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Sunday, March 11, 2012

Seth's Blog: "It's not business, it's personal"



Seth's Blog:

"It's not business, it's personal"

It's too easy to blame the organization and the system and the bottom line for decisions that a person would never be willing to take responsibility for.
Whenever you can, work with people who take it personally.

abstract: Evaluation of ovarian cancer remission markers HE4, MMP7 and Mesothelin by comparison to the established marker CA125 (includes graphic/study of 23 patients)



 Highlights
(in study of 23 patients)

► Three new markers were compared to CA125 for lead time to ovarian cancer recurrence.
► HE4 elevates at recurrence when CA125 does not.
► Mesothelin has less marker potential, MMP7 shows promise and requires confirmation.
  
Evaluation of ovarian cancer remission markers HE4, MMP7 and Mesothelin by comparison to the established marker CA125: Publication year: 2012

Objective 
Evaluate and compare the effectiveness of CA125, HE4, Mesothelin and MMP7 marker levels to monitor ovarian cancer patients after surgery and chemotherapy. Evaluate the lead time of a rise of marker levels before recurrence.

Methods 
The study consists of 23 patients with advanced stage ovarian/fallopian tube cancer. Blood was drawn after front line surgery and chemotherapy treatment and at 3 month intervals thereafter. One patient had chemoresistant disease, two patients remained in remission and 20 patients had recurring disease and were used for marker evaluation.

Results
In five patients HE4 was the only marker to elevate before recurrence with a lead time of up to 4½ months including one patient who did not have a CA125 response at all. In a further two patients, HE4 increased before CA125 did. In four of these seven patients, HE4 levels were consistently at or above threshold during remission when both CA125 and imaging results were negative. MMP7 elevated before recurrence in one patient who was negative for the other markers. Mesothelin elevated in two patients who were also positive for CA125 and HE4.

Conclusions 
HE4 can predict ovarian cancer recurrence earlier than CA125 and it can be elevated in patients that do not express CA125 at sufficient levels to make a clinical decision. MMP7 and Mesothelin have lower potential as markers for ovarian cancer recurrence to complement CA125. A failure of HE4 levels to normalize at completion of standard therapy may indicate a poor prognosis.

Graphical Abstract

image

Highlights

► Three new markers were compared to CA125 for lead time to ovarian cancer recurrence.
► HE4 elevates at recurrence when CA125 does not.
► Mesothelin has less marker potential, MMP7 shows promise and requires confirmation.

repost from December 2011: A study of symptoms described by ovarian cancer survivors



A study of symptoms described by ovarian cancer survivors: Publication year: 2012

A phase I study with an expanded cohort to assess the feasibility of intravenous paclitaxel, intraperitoneal carboplatin and intraperitoneal paclitaxel in patients with untreated ovarian, fallopian tube or primary peritoneal carcinoma: A Gynecologic Oncology Group study



A phase I study with an expanded cohort to assess the feasibility of intravenous paclitaxel, intraperitoneal carboplatin and intraperitoneal paclitaxel in patients with untreated ovarian, fallopian tube or primary peritoneal carcinoma: A Gynecologic Oncology Group study


Objective 
To define the maximum tolerated dose (MTD) and assess the feasibility of intravenous (IV) paclitaxel, intraperitoneal (IP) carboplatin, and IP paclitaxel in women with newly diagnosed Stages II–IV ovarian, fallopian tube, or primary peritoneal carcinoma.

Methods 
Patients received escalating doses of paclitaxel IV and carboplatin IP on day 1 and paclitaxel IP 60mg/m2 on day 8. A standard 3+3 design was used in the escalation phase. A two-stage group sequential design with 20 patients at the MTD was used in the feasibility phase. Patient-reported neurotoxicity was assessed pre and post treatment.

Results 
Patients were treated with paclitaxel 175mg/m2 IV and carboplatin IP from AUC 5–7 on day 1 and paclitaxel 60mg/m2 IP on day 8. The MTD was estimated at carboplatin AUC 6 IP and 25 patients enrolled at this dose level. Within the first 4cycles, seven (35%) of twenty evaluable patients had dose-limiting toxicities (DLTs) including grade 4 thrombocytopenia (1), grade 3 neutropenic fever (3), >2week delay due to ANC recovery (1), grade 3 LFT (1), and grade 3 infection (1). De-escalation to paclitaxel 135mg/m2 IV was given to improve the safety. After six evaluable patients completed 4 cycles without a DLT, bevacizumab was added and six evaluable patients completed 4cycles with one DLT (grade 3 hyponatremia).

Conclusions 
Paclitaxel at 175mg/m2 IV, carboplatin AUC 6 IP day 1 and paclitaxel 60mg/m2 IP day 8 yield 18–56% patients with DLTs. The tolerability of the regimen in combination with bevacizumab was indicated in a small cohort.

abstract: Lymphatic ascites following pelvic and paraaortic lymphadenectomy procedures for gynecologic malignancies



 Blogger's Note: the abstract does not differentiate types of gyn cancers, journal is subscriber based ($$$)

Lymphatic ascites following pelvic and paraaortic lymphadenectomy procedures for gynecologic malignancies

Objective 
Lymphatic ascites is an unusual complication in patients with cancer. In the gynecologic oncology patient population, the most common etiology is operative lymph node dissection. The purpose of this study was to explore the incidence, presenting symptoms, methods of diagnosis and treatment modalities utilized for lymphatic ascites in patients undergoing lymph node dissection for gynecologic cancers.

Methods 
This observational study retrospectively reviewed the charts of patients who underwent lymphadenectomy as part of the surgical management for a gynecologic cancer. Patients that developed postoperative lymphatic ascites between January 2000 and December 2010 were included for analysis. Data extracted from the medical records included tumor pathology, number of harvested lymph nodes, postoperative course, method of diagnosis and treatment.

Results
From a total of 300 surgical staging procedures, 12 patients with lymphatic ascites were identified (4%). The most common reported symptom was leakage of clear fluid per vagina (7, 58%), followed by abdominal distension (4, 33%). The median interval from surgery to development of symptoms was 12.5 days (range 0–22days). 5 patients had complete resolution of symptoms with dietary modifications alone while 7 patients required paracentesis. The median time from surgery to resolution of symptoms was 44days (range 9–99).

Conclusion 
Lymphatic ascites is an under recognized and infrequently reported postoperative complication. Although it usually resolves spontaneously or with conservative management without sequelae, this condition can significantly prolong postoperative recovery and cause patient discomfort. To our knowledge this is the largest group of patients undergoing gynecologic surgical staging procedures to be reviewed for the occurrence of lymphatic ascites.

A phase II study of aflibercept in patients with advanced epithelial ovarian cancer and symptomatic malignant ascites



A phase II study of aflibercept in patients with advanced epithelial ovarian cancer and symptomatic malignant ascites

Objective 
The recombinant fusion protein, aflibercept binds and neutralizes vascular endothelial growth factor (VEGF) A, B and placental growth factor (PlGF). Aflibercept inhibits ascites formation and reduces tumor burden in an ovarian cancer model. This open-label, single-arm, multicenter phase II study assessed the efficacy and safety of aflibercept in patients with advanced chemo-resistant epithelial ovarian cancer and symptomatic malignant ascites.

Methods 
Patients who required ≥3 previous paracenteses at 1-4 paracenteses per month received intravenous aflibercept 4mg/kg every 2weeks. The primary endpoint was repeat paracentesis response rate (RPRR), with response defined as at least a two-fold increase in time to repeat paracentesis compared with the baseline interval.

Results 
Ten out of 16 enrolled patients achieved a response; the RPRR was 62.5% (95% CI 35.4%–84.8%). Aflibercept was considered effective based on a hypothesis that the RPRR was ≥60%. Median time to repeat paracentesis was 76.0 (95% CI 64.0–178.0) days, which was 4.5 times longer than the baseline interval (16.8days). Median progression-free survival was 59.5 (95% CI 41.0–83.0) days. Twelve patients experienced adverse events considered related to aflibercept treatment including hypertension (7 patients), headache, anorexia, and dysphonia (3 patients each). Two patients experienced Grade 3/4 treatment-related adverse events (Grade 3 hypertension and weight loss in one patient, Grade 3 intestinal perforation in one patient).

Conclusion 
Aflibercept 4mg/kg every 2weeks was effective at controlling malignant ascites, reducing the interval between repeat paracenteses. The safety profile was consistent with that reported for anti-VEGF agents.

Outcomes of surgical management of bowel obstruction in relapsed epithelial ovarian cancer (EOC)



Outcomes of surgical management of bowel obstruction in relapsed epithelial ovarian cancer (EOC):

Objective 
To describe the outcomes of surgical management of bowel obstruction in relapsed epithelial ovarian cancer (EOC) so as to define the criteria for patient selection for palliative surgery. Methods 90 women with relapsed EOC underwent palliative surgery for bowel obstruction between 1992 and 2008.

Conclusion 
Surgery for bowel obstruction in relapsed EOC is associated with a high morbidity and mortality rate especially in emergency cases when compared to other gynaecological oncological procedures. Palliation can be achieved in almost two thirds of cases, is equally likely in elective and emergency cases but is less likely in those with ascites.

abstract: Have racial disparities in ovarian cancer increased over time? An analysis of SEER data



Have racial disparities in ovarian cancer increased over time? An analysis of SEER data:

Objective 
Race has been postulated to be a prognostic factor in women with ovarian cancer. The reasons for racial disparities are multifactorial. Recent literature suggests that racial disparities in ovarian cancer survival emerged in the 1980s, when modern treatments such as aggressive surgical debulking and platinum-based chemotherapy first gained widespread use. We suspect that as improvements in treatment have evolved, the effects of access to treatment have amplified racial disparities in survival from ovarian cancer. Methods SEER 9 data were analyzed, including African American and white patients diagnosed with ovarian cancer from 1973 to 2007, with 2008 as the cutoff for follow-up. Using the Kaplan–Meier method, we evaluated racial differences in survival, to determine whether this difference has increased over time.

Results
There were 44,562 white and 3190 African American women available for analysis. Overall African Americans had 1.10 times the crude hazard (95% CI 1.06–1.15) of all-cause mortality compared to whites, with a widening trend over time (p<0.01). Adjusted for SEER registry, age, tumor stage, marital status and time of diagnosis, the hazard ratio (HR) for all-cause mortality comparing African Americans to whites was 1.31 (95% CI 1.26–1.37). When the receipt of surgery was added to the model, the HR for all-cause mortality remained higher for African American women at 1.27 (95% CI 1.21–1.34).

Conclusions 
African Americans diagnosed with ovarian cancer have worse survival than whites, and this disparity has increased over time. Measured differences in treatment, such as receipt of surgery, account for part of the disparity.

Disparities in hospice care among older women (over 65 yrs) dying with ovarian cancer



Disparities in hospice care among older women dying with ovarian cancer:

Background
Timely hospice referral is an essential component of quality end-of-life care, although a growing body of research suggests that for patients with various types of cancer, hospice referrals often occur very late in the course of care, and are marked by sociodemographic disparities. However, little is known about the ovarian cancer patient population specifically. We examined the extent and timing of hospice referrals in ovarian cancer patients over age 65, and the factors associated with these outcomes.

Methods
We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database to identify 8211 women aged 66+ with ovarian cancer who were diagnosed between 2001 and 2005 and died by December 31, 2007. We excluded women who were not eligible for Medicare A continuously during the 6 months prior to death. Outcomes studied included overall hospice use in the last 6months of life and late hospice enrollment, defined as within 3 days of death. We examined variations in these two measures based on year of diagnosis and sociodemographic characteristics (age, race, marital status, rural residence, income, education) and type of Medicare received (fee-for-service vs. managed care).

Results 
Among 8211 women in the cohort who died from ovarian cancer, 39.7% never received hospice care (3257/8211). Overall hospice care increased over the period of observation, from 49.7% in 2001 to 74.9% in 2005, but the proportion of women receiving hospice care within 3days of death did not improve. Among those who received hospice care, 11.2% (556/4954) and 26.2% (1299/4954) received such care within 3 and 7 days of death, respectively. A higher proportion of black women (46.5% vs. 38.4% among whites), women in the lowest income group (42.8% vs. 37.0% in the highest income group), and those receiving fee-for-service Medicare (41.3% vs.33.5% for women in managed care) never received hospice care. In multivariable models, factors associated with lack of hospice care included age younger than 80 years (OR 1.27, 95% CI 1.15–1.40), non-white race (OR 1.44, 95% CI 1.26–1.65), low income (OR 1.17, 95% CI 1.04–1.32) and enrollment in fee-for-service Medicare compared with managed care (OR 1.39, 95% CI 1.24–1.56).

Conclusion 
More older women with ovarian cancer are receiving hospice care over time, however, a substantial proportion receive such care very near death, and sociodemographic disparities in hospice care exist. Our data also support the need to target lower-income and minority women in efforts to increase optimally timed hospice referrals in this population. Our finding that ovarian cancer patients enrolled in managed care plans were more likely to receive hospice care suggests the importance of health care system factors in the utilization of hospice services.

abstract: Combined treatment of L1CAM antibodies and cytostatic drugs improve the therapeutic response of pancreatic and ovarian carcinoma 10.1016/j.canlet.2011.12.035 : Cancer Letters | ScienceDirect.com



Combined treatment of L1CAM antibodies and cytostatic drugs improve the therapeutic response of pancreatic and ovarian carcinoma 10.1016/j.canlet.2011.12.035 : Cancer Letters | ScienceDirect.com

 Abstract

The adhesion molecule L1CAM (CD171) accounts for enhanced motility, invasiveness and chemoresistance of tumor cells and represents a novel marker for various tumor entities including pancreatic and ovarian carcinoma. Recently, we showed that L1CAM inhibition increases the apoptotic response of tumor cells towards cytostatic drugs pointing to the potential of L1CAM to serve as a chemosensitizer in anti-cancer therapy. Thus, the present study evaluated the therapeutic potential of combined treatment with L1CAM antibodies and chemotherapeutic drugs in pancreatic and ovarian carcinoma model systems in vivo.