Monday, November 02, 2015
Dietary fat and fatty acid intake and epithelial ovarian cancer risk: evidence from epidemiological studies
open access
In summary, the findings of the present meta-analysis, which included 1 pooled analysis, 5 cohort studies, and 14 case-control studies, provide limited evidence of an association between dietary fat intake, including total fat, plant-based fat, animal-based fat, dairy-based fat, and saturated, monounsaturated, polyunsaturated, and trans-unsaturated FAs, and EOC risk. Further prospective studies are needed to confirm the associations between specific types of fat and EOC risk, and the results should be stratified by tumor invasiveness and EOC histology.
Efficacy and Interaction of Antioxidant Supplements as Adjuvant Therapy in Cancer Treatment
abstract
Oxidative stress is a key component in carcinogenesis. Although radiation produces reactive oxygen species, some anticancer agents such as alkylating agents, platinum and antitumor antibiotics exert cytotoxicity by generating free radicals. Nonenzymatic exogenous antioxidants such as vitamins, minerals, and polyphenols can quench ROS activity. However, whether antioxidants alter antitumor effects during radiotherapy and some types of chemotherapy remains unclear. In the present study, we reviewed antioxidants as an adjuvant therapy for cancer patients during chemotherapy or radiotherapy. Electronic literature searches were performed to select all randomized controlled clinical trials (RCTs) in which antioxidants were administered to cancer patients along with chemotherapy or radiotherapy. Articles or abstracts written in English were included. In total, 399 reports received primary screening. Duplicated articles and those meeting the exclusion criteria (not RCT, not human, and no oral administration) were excluded. Finally, 49 reports matching the inclusion criteria were included. It was difficult to determine whether antioxidants affect treatment outcomes or whether antioxidants ameliorate adverse effects induced by chemotherapy and radiotherapy. It is desirable to use an evidence-based method to select supplements best suited to cancer patients. Although there are many opinions about risks or benefits of antioxidant supplementation, we could mostly conclude that the harm caused by antioxidant supplementation remains unclear for patients during cancer therapy, except for smokers undergoing radiotherapy.
Friday, October 30, 2015
Is It Time to Centralize Ovarian Cancer Care in the United States?
abstract
Purpose
The purpose of this
article was to broadly review the most up-to-date information pertaining
to the centralization of ovarian cancer care in the United States (US)
and worldwide.
Methods
Much of the present
literature pertaining to disparities in, and centralization of, ovarian
cancer care in the US and internationally was reviewed, and specifically
included original research and review articles.
Results
Data show improved
optimal debulking rates, National Comprehensive Cancer Network (NCCN)
guideline adherence, and overall survival rates in higher-volume, more
specialized hospitals, and amongst higher-volume providers.
Conclusions
Patients with
invasive epithelial ovarian cancer, especially those with higher stages
(III and IV), are better served by centralized care in high-volume
hospitals and by high-volume physicians, who adhere to NCCN guidelines
wherever possible. More research is needed to determine the policy
changes that can increase NCCN guideline adherence in low-volume
hospitals and low-provider caseload scenarios. Policy and future
research should be aimed at increasing patient access, either directly
or indirectly, to high-volume hospital and high-volume providers,
especially amongst Medicare, lower socioeconomic status, and minority
patients.
Thursday, October 29, 2015
The Use of Superlatives in Cancer Research
JAMA
A range of speakers used superlatives, but the majority were journalists (55%), who may not have the expertise to identify the most promising medical therapies, or what magnitude of benefit warrants a superlative. The use of superlatives is common in cancer research news articles. Some of this use may be questioned.
HOTAIR and its surrogate DNA methylation signature indicate carboplatin resistance in ovarian cancer
Genome Medicine | Full text |
Association between HOTAIR (see: gene card) expression and poor outcome is restricted to carboplatin-treated patients
Staging Lymphadenectomy in Patients With Clear Cell Carcinoma of the Ovary
abstract
OBJECTIVE:
The purpose of this study was to assess the rate of lymph node (LN) metastasis in comprehensively staged ovarian clear cell carcinoma (OCCC) clinically confined to the ovary and determine factors associated with LN metastasis.METHODS:
We identified all cases of OCCC treated at 4 institutions from January 1994 through December 2011. We included cases with disease grossly confined to the ovary that had surgical staging performed, including at least 10 LNs sampled. Clinical and pathologic data were abstracted from electronic medical records, and a deidentified data set was compiled and processed at a single institution. Factors potentially associated with LN metastasis were tested. Appropriate statistical tests were performed.RESULTS:
We identified 145 eligible cases that met the criteria for this analysis. Median age was 52.9 years (range, 30-81 years), and median total LN count was 19 (range, 10-74). Seven (4.8%) of 145 comprehensively staged cases had LN metastasis; 6 of these cases (4.1%) were isolated metastasis. Cytologic washings, peritoneal, omental, and fallopian tube involvement were not associated with nodal metastasis. Cases with ovarian surface involvement and positive cytology had a 37.5% incidence of LN positivity, which was statistically meaningful when compared with all other cases (P = 0.003).CONCLUSIONS:
Women who underwent comprehensive staging for clinical stage I OCCC had an LN metastasis rate of 4.8%. The subgroup of cases with both ovarian surface involvement and positive cytology had the highest incidence of LN metastasis. This may influence clinical decision making on whether to perform lymphadenectomy in patients with incidental OCCC found after salpingo-oophorectomy.Challenges for Urologists in the Care of Patients with Lynch Syndrome: Example of A Patient with Muir-Torre Syndrome (MSH2)
abstract
The Muir-Torre syndrome (MTS) is a subtype of the Lynch syndrome (hereditary nonpolyposis colorectal cancer). In addition to tumours typically related to LS, MTS is associated with tumours of the sebaceous gland or keratoacanthoma. MTS is mostly characterised by a mutation of MSH2. In contrast to LS-associated tumours carrying a mutation of MLH1, MSH6 or PMS2, the frequency of urological neoplasms seems to be higher in Lynch syndrome patients with MSH2 mutation. Urological implications for the care of patients with LS or MTS include the early diagnosis of a possible hereditary background in patients presenting with urothelial cancers at an atypically young age and potentially the surveillance of carriers of mutations with an increased risk for urothelial cancers like males harbouring a MSH2 mutation.We report on a patient with various types of LS-associated cancers and cancers without a known association with LS, who died from multifocal metastasis of urothelial cancer. This case report shows that close interdisciplinary cooperation is mandatory for the treatment of patients with complex diseases.
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.
Wednesday, October 28, 2015
Patient-Reported Outcomes After Extensive (Ultraradical) Surgery for Ovarian Cancer
open access
Patient-Reported Outcomes After Extensive (Ultraradical) Surgery for Ovarian Cancer: Results From a Prospective Longitudinal Feasibility Study
In summary, this exploratory study provides useful insight into the impact of extensive surgery on patients. A putative survival gain from such techniques needs to be balanced against potential morbidity, mortality, impact on patient QoL, and resource utilization in health systems. Patients need this information to fully understand the gains versus impacts from undergoing extensive surgery for advanced-stage ovarian cancer.
Lesser-Known Molecules in Ovarian Carcinogenesis
open access
Abstract
Currently, the deciphering of the signaling pathways brings about new advances in the understanding of the pathogenic mechanism of ovarian carcinogenesis, which is based on the interaction of several molecules with different biochemical structure that, consequently, intervene in cell metabolism, through their role as regulators in proliferation, differentiation, and cell death. Given that the ensemble of biomarkers in OC includes more than 50 molecules the interest of the researchers focuses on the possible validation of each one’s potential as prognosis markers and/or therapeutic targets. Within this framework, this review presents three protein molecules: ALCAM, c-FLIP, and caveolin, motivated by the perspectives provided through the current limited knowledge on their role in ovarian carcinogenesis and on their potential as prognosis factors. Their structural stability, once altered, triggers the initiation of the sequences characteristic for ovarian carcinogenesis, through their role as modulators for several signaling pathways, contributing to the disruption of cellular junctions, disturbance of pro-/antiapoptotic equilibrium, and alteration of transmission of the signals specific for the molecular pathways. For each molecule, the text is built as follows: (i) general remarks, (ii) structural details, and (iii) particularities in expression, from different tumors to landmarks in ovarian carcinoma.
1. Introduction
There are several aspects which place the ovarian cancer in the focus of the scientific community. Its high mortality rate, due to the nonspecific symptoms that determine a delay of early diagnosis, the postsurgical treatment relapses, and the lack of favorable response to chemotherapy for most of the cases [1] require a better understanding of its mechanism and, implicitly, of the molecules that govern its behavior.
Although major progresses have been recorded in recent years in the knowledge of the complex signaling pathways involved in ovarian carcinogenesis [2], the deciphering of its pathogenic journey is far from being complete. The information on the genic and proteomic background of ovarian carcinoma (OC) could be regarded as a giant puzzle which is not yet assembled in order to form the entire image. On the basis of the molecular configuration of the signaling pathways, the interest of the researchers is focused on the identification of those components which could represent either new prognosis markers or new therapeutic targets, or both [3]. The difficulty of this endeavor is augmented by the histologic heterogeneity of ovarian tumors [4].
Molecular profiling of low grade serous ovarian tumours identifies novel candidate driver genes
abstract
Low grade serous ovarian tumours are a rare and under-characterised histological subtype of epithelial ovarian tumours, with little known of the molecular drivers and facilitators of tumorigenesis beyond classic oncogenic RAS/RAF mutations. With a move towards targeted therapies due to the chemoresistant nature of this subtype, it is pertinent to more fully characterise the genetic events driving this tumour type, some of which may influence response to therapy and/or development of drug resistance. We performed genome-wide high-resolution genomic copy number analysis (Affymetrix SNP6.0) and mutation hotspot screening (KRAS, BRAF, NRAS, HRAS, ERBB2 and TP53) to compare a large cohort of ovarian serous borderline tumours (SBTs, n = 57) with low grade serous carcinomas (LGSCs, n = 19). Whole exome sequencing was performed for 13 SBTs, nine LGSCs and one mixed low/high grade carcinoma. Copy number aberrations were detected in 61% (35/57) of SBTs, compared to 100% (19/19) of LGSCs. Oncogenic RAS/RAF/ERBB2 mutations were detected in 82.5% (47/57) of SBTs compared to 63% (12/19) of LGSCs, with NRAS mutations detected only in LGSC. Some copy number aberrations appeared to be enriched in LGSC, most significantly loss of 9p and homozygous deletions of the CDKN2A/2B locus. Exome sequencing identified BRAF, KRAS, NRAS, USP9X and EIF1AX as the most frequently mutated genes. We have identified markers of progression from borderline to LGSC and novel drivers of LGSC. USP9X and EIF1AX have both been linked to regulation of mTOR, suggesting that mTOR inhibitors may be a key companion treatment for targeted therapy trials of MEK and RAF inhibitors.
Tuesday, October 27, 2015
Chemotherapy reduces PARP1 in cancers of the ovary: implications for future clinical trials involving PARP inhibitors
Full text
Conclusion
Our data suggest that patients should be screened for PARP1 expression prior to therapy
with PARP inhibitors. Further, the observed reduction of intratumoral PARP1 post-chemotherapy
suggests that treating chemo-naïve patients with PARP inhibitors prior to the administration
of chemotherapy, or concurrently, might increase the responsiveness to PARP1 inhibition.
Thus, a change in the timing of PARP inhibitor administration may be warranted for
future clinical trials.
Six ‘biases’ against patients and carers in evidence-based medicine
Full text
..... Even when patients are ‘informed’, ‘empowered’, and ‘health-literate’ (and especially when they are not), they rarely inhabit a world of controlled experiments, abstracted variables, objective measurement of pre-defined outcomes, average results, or generalizable truths. Rather, they live in the messy, idiosyncratic, and unpredictable world of a particular person in a particular family context (or, for some, in a context of social isolation and/or abandonment by family) [5], [6]. Notwithstanding this, patients may seek out medical information and self-monitor biometric variables, with or without the knowledge or support of their clinician [7]...... The options tabled by the clinician for a ‘shared decision’ may or may not resonate with what has occurred in the patient’s world up to this point. Furthermore, following a (more or less) shared decision, the patient goes away and re-enters what has been termed the ‘lifeworld’ [12] – a world where people rather than biomedical variables have salience and where it is particularities, not mean values or generalizable truths, that matter [13]. In this world, different factors will be at stake; the illness as lived will differ from the disease or risk state in the evidence-based guideline, and may well be at odds with the outcomes (whether ‘patient reported’ or not) measured in the research trial [14]. With the help of particular carers, family, friends, and peers (whether defined as ‘carers’ or not), the patient tries to align the evidence-based model of disease with the actual experience of illness or (assigned) risk.....
Integrated care in ovarian cancer "IgV Ovar": results of a German pilot for higher quality in treatment of ovarian cancer
abstract
INTRODUCTION:
Late-stage ovarian cancer patient's survival depends on complete cytoreduction and chemotherapy. Complete cytoreduction is more often achieved in institutions with a case volume of >20 cases per year. The Integrated care program Ovar (IgV Ovar) was founded in 2005 and started recruiting in 2006 with 21 health insurances and six expert centers of ovarian cancer treatment as a quality initiative. Results of the pilot and outcomes of patients of three participating centers will be presented here.
METHODS:
Data of 1038 patients with ovarian cancer were collected. Adjuvant patients (n = 505) stage FIGO IIB-IV (n = 307) were analyzed for cytoreduction and survival. FIGO IIIC patients were analyzed separately.RESULTS:
Median follow-up was 32.7 months. Progression-free survival (PFS) was 23.1 months and overall survival (OS) was 53.6 months for stage IIB-IV. Patients with FIGO IIIC were completely cytoreduced in 48 %. PFS was 21, 29 months if completely cytoreduced. OS was 47.4, 64.9 months if completely cytoreduced.DISCUSSION:
Although the IgV Ovar Rhineland proved to have some structural problems with recruitment and prospective data collection, cytoreduction rates and outcome of patients prove treatment of patients in expert centers is superior to the national and international mean. Therefore, a new quality initiative will be started to bring more awareness to women and to their gynecologists and general practitioners of just how important a good referral strategy is.Cytoreductive surgery (CRS) and (HIPEC) in pediatric ovarian tumors: a novel treatment approach
abstract
PURPOSE:
Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been used in adults with ovarian carcinoma proving overall survival benefit in randomized trials, but measured in months. Diffuse peritoneal disease from pediatric type ovarian tumors is rare. We applied CRS and HIPEC to pediatric girls with diffuse peritoneal disease as part of a clinical trial.METHODS:
In all patients complete cytoreduction was followed by HIPEC using 100 mg/m2 of cisplatin for 90 min in a closed technique. All received neoadjuvant chemotherapy. Patients with disease outside of the abdominal cavity were excluded.RESULTS:
Of 101 pediatric CRS and HIPEC operations, 8 had ovarian primary tumors and multifocal peritoneal disease. There were three yolk sac tumors (germ cell, mixed teratoma), one Sertoli-Leydig, one PNET of the ovary, one choriocarcinoma, one juvenile granulosa cell tumor and one adenocarcinoma. Age ranged 4-18 years. Three of the 8 (37 %) recurred and died. The remaining 63 % are disease free 2-6 years post HIPEC. Overall survival and relapse-free survival in this cohort was 64 and 62 %, respectively [CI 0.64 (0.34, 1); 0.62 (0.37, 1)].CONCLUSIONS:
This is the first report of CRS and HIPEC in pediatric ovarian tumors. HIPEC may be effective in pediatric-type ovarian tumors. More study is needed in a larger cohort.Circulating tumor cells as trigger to hematogenous spreads and potential biomarkers to predict the prognosis in ovarian cancer
abstract
Despite several improvements in the surgical field and in the systemic treatment, ovarian cancer (OC) is still characterized by high recurrence rates and consequently poor survival. In OC, there is still a great lack of knowledge with regard to cancer behavior and mechanisms of recurrence, progression, and drug resistance. The OC metastatization process mostly occurs via intracoelomatic spread. Recent evidences show that tumor cells generate a favorable microenvironment consisting in T regulatory cells, T infiltrating lymphocytes, and cytokines which are able to establish an "immuno-tolerance mileau" in which a tumor cell can become a resistant clone. When the disease responds to treatment, immunoediting processes and cancer progression have been stopped. A similar inhibition of the immunosuppressive microenvironment has been observed after optimal cytoreductive surgery as well. In this scenario, the early identification of circulating tumor cells could represent a precocious signal of loss of the immune balance that precedes cancer immunoediting and relapse. Supporting this hypothesis, circulating tumor cells have been demonstrated to be a prognostic factor in several solid tumors such as colorectal, pancreatic, gastric, breast, and genitourinary cancer. In OC, the role of circulating tumor cells is still to be defined. However, as opposed to healthy women, circulating tumor cells have been demonstrated in peripheral blood of OC patients, opening a new research field in OC diagnosis, treatment monitoring, and follow-up.
Cancer Research UK response to IARC classification of red and processed meat
Cancer Research UK
"This decision doesn't mean you need to stop eating any red and processed meat. But if you eat lots of it you may want to think about cutting down." - Professory Tim Key, Cancer Research UK
17th National Congress of Medical Oncology (abstract index)
Table of Contents
17th National Congress of Medical Oncology, 23-25 October 2015, Rome, Italy
Volume
26
suppl 6
October 2015
Targeting Programmed Cell Death 1 in Ovarian Cancer (PD-1/PD-L1/Nivolumab)
Editorial - open access
accompanying article doi:10.1200/JCO.2015.62.3397
Safety and Antitumor Activity of Anti–PD-1 Antibody, Nivolumab, in Patients With Platinum-Resistant Ovarian Cancer
Sunday, October 25, 2015
Is adjuvant chemotherapy indicated in ovarian immature teratomas? A combined data analysis from the Malignant Germ Cell Tumor International Collaborative
abstract
BACKGROUND
There
is a debate regarding the management of ovarian immature teratomas
(ITs). In adult women, postoperative chemotherapy is standard except for
stage I, grade 1 disease, whereas surgery alone is standard in
pediatric patients. To determine the role of chemotherapy, a pooled
analysis of pediatric and adult clinical trials was conducted.
METHODS
Data
from 7 pediatric trials and 2 adult trials were merged in the Malignant
Germ Cell International Collaborative data set. Four trials included
patients with newly diagnosed pure ovarian ITs and were selected
(Pediatric Oncology Group/Children's Cancer Group Intergroup Study (INT
0106), Second UKCCSG Germ Cell Tumor Study (GC2), Gynecologic Oncology
Group (GOG 0078 and GOG 0090). Adult and pediatric trials were analyzed
separately. The primary outcome measures were event-free survival (EFS)
and overall survival (OS).
RESULTS
One
hundred seventy-nine patients were included (98 pediatric patients and
81 adult patients). Ninety pediatric patients were treated with surgery
alone, whereas all adult patients received chemotherapy. The 5-year EFS
and OS were 91% and 99%, respectively, for the pediatric cohort and 87%
and 93%, respectively, for the adults. There were no relapses in grade 1
patients, regardless of the stage or age. Only 1 adult patient with a
grade 2 IT relapsed. Among grade 3 patients, the 5-year EFS was 0.92
(0.72-0.98) for stage I/II and 0.52 (0.22-0.75) for stage III in the
pediatric cohort (P = .005) and 0.91 (0.69-0.98) for stage I/II and 0.65 (0.39-0.83) for stage III/IV in the adult cohort (P = .01). Postoperative chemotherapy did not decrease relapses in the pediatric cohort.
CONCLUSIONS
The grade was the most important risk factor for relapse in ovarian ITs. Among grade 3 patients, the stage was significantly associated with relapse. Adjuvant chemotherapy did not decrease relapses in the pediatric cohort; its role in adults remains unresolved
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