Friday, November 08, 2013
Preventing Ovarian Cancer through Genetic Testing: a Population-Based Study
abstract
"Genetic testing for BRCA1 and BRCA2 gene mutations, in conjunction with preventive oophorectomy for mutation carriers, may be used to prevent a proportion of invasive ovarian cancers (‘personalized medicine’). We evaluated the potential utility of this approach at a population level by reviewing the pedigree information and genetic test results from 1,342 ovarian cancer patients in Ontario. Of the 1,342 patients tested, 176 patients had a BRCA1 or BRCA2 mutation; of these, 48 women would have qualified for testing prior to the development of cancer based on the eligibility criteria in place for the province of Ontario. In summary, 48 of 1,342 unselected cases of ovarian cancer (3.6 %) might have been prevented if genetic testing criteria were universally applied to all women in Ontario at risk for ovarian cancer."
Thursday, November 07, 2013
Small fallopian tube carcinoma with extensive upper abdominal dissemination: a case report (Portugal)
a case report - open access
Introduction
Fallopian tube carcinoma is a rare gyncological malignancy with low accuracy detection
preoperatively. The symptoms are unspecific and imaging can be misleading. Since it
was first described in 1847, there have been only a little over 2000 case reports.
Case presentation
This case report describes a 66-year-old Caucasian woman who presented with progressive
diffuse abdominal pain, without other symptoms. After abdominopelvic magnetic resonance
imaging, she was sent to the Portuguese Oncology Institute of Oporto with the suspicion
of peritoneal carcinomatosis of unknown primary tumor. Due to a pelvic palpable mass
(calcified giant uterine fibroid) she was directed to the Gynecology team. Surgery
was performed and a large mass in her upper abdomen was identified. The extemporary
examination revealed a high-grade adenocarcinoma. During surgery a small change of
color and consistency of her left fallopian tube was noted and unilateral adnexectomy
was performed. After pathologic and immunohistochemistry tests, the diagnosis of fallopian
tube carcinoma with peritoneal dissemination was made.
Conclusions
This case is very unique in the way that a small primary fallopian tube carcinoma
was able to disseminate to the upper abdominal quadrant with little pelvic dissemination.
The symptoms and imaging were unspecific. Although a rare occurrence, we should not
forget fallopian tube carcinoma in the differential diagnosis of peritoneal carcinomatosis,
even in the absence of Latzke's triad (symptoms).
Epidermal Growth Factor Receptor (EGFR), HER2 and Insulin Growth Factor Receptor-1 (IGFR-1) Status in Ovarian Adult Granulosa Cell Tumours
abstract
Aims
Adult
granulosa cell tumours (AGCTs) are uncommon ovarian sex cord-stromal
tumours which recur following surgical removal in up to 50% of patients.
Treatment options for recurrent and advanced stage AGCTs are limited
with poor response to chemotherapy and radiotherapy. We aimed to assess
the Epidermal Growth Factor Receptor (EGFR) (HER1), HER2 and Insulin
Growth Factor Receptor-1 (IGFR-1) status in AGCTs with a view to
investigating whether these receptors might be potential therapeutic
targets in these neoplasms.
Methods And Results
Immunohistochemical
staining for EGFR, HER2 and IGFR-1 was undertaken in 31 AGCTs. Tumour
DNA was also analysed for mutations in the tyrosine kinase domain of EGFR
(exons 18-21) by Cobas mutation RT-PCR. 23/31 (74%) AGCTs showed some
degree of EGFR expression, generally with cytoplasmic or mixed
membranous and cytoplasmic staining of variable intensity. 11/27 (41%)
cases exhibited strong membranous and cytoplasmic expression of IGFR-1.
HER2 expression was not seen. No mutations were found in exons 18-21 of
the EGFR gene in hotspots of therapeutic relevance.
Conclusions
This
study raises the possibility that anti-EGFR and/or anti-IGFR-1
therapies may be potential agents in ovarian AGCTs and this requires
further study. Lack of known mutations within the tyrosine kinase domain
of EGFR suggests that EGFR-related tyrosine kinase inhibitors may not
be useful therapeutically.
How well is our health system working? · Canada
NHS England » NHS England launches major exercise to shape the future of specialised services
NHS England-future of specialised services
The scoping event will be held in London on 9 December. Anybody who is interested in being involved in the debate about the future of specialised services and wishes to apply for a place should email dorothy.chen@shca.info.
Canadian Doctors for Medicare: Fraser Institute report on wait times flawed
Canadian Doctors for Medicare E-News November 2013
CDM: Fraser Institute report on wait times flawed
Dr. Ryan Meili questions the usefulness of the Fraser Institute’s latest report on wait times in the National Post.
The Fraser Institute’s annual wait times report is based on a survey,
not objective data, and it looks only at specialists providing elective
surgeries, ignoring Canada’s good record with acute and emergency
surgeries. Respondents are therefore self-selected, and responses are
solicited with the incentive of winning an iPad.
CDM knows that this isn’t a credible way to gather data on wait times. We can be doing better on wait times, but we should be looking at the evidence, not surveys of a self-selected group, to tell us how we’re doing.
National Post
But some question the Fraser Institute report and the conclusions of its authors.
“It is the same old sky-is-falling report,” said Dr. Ryan Meili, a family physician in Saskatoon who is vice-chairman of Canadian Doctors For Medicare.
“Wait times don’t get shorter when you introduced more delivery of care outside of the public system, they get longer. You don’t just draw patients away from the public system, you also draw away providers,” he said.
Dr. Michael Rachlis, a health policy analyst associated with the Canadian Health Coalition, a pro-universal-healthcare organization, said the co-payment plans from abroad “which allow some people to jump the queue” is not the answer to Canada’s wait times.
“We do tend to wait too long but it has nothing to do with us having a public system. It has a lot to do with how we organize services,” Dr. Rachlis said. “We can eliminate virtually every wait time by better management.”
The institute’s (Fraser) questionnaire was sent to practitioners between the beginning of January and the end of April. The response rate to the surveys was 21%.
CDM knows that this isn’t a credible way to gather data on wait times. We can be doing better on wait times, but we should be looking at the evidence, not surveys of a self-selected group, to tell us how we’re doing.
National Post
But some question the Fraser Institute report and the conclusions of its authors.
“It is the same old sky-is-falling report,” said Dr. Ryan Meili, a family physician in Saskatoon who is vice-chairman of Canadian Doctors For Medicare.
“Wait times don’t get shorter when you introduced more delivery of care outside of the public system, they get longer. You don’t just draw patients away from the public system, you also draw away providers,” he said.
Dr. Michael Rachlis, a health policy analyst associated with the Canadian Health Coalition, a pro-universal-healthcare organization, said the co-payment plans from abroad “which allow some people to jump the queue” is not the answer to Canada’s wait times.
“We do tend to wait too long but it has nothing to do with us having a public system. It has a lot to do with how we organize services,” Dr. Rachlis said. “We can eliminate virtually every wait time by better management.”
The institute’s (Fraser) questionnaire was sent to practitioners between the beginning of January and the end of April. The response rate to the surveys was 21%.
Characteristics, treatment and prognostic factors of patients with gynaecological malignancies treated in a palliative care unit at a university hospital
abstract
Background: Limited clinical data have been published on patients suffering from advanced gynaecological malignancies treated in palliative care units, and little is known about prognostic factors.
Methods: In a retrospective study, the data of 225 patients with breast, ovarian and cervical cancer treated in the palliative care unit of a university hospital between 1998 and 2009 were assembled. Clinical aspects and baseline symptoms, laboratory parameters, the clinical course, and outcome were evaluated.
Results: 225 patients (497 cases; cancer diagnoses: breast 79%, ovarian 13%, and cervix 8%) were included in the analysis. The main symptoms were weakness/fatigue (71%), pain (65%), anorexia/nausea (62%), and dyspnea (46%). Pain control was achieved in 85% of all cases, satisfying control of other symptoms in 80%.
Wednesday, November 06, 2013
Is CA72-4 a Useful Biomarker in Differential Diagnosis between Ovarian Endometrioma and Epithelial Ovarian Cancer?
open access
Abstract
Background. Surgical excision of ovarian endometriomas in patients desiring pregnancy has recently been criticized because of the risk of damage to healthy ovarian tissue and consequent reduction of ovarian reserve. A correct diagnosis in cases not scheduled for surgery is therefore mandatory in order to avoid unexpected ovarian cancer misdiagnosis. Endometriosis is often associated with high levels of CA125. This marker is therefore not useful for discriminating ovarian endometrioma from ovarian malignancy. The aim of this study was to establish if the serum marker CA72-4 could be helpful in the differential diagnosis between ovarian endometriosis and epithelial ovarian cancer.
Methods. Serums CA125 and CA72-4 were measured in 72 patients with ovarian endometriomas and 55 patients with ovarian cancer.
Results. High CA125 concentrations were observed in patients with ovarian endometriosis and in those with ovarian cancer. A marked difference in CA72-4 values was observed between women with ovarian cancer (71.0%) and patients with endometriosis (13.8%) ( ).
Conclusions. This study suggests that CA72-4 determination can be useful to confirm the benign nature of ovarian endometriomas in women with high CA125 levels.
1. Introduction
Endometriosis is a common chronic disease, affecting 5–10% of women in reproductive age [1]. The disease is characterized by the presence and growth of endometrial tissue outside the uterine cavity, often associated with infertility and pelvic pain and that tends to recur [2–5]. Endometriosis can be diagnosed by clinical and ultrasound examinations (US), but the most accurate procedure to confirm the diagnosis is laparoscopy that allows visualization of lesions and histological confirmation [6].
Endometriosis is a benign disease but it shares several characteristics with invasive cancer. Cancer antigen 125 (CA125) is a tumor marker used for the differential diagnosis in a postmenopausal woman with an adnexal mass [7]. However, in premenopausal age, CA125 is characterized by a low diagnostic specificity, as abnormally high concentrations can be found in malignancies of different origin including nonovarian gynecological cancer [8], in women with nongynecological diseases such as tuberculosis and liver cirrhosis, and also in pelvic inflammatory disease, uterine fibroids, or physiological conditions such as pregnancy or different phases of the menstrual cycle [9, 10]. In patients with endometriosis, CA125 levels can be high. In fact, CA125 is the most extensively investigated and used peripheral biomarker for monitoring the disease [11]. Thus, CA125 has a limited role in the differential diagnosis between endometriosis and ovarian cancer due to the lack of specificity [12].....
Cancer Drug Trial Put on Partial Hold After Death (Curis - CUDC-427)
CUDC-427 Phase 1 Trial Placed on Partial Clinical Hold by FDA
"The current open-label, single-agent, dose escalation Phase 1 study of CUDC-427 was initiated in the third quarter of 2013 in patients with advanced and refractory solid tumors or lymphomas."
Bevacizumab-induced transient sixth nerve palsy in ovarian cancer: A case report
abstract
"We report a case of transient sixth nerve palsy after systemic administration of bevacizumab. Two days after systemic administration of bevacizumab in conjunction with gemcitabine and carboplatin in a 67-year-old woman with recurrent primary ovarian cancer, the patient developed sixth nerve palsy. After bevacizumab was stopped, the complete left sixth nerve palsy resolved spontaneously over the course of 3 months. This is the first reported case of bevacizumab-induced cranial sixth nerve palsy in the treatment of gynecologic malignancy."
Prevalence of Occult Gynecologic Malignancy at the Time of Risk Reducing and Non Prophylactic Surgery in Patients with Lynch Syndrome
abstract
Highlights
- •
- Surgeons should consider the possibility of malignancy in patients with Lynch syndrome who are undergoing risk-reducing surgery.
- •
- Surgeons should consider pre-operative testing and sending operative specimens for frozen pathology to determine the need for staging.
Objective:
The primary aim of this study was to determine the prevalence of occult
gynecologic malignancy at the time of risk reducing surgery in patients
with Lynch Syndrome. A secondary aim was to determine the prevalence of
occult gynecologic malignancy at the time of surgery for
non-prophylactic indications in patients with Lynch Syndrome.
Methods:
A retrospective review of an Inherited Colorectal Cancer Registry found
76 patients with Lynch syndrome (defined by a germline mutation in a
DNA mismatch repair gene) or hereditary nonpolyposis colorectal cancer
(HNPCC) (defined by Amsterdam criteria) who had undergone hysterectomy
and/or salpingo-oophorectomy for a prophylactic or non-prophylactic
indication. Indications for surgery and the prevalence of cancer at the
time of each operation were reviewed.
Results: 24 of
76 patients underwent prophylactic hysterectomy and/or bilateral
salpingo-oophorectomy for Lynch syndrome or HNPCC. In 9 of these
patients, a benign indication for surgery was also noted. 4 of 24
patients (17%, 95% CI = 5-38%) were noted to have cancer on final
pathology. 20 of 76 patients (26%) undergoing operative management for
any indication were noted to have occult malignancy on final pathology.
Conclusions:
Patients should be counseled about the risks of finding gynecologic
cancer at the time of prophylactic or non-prophylactic surgery for Lynch
syndrome and HNPCC, and the potential need for additional surgery.
Prognostic value of baseline survival determined for 11 types of cancer
science news
Nov. 6, 2013 — Results of an EORTC study published in Cancer point out the prognostic value of baseline recorded health-related quality of life for survival for eleven types of cancer: brain, breast, colorectal, esophageal, head and neck, lung, melanoma, ovarian, pancreatic, prostate, and testicular cancer. For each cancer site, at least one health-related quality of life parameter provided additional prognostic information over and above the clinical and sociodemographic variables.....
"nausea and vomiting for ovarian cancer"
abstract
A global analysis of multitrial data investigating quality of life and symptoms as prognostic factors for survival in different tumor sites
BACKGROUND
The
objective of this study was to examine the prognostic value of baseline
health-related quality of life (HRQOL) for survival with regard to
different cancer sites using 1 standardized and validated patient
self-assessment tool.
METHODS
In
total, 11 different cancer sites pooled from 30 European Organization
for Research and Treatment of Cancer (EORTC) randomized controlled
trials were selected for this study. For each cancer site, univariate
and multivariate Cox proportional hazards modeling was used to assess
the prognostic value (P < .05) of 15 HRQOL parameters using
the EORTC Core Quality of Life Questionnaire (QLQ-C30). Models were
adjusted for age, sex, and World Health Organization performance status
and were stratified by distant metastasis.
RESULTS
In
total, 7417 patients completed the EORTC QLQ-C30 before randomization.
In brain cancer, cognitive functioning was predictive for survival; in
breast cancer, physical functioning, emotional functioning, global
health status, and nausea and vomiting were predictive for survival; in
colorectal cancer, physical functioning, nausea and vomiting, pain, and
appetite loss were predictive for survival; in esophageal cancer,
physical functioning and social functioning were predictive for
survival; in head and neck cancer, emotional functioning, nausea and
vomiting, and dyspnea were predictive for survival; in lung cancer,
physical functioning and pain were predictive for survival; in melanoma,
physical functioning was predictive for survival; in ovarian cancer,
nausea and vomiting were predictive for survival; in pancreatic cancer,
global health status was predictive for survival; in prostate cancer,
role functioning and appetite loss were predictive for survival; and, in
testis cancer, role functioning was predictive for survival.
CONCLUSIONS
The current results demonstrated that, for each cancer site, at least 1 HRQOL domain provided prognostic information that was additive over and above clinical and sociodemographic variables.eNews: Live at the AICR Annual Research Conference (AICR)
eNews
This article appears in the November 7, 2013 issue of AICR's eNews.
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Editorial: A structured approach to uncommon cancers: what should a clinician do?
Abstract
In this issue of Annals of Oncology, Pecuchet et al. [1]
have produced an elegant, original paper describing an innovative
approach to the management of metastatic collecting duct
carcinoma, using bevacizumab, gemcitabine and a
platinum complex. They have shown surprising anticancer activity, which
appears
to have been sustained. They have addressed the
usual concerns about case selection bias, positive response bias and
pathology
review of an uncommon tumor, and thus, this
regimen certainly will bear confirmatory testing in other structured
trials, especially
as this triplet really does seem to give a
different result from the more conventional gemcitabine–cisplatin
combination or
the established MVAC regimen (notwithstanding
the absence of level 1 data at this time).
The editorial review of this manuscript
raised an important generic question, viz. what should a clinician do
when approaching
a patient with a truly uncommon or rare tumor?
Using a cut-off figure of 15 new cases/100 000 of population per year as
a
definition for ‘rare cancers’, Greenlee et al. [2]
have suggested that these tumors cumulatively account for around 25% of
incident cases in the United States. This figure
seems inflated to me, because of their cut-off
value, especially as I do not view testicular cancer as a rare tumor
(yet it
has an incidence of 6.8/100 000 males per year).
Nonetheless, Greenlee et al. make an important point—rare tumors
cumulatively
do constitute a significant proportion of the
total cancers presenting, yet we have remarkably little information
available
to guide management, when compared with the
common tumors that arise in breast, lung, prostate, colon, pancreas and
bladder.
A similar situation appears to apply to oncology
practice in Europe, in a report using a cut-off of less than six new
cases/100
000 of population per year, with the
accompanying suggestion …...
Genome-wide association study of subtype-specific epithelial ovarian cancer risk alleles using pooled DNA
abstract
Epithelial
ovarian cancer (EOC) is a heterogeneous cancer with both genetic and
environmental risk factors. Variants influencing the risk of developing
the less-common EOC subtypes have not been fully investigated. We
performed a genome-wide association study (GWAS) of EOC according to
subtype by pooling genomic DNA from 545 cases and 398 controls of
European descent, and testing for allelic associations. We evaluated for
replication 188 variants from the GWAS [56 variants for mucinous, 55
for endometrioid and clear cell, 53 for low-malignant potential (LMP)
serous, and 24 for invasive serous EOC], selected using pre-defined
criteria.
Genotypes from 13,188 cases and 23,164 controls of European descent were used to perform unconditional logistic regression under the log-additive genetic model; odds ratios (OR) and 95 % confidence intervals are reported. Nine variants tagging six loci were associated with subtype-specific EOC risk at P < 0.05, and had an OR that agreed in direction of effect with the GWAS results. Several of these variants are in or near genes with a biological rationale for conferring EOC risk, including ZFP36L1 and RAD51B for mucinous EOC (rs17106154, OR = 1.17, P = 0.029, n = 1,483 cases), GRB10 for endometrioid and clear cell EOC (rs2190503, P = 0.014, n = 2,903 cases), and C22orf26/BPIL2 for LMP serous EOC (rs9609538, OR = 0.86, P = 0.0043, n = 892 cases). In analyses that included the 75 GWAS samples, the association between rs9609538 (OR = 0.84, P = 0.0007) and LMP serous EOC risk remained statistically significant at P < 0.0012 adjusted for multiple testing. Replication in additional samples will be important to verify these results for the less-common EOC subtypes.
Genotypes from 13,188 cases and 23,164 controls of European descent were used to perform unconditional logistic regression under the log-additive genetic model; odds ratios (OR) and 95 % confidence intervals are reported. Nine variants tagging six loci were associated with subtype-specific EOC risk at P < 0.05, and had an OR that agreed in direction of effect with the GWAS results. Several of these variants are in or near genes with a biological rationale for conferring EOC risk, including ZFP36L1 and RAD51B for mucinous EOC (rs17106154, OR = 1.17, P = 0.029, n = 1,483 cases), GRB10 for endometrioid and clear cell EOC (rs2190503, P = 0.014, n = 2,903 cases), and C22orf26/BPIL2 for LMP serous EOC (rs9609538, OR = 0.86, P = 0.0043, n = 892 cases). In analyses that included the 75 GWAS samples, the association between rs9609538 (OR = 0.84, P = 0.0007) and LMP serous EOC risk remained statistically significant at P < 0.0012 adjusted for multiple testing. Replication in additional samples will be important to verify these results for the less-common EOC subtypes.
Platinum versus platinum-combination chemotherapy in platinum-sensitive recurrent ovarian cancer: a meta-analysis using individual patient data
abstract
BACKGROUND:
The majority of women with ovarian cancer develop recurrent disease. For patients with a platinum-free interval of >6 months, platinum-based chemotherapy is a treatment of choice. The benefit of platinum-based combination chemotherapy in randomized trials varies, and a meta-analysis was carried out to gain more secure information on the size of the benefit of this treatment.MATERIALS AND METHODS:
We initiated a systematic review and meta-analysis following a pre-specified protocol to determine whether combination chemotherapy is superior to single-agent platinum chemotherapy in women with relapsed platinum-sensitive ovarian cancer.RESULTS:
A total of five potentially eligible randomized trials were identified that had used combination-platinum chemotherapy versus single-agent platinum chemotherapy in women with relapsed platinum-sensitive ovarian cancer. For one trial (190 patients), adequate contact with the investigators could not be established. Therefore, four trials that randomly assigned 1300 patients were included, with a median follow-up of 36.1 months. Overall survival (OS) analyses were based on 865 deaths and demonstrated evidence for the benefit of combination-platinum chemotherapy (HR = 0.80; 95% CI, 0.64-1.00; P = 0.05). Progression-free survival (PFS) analyses were based on 1167 events and demonstrated strong evidence for the benefit of combination-platinum chemotherapy (HR = 0.68; 95% CI, 0.57-0.81; P < 0.001). There was no evidence of a difference in the relative effect of combination-platinum chemotherapy on either OS or PFS in patient subgroups defined by previous paclitaxel (Taxol) treatment (OS, P = 0.49; PFS, P = 0.66), duration of treatment-free interval (OS, P = 0.86; PFS, P = 0.48) or the number of previous lines of chemotherapy (OS, P = 0.21; PFS, P = 0.27).CONCLUSIONS:
In this individual patient data (IPD) meta-analysis, we have demonstrated that combination-platinum chemotherapy improves OS and PFS across all subgroups. This provides the strongest evidence to date of the benefit of combination-platinum over single-agent platinum.Single-Port Laparoscopic Extraperitoneal Para-aortic Lymphadenectomy
abstract
Objective: The aim of this study was to evaluate the
feasibility and the safety of single-port extraperitoneal laparoscopic
para-aortic lymphadenectomy for patients with gynecologic cancer.
Methods: From July 2012 to January 2013, a total of 7
patients with gynecologic cancer underwent a laparoscopic pelvic and
para-aortic lymphadenectomy with a single-port device. An
extraperitoneal approach was performed for para-aortic lymphadenectomy
using only one 2.5-cm incision on the left side. In 6 patients,
additionally, hysterectomy and pelvic lymphadenectomy with conventional
laparoscopy were performed to complete the treatment.
Results: Aortic dissection was complete in all cases
without complications. The median age of the patients was 63 years
(range, 48–78 years), and the median patient body mass index was 31 kg/m2 (range, 19–38 kg/m2).
The median number of para-aortic nodes was 17 (range, 10–25); the
median operative time was 204 minutes (range, 120–300 minutes). The
median hospital stay was 4 days (range, 3–6 days). No patient
encountered postoperative complications.
Conclusions: This study demonstrates the feasibility of single-port laparoscopic (youtube) extraperitoneal para-aortic lymphadenectomy.
Incidence and Predictors of Venous Thromboembolism After Debulking Surgery for Epithelial Ovarian Cancer
abstract
Objective: The aim of this study was to determine the
incidence and the risk factors of venous thromboembolism (VTE) within 30
days after primary surgery for epithelial ovarian cancer (EOC).
Methods: In a historical cohort study, we estimated
the postoperative 30-day cumulative incidence of VTE among consecutive
Mayo Clinic patients undergoing primary cytoreduction for EOC between
January 2, 2003, and December 29, 2008. We tested perioperative patient
characteristics and process-of-care variables (defined by the National
Surgical Quality Improvement Program, >130 variables) as potential
predictors of postoperative VTE using the Cox proportional hazards
modeling.
Results: Among 569 cases of primary EOC cytoreduction
and/or staging and no recent VTE, 35 developed symptomatic VTE within 30
days after surgery (cumulative incidence = 6.5%; 95% confidence
interval, 4.4%–8.6%). Within the cohort, 95 (16.7%) received graduated
compression stockings (GCSs), 367 (64.5%) had sequential compression
devices + GCSs, and 69 (12.1%) had sequential compression devices + GCSs
+ postoperative heparin, with VTE rates of 1.1%, 7.4%, and 5.8%,
respectively (P = 0.07, χ2 test). The remaining 38
(6.7%) received various other chemical and mechanical prophylaxis
regimens. In the multivariate analysis, current or past tobacco smoking,
longer hospital stay, and a remote history of VTE significantly
increased the risk for postoperative VTE.
Conclusions: Venous thromboembolism is a substantial
postoperative complication among women with EOC, and the high cumulative
rate of VTE within 30 days after primary surgery suggests that a more
aggressive strategy is needed for VTE prevention. In addition, because
longer hospital stay is independently associated with a higher risk for
VTE, methods to decrease length of stay and minimize factors that
contribute to prolonged hospitalization are warranted.
A Phase 2 Study of Oxaliplatin Combined With Continuous Infusion Topotecan for Patients With Previously Treated Ovarian Cancer
Abstract
Background: Phase 2 trials suggest that prolonged
intravenous (IV) infusion of the topoisomerase 1 inhibitor topotecan may
be less toxic than when given by standard IV bolus 5-day
administration. Oxaliplatin exhibits efficacy in platinum-pretreated
disease and shows preclinical synergy with topoisomerase 1 inhibitors.
We sought to determine the efficacy and safety of oxaliplatin plus
infusion topotecan in recurrent platinum-pretreated ovarian cancer.
Methods: Patients with recurrent epithelial ovarian,
fallopian tube, or primary peritoneal cancers previously treated with 1
to 2 prior regimens including platinum and taxane received oxaliplatin
(85 mg/m2 day 1 and day 15) and topotecan (0.4 mg/m2
per day) by continuous IV infusion over 14 days every 4 weeks. The
primary objective of the trial was to estimate the objective response
rate in platinum-resistant disease (stratum 1) and in platinum-sensitive
disease (stratum 2). Toxicities were assessed in all patients.
Results: Thirty-eight patients received 144 cycles of
therapy (median, 4; range, 1–6). The most common grade 3 and grade 4
toxicities included thrombocytopenia (grade 3, 37%; and grade 4, 19%),
neutropenia (grade 3, 37%; grade 4, 11%), and anemia (grade 3, 15%).
Response occurred in 4 of 19 patients in stratum I (21%; 95% confidence
intervals, 6%–46%) and 9 of 19 patients in stratum 2 (47%; 95% CI,
24%–71%). Three in each stratum had lengthy complete responses.
Conclusions: Biweekly oxaliplatin plus a 14-day
continuous IV infusion of topotecan, given monthly, is an active regimen
in platinum-pretreated ovarian cancer and merits additional evaluation.
Clinical Outcome of Isolated Serous Tubal Intraepithelial Carcinomas (STIC)
abstract
Objective: Risk-reducing salpingo-oophorectomy (RRSO) is recommended for women with BRCA
mutation due to increased risk of pelvic serous carcinoma. Serous tubal
intraepithelial carcinoma (STIC) is a pathologic finding of unknown
clinical significance. This study evaluates the clinical outcome of
patients with isolated STIC.
Materials/Methods: We retrospectively reviewed the medical records of consecutive patients with a germline BRCA1/2
mutation or a high-risk personal or family history of ovarian cancer
who underwent RRSO between January 2006 and June 2011. All patients had
peritoneal washings collected. All surgical specimens were assessed
using the sectioning and extensively examining the fimbria protocol,
with immunohistochemistry when indicated. p53 signature lesions and
secretory cell outgrowths were excluded.
Results: Of 593 patients who underwent RRSO, isolated STIC was diagnosed in 12 patients (2%). Five patients (42%) were BRCA1 positive, 5 patients (42%) were BRCA2
positive, and 2 patients (17%) had high-risk family history.
Preoperatively, all patients with STIC had normal CA-125 levels and/or
pelvic imaging results. Seven patients underwent hysterectomy and
omentectomy, 6 patients (46%) had pelvic node dissections, and 5
patients (39%) had para-aortic node dissections. With the exception of
positive peritoneal washings in 1 patient, no invasive or metastatic
disease was identified. No patient received adjuvant chemotherapy. At
median follow-up of 28 months (range, 16–44 months), no recurrences have
been identified.
Conclusions: Among the cases of isolated STIC after
RRSO reported in the literature, the yield of surgical staging is low,
and short-term clinical outcomes are favorable. Peritoneal washings are
the most common site of disease spread. Individualized management is
warranted until additional data become available.
The Inverse Relationship between 25-Hydroxyvitamin D and Cancer Survival: Discussion of Causation
Free Full-Text
"The best information that we have on disease severity is stage at the time of diagnosis. Most studies included in this review have taken disease severity into account in the analyses, e.g., using stage or other known prognostic factors (Table 1). Generally, these adjustments have had little effect on the relationship between 25-OHD level and cancer survival."
(ovarian cancer) reference:
Schwartz, G.G.; Skinner, H.G. Prospective studies of total and ionized serum calcium in relation to incident and fatal ovarian cancer. Gyn. Oncol. 2013, 129, 169–172.
Saturday, January 19, 2013 (prior blog posting)
Prospective Studies of Total and Ionized Serum Calcium in Relation to Incident and Fatal Ovarian Cancer.
Source
Departments of Cancer Biology, Urology, and Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, North Carolina. Electronic address: gschwart@wakehealth.edu.Abstract
OBJECTIVE:
Biological markers that could aid in the detection of ovarian cancer are urgently needed. Many ovarian cancers express parathyroid hormone-related protein, which acts to raise calcium levels in serum. Thus, we hypothesized that high serum calcium levels might predict ovarian cancer.METHODS:
We examined associations between total and ionized serum calcium and ovarian cancer mortality in the Third National Health and Nutrition Survey (NHANES III) using Cox proportional hazard models. We then examined associations of serum calcium with incident ovarian cancer in a second prospective cohort, the NHANES Epidemiological Follow-up Study (NHEFS).RESULTS:
There were eleven deaths from ovarian cancer over 95,556 person-years of follow-up in NHANES III. After multivariable adjustment, the risk for fatal ovarian cancer was 52% higher for each 0.1mmol/L increase in total serum calcium (RH=1.52, 95% CI 1.06 - 2.19) and 144% higher for each 0.1mmol/L increase in ionized serum calcium (RH=2.44, 95% CI=1.45 - 4.09). Associations persisted after adjusting for nulliparity and the use of oral contraceptives. Eight incident ovarian cancers occurred over 31,089 person-years of follow-up in the NHEFS. After adjusting for covariates, there was a 63% higher risk for ovarian cancer with each 0.1mmol/L increase in total serum calcium (95% CI 1.14 - 2.34). Similar results were observed for albumin-adjusted serum calcium.CONCLUSIONS:
Higher serum calcium may be a biomarker of ovarian cancer. This is the first report of prospective positive associations between indices of calcium in serum and ovarian cancer. Our findings require confirmation in other cohorts.Tuesday, November 05, 2013
Traumatization and chronic pain: a further model of interaction
open access
Up to 80% of patients with severe posttraumatic stress disorder are suffering from “unexplained” chronic pain. Theories about the links between traumatization and chronic pain have become the subject of increased interest over the last several years. We will give a short summary about the existing interaction models that emphasize particularly psychological and behavioral aspects of this interaction. After a synopsis of the most important psychoneurobiological mechanisms of pain in the context of traumatization, we introduce the hypermnesia–hyperarousal model, which focuses on two psychoneurobiological aspects of the physiology of learning. This hypothesis provides an answer to the hitherto open question about the origin of pain persistence and pain sensitization following a traumatic event and also provides a straightforward explanatory model for educational purposes.
Keywords: posttraumatic stress disorder, chronic pain, hypermnesia, hypersensitivity, traumatization
"...We consider that the psychotherapeutically desirable step of reframing is strongly supported by our model: for patients, it is therapeutically very meaningful to conceive trauma-associated sequelae as a “normal” reaction to an extremely “abnormal” event....
Metabolic complications with the use of mTOR inhibitors for cancer therapy
abstract
Interpretation
The risk of all grade
and grade 3–4, hyperglycemia, hypercholesterolemia, and
hypertriglyceridemia, are increase in patients treated with mTOR
inhibitors compared with control.
A phase I study of the combination of ro4929097 and cediranib in patients with advanced solid tumours (PJC-004/NCI 8503)
open access
Background:
The Notch signalling
pathway has been implicated in tumour initiation, progression,
angiogenesis and development of resistance to vascular endothelial
growth factor (VEGF) targeting, providing a rationale for the
combination of RO4929097, a γ-secretase inhibitor, and cediranib, a VEGF receptor tyrosine kinase inhibitor.
(U.S.) ACR Appropriateness Criteria Staging and Follow-up of Ovarian Cancer
Abstract
Purchase this article for 30.00 USD
Imaging
is used to detect and characterize adnexal masses and to stage ovarian
cancer both before and after initial treatment, although the role for
imaging in screening for ovarian cancer has not been established. CT and
MRI have been used to determine the resectability of tumors, the
candidacy of patients for effective cytoreductive surgery, the need for
postoperative chemotherapy if debulking is suboptimal, and the need for
referral to a gynecologic oncologist. Radiographic studies such as
contrast enema and urography have been replaced by CT and other
cross-sectional imaging for staging ovarian cancer. Contrast-enhanced CT
is the procedure of choice for preoperative staging of ovarian cancer.
MRI without and with contrast may be useful after equivocal CT, but is
usually not the best initial procedure for ovarian cancer staging.
Fluorine-18-2-fluoro-2-deoxy-D-glucose–PET/CT may not be needed
preoperatively, but its use is appropriate for detecting and defining
post-treatment recurrence. Ultrasound is useful for evaluating adnexal
disease, but has limited utility for staging ovarian cancer.
The
ACR Appropriateness Criteria are evidence-based guidelines for specific
clinical conditions that are reviewed every 2 years by a
multidisciplinary expert panel. The guideline development and review
include an extensive analysis of current medical literature from
peer-reviewed journals and the application of a well-established
consensus methodology (modified Delphi) to rate the appropriateness of
imaging and treatment procedures by the panel. In those instances where
evidence is lacking or not definitive, expert opinion may be used to
recommend imaging or treatment.
Figures and tables from this article: (requires paid subscription)
Figures and tables from this article: (requires paid subscription)
- Rating scale: 1, 2, 3 = usually not appropriate; 4, 5, 6 = may be appropriate; 7, 8, 9 = usually appropriate.
Napsin A as a marker of clear cell ovarian carcinoma
open access
Background
Clear cell carcinomas are aggressive tumors with a distinct biologic behaviour. In
a genome-wide screening for genes involved in chemo-resistance, NAPA was over-expressed
in cisplatin-resistant cells. The NAPA (protein) Napsin A was described to promote
resistance to cisplatin by degradation of the tumor suppressor p53.
Methods
Totally 131 patients were included in this study all in FIGO-stages I-II; 16 were
clear cell tumors which were compared with 40 Type I tumors and 75 type II tumors
according to the markers Napsin A, p21, p53 and p27 and some clinical features. For
detection of the markers tissue microarrays and immunohistochemistry were used.
Results
Positivity for Napsin A was detected in 12 (80%) out of the 15 clear cell tumors available
for analysis compared with 3 (4%) out of the Type I and II tumors in one group (p
< 0.001). Differences in p21 status, p53 status, and p21 + p53- status were striking
when clear cell tumors were compared with Type I, Type II, and Type I and II tumors
in one group, respectively. The p21 + p53-status was associated to positive staining
of Napsin A (p = 0.0015) and clear cell morphology (p = 0.0003). In two separate multivariate
logistic regression analyses with Napsin A as endpoint both clear cell carcinoma with
OR = 153 (95% C.I. 21--1107); (p < 001) and p21 + p53- status with OR = 5.36 (95%
C.I. 1.6-17.5); (p = 0.005) were independent predictive factors. ROC curves showed
that AUC for Napsin A alone was 0.882, for p21 + p53- it was 0.720 and for p21 + p53-Napsin
A + AUC was 0.795. Patients with clear cell tumors had lower (p = 0.013) BMI than
Type I patients and were younger (p = 0.046) at diagnosis than Type II patients. Clear
cell tumors had a higher frequency (p = 0.039) of capsule rupture at surgery than
Type I and II tumors.
Conclusions
Positivity of Napsin A in an epithelial ovarian tumor might strengthen the morphological
diagnosis of clear cell ovarian carcinoma in the process of differential diagnosis
between clear cell ovarian tumors and other histological subtypes.
The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.
"...Our findings related to the clinico-pathological differences are supported by earlier studies[4,7,10] but results about the immunohistochemical profile for Napsin A is new. Clear cell carcinomas resembles Type I tumors based on relative genetic stability and
frequent presentation in stage I, but on the other hand, clear cell carcinoma is high grade at diagnosis. Furthermore, wild-type p53 is mostly present and mutations are uncommon in clear cell tumors contrary to Type II tumors, which are genetically unstable and have a highrequency of p53 mutations [10,11]. Ovarian clear cell carcinomas constitute a heterogeneous disease at the genomic level despite having similar histological
features. Previous data fromTan et al [11] has suggested that the pattern of genome-wide copy number aberrations may predict clinical outcome...
Privacy and All That (sharing)
NEJM (requires paid subscription to view)
"The two men
had sat in neighboring chemotherapy chairs, swapping tales of side
effects, antiemetics, their childhoods, religion. When one died, it
affected the other profoundly. But there's no protocol for sharing
information with patients about their fellow travelers."
Patient Portals Increase Access And Reduce Misinformation
Diagnostic Imaging
Already
gaining popularity in health systems nationwide, patient portals could
now play a more significant role in radiology by automatically
structuring and combining radiology reports with related imaging
studies. This integration would give patients greater access to helpful
information about their health status.
In a study
published in the November issue of the Journal of the American Medical
Informatics Association, the University of California-Los Angeles
developed as web-based patient portal for individuals with brain cancer.
Allowing
patients to view their radiology reports makes sense even if patients
can’t fully understand the studies, the authors wrote, because the
patient interest is there.
“Even
though radiology test results are one of the most difficult portions of
the clinical record for lay people to understand, they are one of the
most frequently accessed pieces of information via patient portals when
available,” they wrote.
- See more at:
http://www.diagnosticimaging.com/pacs-and-informatics/patient-portals-increase-access-and-reduce-misinformation#sthash.KubvbFbT.dpufImaging informatics for consumer health: towards a radiology patient portal
Abstract
Objective
With the increased routine use of advanced imaging in clinical diagnosis
and treatment, it has become imperative to provide
patients with a means to view and
understand their imaging studies. We illustrate the feasibility of a
patient portal that
automatically structures and
integrates radiology reports with corresponding imaging studies
according to several information
orientations tailored for the
layperson.
Methods
The imaging patient portal is composed of an image processing module for
the creation of a timeline that illustrates the
progression of disease, a natural
language processing module to extract salient concepts from radiology
reports (73% accuracy,
F1 score of 0.67), and an
interactive user interface navigable by an imaging findings list. The
portal was developed as a Java-based
web application and is demonstrated
for patients with brain cancer.
Results and discussion
The system was exhibited at an international radiology conference to
solicit feedback from a diverse group of healthcare
professionals. There was wide
support for educating patients about their imaging studies, and an
appreciation for the informatics
tools used to simplify images and
reports for consumer interpretation. Primary concerns included the
possibility of patients
misunderstanding their results, as
well as worries regarding accidental improper disclosure of medical
information.
Conclusions
Radiologic imaging composes a significant amount of the evidence used
to make diagnostic and treatment decisions, yet there
are few tools for explaining this
information to patients. The proposed radiology patient portal provides a
framework for
organizing radiologic results into
several information orientations to support patient education.
The combination of gemcitabine and carboplatin shows similar efficacy in the treatment of platinum-resistant and platinum-sensitive recurrent epithelial ovarian cancer patients
abstract
The
aim of this study was to evaluate progression-free survival, overall
survival (OS), response rate (RR), and clinical benefit in recurrent
ovarian cancer patients treated with gemcitabine and carboplatin and to
compare the outcome among platinum-resistant and platinum-sensitive
patients. A retrospective study using the medical records of patients
diagnosed and treated for recurrent epithelial ovarian cancer, fallopian
tube carcinoma, or primary peritoneal carcinoma with gemcitabine and
carboplatin from 2005 through 2012 at the Tel Aviv Sourasky Medical
Center. The treatment regimen was carboplatin (area under the curve=5)
administered on day 1 and gemcitabine 850 mg/m administered on days 1
and 8 in a 21-day cycle. Seventy patients with a median age of 57 years
(range: 38-86) were included in the study. Most patients (94.3%) were
initially diagnosed with stage III-IV disease and 44.3% had
platinum-sensitive disease. Median progression-free survival in
platinum-sensitive patients was 6.3 months [95% confidence interval
(CI): 4.3-8.3] and 6.3 months (95% CI: 4.6-7.9) in platinum-resistant
patients. Median overall survival was 15.8 months (95% CI: 13.6-18.1) in
the platinum-sensitive patients and 18.4 months (95% CI: 10.0-27.8) in
the platinum-resistant patients. Platinum-sensitive patients had a RR of
43.2% and platinum-resistant patients had a RR of 39.1%. The clinical
benefit was 70.5% in platinum-sensitive patients and 65.2% in
platinum-resistant patients. Overall treatment had a favorable safety
profile. Gemcitabine and carboplatin demonstrate moderate toxicity with
similar efficacy in both platinum-sensitive and platinum-resistant
epithelial ovarian cancer, suggesting reversal of platinum resistance by
gemcitabine.
Stereotactic radiosurgery in the treatment of brain metastases: The current evidence
open access
Introduction
According to conservative estimates about 8% of cancer patients will develop brain metastases,1 which often cause the leading symptoms.....Monday, November 04, 2013
Destruction of the bladder by single dose Mitomycin C for low-stage transitional cell carcinoma (TCC) – avoidance, recognition, management and consent (Lynch syndrome patients note)
Blogger's Note: of interest to Lynch Syndrome patients with upper tract urothelial carcinoma (UTUC) and prophylaxis MMC to reduce the risk of bladder cancer after radical nephroureterectomy; note this study included bladder cancer patients
abstract
Keywords:
- bladder perforation;
- intravesical mitomycin;
- consent;
- extravasation
Objectives
- To identify a cohort of patients under our care who have had significant and in some cases irreparable damage to their bladders after Mitomycin C (MMC) instillation.
- To highlight the importance of avoidance and recognition of bladder perforations during transurethral resection of bladder tumour (TURBT) and explore the issue of consent regarding MMC given the serious complications that may occur after its instillation.
Patients and Methods
- Patients referred to our tertiary centre for a second opinion to manage their complications after a suspected MMC leak was identified from the departmental database between January 2000 and December 2010.
- After collection of all the records, we established a cohort of six patients.
- All patients had their initial tumour resection elsewhere and were referred for specialist management thereafter. Details of the operating surgeon and cystoscopic findings were known only in half of the cases.
- Retrospective analysis of their notes including documentation from the referring centre was undertaken. This included a review of all the histology and imaging.
Results
- All patients had immediate severe pelvic pain on instillation of the MMC. Four of the six continue to have chronic pelvic pain.
- Two patients had urinary retention and three had severe lower urinary tract symptoms. One patient developed a frozen pelvis.
- Initial treatment was with an indwelling catheter for a period of 2–52 weeks to aid healing.
- Two patients had reconstructive surgery, one with success and the other with failure, as an intestinal patch failed to close the fistula and he continues with a catheter. One patient had an ileal conduit.
- No patient was warned of such complications.
Conclusions
- Although rare, prophylactic MMC can have devastating consequences.
- Patients should be aware of such major risks.
- Strong emphasis should be placed on the quality of the initial TURBT coupled with the judgement of an experienced surgeon before to MMC instillation. The real clinical benefit could be reviewed and intravesical MMC offered only to patients who have a good chance of benefit.
Nov 2013 Scottish Intercollegiate Guidelines Network: Management of Epithelial Ovarian Cancer
open access
Scottish Intercollegiate Guidelines Network
Management of epithelial ovarian cancer
A national clinical guideline
International Ovarian & Testicular Stromal Tumor Registry - Full Text View - ClinicalTrials.gov
Tumor Registry
Purpose
Rare tumors are understudied, yet have the potential to shed light on vast areas of cancer research. Ovarian sex cord-stromal tumors, rare tumors of childhood and young adulthood, have recently been found to be associated with a lung cancer of early childhood called pleuropulmonary blastoma (PPB). The cause of these ovarian tumors
is unknown. DICER1 mutations are seen in the majority of children with
PPB. Research shows DICER1 mutations are also seen in some patients with
ovarian tumors. Like PPB, ovarian stromal tumors
are highly curable when found in early stage; however, later forms of
the disease are aggressive and often fatal. The International Ovarian Stromal Tumor Registry collects clinical and biologic data to understand why these tumors occur and how to treat them. Current work involves the study the role of DICER1 and miRNA expression in ovarian stromal tumors. Understanding the clinical history, predisposing factors and DICER1 and miRNA expression in these ovarian tumors
of childhood will lead to targeted screening and risk stratification
for evidence-based treatment and biologically rational therapies. These
efforts will improve the lives of children by increasing survival and
reducing late effects.
The specific goals of the International Ovarian and Testicular Stromal Tumor Registry are:
- to understand risk factors by studying age, pathologic subtype, histopathologic features, tumor invasiveness, degree of differentiation, presence of metastasis
- to collect information on personal and family history in order to refine the clinical characteristics of patients and families with and without germline DICER1 mutations and other genetic predisposing factors
- to determine whether there is a pattern of gene expression or DNA alterations that correlate with predisposition to ovarian tumors, biologic behavior and clinical outcome
- to determine optimal screening regimens
- to use clinical data obtained through the Registry to refine treatment algorithms
- to establish a collection of annotated biology specimens (tumor tissue and germline DNA) for future research
Condition |
---|
Ovarian Stromal Tumor Testicular Stromal Tumors Ovarian Small Cell Carcinoma |
Can patient reported outcomes help identify the optimal outcome in palliative surgery?
abstract
Background
The
purpose of this pilot study was to determine whether an open-ended
questionnaire captures severe symptoms in cancer patients undergoing
palliative surgical consultation that a structured, validated
quality-of-life assessment does not capture.
Methods
We
prospectively used the Functional Assessment of Cancer Therapy–General
(FACT-G) and an open-ended questionnaire to assess the symptoms of
patients with incurable malignancies who underwent palliative surgical
consultation at our institution between January 2011 and September 2012.
Results
Of
the 69 patients enrolled, the most common indications for consultation
were bowel obstruction (54%), jaundice (13%), wound problems (10%), and
gastrointestinal bleeding (7%). Of the severe symptoms patients
reported, 76% were identified with the FACT-G alone, 22% were identified
with the open-ended questionnaire alone, and 2% were duplicate
responses captured with both the FACT-G and open-ended questionnaire.
The open-ended questionnaire captured 68 instances of severe symptoms in
47 patients that the FACT-G did not capture; of these symptoms, 52 were
considered to be highly relevant to surgery and potential outcome
measures.
Conclusions
An open-ended questionnaire can identify severe symptoms that a global quality of life survey cannot capture and could be used in conjunction with a global survey to reassess symptoms after palliative surgical consultation.Clinical Research in Surgical Oncology: An Analysis of ClinicalTrials.gov
abstract
Background
The objective of
this study was to provide a descriptive analysis of registered clinical
trials in surgical oncology at ClinicalTrials.gov.
Methods
Data was extracted
from ClinicalTrials.gov using the following search engine criteria:
“Cancer” as Condition, “Surgery OR Operation OR Resection” as
Intervention, and Non-Industry sponsored. The search was limited to
Canada and the United States and included trials registered from January
1, 2001 to January 1, 2011.
Results
Of 9,961 oncology
trials, 1,049 (10.5 %) included any type of surgical intervention. Of
these trials, 125 (11.9 %, 1.3 % of all oncology trials) assessed a
surgical variable, 773 (73.7 %) assessed adjuvant/neoadjuvant therapies,
and 151 (14.4 %) were observational studies. Of the trials assessing
adjuvant therapies, systemic treatment (362 trials, 46.8 %) and
multimodal therapy (129 trials, 16.7 %) comprised a large focus. Of the
125 trials where surgery was the intervention, 59 trials (47.2 %)
focused on surgical techniques or devices, 45 trials (36.0 %) studied
invasive diagnostic methods, and 21 trials (16.8 %) evaluated surgery
versus no surgery. The majority of the 125 trials were nonrandomized
(72, 57.6 %).
Conclusions
The number of
registered surgical oncology trials is small in comparison to oncology
trials as a whole. Clinical trials specifically designed to assess
surgical interventions are vastly outnumbered by trials focusing on
adjuvant therapies. Randomized surgical oncology trials account for
<1 % of all registered cancer trials. Barriers to the design and
implementation of randomized trials in surgical oncology need to be
clarified in order to facilitate higher-level evidence in surgical
decision-making.
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