Tuesday, September 29, 2015
Adjuvant Hormone Therapy May Improve Survival in Epithelial Ovarian Cancer: Results of the AHT Randomized Trial
Abstract
Purpose To assess the effects of adjuvant hormone therapy (AHT) on survival and disease outcome in women with epithelial ovarian
cancer.
Patients and Methods
Participants were premenopausal and postmenopausal women who had been
diagnosed with epithelial ovarian cancer (any International
Federation of Gynecology and Obstetrics stage) 9
or fewer months previously. Ineligible patients included those with
deliberately
preserved ovarian function, with a history of a
hormone-dependent malignancy, or with any contraindications to
hormone-replacement
therapy. Patients were centrally randomly
assigned in a 1:1 ratio to either AHT for 5 years after random
assignment or no
AHT (control). Main outcome measures were
overall survival (OS), defined as time from random assignment to death
(any cause),
and relapse-free survival, defined as time from
random assignment to relapse or death (any cause). Patients who
continued,
alive and relapse free, were censored at their
last known follow-up.
Results A total of 150
patients (n = 75, AHT; n = 75, control) were randomly assigned from
1990 to 1995 from 19 centers in the United
Kingdom, Spain, and Hungary; all patients were
included in intention-to-treat analyses. The median follow-up in alive
patients
is currently 19.1 years.
Attitudes and Beliefs Toward Supportive and Palliative Care Referral Among Hematologic and Solid Tumor Oncology Specialists
theoncologist (subscriber based)
Abstract
Background.
Palliative care (PC) referrals are
often delayed for patients with hematologic malignancies. We examined
the differences in
attitudes and beliefs toward PC referral between
hematologic and solid tumor specialists and how their perception
changed
with use of the service name “supportive care”
(SC).
Materials and Methods.
We randomly surveyed 120 hematologic and 120 solid tumor oncology specialists at our tertiary care cancer center to examine
their attitudes and beliefs toward PC and SC referral.
Maintenance Therapy in Ovarian Cancer with Targeted Agents Improves PFS and OS: A Systematic Review and Meta-Analysis
open access
Background
Maintenance therapy with targeted agents for prolonging remission for ovarian cancer patients remains controversial. As a result, a meta-analysis was conducted to assess the effectiveness and safety of using maintenance therapy with targeted agents for the treatment of ovarian cancer.Subgroup analysis
Two subgroups were initially divided based on whether targeted agents were combined with first-line therapy. In 2 trials, standard chemotherapy was combined with targeted agents as the first-line therapy, whereas in the remaining 11 trials the first-line therapy was standard chemotherapy only. There were no significant differences in therapeutic effectiveness (PFS, OS) between subgroups. There were also no significant differences between subgroups according to which targeted agents were employed (monoclonal antibody vs. small molecules). Finally, 2 subgroups were divided according to the withdrawal rate (>30% vs. <30%) of targeted maintenance therapy, and the results indicated that there were significant differences among them. One of the subgroups was insufficiently studied, which reduces the credibility of the results that were obtained in the above subgroup analyses.In conclusion, the results of our meta-analysis suggested that maintenance therapy with targeted agents may not only postpone the progress of ovarian cancer but may also improve survival. However, this treatment approach also increases the incidence of adverse events that are related to ovarian cancer. In our opinion, the above discussed pros and cons must be weighed with respect to the clinical application of using targeted maintenance therapy in ovarian cancer patients. Additional multi-center RCTs with larger patient cohorts should be required before maintenance therapy with targeted agents becomes a widely used clinical choice for the treatment of ovarian cancer.
A Systematic Review of Nonpharmacologic Interventions for Treatment-Related Symptoms in Women With Ovarian Cancer
Abstract
BACKGROUND:
Women with ovarian cancer have a continued high symptom burden in comparison to other cancer survivors secondary to ongoing chemotherapy treatment. Prolonged or ineffective management of treatment-related symptoms can contribute to treatment noncompliance, worsening of symptoms, and reduced health-related quality of life.OBJECTIVES:
This review of the literature was conducted to describe experimental and quasi-experimental research addressing nonpharmacologic interventions for the treatment-related symptoms of sleep disturbance, pain, anxiety, depression, and low energy or fatigue in women with ovarian cancer and to critique the quality of interventions.METHODS:
A systematic search of the literature was conducted in PubMed and yielded 136 articles. Eight articles met the inclusion criteria and were evaluated.FINDINGS:
Nonpharmacologic interventions for treatment-related symptoms were complex, with an average of 4.4 components. Intervention delivery, setting, and exposure varied widely across studies. Only three studies contained details sufficient to replicate the intervention. Lack of clarity in intervention reporting may explain perceptions of clinically inefficacious symptom management in this context. Greater attention to reporting would facilitate better translation of interventions into practice and when addressing complex cancer symptom clusters.Monday, September 28, 2015
Sunday, September 27, 2015
Evidence Network.ca (more research entities scrapped)
Evidence Network Canada
Canadian Institutes of Health Research (CIHR) funding, Centre for Healthcare Innovation and Research Manitoba contributions for Evidence Network will all come to an end in 2016.
9TH ANNUAL OVARIAN SURVIVORS WEEKEND
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Pancreatic cancer: BRCA mutation and personalized treatment
Pancreatic cancer
The highly heterozygous nature of pancreatic cancer is partially responsible for its therapeutic ineffectiveness and resistance. Therefore, the ability to identify subgroups of pancreatic cancer with unique biological characteristics and treatment response is urgently needed. In addition to breast and ovarian cancer, pancreatic cancer is the third most common cancer type that is related to the early onset (BRCA) gene mutation in breast cancer. Mounting evidence has demonstrated that BRCA1/2-mutant breast and ovarian cancers are highly sensitive to DNA damage-related treatment, including poly(ADP-ribose) polymerase inhibitors (PARPi) and platinum-based agents. Preliminary evidence also showed promising results for DNA damage-related treatment in BRCA1/2-mutant pancreatic cancer. Importantly, several prospective clinical trials of PARPi-based regimens are underway for BRCA1/2-mutated pancreatic cancer. Pancreatic cancer with a BRCA1/2 mutation is a small subgroup with a promising therapeutic strategy.
Maintenance Therapy in Ovarian Cancer with Targeted Agents Improves PFS and OS: A Systematic Review and Meta-Analysis
open access
The articles included in our analysis were published between 2006 and 2014; thus, they provided relatively new data.
Background
Maintenance therapy with targeted agents for prolonging remission for ovarian cancer patients remains controversial. As a result, a meta-analysis was conducted to assess the effectiveness and safety of using maintenance therapy with targeted agents for the treatment of ovarian cancer.....Almost half of the trials that were included in our meta-analysis were high-quality phase III RCTs. Furthermore, the majority of them were conducted in the United States, and the remaining were conducted in various European countries. Many of the trials included in our analysis were conducted by representative multi-center tumor cooperative groups, such as the Gynecologic Oncology Group, the Canada Clinical Trials Group Study, and the European Organization for Research and Treatment of Cancer-Gynecological Cancer Group (EORTC-GCG). However, more than half of the included trials had relatively small sample sizes with respect to the targeted maintenance therapy groups. As inherent limitations and inconsistent conclusions were found among previous trials, it was therefore necessary for us to synthesize as many trials as possible to obtain the most credible evidence.....
Secondary Primary Malignancy Risk in Patients With Ovarian Cancer in Taiwan
open access
Secondary Primary Malignancy Risk in Patients With Ovarian Cancer in Taiwan: A Nationwide Population-Based Study
DISCUSSION
This present study is the first to distinctly demonstrate a significantly increased SIR for metachronous SPM among ovarian cancer patients in Asia..... Several studies have focused on the issue of SPM after ovarian cancer.5–9,11–21 Most of these studies demonstrated an increased risk of SPM,5–8,12,14,15,17,18,20 but others did not.9,11,13 Bergfeldt et al9 proposed that findings of increased occurrence of secondary primary cancer in patients with ovarian cancer have been biased by misclassification. A study conducted in the UK confirmed the high incidence of synchronous cancer in patients with ovarian cancer, which may also bias estimates of SPM incidence.14 In addition, most previous studies were single-institute case series; few nationwide or multiple-institute cohort studies have been conducted with reference groups to examine the SIR or relative risk of SPM. Furthermore, recent changes in chemotherapy regimens may also influence the risk of SPM. To avoid surveillance bias, we strictly excluded SPMs occurring within 1 year after ovarian cancer diagnosis.....
Impact of Pelvic and Para-aortic Lymphadenectomy in Advanced Ovarian Cancer After Neoadjuvant Chemotherapy
abstract
Aim: The aim of our study was to evaluate the impact of systemic pelvic and para-aortic lymphadenectomy on survival in patients with advanced ovarian cancer after neoadjuvant chemotherapy.
Patients and Methods: This multi-centric descriptive study included patients with initially inoperable advanced ovarian cancer, undergoing neoadjuvant chemotherapy followed by cytoreductive surgery with no residual tumor between 1998 and 2012. They were distributed into two groups depending on if they underwent lymphadenectomy or not during the interval surgery.
Results: Among the 101 included patients, 54 underwent lymphadenectomy and 47 did not. The multivariate analysis for overall survival showed no significant difference between the two groups [hazard ratio (HR)=1.88, confidence interval (CI)=0.89-3.94; p=0.08]. The multivariate analysis for progression-free survival showed no significant difference (HR=1.43, 95% CI=0.86-2.39; p=0.17).
Conclusion: In patients with advanced ovarian cancer, treated by neoadjuvant chemotherapy and interval surgery with no residual tumor, lymphadenectomy does not seem to improve the survival rate.
View larger version:
Overall survival in patients with advanced ovarian cancer treated by neoadjuvant chemotherapy and interval debulking surgery
without (group 1) and with (group 2) lymphadenectomy.
The Saudi Hereditary Colorectal Tumor Registry: status and challenges
abstract
The Saudi Hereditary Colorectal Tumor Registry was established in 2008 at the King Faisal Specialist Hospital and Research Center in Riyadh, Saudi Arabia, providing registration of individuals and families with hereditary colorectal diseases, including, but not limited to, familial adenomatous polyposis and Lynch syndrome. The registry has faced numerous challenges, including the inability to recruit experienced qualified staff and fulfill all molecular genetic services required, and most importantly, the lack of a national policy to refer all patients with hereditary colorectal tumours to the registry. The authors suggest that a robust registry service for hereditary colorectal tumors in Saudi Arabia requires the formulation of a national committee, to identify all challenges and develop national solutions as part of a strategic plan with well-defined targets and goals. This article discusses how local and global challenges are affecting the growth of the Saudi Hereditary Colorectal Tumor Registry.
Intestinal Tumorigenesis: Mechanisms of Development & Progression
Google Books
Contents
Hereditary CRC Syndromes
1
Microsatellite Instability and Intestinal Tumorigenesis
29
Biology of Intestinal Epithelial Stem Cells
55
The Role of PI3K Signaling Pathway in Intestinal Tumorigenesis
100
The Epigenetics in Intestinal Tumorigenesis
137
MicroRNA Involvement in Intestinal Tumorigenesis
169
Microbiome Implications in Intestinal Tumorigenesis
189
Inflammation and colorectal cancer
210
Sphingolipids in Intestinal Inflammation and Tumorigenesis
257
An Etiological Factor in The Development of Intestinal Tumorigenesis
287
Epithelial to Mesenchymal Transition EMT and Intestinal Tumorigenesis
309
Omics and Biomarkers Development for Intestinal Tumorigenesis
365
Targeted Therapies For Intestinal Tumorigenesis
391
Index
441
Copyright
Ovarian clear cell carcinoma, outcomes by stage: The MSK experience
abstract
OBJECTIVE:
Ovarian clear cell carcinomas (OCCCs) are rare, and uncertainty exists as to the optimal treatment paradigm and validity of the FIGO staging system, especially in early-stage disease.METHODS:
We performed a retrospective cohort study of all OCCC patients diagnosed and treated at Memorial Sloan Kettering Cancer Center between January 1996 and December 2013. Progression-free survival (PFS) and overall survival (OS) were calculated by stage and race, and comparisons were made using the log-rank test. Statistical significance was set at p<0.05. Type and duration of treatment were also recorded.RESULTS:
There were 177 evaluable patients. The majority of patients were stage I at diagnosis (110/177, 62.2%). Of these, 60/110 (54.6%) were stage IA, 31/110 (28.2%) were stage IC on the basis of rupture-only, and 19/110 (17.3%) were stage IC on the basis of surface involvement and/or positive cytology of ascites or washings. Patients with stage IA and IC based on rupture-only had similar PFS/OS outcomes. Patients with stage IC based on surface involvement and/or positive cytology had a statistically significant decrement in PFS/OS. Stage was an important indicator of PFS/OS, while race was not.CONCLUSIONS:
OCCC often presents in early stage. Women with stage IA OCCC have excellent prognosis, and future studies should explore whether they benefit from adjuvant chemotherapy. Women with IC OCCC need further staging clarification, as surgical rupture alone affords better prognosis than surface involvement and/or positive cytology. Women with advanced OCCC have poor survival and are often chemotherapy resistant/refractory. New treatment paradigms are needed.Increased risk of severe infections in cancer patients treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors: a meta-analysis
open access
Exploratory subgroup analysis showed no effect of tumor types, phase of trials, or agent used on the Peto OR of severe infections. When stratified according to specific infectious events, the risks of high-grade febrile neutropenia, pneumonia, fever, and sepsis were increased compared with controls....
Conclusion: The use of VEGFR-TKIs significantly increases the risk of developing severe and fatal infectious events in cancer patients. A close monitoring for any signs of infections is recommended for patients treated with VEGFR-TKIs.
Exploring research participation among (UK) cancer patients: analysis of a national survey and an in-depth interview study
Full text
Breast and urological cancer patients had the highest and lowest proportions of research discussion.
Since your diagnosis, has anyone discussed with you whether you would like to take part in cancer research?
Overall, 30.4 % of respondents (n = 20,356) reported that, since their diagnosis, someone had discussed with them whether they would like to take part in cancer research.Did you go on to take part in cancer research?
Of the 20,356 patients with whom research participation was discussed, 62.3 % (n = 12,682) reported that they went on to take part.Trial of Personalized Cancer Care Disappoints/One Biopsy not enough
medscape
....The results from this trial, known as SHIVA, were published online September 3 in Lancet Oncology. The study was also presented earlier this year at the American Society of Clinical Oncology (ASCO) 2015 annual meeting.
The trial was conducted in 195 patients with metastatic cancer (any solid tumor) refractory to standard of care....
also:
Editors' Recommendations
JTM | Full text | Molecular magnetic resonance imaging in cancer
Full text
Conclusions
Molecular MR imaging is well suited to measure molecular and cellular processes including
metabolism, apoptosis, cell proliferation and biosynthetic pathways of different metabolites
in vivo in cancer. Molecular imaging can play an important role in every aspect of
oncology practice, including early disease detection, diagnosis, staging, personalized
treatment, and treatment monitoring. Prostate, ovarian and lung cancer are just a
few of the many types of cancer in which molecular imaging truly changed the direction
and outcome of the patient care. The ability of molecular imaging to detect abnormalities
very early in the progression of disease has the potential to change medicine from
reactive to proactive, detecting and curing disease in its most treatable phase and
saving countless lives. In medical setup, molecular MRI will pave the way toward a
significant improvement in early detection of disease, therapy planning and monitoring
the therapeutic outcomes.
Long-term primary culture of a clear cell ovarian carcinoma reveals an epithelial–mesenchymal cooperative interaction
Full text
Background
Cell lines that can be propagated indefinitely in culture are a helpful resource with
which to study biological processes in cancer biology and experimental therapy. A
large number of human cancer cell lines has been generated in the past few decades,
and vast scientific information has been gathered from experimental exploitation of
these cell lines; however, expanding literature suggests that predictions made based
on the behavior of cancer cell lines in vitro, or xenografted into immunosuppressed
mice, do not always materialize in clinical applications. In the case of ovarian cancer,
this occurrence is highly remarkable. Over 100 human epithelial ovarian cancer (EOC)
cell lines have been characterized [1]–[3] in the past few decades, facilitating the discovery of many pathobiological mechanisms
and allowing preclinical testing of novel anti-cancer drugs. Nevertheless, the standard
of care for this disease has not changed since the introduction of the platinum/taxane
drug combination in the mid-1990s [4]. This leads us to reflect that the experimental models we are using to study cancer
in general and ovarian cancer in particular, while useful, are not entirely comprehensive....
Comparing gene expression data from formalin-fixed, paraffin embedded tissues and qPCR with that from snap-frozen tissue and microarrays for modeling outcomes of patients with ovarian carcinoma
Full text
Background
Using gene expression and clinical data from The Cancer Genome Atlas (TCGA), we previously
developed a model that predicts variations in response of high-grade serous ovarian
cancer to cytotoxic chemotherapies. In that publication [1], we described a method for reducing the list of genes needed to predict clinical
outcomes to fewer than 100. We selected those genes from more than 10,000 possibilities
by identifying genes within a core group of 12 cancer pathways [2], [3] whose variation in expression had the greatest effect on disease progression. Predictions
of response to specific chemotherapeutic agents were suggested by the cumulative levels
of gene expression among the 91 genes selected from the 12 pathways. Three of the
pathways did not have genes identified, leaving 9 core pathways informative. We defined
the predictions made by gene expression within these pathways as the Patient-Specific
Risk Profile (PSRP).
Gene expression levels reported by Affymetrix microarrays and qPCR may differ significantly,
creating potential difficulties for models developed on one platform and utilized
in the other [4]......
Thursday, September 24, 2015
PARP14 promotes the Warburg effect in hepatocellular carcinoma by inhibiting JNK1-dependent PKM2 phosphorylation and activation (sugar)
Nature - open access (highly technical)
plain english link - Starving cancer cells of sugar could be the key to future treatment
also: Warburg Effect as referenced in Nature publication (Wiki)
Warburg effect
From Wikipedia, the free encyclopedia
The phrase "Warburg effect" (/ˈvɑrbʊərɡ/) is used for two unrelated observations in biochemistry, one in plant physiology and the other in oncology, both due to Nobel laureate Otto Heinrich Warburg.
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