Editorial
excerpt:
Tuesday, October 11, 2016
The association between reproductive and hormonal factors and ovarian cancer by estrogen-α and progesterone receptor status
abstract:
The association between reproductive and hormonal factors and ovarian cancer by estrogen-α and progesterone receptor status
Highlights
Objective
We assessed the association between reproductive and hormonal factors and ovarian cancer incidence characterized by estrogen receptor-α (ERα) and progesterone receptor (PR) status.Conclusions
Postmenopausal women have an increased risk of developing PR(–) ovarian tumors compared to premenopausal women. The associations observed for ovarian cancer differ from those seen for breast cancer suggesting that the biology for tumor development through ERα and PR pathways may differ.
Monday, October 10, 2016
(p53/APR-246/serous +carbo) Trial Shows Ovarian Cancer Drug Safety, Therapy Potential
Science news
10 October 2016. A clinical trial shows an experimental therapy addressing a common cancer-causing mutation is safe, with early indications of its efficacy against ovarian cancer. The report by biopharmaceutical company Aprea Therapeutics of the study testing its treatment candidate code-named APR-246 was presented today at a meeting of the European Society for Medical Oncology, or Esmo, in Copenhagen.
Aprea Therapeutics, in Stockholm and Boston, develops treatments that target the p53 tumor suppressor gene, whose mutations are involved with more than half of all tumors. These mutations are associated with a wide range of tumor types, and tumors expressing proteins from these mutations are also increasingly resistant to chemotherapy.
In its original, or non-mutated form, the p53 gene activates proteins that start a series of events attacking and killing tumor candidate cells before they become cancerous, thus suppressing the formation of tumors. Should the p53 gene be compromised, through genetic inheritance or environmental factors, that protective function can stop, allowing tumors to form and grow unchecked. Moreover, dysfunctional forms of p53 up to now needed treatments addressing those specific variations, thus therapies targeting specific p53 mutations had limited benefits.
Aprea designed APR-246 as a small-molecule, or low molecular-weight, drug that binds to and refolds proteins coded by mutant p53 genes. This process, says the company, stabilizes the mutant p53 proteins and restores their original protective functions that suppress tumor growth. Aprea says APR-246 was tested in preclinical studies on models of blood-related and solid tumor cancers, including ovarian cancer, small cell lung cancer, esophageal cancer, and acute myeloid leukemia.
The clinical trial reported at the Esmo meeting is testing APR-246 among 28 women diagnosed with serous ovarian cancer, the most common form of the disease, accounting for about two-thirds of all cases. The early-stage trial is testing the safety of APR-246 at 3 dosage levels. APR-246 is administered in combination with the chemotherapy drug carboplatin, often prescribed to treat ovarian cancer, and a formulation of doxorubicin, another chemotherapy drug, in polymer-coated liposomes, or natural oil bubbles, that extends its circulation time. The study is also measuring the chemical activity of APR-246 in the body and early indicators of efficacy.
Aprea reports the results show patients receiving all 3 dosage levels of APR-246 experience low-grade adverse effects including nausea, vomiting, dizziness, fatigue, and low white blood cell and blood platelet counts. In addition, APR-246 does not appear to accumulate in the body, nor does it interact with the chemotherapy drugs, suggesting that APR-246 can be used with chemotherapy.
Of the 28 participants, 22 have tumors with measurable lesions, and of that sub-group 3 report a complete response to the treatment, and 10 show a partial response. The median progression-free survival time of these patients is 316 days. Of 2 other patients with non-measurable disease, 1 reports a complete response, and the other has a disease still progressing.
The results show the highest dose level is safe enough to continue into a second part of the same clinical trial, an intermediate-stage study testing APR-246 among women with serous ovarian cancer, combined with the chemotherapy drugs, against the chemotherapy drugs alone. The company is now recruiting participants for the trial, conducted at a number of sites in the U.K. and Europe.
Is Heart Disease or Cancer the Leading Cause of Death in United States Women?
abstract
Purpose
This paper compares the mortality burden of heart disease versus cancer among women by age, race, and ethnicity.
Methods
U.S.
death and population data for the years 2000 through 2013 were used to
calculate heart disease and cancer death rates. Detailed analyses
focused on age (15–19 years old to ≥100 years old) and race and
ethnicity (Whites, Blacks, Hispanics, Asians and Pacific Islanders
(A/PIs), and American Indians and Alaska Natives (AI/ANs)).
Results
Among
women aged 15 years and older, there were 289,467 heart disease deaths
and 276,716 cancer deaths in 2013. The majority of heart disease deaths
(51.6%) occurred among women 85 years or older, compared with 18.9% of
female cancer deaths. The age-adjusted death rates (per 100,000
population) were 171 (95% confidence interval [CI], 170–171) for heart
disease versus 177 (95% CI, 176–178) for cancer. For all racial and
ethnic groups, cancer mortality was significantly higher than heart
disease mortality among women younger than 80 years of age. For all ages
combined, cancer deaths exceeded heart disease deaths among Hispanics,
A/PIs, and AI/ANs. Black non-Hispanic women were the only racial/ethnic
group who had a higher age-adjusted death rate for heart disease than
for cancer: 224 (95% CI, 222–226) versus 207 (95% CI, 205–209).
Conclusions
Heart
disease remains the leading cause of death among all women combined in
the United States by a narrow margin. However, cancer predominantly
kills middle-aged and young women, whereas heart disease predominantly
kills the very old. New research on the over reporting of heart disease
on death certificates for elderly women is needed. National summary
statistics obscure the fact that cancer is already the overall leading
cause of death for Hispanic women, Asian and Pacific Islander women, and
American Indian and Alaska Native women.
- Disclosures: The author is a past recipient of research funding from the American Heart Association. She has no other interests, financial or otherwise, to declare. This study was unfunded, and all data analyzed are in the public domain.
Does time interval between surgery and IP administration in advanced ovarian cancer carry a prognostic impact?
abstract:
Does time interval between surgery and intraperitoneal chemotherapy administration in advanced ovarian cancer carry a prognostic impact? An NRG Oncology/Gynecologic Oncology Group study ancillary study
Hence, the relationship between IP chemotherapy initiation and time from surgery needs to be studied further.
Highlights
- •
- Time from surgery to IP chemotherapy initiation (TSIC) did not impact survival.
- •
- Gross residual disease was significantly associated with shorter TSIC.
- •
- Gross residual disease significantly associated with higher risk of progression.
Objectives
To
determine the relationship of the time from surgery to intraperitoneal
(IP) chemotherapy (TSIC) initiation with survival of patients with stage
III epithelial ovarian cancer (EOC) patients using ancillary data from
cooperative group clinical trials.
Methods
Data
from 420 patients with stage III EOC treated with IP chemotherapy under
GOG-0114 and 172 were reviewed.
Surgical treatment of early stage ovarian cancer
abstract
Highlights
- •
- Early stage (I-IIA) epithelial ovarian cancer can only be properly defined by a thorough and comprehensive surgical staging.
- •
- The completeness of surgical staging is an independent prognostic factor for survival and disease free survival in early stage ovarian carcinoma.
- •
- The effectiveness of adjuvant chemotherapy in properly staged early stage ovarian carcinoma is questionable.
The
treatment of early stage (stage I-IIA) ovarian carcinoma is
predominantly surgical and the surgical staging is the most relevant
step in the treatment of this disease. The significance of surgical
staging is twofold. First, proper staging distinguishes between ‘real’
early stage ovarian carcinoma and ‘perhaps’ early stage disease. The
latter carries an appreciable likelihood of unappreciated residual
disease in between 16 and 42% of cases. Second, there is solid proof
that proper surgical staging is an independent prognostic factor for
improved disease-free and overall survival in early stage ovarian
carcinoma. The relevance of various staging steps are discussed and
surgical guidelines are given in this chapter.
The
indication for adjuvant chemotherapy after surgery is closely related
to the adequacy of surgical staging. Adjuvant chemotherapy only works in
patients in whom surgical staging was inadequate and who, thus, remain
with a certain risk of unnoticed residual intraperitoneal or
retroperitoneal tumour spread. On the other hand, there is no indication
that adjuvant chemotherapy is of any value after an adequate,
comprehensive staging procedure. Controversies and misunderstandings on
this important issue are discussed.
open access - NEJM: Niraparib Maintenance Therapy in Platinum- Sensitive, Recurrent Ovarian Cancer
CONCLUSIONSAmong patients with platinum-sensitive, recurrent ovarian cancer, the median duration of progression-free survival was significantly longer among those receiving niraparib than among those receiving placebo, regardless of the presence or absence
of gBRCA mutations or HRD status, with moderate bone marrow toxicity. (Funded
by Tesaro; ClinicalTrials.gov number, NCT01847274.)
Brain metastases in patients with EOC: Clinico-pathological and prognostic factors....
Brain metastases in patients with EOC: Clinico-pathological and prognostic factors. A multicentric retrospective analysis from the MITO group (MITO 19)
BACKGROUND:
Brain metastases (BM) from epithelial ovarian cancer (EOC) are considered a rare and unfavourable event. There is no consensus regarding the best management of these patients.METHODS:
A multicenter retrospective analysis of patients with BM from EOC treated between 1997 and 2014 in 18 institutions of the MITO (Multicenter Italian Trials in Ovarian cancer) group was conducted. Univariate and multivariate analysis were performed.RESULTS:
A total of 174 women were identified as having BM from EOC. The median time interval between primary diagnosis of EOC and occurrence of BM was 26months (range 2-129months).Upper tract urothelial carcinomas: frequency of association with mismatch repair protein loss and Lynch Syndrome (and Muir-Torre)
Abstract - Modern Pathology
Increased risk for upper tract urothelial carcinoma is described in patients with Lynch syndrome, caused by germline mutations in mismatch repair genes. We aimed to identify the frequency of mismatch repair protein loss in upper tract urothelial carcinoma and its potential for identifying an association with Lynch syndrome. We queried our database to identify upper tract urothelial carcinomas. Patients were cross-referenced for history of colorectal carcinoma or other common Lynch syndrome-associated neoplasms to enrich for potential Lynch syndrome cases. Tumor histopathologic characteristics were reviewed and each case was analyzed for loss of mismatch repair proteins, MLH1, MSH2, MSH6, and PMS2, by immunohistochemistry. Of 444 patients with upper tract urothelial carcinoma, a subset of 215 (encompassing 30 with upper tract urothelial carcinoma and another common Lynch syndrome-associated neoplasm) was analyzed for loss of mismatch repair protein expression. Of 30 patients with Lynch syndrome-associated neoplasms, six had documented Lynch syndrome, including two with Muir–Torre syndrome. Mismatch repair protein loss was identified in 7% of total upper tract urothelial carcinomas and 30% of patients with Lynch syndrome-associated neoplasms (including all patients with Lynch syndrome/Muir–Torre syndrome). Of patients without history of Lynch syndrome-associated neoplasms, 5 of 184 (2.7%) had loss of mismatch repair protein expression. Twelve cases with mismatch repair protein loss demonstrated loss of MSH2 and MSH6, and 2 had isolated loss of MSH6. MLH1 and PMS2 expression were consistently retained. Although increased intratumoral lymphocytes, inverted growth, pushing tumor-stromal interface, and lack of nuclear pleomorphism were more commonly seen in cases with mismatch repair protein loss, only intratumoral lymphocytes and presence of pushing borders were statistically significant. MLH1 and PMS2 testing appear to have little utility in upper tract urothelial carcinoma; however, mismatch repair protein loss of MSH2 and/or MSH6 by immunohistochemistry seems relatively sensitive and specific for identifying patients with potential Lynch syndrome.
Sunday, October 09, 2016
Prexasertib Shows Promising Activity in High-grade Ovarian Cancer (phase 2)- ESMO
medical news
Prexasertib, an investigational kinase inhibitor of checkpoint kinases 1 and 2, demonstrates promising activity in patients with BRCA wild type sporadic high-grade serous ovarian cancer, according to a study presented at the European Society for Medical Oncology (ESMO) 2016 Congress.1
Reference
- Lee J, Karzai FH, Zimmer A, et al. A phase II study of the cell cycle checkpoint kinases 1 and 2 inhibitor (LY26063368; prexasertib monomesylate monohydrate) in sporadic high-grade serous ovarian cancer (HGSOC) and germline BRCA mutation-associated ovarian cancer (gBRCAm+ OvCa). Paper presented at: European Society for Medical Oncology (ESMO) 2016 Congress; October 7-11, 2016; Copenhagen, Denmark.
The Precise–and Wild–Genomics Revolution
IEEE PULSE
As genetics and environment come together, we will have a more detailed, data-driven account of the complex relationship between nature and nurture and how they express themselves as both health and disease.
Besides a deficit of knowledge about which tests to order, once a test is ordered, the results are not necessarily clear-cut. It’s not a matter of simply finding out whether the patient has a mutation or not. “Those test results,” Diamond says, “… if you ever saw the results, they’re … gobbledygook. It doesn’t just come back and say, ‘Yes, [the] patient has ovarian cancer risk.’”
By the Numbers: Not So Good at Saying Sorry (plus comments including mine)
Medpage Today
October 8th, 2016 - Add Your Knowledge: As an ovarian cancer survivor I was involved in WHO's first conferences regarding Patient Safety and the 'sorry campaigns' were about to start. While the original intents were honorable and compassionate it became 'legalized' ad nauseam (read cya). It is a sad world when a physician (or other hcp) is unable to say they are sorry and it is a sad world to know and recognize that patients understand unintended complications - yet?. To further exasperate the issue now every politician (name your choice)....has taken on the 'sorry campaigns' to absolve themselves of any responsibility. This was not the intent. It is not working. The fear for hcp's and physicians remains even after all of this time to endeavor to change the system. I don't know that we can ever get back to just being human beings with all of our human frailties. I am not excusing those with dishonorable intents - professional or patients but surely these are the minority of cases. Lost in transition comes to mind.
Sandi Pniauskas
(Lynch Syndrome/multiple primary cancers)
By the Numbers: Not So Good at Saying Sorry
Most docs stay mum after botching care
Saturday, October 08, 2016
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