despite frequent overexpression of this receptor. Photochemical internalization (PCI) is a modality for cytosolic drug delivery, currently undergoing clinical evaluation. In the present project we studied the application of PCI in combination with the HER2-targeted recombinant fusion toxin, MH3-B1/rGel, for the treatment of ovarian cancer. The SKOV-3 cell line, resistant to trastuzumab- and MH3-B1/rGel- monotherapy, was shown to respond strongly to PCI of MH3-B1/rGel to a similar extent as observed for the treatment-sensitive SK-BR-3 breast cancer cells. Extensive hydrolytic degradation of MH3-B1/rGel in acidic endocytic vesicles was indicated as the mechanism of MH3-B1/rGel resistance in SKOV-3 cells. This was shown by the positive Pearson's correlation coefficient between Alexa488-labeled MH3-B1/rGel and Lysotracker in SKOV-3 cells in contrast to the negative Pearson's correlation coefficient in SK-BR-3 cells. The application of PCI to induce the release of MH3-B1/rGel was also demonstrated to be effective on SKOV-3 xenografts. Application of PCI with MH3-B1/rGel was further found highly effective in the HER2 expressing HOC-7 and NuTu-19 ovarian cancer cell lines. The presented results warrant future development of PCI in combination with MH3-B1/rGel as a novel therapeutic approach in preclinical models of ovarian cancer.

The Significance of Paracardiac Lymph-Node Enlargement In Patients With Newly Diagnosed Stage IIIC Ovarian Cancer



abstract

OBJECTIVE:

Extra-abdominal metastases in epithelial ovarian cancer (EOC) are relatively rare. Interpreting computed tomography (CT) scans, during initial work-up, little attention is focused on enlargement of paracardiac lymph nodes (PCLN) and their significance is not clear. We aimed to examine whether the presence of PCLN during initial diagnosis of EOC influences prognosis.

METHODS:

A retrospective study comparing patients with stage 3 EOC who were diagnosed with PCLN on CT scan during initial evaluation to stage 3C patients without PCLN. Scans were reviewed by a single radiologist for peritoneal involvement, distal metastases and presence of PCLN. Disease status at diagnosis, results of surgery, chemotherapy and response, disease free interval (DFI) and overall survival (OS) were recorded.

RESULTS:

Thirty one patients with stage 3C EOC with PCLN on initial CT scan were included and compared with 41 controls. There was no significant difference between groups in abdominal optimal cytoreduction rate. Lower rates of complete response (CR) to initial treatment were detected in the study group (45.2% vs. 78.0%, p=.004). In survival analysis, the DFI for patients with PCLN was shorter (median 9.0 vs. 24.0months, p=.0097) and overall survival was shorter (median 31.7 vs. 61.3months, p=.001). Multivariate analysis showed that PCLN was significantly associated with a lower rate of CR, a shorter DFI and a shorter OS.

CONCLUSION:

The presence of enlarged PCLN at presentation appears to be associated with poor prognosis in Stage 3C EOC. Further attention should be given to detection and follow-up of such findings when considering treatment.

Cytokine Profiling of Ascites at Primary Surgery Identifies an Interaction of Tumor Necrosis Factor-α and Interleukin-6



abstract


Cytokine Profiling of Ascites at Primary Surgery Identifies an Interaction of Tumor Necrosis Factor-α and Interleukin-6 in Predicting Reduced Progression-Free Survival in Epithelial Ovarian Cancer.

 OBJECTIVES: 

Epithelial ovarian cancer (EOC) typically presents with advanced disease. Even with optimal debulking and response to adjuvant chemotherapy, the majority of patients will have disease relapse. We evaluated cytokine and chemokine profiles in ascites at primary surgery as biomarkers for progression-free survival (PFS) and overall survival (OS) in patients with advanced EOC.

METHODS:

Retrospective analysis of patients (n =70) who underwent surgery at Roswell Park Cancer Institute between 2002-12, followed by platinum-based chemotherapy.

RESULTS:

The mean age at diagnosis was 61.8 years, 85.3% had serous EOC, and 95.7% had stage IIIB, IIIC, or IV disease. Univariate analysis showed that ascites levels of tumor necrosis factor (TNF)-α were associated with reduced PFS after primary surgery. Although the ascites concentration of interleukin (IL)-6 was not by itself predictive of PFS, we found that stratifying patients by high TNF-α and high IL-6 levels identified a sub-group of patients at high risk for rapid disease relapse. This effect was largely independent of clinical prognostic variables.

CONCLUSIONS:

The combination of high TNF-α and high IL-6 ascites levels at primary surgery predicts worse PFS in patients with advanced EOC. These results suggest an interaction between ascites TNF-α and IL-6 in driving tumor progression and resistance to chemotherapy in advanced EOC, and raise the potential for pre-treatment ascites levels of these cytokines as prognostic biomarkers. This study involved a small sample of patients and was an exploratory analysis; therefore, findings require validation in a larger independent cohort.

Neoadjuvant chemotherapy for ovarian cancer: do we have enough evidence?



abstract - the Lancet


"Although primary cytoreductive surgery followed by chemotherapy has been the standard treatment for advanced ovarian cancer for many years, neoadjuvant chemotherapy followed by interval debulking surgery has emerged as a new alternative treatment of advanced ovarian cancer after the EORTC-NCIC trial.1 In The Lancet, Sean Kehoe and colleagues2 show the benefits of using neoadjuvant chemotherapy for patients with advanced ovarian cancer. In a comparison of primary surgery versus primary chemotherapy in 552 patients with advanced ovarian cancer, they showed that primary chemotherapy was not only equally effective but also a substantially safer strategy."

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Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS)



abstract

BACKGROUND:

The international standard of care for women with suspected advanced ovarian cancer is surgical debulking followed by platinum-based chemotherapy. We aimed to establish whether use of platinum-based primary chemotherapy followed by delayed surgery was an effective and safe alternative treatment regimen.

METHODS:

In this phase 3, non-inferiority, randomised, controlled trial (CHORUS) undertaken in 87 hospitals in the UK and New Zealand, we enrolled women with suspected stage III or IV ovarian cancer. We randomly assigned women (1:1) either to undergo primary surgery followed by six cycles of chemotherapy, or to three cycles of primary chemotherapy, then surgery, followed by three more cycles of completion chemotherapy. Each 3-week cycle consisted of carboplatin AUC5 or AUC6 plus paclitaxel 175 mg/m2, or an alternative carboplatin combination regimen, or carboplatin monotherapy. We did the random assignment by use of a minimisation method with a random element, and stratified participants according to the randomising centre, largest radiological tumour size, clinical stage, and prespecified chemotherapy regimen. Patients and investigators were not masked to group assignment. The primary outcome measure was overall survival. Primary analyses were done in the intention-to-treat population. To establish non-inferiority, the upper bound of a one-sided 90% CI for the hazard ratio (HR) had to be less than 1·18. This trial is registered, number ISRCTN74802813, and is closed to new participants.

FINDINGS:

Between March 1, 2004, and Aug 30, 2010, we randomly assigned 552 women to treatment. Of the 550 women who were eligible, 276 were assigned to primary surgery and 274 to primary chemotherapy. All were included in the intention-to-treat analysis; 251 assigned to primary surgery and 253 to primary chemotherapy were included in the per-protocol analysis. As of May 31, 2014, 451 deaths had occurred: 231 in the primary-surgery group versus 220 in the primary-chemotherapy group. Median overall survival was 22·6 months in the primary-surgery group versus 24·1 months in primary chemotherapy. The HR for death was 0·87 in favour of primary chemotherapy, with the upper bound of the one-sided 90% CI 0·98 (95% CI 0·72-1·05). Grade 3 or 4 postoperative adverse events and deaths within 28 days after surgery were more common in the primary-surgery group than in the primary-chemotherapy group (60 [24%] of 252 women vs 30 [14%] of 209, p=0·0007, and 14 women [6%] vs 1 woman [<1%], p=0·001). The most common grade 3 or 4 postoperative adverse event was haemorrhage in both groups (8 women [3%] in the primary-surgery group vs 14 [6%] in the primary-chemotherapy group). 110 (49%) of 225 women receiving primary surgery and 102 (40%) of 253 receiving primary chemotherapy had a grade 3 or 4 chemotherapy related toxic effect (p=0·0654), mostly uncomplicated neutropenia (20% and 16%, respectively). One fatal toxic effect, neutropenic sepsis, occurred in the primary-chemotherapy group.

INTERPRETATION:

In women with stage III or IV ovarian cancer, survival with primary chemotherapy is non-inferior to primary surgery. In this study population, giving primary chemotherapy before surgery is an acceptable standard of care for women with advanced ovarian cancer.

Friday, May 22, 2015

Lynch Syndrome - NORD (National Organization for Rare Disorders)



National Organization for Rare Disorders (basic general report)

 NORD gratefully acknowledges Albert de la Chapelle, MD, PhD, Distinguished University Professor, Department of Molecular Virology, Immunology, and Medical Genetics, and Heather Hampel, MS, CGC, Clinical Associate Professor, Genetic Counselor, Department of Internal Medicine, at the Ohio State University Comprehensive Cancer Center, for assistance in the preparation of this report.

Oncology patients overwhelmingly support tissue banking



Full text (included gyn patients)

 Factors influencing decisions for tissue to be used

Possible benefits to the health of family in the future (88 %), to the individual’s own health (85 %), and benefit to future patients (82 %) were factors the majority of participants indicated would influence their decision to participate in tissue banking (Table 4). Eighteen percent of participants were concerned that refusing to donate tissue might negatively affect the care they received and/or their relationships with healthcare staff.....

Patient experiences living with pancreatic cancer risk (eg. HBOC/Lynch Syndrome/PJS...)



open access (small study)

....Within the general population, an individual has approximately a 1.41 % lifetime risk for developing PancCa [4]. However, PancCa is now considered both a familial risk related cancer and a component of hereditary cancer predisposition syndromes [5]. Based on consensus agreement [6], individuals are considered at high risk for PancCa due to family history if two or more first degree relatives or any three or more relatives, including at least one first degree relative, have a diagnosis of PancCa. Additionally, individuals with Peutz- Jeghers Syndrome and those with p16, Hereditary Breast and Ovarian Cancer Syndrome (HBOC) or BRCA1/2, ATM, PALB2, or Lynch syndrome gene mutations and one or more first degree relatives with PancCa are also considered at risk [4–6] due to genetic factors.Individuals who meet these criteria have higher risk burden ranging from a lifetime risk of
3.6 to 40 % [5, 6]. Consequently individuals with elevated risk live with the awareness that if diagnosed with PancCa most will die......

open access: Targeted deep sequencing of mucinous ovarian tumors



open access: BMC Cancer | Abstract | Targeted deep sequencing of mucinous ovarian tumors reveals multiple overlapping RAS-pathway activating mutations in borderline and cancerous neoplasms

The Danish cancer pathway for patients with serious non-specific symptoms and signs of cancer–a cross-sectional study of pt characteristics/cancer probability



BMC Cancer | open access

.....The majority of patients with cancer have a symptomatic presentation of the disease [6].Symptoms are often diverse and may evolve over time as the cancer develops.....

.... A strong association was found between GP-estimated cancer risk at referral and probability of cancer.

Conclusions In total, 16.2 % of the patients referred through the NSSC-CPP had cancer. They constituted a heterogeneous group with many different symptoms and clinical findings. The GP’s gut feeling was a common reason for referral which proved to be a strong predictor of cancer. The GP’s overall estimation of the patient’s risk of cancer at referral was associated with the probability of finding cancer.

Wednesday, May 20, 2015

Agenda: The 18th Ovarian Cancer National Conference presented by the Ovarian Cancer National Alliance July 24-26, San Diego, California



Agenda



Targeted deep sequencing of mucinous ovarian tumors reveals multiple overlapping RAS-pathway activating mutations in borderline and cancerous neoplasms



abstract

 BACKGROUND: 

Mucinous ovarian tumors represent a distinct histotype of epithelial ovarian cancer. The rarest (2-4% of ovarian carcinomas) of the five major histotypes, their genomic landscape remains poorly described. We undertook hotspot sequencing of 50 genes commonly mutated in human cancer across 69 mucinous ovarian tumors. Our goals were to establish the overall frequency of cancer-hotspot mutations across a large cohort, especially those tumors previously thought to be "RAS-pathway alteration negative", using highly-sensitive next-generation sequencing as well as further explore a small number of cases with apparent heterogeneity in RAS-pathway activating alterations.

METHODS:

Using the Ion Torrent PGM platform, we performed next generation sequencing analysis using the v2 Cancer Hotspot Panel. Regions of disparate ERBB2-amplification status were sequenced independently for two mucinous carcinoma (MC) cases, previously established as showing ERBB2 amplification/overexpression heterogeneity, to assess the hypothesis of subclonal populations containing either KRAS mutation or ERBB2 amplification independently or simultaneously.

RESULTS:

We detected mutations in KRAS, TP53, CDKN2A, PIK3CA, PTEN, BRAF, FGFR2, STK11, CTNNB1, SRC, SMAD4, GNA11 and ERBB2. KRAS mutations remain the most frequently observed alteration among MC (64.9%) and mucinous borderline tumors (MBOT) (92.3%). TP53 mutation occurred more frequently in carcinomas than borderline tumors (56.8% and 11.5%, respectively), and combined IHC and mutation data suggest alterations occur in approximately 68% of MC and as many as 20% of MBOT. Proven and potential RAS-pathway activating changes were observed in all but one MC. Concurrent ERBB2 amplification and KRAS mutation were observed in a substantial number of cases (7/63 total), as was co-occurrence of KRAS and BRAF mutations (one case). Microdissection of ERBB2-amplified regions of tumors harboring KRAS mutation suggests these alterations are occurring in the same cell populations, while consistency of KRAS allelic frequency in both ERBB2 amplified and non-amplified regions suggests this mutation occurred in advance of the amplification event.

CONCLUSIONS:

Overall, the prevalence of RAS-alteration and striking co-occurrence of pathway "double-hits" supports a critical role for tumor progression in this ovarian malignancy. Given the spectrum of RAS-activating mutations, it is clear that targeting this pathway may be a viable therapeutic option for patients with recurrent or advanced stage mucinous ovarian carcinoma, however caution should be exercised in selecting one or more personalized therapeutics given the frequency of non-redundant RAS-activating alterations.

The influence of neighborhood socioeconomic status and race on survival from ovarian cancer: Cook County, Illinois



abstract
 

PURPOSE:

Despite significant improvements in treatment for ovarian cancer, survival is poorer for non-Hispanic black (NHB) women compared to non-Hispanic white (NHW) women. Neighborhood socioeconomic status (SES) has been implicated in racial disparities across a variety of health outcomes and may similarly contribute to racial disparities in ovarian cancer survival. The purpose of this analysis is to assess the influence of neighborhood SES on NHB-NHW survival differences after accounting for differences in tumor characteristics and in treatment.

METHODS:

Data were obtained from 2432 women (443 NHB and 1989 NHW) diagnosed with epithelial ovarian cancer in Cook County, Illinois between 1998 and 2007. Neighborhood (i.e., census tract) SES at the time of diagnosis was calculated for each woman using two well-established composite measures of affluence and disadvantage. Cox proportional hazard models measured the association between NHB race and survival after adjusting for age, tumor characteristics, treatment, year of diagnosis, and neighborhood SES.

RESULTS:

There was a strong association between ovarian cancer survival and both measures of neighborhood SES (P < .0001 for both affluence and disadvantage). After adjusting for age, tumor characteristics, treatment, and year of diagnosis, NHB were more likely than NHW to die of ovarian cancer (hazard ratio [HR] = 1.47, 95% confidence interval [CI]: 1.28-1.68). The inclusion of neighborhood affluence and disadvantage into models separately and together attenuated this risk (HRaffluence = 1.37, 95% CI: 1.18-1.58; HRdisadvantage = 1.28, 95% CI: 1.08-1.52; and HRaffluence + disadvantage = 1.28, 95% CI: 1.08-1.52.

CONCLUSIONS:

Neighborhood SES, as measured by composite measures of affluence and disadvantage, is a predictor of survival in women diagnosed with ovarian cancer in Cook County, Illinois and may contribute to the racial disparity in survival.

Feeling Powerless: Locus of Control as a potential target for supportive care interventions to increase QOL & decrease anxiety in ovarian cancer patients



abstract

PURPOSE:

To evaluate if an individual's Locus of Control (LOC) predicts various quality of life (QOL) and mental well-being measures. To identify targets that might enhance the overall spiritual well-being and QOL of ovarian cancer patients.

METHODS:

Multi-site analysis of women with newly diagnosed stages II-IV ovarian, primary peritoneal or fallopian tube cancer. Patients completed the following surveys: Locus of Control Scale (LOC), Functional Assessment of Chronic Illness Therapy-Ovarian (FACT-O), Functional Assessment of Chronic Illness Therapy - Spiritual (FACIT-Sp), Edmonton Symptom Assessment score (ESAS), Hospital Anxiety Depression Scale (HADS), Templer's Death Anxiety Scale (DAS), and Herth Hope Index (HHI). Regression models were created to examine the effect of LOC upon QOL, symptoms, and other measures of mental well-being. These models adjusted for the effect of site of care, race, and partnership status as potential confounders.

RESULTS:

This study enrolled 104 patients from three separate treatment facilities. After adjusting for site, race and partnership status, higher levels of external LOC predicted decreased QOL (FACT-O) (p< 0.05). Higher levels of external LOC also correlated with increased death anxiety and general anxiety (p≤0.05). Additionally, higher levels of external LOC predicted decreased hope (HHI) (p≤0.01).

DISCUSSION:

Ovarian cancer patients with a high external LOC may be at risk for decreased QOL at the time of their cancer diagnosis. They may also experience higher levels of anxiety and decreased feelings of hope. Identification of these women and interventions designed to increase a woman's sense of control over her situation may improve QOL and overall mental well-being.

Identification of a Variety of Mutations in Cancer Predisposition Genes in Patients with Suspected Lynch Syndrome (including BRCA...)



abstract
 

BACKGROUND & AIMS:

Multigene panels are commercially available tools for hereditary cancer risk assessment that allow for next-generation sequencing of numerous genes in parallel. However, it is not clear if these panels offer advantages over traditional genetic testing. We investigated the number of cancer predisposition gene mutations identified by parallel sequencing in individuals with suspected Lynch syndrome.

METHODS:

We performed germline analysis with a 25-gene next-generation sequencing panel using DNA from 1260 individuals who underwent clinical genetic testing for Lynch syndrome from 2012 through 2013. All subjects had a history of Lynch syndrome-associated cancer and/or polyps. We classified all identified germline alterations for pathogenicity and calculated the frequencies of pathogenic mutations and variants of uncertain significance (VUS). We also analyzed data on patients' personal and family history of cancer, including fulfillment of clinical guidelines for genetic testing.

RESULTS:

Of the 1260 subjects, 1112 met National Comprehensive Cancer Network (NCCN) criteria for Lynch syndrome testing (88%; 95% confidence interval [CI], 86%-90%). Multigene panel testing identified 114 probands with Lynch syndrome mutations (9.0%; 95% CI, 7.6%-10.8%) and 71 with mutations in other cancer predisposition genes (5.6%; 95% CI, 4.4%-7.1%). Fifteen individuals had mutations in BRCA1 or BRCA2; 93% of these met the NCCN criteria for Lynch syndrome testing and 33% met NCCN criteria for BRCA1 and BRCA2 analysis (P=.0017). An additional 9 individuals carried mutations in other genes linked to high lifetime risks of cancer (5 had mutations in APC, 3 had bi-allelic mutations in MUTYH, and 1 had a mutation in STK11); all of these patients met NCCN criteria for Lynch syndrome testing. Four hundred seventy-nine individuals had ≥1 VUS (38%; 95% CI, 35%-41%).

CONCLUSIONS:

In individuals with suspected Lynch syndrome, multigene panel testing identified high-penetrance mutations in cancer predisposition genes, many of which were unexpected based on patients' histories. Parallel sequencing also detected a high number of potentially uninformative germline findings, including VUS.

Sunday, May 17, 2015

Anti-Angiogenesis Therapy in Gynecologic Malignancies



open access

Discussion

The reason bevacizumab resulted in an OS advantage in cervical cancer and not in ovarian cancer may lie in the biological differences between these two gynecologic cancers. Ovarian carcinogenesis is characterized by tumor heterogeneity stemming from genomic instability, nonequivalent gene expression, and copy number alterations.......
Another salient difference between epithelial ovarian cancer and cervical cancer with regard to clinical trial endpoints is the role of post-progression therapy. At the 2014 SGO Annual Meeting, Aghajanian and colleagues presented the final analysis of OS in the OCEANS trial that compared the addition of bevacizumab to the carboplatin/gemcitabine doublet vs carboplatin/gemcitabine plus placebo.[67] More than 88% of patients in the bevacizumab-containing arm and 90% of those in the placebo arm went on to receive anticancer therapy, with a median of 5 additional regimens. The chemosensitivity of ovarian cancer makes OS in late-phase clinical trials a controversial and potentially biased metric for multiple reasons. Both imbalanced treatment crossover after randomization and post-progressive therapies can dilute the effect of the study drug on OS. Detecting an OS advantage that derives from an improvement in PFS requires a short median post-progression interval (approximately 6 months),[68] a clinical scenario more often seen in advanced cervical carcinoma.

Conclusion

Anti-angiogenic therapies have a clear role in the treatment of gynecologic cancers. In 2014, the FDA approved the use of bevacizumab in advanced cervical cancer and platinum-resistant ovarian cancer, providing viable options for high-risk subgroups that previously had none. For most patients with gynecologic cancers, the response seen with anti-angiogenic therapy is unlikely to result in cure, and exploration of alternate therapies remains necessary. The discovery of new therapeutic agents and inevitably longer disease-free intervals will give rise to a new population of gynecologic cancer survivors, who will present novel challenges. Multimodal treatment strategies that include surgery, CT, radiotherapy, anti-angiogenesis therapy, and immunotherapy will allow patients with gynecologic malignancies to maximize their survival potential.

Financial Disclosure: Dr. Tewari has served in a limited capacity as a consultant and advisory board member for Roche-Genentech. Drs. Cripe and Liu have no significant financial interest in or other relationship with the manufacturer of any product or provider of any service mentioned in this article

Empathy: The Human Connection to Patient Care (video) Cleveland Clinic



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

Saturday, May 16, 2015

Cancer survivors have evolving information needs



Cancer survivors

 Judging by the nature and topics of their information seeking, cancer patients' information needs appear to differ depending on the type of cancer they have and where they are in their survivorship. Clinicians caring for cancer survivors may need to understand these needs in order to better address survivors' concerns about cancer recurrence, late effects, and family members' risks.....

 Across all participants, reducing the chance of cancer coming back was the number one researched subject in all three surveys.

Barbara Platzer - St. Louis Jewish Light: Obituaries



Barbara Platzer 

 Barbara PlatzerBarbara Platzer, died May 14, 2015. Beloved wife of Robert Platzer; dear mother and mother-in-law of Cynthia Becker and James (Heather) Platzer; dear grandmother of Lawrence Jacob “Jake” Becker and Aliyah Becker; dear mother-in-law of Ed Becker. Dear friend to many. Mrs. Platzer graduated from Northwestern University. Funeral service Monday, May 18, 10:30 a.m. at United Hebrew Congregation, 13788 Conway Road. Visitation begins at 9:30 AM. Interment follows the funeral service at Beth Hamedrosh Hagodol Cemetery, 9125 Ladue Road. Contributions to St. Louis Ovarian Cancer Awareness (SLOCA), 12015 Manchester Road, Suite 130, St. Louis, Mo. 63131. Berger Memorial

A case of squamous cell carcinoma of the skin due to the molecularly confirmed Lynch Syndrome (MLH1)



open access

 Case report

Patients with Lynch Syndrome are at high risk for developing a variety of cancers including cancers of the colon or rectum, small bowel, stomach, uterus, renal pelvis, ureter, biliary tract, ovaries, brain and pancreas (N Engl J Med 348: 919-32, 2003; Gut 57:1097-101, 2008; NCCN, Inc Guideline. Ft. Washington, PA. Online Version 2.2014). Lack of MLH-1 and MSH-2 expression commonly result from germline mutations in this inherited cancer syndrome. Here, we report the case of a patient with a molecularly confirmed germline mutation in MLH-1 along with a colon cancer showing lack of expression of MLH-1 as well as a squamous cell cancer of the skin from the abdominal wall also demonstrating lack of expression of MLH-1. This case appears to represent the second case report of a squamous cell skin cancer apparently due to the Lynch Syndrome and further supports a proposed relationship between Lynch Syndrome and these tumors. 

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.


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Friday, May 15, 2015

Napsin A is frequently expressed in clear cell carcinoma of the ovary and endometrium



Abstract

 Napsin A is a reliable marker for pulmonary adenocarcinoma and is expressed in a subset of ovarian clear cell carcinomas (O-CCCs), endometrial (EM) CCCs, and endometrioid carcinomas (EC). We investigated napsin A levels in O-CCC and EM-CCC and compared these with levels in other nonmucinous ovarian carcinomas and EM-EC, respectively. Napsin A, thyroid transcription factor (TTF)-1, paired box (PAX) 8, and cancer antigen (CA) 125 expression was evaluated in 111 ovarian and uterine carcinoma cases (22 O-CCC, 15 EM-CCC, 13 ovarian EC (O-EC), 39 high-grade serous carcinoma [HGSC], and 22 EM-EC) using immunohistochemistry. Napsin A immunoreactivity was observed in 21 (95.5%) of 22 O-CCC and 10 (66.7%) of 15 EM-CCC cases but was rare in O-EC and EM-EC (7.7% and 4.5%) and undetectable in HGSC cases. Thyroid transcription factor 1 was not expressed in O-CCC but was detected in 1 (6.7%) of 15 EM-CCC, 3 (23.1%) of 13 O-EC, 2 (5.1%) of 39 HGSC, and 1 (4.5%) of 22 EM-EC cases. All 111 cases examined were positive for PAX8, whereas 3 (20.0%) of 15 of EM-CCC and 1 (4.5%) of 22 EM-EC cases were negative for CA125. There were no napsin A/TTF-1 double-positive cases, except for 1 EM-CCC, in which cells had a focal expression pattern. All napsin A- and/or TTF-1-positive cases expressed PAX8 and CA125. In conclusion, napsin A is frequently expressed in O-CCC and EM-CCC, rarely in O-EC and EM-EC, and never in HGSC cases. These findings confirm the importance of using a panel of antibodies that includes napsin A, TTF-1, and PAX8 when evaluating metastatic carcinomas of unknown origin, particularly when gynecologic and pulmonary adenocarcinomas are included in the differential diagnosis.

Circulating 25-hydroxyvitamin D and survival in women with ovarian cancer



abstract

BACKGROUND: 

Vitamin D status might be associated with cancer survival. Survival after ovarian cancer is poor, but the association with vitamin D has rarely been examined.

OBJECTIVE:

We evaluated the association between serum 25-hydroxyvitamin D [25(OH)D], a marker of vitamin D status, and ovarian cancer survival.

DESIGN:

Participants were women with invasive ovarian cancer diagnosed between 2002 and 2005 who participated in the Australian Ovarian Cancer Study. Serum samples, collected at diagnosis (n = 670) or after completion of primary treatment and before recurrence (n = 336), were assayed for 25(OH)D. Sociodemographic, dietary, and lifestyle data came from questionnaires self-completed at recruitment, and clinical and survival data were from medical records, supplemented by linkage to the Australian National Death Index (October 2011). Cox proportional hazards regression was used to estimate HRs and 95% CIs for the association between circulating 25(OH)D and survival.

RESULTS:

Overall, 59% of the women died during follow-up, with 95% of deaths resulting from ovarian cancer. Circulating 25(OH)D concentrations (mean: 44 nmol/L) were significantly associated with age, state of residence, season of blood collection, and body mass index but not with tumor histology, stage or grade, or comorbidities. Higher 25(OH)D concentrations at diagnosis were significantly associated with longer survival (adjusted HR: 0.93; 95% CI: 0.88, 0.99 per 10 nmol/L), but there was no significant association with progression-free survival or for 25(OH)D measured after primary treatment.

CONCLUSIONS:

In our cohort, higher serum 25(OH)D concentrations at diagnosis were associated with longer survival among women with ovarian cancer. If confirmed in other studies, this suggests that vitamin D status at diagnosis may be an independent predictor of prognosis. Furthermore, if the association is found to be causal, improving vitamin D status may improve ovarian cancer survival rates.
© 2015 American Society for Nutrition

Germline TP53 Mutations in Patients With Early-Onset Colorectal Cancer (Li-Fraumeni syndrome-ovarian cancer...)



JAMA - open access

....Li-Fraumeni syndrome is an inherited cancer syndrome, usually caused by germline TP53 mutations, in which patients classically develop early-onset cancers, including leukemias, brain tumors, sarcomas, breast carcinomas, and adrenocortical carcinomas.710 Beyond these so-called core cancers, data have shown that TP53 mutation carriers are also at increased risk for a wide array of other malignant neoplasms, including bronchoalveolar, pancreatic, gastric, ovarian, and colorectal cancers.6,10- ....

eg. .... This proband’s family history included a sister with ovarian cancer at age 39 years, a mother with breast and ovarian cancers at ages 60 and 65 years, respectively, and a daughter with glioblastoma at age 41 years, none of whom had had testing for the TP53 or BRCA2 mutations.30.....


At a Glance
  • Individuals with Li-Fraumeni syndrome (LFS) caused by germline TP53 mutations are estimated to have a 73% to 100% lifetime risk of cancer, including colorectal cancer (CRC).
  • The purpose of this study was to determine the frequency of germline TP53 alterations in individuals with early-onset CRC.
  • Of 457 participants diagnosed as having CRC at age 40 years or younger, 1.3% carried germline TP53 alterations.
  • None of the TP53 probands in this study had a personal or family cancer history that fulfilled clinical LFS criteria.
  • Cancer risk in TP53 mutation carriers may be different in patients presenting with early-onset CRC compared with those who present with classic LFS family histories.


Thursday, May 14, 2015

coming soon (new) - National Cancer Institute



NCI

Spanish version

Coming Soon: The New Cancer.gov

On May 15, the National Cancer Institute (NCI) will launch a new version of this website designed to more effectively deliver information about cancer, cancer research, and training whenever and wherever you want it – on your computer, tablet, or smartphone. View the video for a quick peek at what you can expect from the new Cancer.gov.....


ALDH1A1 Expression in the Pathogenesis of Ovarian Carcinoma



open access

Discussion

ALDH1A1 has been proposed as a marker for cancer stem cells or cancer initiating cells in various types of human cancer, including ovarian carcinoma. Previous experimental work demonstrated ALDH1A1-positive ovarian cancer cells to be more tumorigenic than ALDH1A1-negative cells.[22,23] It is therefore plausible that these ALDH1A1-expressing tumor cells may be derived from somatic stem cells, likely from the fallopian tube. Indeed, the mouse ovarian hilum has recently been shown to be enriched for ALDH1A1-positive stem cells with increased susceptibility to malignant transformation.[16] The purpose of this study was to comprehensively characterize the expression of ALDH1A1 in normal human fallopian tube, tubal–mesothelial junctions, ovarian surface epithelium, and in lesions thought to represent different stages of tumor progression - namely, p53 signatures, serous tubal intraepithelial carcinoma, and primary and recurrent high-grade serous carcinomas.......

...... In summary, we demonstrate that ALDH1A1-expressing epithelial cells are abundant in the normal fallopian tube, but not in p53 signatures or serous tubal intraepithelial carcinoma. ALDH1A1-positive cells can occasionally be observed in some high-grade serous carcinomas, but usually restricted to only a few tumor cells. These findings suggest that ALDH1A1 is probably not a specific marker for fallopian tube stem cells, and demonstrate that its loss of expression is an early event in the development of high-grade serous carcinoma. Identification of more specific markers of Müllerian epithelial stem cells is necessary to identify the putative somatic stem cell population involved in the pathogenesis of this malignancy


Who Should Get 'Compassionate Use' Drugs?



medscape

JAMA Dermatology | Patients' Preferences for Biopsy Result Notification in an Era of Electronic Messaging Methods



 Patients' Preferences 

Wednesday, May 13, 2015

Expression of the Carboxy-Terminal Portion of MUC16/CA125 Induces Transformation and Tumor Invasion



PLOS ONE - open access (technical)

....These findings are the first to describe MUC16-linked changes in cellular behavior and gene transcription. The in vitro and in vivo models are consistent with the adverse effects of MUC16 expression levels in serous ovarian cancer and promote the understanding of MUC16 as a pathogenic contributor to the behaviors of ovarian cancer. The adverse impact of increasing CA125 expression is consistent with increased in vivo tumor growth and lethality of MUC16-positive 3T3 transfectants. Additional work of the precise mechanisms initiating MUC16 signaling, the effects of MUC16 binding to stromal elements, and the identification of the key molecular partners of cell surface MUC16 are likely to further enhance our understanding of ovarian cancer biology.

Population-based Analysis of the Clinical Features of Primary Small Cell Carcinoma of the Ovary



abstract


CONCLUSION:

SCCO presents at a younger age than SCLC but has a similar stage distribution. Patients with localized SCCO have a more favorable prognosis than patients with SCLC but patients with regional and distant disease have similar outcomes.

Methods and Baseline Cardiovascular Data From the Early Versus Late Intervention Trial With Estradiol Testing the Menopausal Hormone Timing Hypothesis



Medscape

 Conclusions

The randomized trial data show that HT reduces the incidence of CHD and total mortality in young postmenopausal women (younger than 60 y) who initiate HT near menopause (< 10 y since menopause; ).[1] These findings are consistent with the reductions in CHD and total mortality reported from observational studies, where most women initiated HT within 6 years of menopause.[21,22] Although the cumulative literature is more than suggestive of this conclusion, no clinical trial has specifically tested the timing hypothesis with regard to CHD or cognitive outcomes. In this respect, ELITE is both timely and unique. During the past decade, the timing hypothesis pertaining to CHD has matured into a well-supported hypothesis awaiting more definitive study. For cognitive decline in the absence of dementia, the timing hypothesis remains of critical concern,[34] although supportive data are less fully developed than for CHD. As postrandomization baseline data indicate, ELITE is well-positioned to test the timing hypothesis of HT in relation to atherosclerosis progression, CAD, and cognitive changes.

Shooting at the Moon To Improve Ovarian Cancer



Clinical Oncology News


....The algorithm recommends presurgical chemotherapy for patients in whom complete surgical removal is unlikely. Such patients typically undergo three rounds of chemotherapy, with responders then undergoing surgery.

Maurie Markman, MD, the president of CTCA Medicine and Science and a clinical professor of medicine at Drexel University College of Medicine, in Philadelphia, called the report interesting, but said other groups have attempted to develop similar ovarian cancer cytoreduction algorithms that have not gained widespread acceptance.
“The novelty of this particular report is that laparoscopic assessment with direct visualization of the cancer is included, which is almost certainly a superior approach to any external imaging strategy,” he said, adding that being able to determine whether other groups of gynecologic oncologists can replicate the results (including use of the scoring system) will be important.
“It is also critical to acknowledge that this report does not indicate the strategy actually improves clinical outcomes,” Dr. Markman said. “Rather, it may be possible to more critically define the patient populations most appropriate for primary surgical cytoreduction versus a neoadjuvant approach.”

Conventional Chemotherapy and Oncogenic Pathway Targeting in Ovarian Carcinosarcoma Using a Patient-Derived Tumorgraft



open access

Ovarian carcinosarcoma is a rare subtype of ovarian cancer with poor clinical outcomes. The low incidence of this disease makes accrual to large clinical trials challenging. However, studies have shown that treatment responses in patient-derived xenograft (PDX) models correlate with matched-patient responses in the clinic, supporting their use for preclinical testing of standard and novel therapies. An ovarian carcinosarcoma PDX is presented herein and showed resistance to carboplatin and paclitaxel (similar to the patient) but exhibited significant sensitivity to ifosfamide and paclitaxel......

Clinical Analysis of 152 Cases of Multiple Primary Malignant Tumors in 15,398 Patients with Malignant Tumors (China)



open access

(MPMT = multiple primary malignant tumors)