- •GR activation promotes cell survival in GR-positive high-grade serous ovarian carcinoma (HGS-OvCa) cell lines treated with chemotherapy.
- •GR antagonism increases chemotherapy-induced cell death in a GR-positive HGS-OvCa xenograft model.
- •GR is expressed in the majority of primary HGS-OvCas examined.
Monday, June 29, 2015
...patient self-administered cancer family history questionnaire in identification of gyn cancer pts suspected of Lynch syndrome (Japan)
abstract
Usefulness of the patient self-administered cancer family history questionnaire in identification of gynecological cancer patients suspected of Lynch syndrome: KCOG-G1302 study
Background: Detailed family history collection is necessary to detect gynecological cancer patients suspected of Lynch syndrome (LS). However, clinicians have little time for family history interviews. In addition, there is a lack of genetic counselors in Japan. Therefore, information from medical records on the first visit (MR) is insufficient to determine if a patient may be at risk of LS. We showed that using the self-administered cancer family history questionnaire (SACFHQ) improves identification of patients suspected of LS.
Methods: We recruited endometrial or ovarian cancer patients already diagnosed or newly diagnosed from research participating institutions. After consent was obtained, participants completed the questionnaire. By referring to the cancer family history obtained from MR and SACFHQ, we referred to cases that met the Amsterdam criteria II(AMSII), the SGO20-25% criteria (SGO20-25%), ACOG’s clinical bulletin 2014 criteria (ACOG2014).
Results: There was a total of 493 participants. 38 patients were excluded by exclusion criteria. Finally, 455 were eligible. Median age at diagnosis was 56 (range21-84). 243 participants were endometrial cancer patients, and 213 were ovarian cancer, including peritoneal and tubal cancer. 12 cases had either synchronous/metachronous endometrial and colorectal cancer. 4 cases had either synchronous/metachronous ovarian and colorectal cancer. Among these 16 cases, endometrial or ovarian cancer was sentinel in 8 cases. By using MR, 0/455 (0%), 4/455 (0.9%), and 170/455 (37%) cases met AMSII, SGO20-25%, ACOG2014 criteria, respectively. By using SACFHQ, 6/455 (1.3%), 9/455 (2.0%), and 217/455 (48%) cases met AMSII, SGO20-25%, ACOG2014 criteria, respectively. All 6 cases that met AMSII were endometrial cancer patients. 8 of 9 patients who met SGO20-25% were endometrial cancer patients, and one patient was ovarian cancer.
Conclusions: Family cancer history obtained from MR was shown to be insufficient to identify individuals at risk of LS. SACFHQ (self-administered cancer family history questionnaire) improves identification of gynecological cancer patients suspected of LS. Clinical trial information: 000013192.
The Ovarian Cancer Consortium for Long-Term Survival - seeking OC patient participation
Massachusetts General Hospital, Boston, MA
The Consortium for Long-Term Survival, led by the Mass General Cancer Center and funded by the Department of Defense, is a research group seeking long-term survivors of ovarian cancer. If you are a 8 year or more stage III or stage IV ovarian cancer survivor, your participation can help to improve the treatment, survival, and survivorship of all women.
We now have the technological tools to try to unlock the reasons why some women do much better than others who face advanced ovarian cancer. We hope to find the key to long-term survival.
With your help, we want to better define five aspects of ovarian cancer in long-term survivors of the condition:
- The ability of their tumor cells to grow and survive, even after surgery
- Just how capable these tumors are to grow their own blood supply channels
- How these cancers interact and invade surrounding structures
- How women coped with their cancer in the past and in the present
- What their quality of life is like now, compared to how it was in various times in their cancer journey
If you would like more information about this research program, click here to contact Giulia Fulci, Project Co-Ordinator
The Value of Intraoperative Near-Infrared Fluorescence Imaging Based on Enhanced Permeability and Retention of Indocyanine Green: Feasibility and False-Positives in Ovarian Cancer
open access
Objective
In ovarian cancer, two of the most important prognostic factors for survival are completeness of staging and completeness of cytoreductive surgery. Therefore, intra-operative visualization of tumor lesions is of great importance. Preclinical data already demonstrated tumor visualization in a mouse-model using near-infrared (NIR) fluorescence imaging and indocyanine green (ICG) as a result of enhanced permeability and retention (EPR). The aim of this study was to determine feasibility of intraoperative ovarian cancer metastases imaging using NIR fluorescence imaging and ICG in a clinical setting.
Methods
Ten patients suspected of ovarian cancer scheduled for staging or cytoreductive surgery were included. Patients received 20 mg ICG intravenously after opening the abdominal cavity. The mini-FLARE NIR fluorescence imaging system was used to detect NIR fluorescent lesions.Results
6 out of 10 patients had malignant disease of the ovary or fallopian tube, of which 2 had metastatic disease outside the pelvis. Eight metastatic lesions were detected in these 2 patients, which were all NIR fluorescent. However, 13 non-malignant lesions were also NIR fluorescent, resulting in a false-positive rate of 62%. There was no significant difference in tumor-to-background ratio between malignant and benign lesions (2.0 vs 2.0; P=0.99).Conclusions
This is the first clinical trial demonstrating intraoperative detection of ovarian cancer metastases using NIR fluorescence imaging and ICG. Despite detection of all malignant lesions, a high false-positive rate was observed. Therefore, NIR fluorescence imaging using ICG based on the EPR effect is not satisfactory for the detection of ovarian cancer metastases. The need for tumor-specific intraoperative agents remains.Trial Registration
ISRCTN Registry ISRCTN16945066.....Clinical feasibility trials using this effect with ICG in breast cancer patients in a pre-operative diagnostic setting and in gastric cancer patients during endoscopic surgery showed that it was possible to distinguish tumor from surrounding tissue [18–23]. In addition, Kosaka et al.[24] detected small ovarian (1–2 mm in size) cancer implants using NIR fluorescent imaging after intravenous (IV) administration of ICG in a mouse model. Pathophysiological heterogeneity of solid tumors, for examples in size, presence of necrosis, or presence of vascular mediators may influence accumulation of macromolecules in tumor tissue [25,26]. It is therefore not clear if all preclinical results can be translated to the clinic.
Postoperative Complications After Distal Pancreatectomy Performed During Cytoreductive Surgery for Gynecologic Malignancies
abstract
Objectives: To investigate the incidence of pancreatic
leak and other postoperative complications after distal pancreatectomy
performed during debulking surgery for gynecologic malignancies.
Methods: All patients who underwent distal
pancreatectomy during their debulking surgery from 2010 to 2014 were
identified. Postoperative complications within 30 days and pancreatic
leak within 120 days after surgery were included.
Results: Eighteen patients met the inclusion criteria.
The median age was 62 years (36–78 years). Four patients (22%) were
admitted to the intensive care unit, and the average length of hospital
stay was 10 days. Nine patients developed postoperative complications
within 30 days after surgery (50%) with no perioperative mortality up to
90 days after surgery. No patients required reexploration.
Impact of Age on 30-Day Mortality and Morbidity in Patients Undergoing Surgery for Ovarian Cancer
abstract
OBJECTIVE:
To examine the effect of age on postoperative 30-day morbidity andmortality after surgery for ovarian cancer.
METHODS:
The American College of Surgeons National Surgical QualityImprovement Program files were used to identify patients with ovarian
cancer who underwent surgery in 2005 to 2011. Women were divided
into 4 age groups: <60, 60 to 69, 70 to 79, and ≥80 years. Multivariable
logistic regression models were performed.
RESULTS:
Of 2087 patients included, 47% were younger than 60 years, 28% were60 to 69 years old, 18% were 70 to 79 years old, and 7% were 80 years
or older. Overall 30-day mortality and morbidity rates were 2% and 30%.
Elderly patients 80 years or older were more likely to die within 30 days
compared with patients younger than 60 years, 60 to 69 years old, and
70 to 79 years old (9.2% vs. 0.6% vs .2.8% vs 2.5%, P < 0.001). Elderly
patient aged 80 years or older were more likely to develop pulmonary
(9% vs 2% vs 5% vs 3%, P < 0.001) and septic (9% vs 3% vs 5% vs
4%, P = 0.01) complications compared with patients younger than
60 years, 60 to 69 years old, and 70 to 79 years old, respectively.
Make New Friends But Keep the Old: Minimally Invasive Surgery Training in Gynecologic Oncology Fellowship Programs
abstract
Objectives: To evaluate the role of minimally invasive
surgery (MIS) in gynecologic oncology fellowship training and fellows’
predictions of their use of MIS in their future practice.
Methods: All fellows-in-training in American Board of
Obstetrics and Gynecology–approved training programs were surveyed in
2012 through an online or mailed-paper survey. Data were analyzed and
compared to results of a similar 2007 survey.
Results: Of 172 fellows, 69 (40%) responded. Ninety-nine percent of respondents (n = 68) indicated that MIS was either very important or important
in gynecologic oncology, a proportion essentially unchanged from 2007
(100%). Compared to 2007, greater proportions of fellows considered
laparoscopic radical hysterectomy and node dissection for cervical
cancer (87% vs 54%; P < 0.0001) and trachelectomy and staging for cervical cancer (83% vs 32%; P < 0.0001) appropriate for MIS. Of the respondents, 92% believed that maximum or some emphasis
should be placed on robotic-assisted surgery and 89% on traditional
laparoscopy during fellowship training. Ten percent rated their
fellowship training in laparoendoscopic single-site surgery as very poor; 44% said that the question was not applicable.
Role of Minimally Invasive Surgery in Gynecologic Oncology - update SGO
abstract
Objectives: To evaluate the current patterns of use of
minimally invasive surgical procedures, including traditional,
robotic-assisted, and single-port laparoscopy, by Society of Gynecologic
Oncology (SGO) members and to compare the results to those of our 2004
and 2007 surveys.
Methods: The Society of Gynecologic Oncology members
were surveyed through an online or mailed-paper survey. Data were
analyzed and compared with results of our prior surveys.
Results: Four hundred six (32%) of 1279 SGO members
responded. Eighty-three percent of respondents (n = 337) performed
traditional laparoscopic surgery (compared with 84% in 2004 and 91% in
2007). Ninety-seven percent of respondents performed robotic surgery
(compared with 27% in 2007). When respondents were asked to indicate
procedures that they performed with the robot but not with traditional
laparoscopy, 75% indicated radical hysterectomy and pelvic
lymphadenectomy for cervical cancer. Overall, 70% of respondents
indicated that hysterectomy and staging for uterine cancer was the
procedure they most commonly performed with a minimally invasive
approach. Only 17% of respondents who performed minimally invasive
surgery performed single-port laparoscopy, and only 5% of respondents
indicated that single-port laparoscopy has an important or very important role in the field.
Conclusions: Since our prior surveys, we found a
significant increase in the overall use and indications for robotic
surgery. Radical hysterectomy or trachelectomy and pelvic
lymphadenectomy for cervical cancer and total hysterectomy and staging
for endometrial cancer were procedures found to be significantly more
appropriate for the robotic platform in comparison to traditional
laparoscopy. The indications for laparoscopy have expanded beyond
endometrial cancer staging to include surgical management of early-stage
cervical and ovarian cancers, but the use of single-port laparoscopy
remains limited.
Thrombocytosis is Predictive of Postoperative Pulmonary Embolism in Patients With Gynecologic Cancer
abstract
Objectives: The prompt diagnosis of postoperative
pulmonary embolism (PE) in gynecologic oncology patients is imperative,
but the clinical presentation is nonspecific in this high-risk group. We
sought to determine risk factors and clinical findings that may assist
clinicians in diagnosing PE in the inpatient setting.
Methods: Radiology data were queried to identify
patients with gynecologic cancer who had a postoperative PE evaluation
with computed tomography pulmonary angiography (CT-PA). Patient clinical
findings at the time of the PE evaluation were abstracted, and
univariate and multivariate regression analyses were performed to
identify predictors of PE.
Results: For 6 years, there were 2498 major
gynecologic oncology surgical procedures performed at our institution.
Within 14 days of surgery, 107 CT-PA studies were obtained with a
positive study rate of 24.3%. In patients with and without PE, there was
no significant difference noted for age, oxygen saturations, body mass
index and heart rate. After controlling for stage, history of venous
thromboembolism (VTE), heart rate, and oxygen saturation, platelet count and history of VTE (odds ratio, were identified as independent predictors of PE in the multivariate model.
Conclusions: Although clinicians often use tachycardia
and low oxygen saturation as triggers to order PE imaging studies,
these signs have a very low specificity. Given the findings of our
study, accounting for high platelet count and history of VTE increases
the pretest probability of CT-PA study.
Epirubicin, Cisplatin, and Capecitabine for Primary Platinum-Resistant or Platinum-Refractory Epithelial Ovarian Cancer:
open access
Epirubicin, Cisplatin, and Capecitabine for Primary Platinum-Resistant or Platinum-Refractory Epithelial Ovarian Cancer: Results of a Retrospective, Single-Institution Study
.... It should be noted that because there were no responses in patients
with platinum-refractory or clear cell disease, logistic regression results for these parameters were nonestimable....Although the regression models
suggest that platinum-refractory status is a stronger predictor
of poor outcomes than clear cell histology, examination of a
larger data set is needed to increase confidence in this conclusion.....
Objective: Primary platinum-resistant epithelial
ovarian cancer (EOC) is an area of unmet medical need. There is limited
evidence from small studies that platinum-based combinations can
overcome “resistance” in a proportion of patients. We investigated the
efficacy and toxicity of platinum-based combination chemotherapy in the
platinum-resistant and platinum-refractory setting.
Sunday, June 28, 2015
Does one size fit all? The updated ovarian cancer staging: Still a work in progress
Editorial - abstract
The International Federation of Gynecology and Obstetrics (FIGO) has recognized serous tubal intraepithelial carcinoma as a precursor lesion for high-grade serous epithelial ovarian cancer. Future staging systems should consider reclassifying stage based on tumor biologic behavior.
Abridged republication of FIGO's staging classification for cancer of the ovary, fallopian tube, and peritoneum
Abstract
Ovarian, fallopian tube, and peritoneal cancers have a similar clinical presentation and are treated similarly, and current evidence supports staging all 3 cancers in a single system. The primary site (i.e. ovary, fallopian tube, or peritoneum) should be designated where possible. The histologic type should be recorded. Intraoperative rupture (“surgical spill”) is IC1; capsule ruptured before surgery or tumor on ovarian or fallopian tube surface is IC2; and positive peritoneal cytology with or without rupture is IC3. The new staging includes a revision of stage III patients; assignment to stage IIIA1 is based on spread to the retroperitoneal lymph nodes without intraperitoneal dissemination. Extension of tumor from omentum to spleen or liver (stage IIIC) should be differentiated from isolated parenchymal metastases (stage IVB).
Rheumatoid Arthritis as a Therapeutic Challenge in a Patient with Lynch Syndrome
open access
American Journal of Case Reports
Rheumatoid Arthritis as a Therapeutic Challenge in a Patient with Lynch Syndrome
Hossam Abdalla, Arindam Bagchi, Sabiha Bandagi
Am J Case Rep 2015; 16:390-392
DOI: 10.12659/AJCR.892906
..... With relation to RA treatment options, effectively decreasing systemic inflammation may in fact reduce the risk for cancer, but treatment of RA using the newer biologic agents like infliximab or adalimumab has been associated with increasedrisk of malignancy, specifically lymphoma [16,20,21].....
BACKGROUND:
Lynch syndrome (LS) is an inherited colorectal cancer (CRC) syndrome
accounting for about 3–5% of all cases and involves significantly higher
risk of subsequent malignancies, colonic as well as extra-colonic.
Increased risk of malignancies, especially lymphoid malignancies, have
been described in patients with autoimmune diseases like rheumatoid
arthritis (RA), systemic lupus erythematosus, and Sjögren’s syndrome.
Epidemiological studies demonstrated that hematopoietic, lung, skin, and
prostate cancers are increased in RA, while breast and colon cancers
are decreased, with an overall slight increase in all cancers.
CASE REPORT: Our case demonstrates the development of CRC, endometrial cancer, and breast cancer as a presentation of LS in a patient with RA and presents a therapeutic challenge for RA treatment.
CONCLUSIONS: We describe a patient with LS and RA presenting a therapeutic challenge because biologic agents commonly used to treat severe RA need to be used cautiously in patients with history of malignancy.
Keywords: Arthritis, Rheumatoid, Biological Therapy, Lynch Syndrome II
Investigating the performance/cost-effectiveness of the simple ultrasound-based rules compared to the risk of malignancy index in the diagnosis of ovarian cancer
BMC Cancer - open access
Investigating the performance and cost-effectiveness of the simple ultrasound-based rules compared to the risk of malignancy index in the diagnosis of ovarian cancer (SUBSONiC-study): protocol of a prospective multicenter cohort study in the Netherlands http://ovariancancerandus.blogspot.com/feeds/posts/default
Background Estimating the risk of malignancy is essential in the management of adnexal
masses. An accurate differential diagnosis between benign and malignant masses will
reduce morbidity and costs due to unnecessary operations, and will improve referral
to a gynecologic oncologist for specialized cancer care, which improves outcome and
overall survival. The Risk of Malignancy Index is currently the most commonly used
method in clinical practice, but has a relatively low diagnostic accuracy (sensitivity
75–80 % and specificity 85–90 %). Recent reports show that other methods, such as
simple ultrasound-based rules, subjective assessment and (Diffusion Weighted) Magnetic
Resonance Imaging might be superior to the RMI in the pre-operative differentiation
of adnexal masses.
Methods/Design A prospective multicenter cohort study will be performed
in the south of The Netherlands. A total of 270 women diagnosed with at least one
pelvic mass that is suspected to be of ovarian origin who will undergo surgery, will
be enrolled. We will apply the Risk of Malignancy Index with a cut-off value of 200
and a two-step triage test consisting of simple ultrasound-based rules supplemented
-if necessary- with either subjective assessment by an expert sonographer or Magnetic
Resonance Imaging with diffusion weighted sequences, to characterize the adnexal masses.
The histological diagnosis will be the reference standard. Diagnostic performances
will be expressed as sensitivity, specificity, positive and negative predictive values
and likelihood ratios.
Discussion We hypothesize that this two-step triage test, including
the simple ultrasound-based rules, will have better diagnostic accuracy than the Risk
of Malignancy Index and therefore will improve the management of women with adnexal
masses. Furthermore, we expect this two-step test to be more cost-effective. If the
hypothesis is confirmed, the results of this study could have major effects on current
guidelines and implementation of the triage test in daily clinical practice could
be a possibility. Trial registration ClinicalTrials.gov: registration number NCT02218502
The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.
Cancer risk among parous women following assisted reproductive technology
open access
STUDY QUESTION Do women who give birth after assisted reproductive technology (ART) have an increased risk of cancer compared with women
who give birth without ART?
SUMMARY ANSWER Without
correction, the results indicate an increase in overall cancer risk, as
well as a 50% increase in risk of CNS cancer
for women giving birth after ART, however the
results were not significant after correcting for multiple analyses.
How Do You Triage Abdominal Pain in a Patient With Ovarian Cancer?
open access
History
B.V.
is a 53-year-old nulliparous woman who was initially diagnosed with
recurrent stage 3C epithelial ovarian carcinoma in 2011. She underwent a
hysterectomy, bilateral salpingo-oophorectomy, and optimal tumor
debulking. Adjuvant therapy consisted of a clinical trial (Gynecologic
Oncology Group [GOG] 262) protocol of 6 cycles of IV carboplatin,
paclitaxel, and bevacizumab (Avastin) followed by bevacizumab every 3
weeks.
In 2013, B.V. was diagnosed with invasive
ductal breast cancer, which necessitated discontinuation of bevacizumab
after 12 months of maintenance therapy. She underwent lumpectomy and
adjuvant radiation therapy, which was completed in January 2014. Her
breast tumor was estrogen-/progesterone-receptor (ER/PR) positive. She
was started on tamoxifen.
In February 2014, B.V. had a recurrence of her ovarian cancer......
Diagnosis of Constitutional Mismatch Repair-deficiency Syndrome Based on Microsatellite Instability and Lymphocyte Tolerance to Methylating Agents
abstract
Background & Aims
Patients with bi-allelic germline mutations in mismatch repair (MMR) genes (MLH1, MSH2, MSH6, or PMS2) develop a rare but severe variant of Lynch syndrome called constitutional MMR deficiency (CMMRD). This syndrome is characterized by early-onset colorectal cancers, lymphomas or leukemias, and brain tumors. There is no satisfactory method for diagnosis of CMMRD because screens for mutations in MMR genes are non-informative for 30% of patients. MMR-deficient cancer cells are resistant to genotoxic agents and have microsatellite instability (MSI), due to accumulation of errors in repetitive DNA sequences. We investigated whether these features could be used to identify patients with CMMRD.Screening for Occult Cancer in Unprovoked Venous Thromboembolism — SOME trial
open access + Commentary
Venous thromboembolism, which comprises
deep-vein thrombosis and pulmonary embolism, is the third most common
cardiovascular disorder.1-3
It is classified as provoked when it is associated with a transient
risk factor (e.g., trauma, surgery, prolonged immobility, or pregnancy
or the puerperium) and as unprovoked when it is associated with neither a
strong transient risk factor nor overt cancer.
Unprovoked venous thromboembolism may be the earliest sign of cancer4,5; up to 10% of patients with unprovoked venous thromboembolism receive a diagnosis of cancer in the year after their diagnosis of venous thromboembolism.6 More than 60% of occult cancers are diagnosed shortly after the diagnosis of unprovoked venous thromboembolism.6 Thereafter, the incidence rate of cancer diagnosis gradually declines and returns to the rate in the general population after 1 year.5-7
Faced with these troubling statistics, clinicians, patients, and policymakers struggle with how aggressive to be in screening for occult cancers in patients who present with unprovoked venous thromboembolism.
Unprovoked venous thromboembolism may be the earliest sign of cancer4,5; up to 10% of patients with unprovoked venous thromboembolism receive a diagnosis of cancer in the year after their diagnosis of venous thromboembolism.6 More than 60% of occult cancers are diagnosed shortly after the diagnosis of unprovoked venous thromboembolism.6 Thereafter, the incidence rate of cancer diagnosis gradually declines and returns to the rate in the general population after 1 year.5-7
Faced with these troubling statistics, clinicians, patients, and policymakers struggle with how aggressive to be in screening for occult cancers in patients who present with unprovoked venous thromboembolism.
Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7): phase 3l
open access
Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7): overall survival results of a phase 3 randomised trial
Published online June 24, 2015
Background
The ICON7 trial previously reported improved progression-free survival in women with ovarian cancer with the addition of bevacizumab to standard chemotherapy, with the greatest effect in patients at high risk of disease progression. We report the final overall survival results of the trial.
Interpretation
Bevacizumab, added to platinum-based chemotherapy, did not increase overall survival in the study population as a whole. However, an overall survival benefit was recorded in poor-prognosis patients, which is concordant with the progression-free survival results from ICON7 and GOG-218, and provides further evidence towards the optimum use of bevacizumab in the treatment of ovarian cancer.
Comment
.....Although the results of ICON7 offer the tantalising possibility that a patient subgroup might derive an overall survival benefit from first-line bevacizumab, caution should be exercised when interpreting subset analyses, and additional questions remain unanswered regarding the use of bevacizumab in newly diagnosed ovarian cancer. Only a small proportion of patients in ICON7 received bevacizumab after disease recurrence, and therefore whether or not bevacizumab use in the recurrent setting could off set the overall survival benefits recorded in this high-risk population remains unknown. Additional studies to understand the effect of subsequent bevacizumab treatment on survival and to further identify and validate molecular markers of anti- angiogenic response will be important to better define our understanding of the role of bevacizumab therapy inovarian cancer.
SNP of the EpCAM-coding gene TACSTD1 in patients with ovarian cancer and their potential translational aspects (catumaxomab)
abstract - Single nucleotide polymorphisms of the EpCAM-coding gene TACSTD1 in patients with ovarian cancer and their potential translational aspects
PURPOSE:
EpCAM is overexpressed in many neoplasms including ovarian cancer. We screened the EpCAM-coding gene TACSTD1 for single nucleotide polymorphisms (SNPs), which could alter ovarian cancer risk, impact upon disease progression, or alter binding of the therapeutic EpCAM-binding antibody, catumaxomab.METHODS:
DNA fragments of 10 healthy volunteers were analyzed to identify SNPs. Subsequently, DNA of ovarian cancer patients (n = 117) and age-matched healthy controls (n = 115) was genotyped by restriction fragment length polymorphism and pyrosequencing. TACSTD1 genotypes 4461T>C were cloned into a gene expression vector; Hek293 cells were subsequently used for stable transfection. FACS analysis of the transfected Hek293 cells was conducted with HO-3-the EpCAM binding site of catumaxomab-to determine antibody binding.Development of a Risk Stratification System to Guide Treatment for Female Germ Cell Tumors
abstract
OBJECTIVE:
Due to their rarity, little is known about prognostic factors in female germ cell tumors (GCTs) or outcomes following systemic therapy. Management is largely based on studies of male GCT and epithelial ovarian cancer.METHODS:
Chart review was performed for all females with GCT seen at Memorial Sloan Kettering Cancer Center (MSKCC) from 1990 to 2012. Patients receiving chemotherapy were stratified using a modification of the male IGCCCG risk system, and the classifier was correlated with outcome.Glucocorticoid Receptor Activation Inhibits Chemotherapy-induced Cell Death in High-grade Serous Ovarian Carcinoma
abstract
Highlights
Objectives
To test the hypothesis that glucocorticoid receptor (GR) activation increases resistance to chemotherapy in high-grade serous ovarian cancer (HGS-OvCa) and that treatment with a GR antagonist will improve sensitivity to chemotherapy.ASCO 51st Annual Meeting 2015: An overview and summary of selected abstracts
abstract
On May 29 to June 2, 2015, the American Society of
Clinical Oncology (ASCO) held its annual meeting in Chicago, IL, USA.
The theme of the meeting this year was “Illumination and Innovation” and
the data presented held up to this high aspiration. The main plenary
session focused on novel immunotherapy in melanoma, pediatric cancer
survivorship, and the cost of new cancer therapy. There were 11
gynecologic oncology abstracts selected for poster discussion and 14
abstracts in gynecologic oncology presented as oral presentations in
three different sessions.
Hormone Receptors as a Marker of Poor Survival in Epithelial Ovarian Cancer
abstract
OBJECTIVE:
Androgen receptor (AR), estrogen receptor α and β (ERα, ERβ), and progesterone receptor (PR) are potential therapeutic targets in epithelial ovarian cancer. In this study we evaluate the prognostic value of these hormone receptors in ovarian cancer patients.METHODS:
In a prospective multicenter randomized controlled phase II trial 196 ovarian cancer patients were randomized to carboplatin/docetaxel±celecoxib. Of 121 patients sufficient tumor tissue was available for hormone receptor analysis. Tissue micro-arrays were stained for AR, ERα, ERβ, and PR. Cluster analysis was performed to identify subgroups based on hormone receptor expression profile. Receptor expression was correlated to progression-free survival (PFS) and overall survival (OS) in uni- and multivariate analysis.RESULTS:
AR, ERα, ERβ, and PR were expressed in respectively 10%, 31%, 73%, and 19%. In patients with synchronous metastasis tissue available (n=69 patients), discordant receptor expression was observed in 9-32%. ERβ-expression was associated with poor PFS and OS (hazard ratios 1.88 and 1.92). Clustering analysis revealed a subgroup with hormone receptor negative disease that had a favorable PFS and OS.CONCLUSION:
Hormone receptors are expressed in the majority of ovarian cancer tumors and may serve as therapeutic targets. Clustering analysis can reveal subgroups with different outcome, which may prove valuable in selecting patients for endocrine therapy.Immuno-PET of epithelial ovarian cancer: harnessing the potential of CA125 for non-invasive imaging
abstract - in research (preclinical)
BACKGROUND:
Epithelial ovarian cancer (EOC) is characterized by the overexpression of cancer antigen 125 (CA125), a mucinous glycoprotein that serves as a tumor biomarker. Early diagnosis of EOC is plagued by its asymptomatic nature of progression and the limitations of currently used immunoassay techniques that detect CA125 as a shed antigen in serum samples. Presently, there is no technique available for the in vivo evaluation of CA125 expression in malignant tissues. Moreover, there could be an unexplored pathophysiological time window for the detection of CA125 in EOC, during which it is expressed on tumor cells prior to being shed into the bloodstream. A method for the in vivo evaluation of CA125 expression on ovarian neoplasms earlier along disease progression and/or recurrence can potentially contribute to better disease management. To this end, the present work utilizes an anti-CA125 monoclonal antibody (MAb) and a single-chain variable fragment (scFv) labeled with the positron-emitting radionuclide (64)Cu for preclinical molecular imaging of CA125 expression in vivo.METHODS:
Anti-CA125 MAb and scFv were prepared and functionally characterized for target binding prior to being tested as radiotracers in a preclinical setting.Ovarian Sertoli-Leydig Cell Tumor with Predominant Heterologous Mucinous Differentiation and Foci of Hepatocytic Differentiation
abstract: Ovarian Sertoli-Leydig Cell Tumor with Predominant Heterologous Mucinous Differentiation and Foci of Hepatocytic Differentiation: Case Report and Review of the Literature
Sertoli-Leydig cell tumor is a rare ovarian neoplasm and belongs to the group of sex cord stromal tumors. We present a case of a 15-year old girl diagnosed with Sertoli-Leydig cell tumor with heterologous elements consisting predominantly of mucinous epithelium and a sparse Sertoli-Leydig cell component, mimicking mucinous neoplasm. Furthermore, foci of hepatocytic differentiation were also identified. Immunohistochemical stains showed the component of Sertoli cell differentiation was positive for cytokeratin 18 and inhibin. The component of Leydig cell differentiation was strongly positive for inhibin. The component of hepatocytic differentiation was positive for low molecular weight keratin, HepPar1, alpha-fetoprotein and weakly positive for inhibin. Thus, this was a very rare case which created a challenge for pathologists, especially on frozen sections.
Value in Cancer Care | ASCO.org - online survey
Value in Cancer Care
Please let us know what you think by taking our online survey.
ASCO Releases Value Framework
ASCO has released a conceptual framework for assessing the value of new cancer therapies based on treatment benefits, toxicities, and costs. The initial version of the ASCO Value Framework was published on June 22, 2015 in the Journal of Clinical Oncology.
Developed by the ASCO Value in Cancer Care Task Force, the framework will ultimately serve as the basis for user-friendly, standardized tools that physicians can use with their patients to discuss the relative value of new cancer therapies as compared with established treatments.
Seeking comment from all stakeholders
ASCO will be soliciting comments from all interested stakeholders on the value framework through August 21, 2015. Comments will inform the evolution of the value framework, which will be modified in response to feedback and updated as new data are developed about the utility and impact of new treatments in different clinical scenarios. Please let us know what you think by taking our online survey.
Saturday, June 27, 2015
Top 5 viewed items week of June 20-27, 2015 https://ovariancancerandus.blogspot.com
Top 5 viewed items week of June 20-27, 2015
June 2015 - top 5 read articles: https://ovariancancerandus.blogspot.com
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Estrogen pathway mutations and cancer (MMR/Lynch Syndrome/estrogen)
open access
Estrogen pathway mutations and cancer
Abstract
Cancer is caused by an accumulation of mutations in a stem
cell. A defective mismatch repair (MMR) system can lead to such an
accumulation of mutations. MMR defects are found in a cancer syndrome
called Lynch Syndrome, and tumors of this syndrome are indeed
characterized by such an accumulation of mutations, particularly in
short repetitive DNA sequences, called microsatellites. When such
mutated microsatellites are located in the coding sequences of genes
with essential roles for tumorigenesis, we speak of ‘target genes’. Many
such target genes have been found and in this review we focus the
possible involvement of target genes involved in the estrogen-receptor
pathway (ER).
We recently identified NRIP1, encoding the nuclear receptor-interacting protein 1, as the most frequently mutated gene in microsatellite instable (MSI) endometrial cancer (EC). NRIP1 is a known corepressor of the ER pathway, the pathway essential in regulating the concentrations of estrogens, a hormone for which the endometrium is highly responsive. This in combination with the fact that high exposure to estrogens is currently considered the major risk factor for EC - approximately 80% of all sporadic EC tumors are estrogen dependent carcinomas - make NRIP1 the perfect target gene for EC.
Interestingly, mutations in NRIP1 were also detected in MSI colorectal carcinoma (CRC) samples. Finding mutations in an estrogen receptor signaling protein in colorectal tissue might not be that expected, as colon is not typically associated with being responsive to estrogens. However, evidence is accumulating to better understand this finding. For instance, it was shown that NRIP1, in colon tissue, stimulates APC gene transcription and inhibits β-catenin activation. Moreover, some studies suggested that estrogens can increase the expression of MLH1 in colon cancer cells, highlighting the implications of estrogen protecting against colon cancer, by regulating the MMR system.
All in all we conclude that genes involved in the estrogen pathway are the perfect candidates to be studied in MMR-deficient tumors, especially those developing in hormonal responsive tissues.
We recently identified NRIP1, encoding the nuclear receptor-interacting protein 1, as the most frequently mutated gene in microsatellite instable (MSI) endometrial cancer (EC). NRIP1 is a known corepressor of the ER pathway, the pathway essential in regulating the concentrations of estrogens, a hormone for which the endometrium is highly responsive. This in combination with the fact that high exposure to estrogens is currently considered the major risk factor for EC - approximately 80% of all sporadic EC tumors are estrogen dependent carcinomas - make NRIP1 the perfect target gene for EC.
Interestingly, mutations in NRIP1 were also detected in MSI colorectal carcinoma (CRC) samples. Finding mutations in an estrogen receptor signaling protein in colorectal tissue might not be that expected, as colon is not typically associated with being responsive to estrogens. However, evidence is accumulating to better understand this finding. For instance, it was shown that NRIP1, in colon tissue, stimulates APC gene transcription and inhibits β-catenin activation. Moreover, some studies suggested that estrogens can increase the expression of MLH1 in colon cancer cells, highlighting the implications of estrogen protecting against colon cancer, by regulating the MMR system.
All in all we conclude that genes involved in the estrogen pathway are the perfect candidates to be studied in MMR-deficient tumors, especially those developing in hormonal responsive tissues.
Full Text:
PDFDOI: http://dx.doi.org/10.14800/rci.635
Friday, June 26, 2015
Development of biosimilars in an era of oncologic drug shortages
biosimilars
..... Preclinical and clinical characterization is ongoing for potential biosimilars of trastuzumab, rituximab, and bevacizumab, with promising results.
Keywords: biologics, monoclonal antibody, cancer, rituximab, safety, trastuzumab
Download Article [PDF]
British Journal of Cancer - Comment on: /`Evaluation of chemoresponse assays as predictive markers/'
Comment open access
DJS received compensation for consulting work from Helomics Corporation. MJG, SLB and CT are paid employees of Helomics Corporation.
.....We agree with Korn and Freidlin (2015) that evaluating the predictive value of chemoresponse assays is challenging. As with any observational study, it is impossible to entirely exclude bias, and a definitive answer relies on randomised clinical trials. However, randomised trials to evaluate predictive markers are highly challenging in rare tumour types such as recurrent ovarian cancer, particularly when a large number of treatment options are available. The length of time for patient accrual alone is likely to obfuscate clinical utility. Thus, observational studies and other non-randomised prospective studies must continue to have an important role in evaluating chemoresponse assays in this cancer type. We feel that in the appropriate circumstance, our proposed match/mismatch analysis can provide helpful information regarding an assay’s potential prognostic and/or predictive value.
References
Wednesday, June 24, 2015
Standard chemotherapy with/without bevacizumab for women with newly diagnosed ovarian cancer (ICON7).....
open access
Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7): overall survival results of a phase 3 randomised trial
Background
The ICON7 trial previously reported improved progression-free survival in women with ovarian cancer with the addition of bevacizumab to standard chemotherapy, with the greatest effect in patients at high risk of disease progression. We report the final overall survival results of the trial.Panel
Research in context
Bevacizumab in newly diagnosed ovarian cancer - The Lancet Oncology + references
Comment - open access
Several studies have assessed the activity of bevacizumab
when added to chemotherapy in ovarian cancer. In Europe, bevacizumab is
approved by the European Medicines Agency in combination with
carboplatin and paclitaxel in newly diagnosed ovarian cancer, with
carboplatin and gemcitabine in platinum-sensitive relapse ovarian
cancer, and with chemotherapy in platinum-resistant relapse ovarian
cancer. In the USA, bevacizumab is approved by the Food and Drug
Administration when combined with chemotherapy for platinum-resistant
relapse ovarian cancer. These approvals were based on progression-free
survival improvements, but so far no overall survival benefit has been
noted with the addition of bevacizumab to chemotherapy in any overall
study population.2, 3, 4, 5
In The Lancet Oncology, Amit Oza and colleagues1
report the mature overall survival data from ICON7, an open-label
randomised phase 3 trial comparing bevacizumab plus six 3-weekly cycles
of carboplatin and paclitaxel chemotherapy followed by bevacizumab
maintenance versus the carboplatin and paclitaxel chemotherapy regimen
alone. The study participants were patients with newly diagnosed ovarian
cancer following cytoreductive surgery or patients with advanced-stage
disease who had no further surgery planned.1 The primary endpoint of this trial, progression-free survival, has been reported previously.2 Concordant with the results of GOG-218,3 another phase 3 trial comparing chemotherapy and bevacizumab versus chemotherapy alone in upfront therapy for ovarian cancer.....References
- Oza, AM, Cook, AD, Pfisterer, J et al. Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7): overall survival results of a phase 3 randomised trial. Lancet Oncol. 2015; (published online June 23.)http://dx.doi.org/10.1016/S1470-2045(15)00086-8.
- Perren, TJ, Swart, AM, Pfisterer, J et al. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med. 2011; 365: 2484–2496
- Burger, RA, Brady, MF, Bookman, MA et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 2011; 365: 2473–2483
- Aghajanian, C, Blank, SV, Goff, BA et al. OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J Clin Oncol. 2012; 30: 2039–2045
- Pujade-Lauraine, E, Hilpert, F, Weber, B et al. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: the AURELIA open-label randomized phase III trial. J Clin Oncol. 2014; 32: 1302–1308
- Coleman, R, Burger, RA, Brady, MF et al. Analysis of survivorship in high-risk patients on treated on GOG-218. Gynecol Oncol. 2013; 130: e112–e113
- Katsumata, N, Yasuda, M, Isonishi, S et al. Long-term results of dose-dense paclitaxel and carboplatin versus conventional paclitaxel and carboplatin for treatment of advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer (JGOG 3016): a randomised, controlled, open-label trial. Lancet Oncol. 2013; 14: 1020–1026
- Chan, J, Brady, MF, Penson, RT et al. Phase III trial of every-3-weeks paclitaxel versus dose dense weekly paclitaxel with carboplatin +/- bevacizumab in epithelial ovarian, peritoneal, fallopian tube cancer: GOG 262 (NCT0116712). Int J Gynecol Cancer. 2013; 23: 9–10
- Kehoe, S, Hook, J, Nankivell, M et al. Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS): an open-label, randomised, controlled, non-inferiority trial. Lancet. 2015; (published online May 19.)http://dx.doi.org/10.1016/S0140-6736(14)62223-6.
- Vergote, I, Trope, CG, Amant, F et al. Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med. 2010; 363: 943–953
Tuesday, June 23, 2015
Prediction of Optimal Cytoreductive Surgery of Serous Ovarian Cancer With Gene Expression Data
abstract
OBJECTIVES:
Cytoreductive surgery is the cornerstone of ovarian cancer (OVCA) treatment. Detractors of initial maximal surgical effort argue that aggressive tumor biology will dictate survival, not the surgical effort. We investigated the role of biology in achieving optimal cytoreduction in serous OVCA using microarray gene expression analysis.METHODS:
For the initial model, we used a gene expression signature from a microarray expression analysis of 124 women with serous OVCA, defining optimal cytoreduction as removal of all disease greater than 1 cm (with 64 women having optimal and 60 suboptimal cytoreduction). We then applied this model to 2 independent data sets: the Australian Ovarian Cancer Study (AOCS; 190 samples) and The Cancer Genome Atlas (TCGA; 468 samples). We performed a second analysis, defining optimal cytoreduction as removal of all disease to microscopic residual, using data from AOCS to create the gene signature and validating results in TCGA data set.RESULTS:
Of the 12,718 genes included in the initial analysis, 58 predicted accuracy of cytoreductive surgery 69% of the time (P = 0.005). The performance of this classifier, measured by the area under the receiver operating characteristic curve, was 73%. When applied to TCGA and AOCS, accuracy was 56% (P = 0.16) and 62% (P = 0.01), respectively, with performance at 57% and 65%, respectively. In the second analysis, 220 genes predicted accuracy of cytoreductive surgery in the AOCS set 74% of the time, with performance of 73%. When these results were validated in TCGA set, accuracy was 57% (P = 0.31) and performance was at 62%.CONCLUSION:
Gene expression data, used as a proxy of tumor biology, do not predict accurately nor consistently the ability to perform optimal cytoreductive surgery. Other factors, including surgical effort, may also explain part of the model. Additional studies integrating more biological and clinical data may improve the prediction model.Tumour spectrum in non-BRCA hereditary breast cancer families in Sweden
open access
Results
We found that endometrial cancer was overrepresented in the non-BRCA families with
a 6.36 % proportion (CI 4.67–8.2) compared to the proportion in the general population
in the reference years 1970 (3.07 %) and 2010 (2.64 %). Moreover tumours of the ovary,
liver, pancreas and prostate were overrepresented.
Conclusions
To summarise, we found an overrepresentation of endometrial cancer in our cohort of
hereditary non-BRCA families, which supports earlier findings that breast and endometrial
cancer may constitute a breast cancer syndrome. Since results from studies are divergent
this issue needs to be resolved by further studies preferably on cohorts with two
close relatives or more affected by breast cancer or bilateral breast cancer. The
conflicting results could be due to methodology since the association may only be
evident in families with a strong pattern of breast cancer susceptibility. Identifying
new breast cancer syndromes is of importance to reach more women at increased risk
of cancer with preventive programmes. It is also a first step towards detection of
new susceptibility genes.
Prognostic Value of Circulating Tumor Cells in Ovarian Cancer: A Meta-Analysis
open access
Introduction
Ovarian cancer is the second leading cause of death among gynecologic malignancies in the world [1] owing to the fact that a majority of patients are diagnosed in late stages of the disease [2]. In such a setting, identifying prognostic indicators for patients with ovarian cancer is crucial. CA-125 is a frequently used biomarker in ovarian cancer, but some non-malignant conditions also cause elevated serum CA-125 concentrations [3]. Thus additional prognostic markers are urgently needed for ovarian cancer.
Discussion
Many studies have reported the prognostic value of CTCs in patients with ovarian cancer, and this is the first meta-analysis evaluating the value of CTCs in these patients. Overall, our results demonstrated that patients in CTC-positive group had a worse OS and PFS/DFS compared with CTC- negative group; moreover, the presence of CTCs was associated with elevated CA-125.Morphologic and Molecular Characteristics of Mixed Epithelial Ovarian Cancers
abstract
Epithelial ovarian cancer (EOC) consists of 5 major histotypes: high-grade serous carcinoma (HGSC), endometrioid carcinoma (EC), clear cell carcinoma (CCC), mucinous carcinoma (MC), and low-grade serous carcinoma (LGSC). Each can have a broad spectrum of morphologic appearances, and 1 histotype can closely mimic histopathologic features more typical of another. Historically, there has been a relatively high frequency of mixed, defined by 2 or more distinct histotypes present on the basis of routine histopathologic assessment, histotype carcinoma diagnoses (3% to 11%); however, recent immunohistochemical (IHC) studies identifying histotype-specific markers and allowing more refined histotype diagnoses suggest a much lower incidence. We reviewed hematoxylin and eosin-stained slides from 871 cases of EOC and found the frequency of mixed carcinomas to be 1.7% when modern diagnostic criteria are applied. Through international collaboration, we established a cohort totaling 22 mixed EOCs, consisting of 9 EC/CCC, 4 EC/LGSC, 3 HGSC/CCC, 2 CCC/MC, and 4 other combinations. We interrogated the molecular differences between the different components of each case using IHC, gene expression, and hotspot sequencing analyses. IHC data alone suggested that 9 of the 22 cases were not mixed tumors, as they presented a uniform immuno-phenotype throughout, and these cases most probably represent morphologic mimicry and variation within tumors of a single histotype. Synthesis of molecular data further reduces the incidence of mixed carcinomas. On the basis of these results, true mixed carcinomas with both morphologic and molecular support for the presence of >1 histotype within a given tumor represent <1% of EOCs.
Monday, June 22, 2015
Phase I Study of IV Docetaxel and IP Oxaliplatin in Recurrent Ovarian and Fallopian Tube Cancer
abstract
Highlights
- •We defined the MTD of IV docetaxel and IP oxaliplatin in recurrent ovarian cancer.
- •Most patients had PR or SD, with patient-reported outcomes showing temporary but tolerable decrements in QoL.
- •IP oxaliplatin provides a significant peritoneal PK advantage.
Sarcoma: A Lynch syndrome (LS)-associated malignancy?
abstract
Conclusions: From a large sample of nearly 1000 LS families, our findings suggest sarcomas may be a rare manifestation of LS, especially MSH2+ LS. More research of genotype-phenotype correlations in LS is needed.
Quality of patient-reported outcome reporting across cancer randomized controlled trials....
Quality of patient-reported outcome reporting across cancer randomized controlled trials according to the CONSORT patient-reported outcome extension: A pooled analysis of 557 trials
Keywords:
- cancer;
- clinical trials;
- Consolidated Standards of Reporting Trials (CONSORT);
- patient-reported outcomes;
- quality of life
BACKGROUND
The
main objectives of this study were to identify the number of randomized
controlled trials (RCTs) including a patient-reported outcome (PRO)
endpoint across a wide range of cancer specialties and to evaluate the
completeness of PRO reporting according to the Consolidated Standards of
Reporting Trials (CONSORT) PRO extension.
METHODS
RCTs
with a PRO endpoint that had been performed across several cancer
specialties and published between 2004 and 2013 were considered. Studies
were evaluated on the basis of previously defined criteria, including
the CONSORT PRO extension and the Cochrane Collaboration's tool for
assessing the risk of bias of RCTs. Analyses were also conducted by the
type of PRO endpoint (primary vs secondary) and by the cancer disease
site.
RESULTS
A
total of 56,696 potentially eligible records were scrutinized, and 557
RCTs with a PRO evaluation, enrolling 254,677 patients overall, were
identified. PROs were most frequently used in RCTs of breast (n = 123),
lung (n = 85), and colorectal cancer (n = 66). Overall, PROs were
secondary endpoints in 421 RCTs (76%). Four of 6 evaluated CONSORT PRO
items were documented in less than 50% of the RCTs. The level of
reporting was higher in RCTs with a PRO as a primary endpoint. The
presence of a supplementary report was the only statistically
significant factor associated with greater completeness of reporting for
both RCTs with PROs as primary endpoints (β = .19, P = .001) and RCTs with PROs as secondary endpoints (β = .30, P < .001).
CONCLUSIONS
Implementation of the CONSORT PRO extension is equally important across all cancer specialties. Its use can also contribute to revealing the robust PRO design of some studies, which might be obscured by poor outcome reporting.
(repost) Risk Algorithm Using Serial Biomarker Measurements Doubles # of Screen-Detected Ovarian Cancers...
open access
Risk Algorithm Using Serial Biomarker Measurements Doubles the Number of Screen-Detected Cancers Compared With a Single-Threshold Rule in the United Kingdom Collaborative Trial of Ovarian Cancer Screening
..... Although HE4 does not improve CA-125 lead time,22,23 it could help confirm ovarian cancer risk and reduce time to surgery. In the presence of an increasing CA-125, HE4 was increased in samples from 27 of 39 women with ovarian cancer in the PLCO trial.21 TVS does not seem to have the resolution to detect iEOC at low CA-125 levels. Twenty-nine (41%) of 70 women with iEOCs in subgroup A had no abnormality on the initial level II scan, and TVS was abnormal in only 17 of the 39 women in the study by Urban et al.21 The potential of newer technology....
In conclusion, our data support use of velocity-based algorithms as opposed to a predefined single-threshold rule in cancer screening strategies that use blood biomarkers.
ASCO Statement: A Conceptual Framework to Assess the Value of Cancer Treatment Options
open access
CALL FOR COMMUNITY COMMENT
We appreciate that developing a method
for establishing value of specific cancer treatment regimens is a
daunting task. ASCO
views this as an iterative process and encourages
comments from all interested parties regarding the elements we have
included
in the value framework and its utility in
facilitating discussion between providers and patients on the value of
available
treatment options. Comments may be submitted
through August 21, 2015, at www.asco.org/value.
Clear cell carcinomas of the gynecologic tract and thromboembolic events: what do we know so far?
open access (2014)
..... specific malignancies that have been found to increase the risk of thromboembolic events (including gliomas, renal, gastric and pancreatic carcinomas) [2,5,6]. In ovarian cancer patients......
...... The occurrence of thromboembolic events has been found to adversely impact survival in several reports, even in patients with localized disease [6–8]......
The observation that cancer patients may have an increased risk for thromboembolic events was originally made by the French internist Armand Trousseau in 1865 [1]. Almost 150 years later, it is now well-recognized that cancer patients have a four- to seven-fold increase in their risk for venous thromboembolic events relative to their counterparts without cancer, and that 1–15% of cancer patients develop clinical thromboembolic events over the course of their care [2–4]. This increased risk has a multifactorial basis, the precise components of which are not entirely clear at the present time. However, in cancer patients, risk factors for increased thrombosis often abound, including the presence of medical comorbidities......
A patient-initiated voluntary online survey of adverse medical events: the perspective of 696 injured patients/families
open access
Adverse event categories and relative frequency
As shown in table 1,
the leading category of error reported by patients was failure in
diagnosis and treatment. Further breakdown of this category
revealed the leading event
(subcategory) was a delay in diagnosis and treatment. Misdiagnosis was
another frequent event,
as was failure to rescue a patient
whose clinical condition was worsening. The second most common category
was surgical or
procedural complications. Wrong site
surgery was surprisingly common in our survey (4.3%), as were foreign
objects left in
the patient (3.6%).
Hospital-associated infections were the third most common category,
sepsis being the most frequently reported
complication, followed by
postoperative infections, Clostridium difficile intestinal
infection and urinary tract infections. Medication errors were the
fourth major category in our survey. It is
of interest that a significant
percentage (12.8%) reported receiving medications that they were known
to have had an allergic
reaction to in the past.
Common Genetic Variation In Cellular Transport Genes and Epithelial Ovarian Cancer (EOC) Risk
eg. SERPINA7 (clear cell) = thyroid
open access (technical)
Results
The most significant evidence of an association for all invasive cancers combined and for the serous subtype was observed for SNP rs17216603 in the iron transporter gene HEPH (invasive: OR = 0.85, P = 0.00026; serous: OR = 0.81, P = 0.00020); this SNP was also associated with the borderline/low malignant potential (LMP) tumors (P = 0.021). Other genes significantly associated with EOC histological subtypes (p<0.05) included the UGT1A (endometrioid), SLC25A45 (mucinous), SLC39A11 (low malignant potential), and SERPINA7 (clear cell carcinoma). In addition, 1785 SNPs in six genes (HEPH, MGST1, SERPINA, SLC25A45, SLC39A11 and UGT1A) were imputed from the 1000 Genomes Project and examined for association with INV EOC in white-European subjects. The most significant imputed SNP was rs117729793 in SLC39A11 (per allele, OR = 2.55, 95% CI = 1.5-4.35, p = 5.66x10-4).Conclusion
These results, generated on a large cohort of women, revealed associations between inherited cellular transport gene variants and risk of EOC histologic subtypes.Family with MSH2 mutation presenting with keratoacanthoma and precancerous skin lesions
abstract
Muir–Torre syndrome (MTS) is a familial cancer syndrome characterized by a predisposition to keratoacanthoma (KA) and sebaceous tumors. Although MTS and hereditary non-polyposis colorectal cancer (HNPCC) share the same genetic alterations in mismatch repair (MMR) genes, the other skin lesions in MTS or HNPCC have been only rarely reported. We report a family with an MSH2 mutation c.1126_1127delTT (p.Leu376Thrfs*12). A 46-year-old male proband developed KA with sebaceous differentiation, colon cancer and gastric cancer, and fulfilled the diagnostic criteria for MTS. His 80-year-old mother, diagnosed with HNPCC, presented with multiple gastrointestinal tract cancers, Bowen's disease and actinic keratosis. Immunostaining revealed attenuated MSH2 protein expression in KA, as well as in Bowen's disease and actinic keratosis lesions. These findings suggest that MMR gene abnormality is also critical in the development of benign or malignant cutaneous tumors such as actinic keratosis and Bowen's disease in MTS/HNPCC patients.
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