[Show abstract][Hide abstract] ABSTRACT: Objective
Despite the rarity of uterine papillary serous carcinoma (UPSC) and uterine clear cell carcinoma (UCCC), they contribute disproportionately to endometrial cancer deaths. Sufficient clinical information regarding treatment and prognosis is lacking. The aim of this study is to evaluate treatment outcomes in a rare cancer cohort based on the experience at two tertiary care cancer centers.
Clinicopathologic data were retrospectively collected on 279 patients with UPSC and UCCC treated between 1995 to 2011. Mode of surgery, use of adjuvant treatment, and dissection of paraaoritc lymph nodes were evaluated for their association with overall survival (OS) and progression-free survival (PFS).
40.9% of patients presented with stage I disease, 6.8% of patients presented with stage II disease and 52.3% of patients presented with stages III and IV. Median follow-up was 31 months (range, 1 to 194 months). OS and PFS at 5 years were 63.0% and 51.9%, respectively. OS and PFS were not affected by mode of surgery (open vs. robotic approach; OS: hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.28 to 1.62; PFS: HR, 0.78; 95% CI, 0.40 to 1.56). Adjuvant treatment was associated with improved OS in stages IB-II (HR, 0.14; 95% CI, 0.02 to 0.78; p=0.026) but not in stage IA disease. There was no difference in OS or PFS based on the performance of a paraaoritc lymph node dissection.
Minimally invasive surgical staging appears a reasonable strategy for patients with non-bulky UPSC and UCCC and was not associated with diminished survival. Adjuvant treatment improved 5-year survival in stages IB-II disease.
[Show abstract][Hide abstract] ABSTRACT: PURPOSELongitudinal algorithms incorporate change over time in biomarker levels to individualize screening decision rules. Compared with a single-threshold (ST) rule, smaller deviations from baseline biomarker levels are required to signal disease. We demonstrated improvement in ovarian cancer early detection by using a longitudinal algorithm to monitor annual CA125 levels.Patients And methodsWe retrospectively evaluated serial preclinical serum CA125 values measured annually in 44 incident ovarian cancer cases identified from participants in the PLCO (Prostate Lung Colorectal and Ovarian) Cancer Screening Trial to determine how frequently and to what extent the parametric empirical Bayes (PEB) longitudinal screening algorithm identifies ovarian cancer earlier than an ST rule.ResultsThe PEB algorithm detected ovarian cancer earlier than an ST rule in a substantial proportion of cases. At 99% specificity, which corresponded to the ST-rule CA125 cutoff ≥ 35 U/mL that was used in the PLCO trial, 20% of cases were identified earlier by using the PEB algorithm. Among these cases, the PEB signaled abnormal CA125 values, on average, 10 months earlier and at a CA125 concentration 42% lower (20 U/mL) than the ST-rule cutoff. The proportion of cases detected earlier by the PEB algorithm and the earliness of detection increased as the specificity of the screening rule was reduced. CONCLUSION
The PEB longitudinal algorithm identifies ovarian cancer earlier and at lower biomarker concentrations than an ST screening algorithm adjusted to the same specificity. Longitudinal biomarker assessment by using the PEB algorithm may have application for screening other solid tumors in which biomarkers are available.
[Show abstract][Hide abstract] ABSTRACT: Forty percent of women with ovarian carcinoma have circulating free neoplastic DNA identified in plasma. Angiogenesis is critical in neoplastic growth and metastasis. We sought to determine whether circulating neoplastic DNA results from alterations in the balance of angiogenesis activators and inhibitors.
Sixty patients with invasive ovarian carcinomas with somatic TP53 mutations that had been characterized for circulating neoplastic DNA had carcinoma analyzed for microvessel density using immunohistochemistry with CD31 and for the expression of VEGF, ANGPT1, ANGPT2, PTGS2, PLAU, THBS1, CSF1, PIK3CA, HIF1A, IL8, MMP2, and MMP9 message by real-time quantitative polymerase chain reaction. The expression of each gene was calculated relative to GAPDH expression for each neoplasm. Patient plasma had been tested for circulating neoplastic DNA using a ligase detection reaction.
MMP2 expression was significantly correlated with free plasma neoplastic DNA (P = .007). Microvessel density was not correlated with plasma neoplastic DNA or BRCA1/2 mutation status. The expression pattern of other angiogenic factors did not correlate with plasma neoplastic DNA but correlated with each other. BRCA1/2 mutated carcinomas had significantly different expression profiles of angiogenesis activators and inhibitors in comparison to sporadic carcinomas.
MMP2 expression is associated with the presence of circulating neoplastic DNA in women with ovarian carcinoma. These data are consistent with the proinvasive properties of MMP2 and suggest that the presence of circulating neoplastic DNA indicates a more aggressive malignant phenotype. Carcinomas with germ line BRCA1/2 mutations had a lower angiogenic profile than those without mutations.
[Show abstract][Hide abstract] ABSTRACT: To examine outcomes after pelvic exenteration in women treated with modern chemoradiation and surgical techniques.
All patients at our institution with a diagnosis of gynecologic malignancy who underwent pelvic exenteration after treatment with chemoradiation between 1/90 and 6/08 were evaluated with a retrospective chart review.
44 women were identified, of whom 29 (66%) had cervical, 6 (14%) had uterine, 5 (11%) had vaginal, and 4 (9%) had vulvar cancer. The majority of patients (82%) were initially treated with external beam whole-pelvic radiation with concurrent cisplatin. 38 patients (86%) underwent exenteration for a central pelvic recurrence, and the remaining 6 patients (14%) for radiation necrosis. The most common surgical complication was transfusion requirement in 36 patients (82%), followed by wound infection in 15 (34%), small bowel obstruction in 8 (18%), and sepsis in 6 (14%). The median time spent in the ICU post-operatively was 2 days. One patient (2%) died during her post-operative hospital stay. The mean EBL overall was 2497 cc and the mean operative time was 544 min. Use of electrothermal bipolar coagulation, which was used in 64% of the exenterations, significantly reduced blood loss (3679 cc vs. 1836 cc, p=0.014). After exenteration, 21 patients (48%) were diagnosed with a recurrence of cancer, and the mean progression free survival was 31 months. Patients who received exenteration less than 2 years after their initial chemoradiation had a significantly shorter overall survival time (8 months vs. 33 months, p=0.016).
Approximately 50% of women develop recurrence following exenterations done after chemoradiation. Survival is significantly longer in patients who necessitate exenteration greater than 2 years out from initial treatment. Electrothermal bipolar coagulation appears to significantly reduce blood loss during these surgeries.
[Show abstract][Hide abstract] ABSTRACT: We sought to examine outcomes in an expanding robotic surgery (RS) program.
In all, 1000 women underwent RS from May 2006 through December 2009. We analyzed patient characteristics and outcomes. A total of 377 women undergoing RS for endometrial cancer staging (ECS) were compared with the historical data of 131 undergoing open ECS.
For the entire RS cohort of 1000, the conversion rate was 2.9%. Body mass index increased over 3 time intervals: T1 = 26.2, T2 = 29.5, T3 = 30.1 (T1:T2, P = .01; T1:T3, P = .0001; T2:T3, P = .037). Increasing body mass index was not associated with increased major complications: T1 = 8.7%, T2 = 4.3%, T3 = 5.7%. In the ECS cohort, as compared with open ECS, women undergoing RS had lower blood loss (46.9 vs 197.6 mL, P < .0001), shorter hospitalization (1.4 vs 5.3 days, P < .0001), fewer major complications (6.4% vs 20.6%, P < .0001), with higher lymph node counts (15.5 vs 13.1, P = .007).
RS is associated with favorable morbidity and conversion rates in an unselected cohort. Compared to laparotomy, robotic ECS results in improved outcomes.
American journal of obstetrics and gynecology 03/2011; 204(6):551.e1-9. DOI:10.1016/j.ajog.2011.01.059 · 3.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recent studies have suggested inferior outcomes for elderly women with ovarian cancer. Our goal was to evaluate neoadjuvant chemotherapy versus primary cytoreduction in elderly women.
A retrospective chart review was performed for women aged 65+ diagnosed with ovarian cancer at our institution between 1997 and 2007. Univariate and multivariate logistic regression models were used to evaluate complication rates. Survival was evaluated with Cox regression and the Kaplan-Meier method.
One hundred seventy-five patients were identified, 34 (19%) of whom were aged 80+. Those aged 65-79 and those 80+ received neoadjuvant chemotherapy with equal frequency (19% vs. 21%, p=0.92). Treatment with neoadjuvant chemotherapy was associated with odds ratios of 0.80 (95% CI 0.37-1.75) for surgical complications and 0.79 (95% CI 0.33-1.90) for chemotherapeutic complications. In those aged 80+, the frequency of surgical complications (OR 1.01, p=0.62) and chemotherapeutic complications (OR 1.04, p=0.78) did not differ compared to younger patients. Overall survival did not differ based on initial treatment regimen, with 34 months in the primary surgery group and 29 months in the neoadjuvant chemotherapy group (p=0.65). The median disease specific survival for those aged 65-79 was 35 months, and 24 months in those aged 80+ (p=0.15). Post-operative mortality for patients aged 80+ was zero.
In our patient population, those aged 80+ have similar surgical and chemotherapy-related complication rates and comparable survival to those aged 65-79. The choice of initial treatment modality does not appear to impact survival when the decision is made in a selective fashion.
[Show abstract][Hide abstract] ABSTRACT: GOG 172 showed a survival benefit with intraperitoneal (IP) cisplatin for advanced ovarian cancer, but patients tolerated the regimen poorly. We hypothesized that women treated with alternative IP chemotherapy strategies may have less toxicity and improved compliance.
We reviewed the records of women with ovarian cancer and optimal surgical debulking who underwent IP chemotherapy at our institution. Primary outcomes analyzed were completion rates and toxicities of IP chemotherapy. Secondary outcomes were progression-free and overall survival. Statistical analysis was performed using STATA 10.0.
Thirty-nine patients with primary ovarian or peritoneal cancer who underwent IP chemotherapy were identified over a 2 year period. Patients were treated with IV paclitaxel followed by IP cisplatin (64%) or IP carboplatin (36%). Median two cycles of intravenous (IV) taxane and carboplatin were given prior to initiating IP therapy in 77% of patients. Median number of IP chemotherapy cycles was 5 and median total number of cycles was 8. Seventy-four percent (74%) of patients received four or greater cycles of IP chemotherapy. There was a higher rate of completion of intended number of IP cycles in the carboplatin group (92%) versus 60% in the IP cisplatin group (p=0.05). Grade 3 non-hematologic toxicities were more common in the IP cisplatin group than in the IP carboplatin group (24% and 0%, p=0.046). At median follow-up of 24 months, the median progression-free interval and overall survival have not yet been reached for either group.
Intraperitoneal chemotherapy regimens using carboplatin or cisplatin and dropping day 8 IP paclitaxel have less toxicity and less discontinuation of therapy.
[Show abstract][Hide abstract] ABSTRACT: To evaluate the effect of ovarian cancer risk on the performance of the serum biomarkers mesothelin, human epididymis protein 4 (HE4), and CA125.
We measured mesothelin, HE4, and CA125 levels from women with invasive ovarian cancer (n = 143), benign gynecologic conditions (n = 124), and controls (n = 344). Demographic, epidemiologic, reproductive, medical, and family history data were collected using a standardized questionnaire. Pedigree and BRCA 1/2 test results were used to stratify women into average and high-risk groups. The diagnostic accuracy of each biomarker was characterized using receiver operating characteristic curve methods.
Baseline characteristics did not vary by risk or case status. The distribution of stage and histology was similar in average and high-risk women. All three markers discriminated ovarian cancer cases from risk-matched healthy and benign controls. Marker performance did not vary by risk status. The sensitivity at 95% specificity for discriminating cases from risk-matched healthy control women in the average and high-risk groups, respectively, was 53.9% and 39.0% for mesothelin, 80.4% and 87.8% for HE4, and 79.4% and 82.9% for CA125. The performance of the markers was not as robust when cases were compared with benign controls. Area under the curve values for cases versus healthy and benign controls did not vary by risk status.
The ability of serum mesothelin, HE4, and CA 125 levels to discriminate ovarian cancer cases from healthy and benign controls is not influenced by risk status. Our findings support the pursuit of additional studies evaluating the early detection potential of these markers in high-risk populations.
[Show abstract][Hide abstract] ABSTRACT: To estimate the current effect of demographics, pathology, and treatment on mortality among women with vaginal cancer.
Using data from 17 population-based cancer registries that participate in the Surveillance, Epidemiology, and End Results program, 2,149 women diagnosed with primary vaginal cancer between 1990 and 2004 were identified. The association between various demographic factors, tumor characteristics, and treatments and risk of vaginal cancer mortality were evaluated using Cox proportional hazards modeling.
The mean age+/-standard deviation at diagnosis was 65.7+/-14.3 years. Approximately 66% of all cases were non-Hispanic whites. Incidence was highest among African-American women (1.24 per 100,000 person-years). The 5-year disease-specific survival was 84% (stage I), 75% (stage II), and 57% (stage III/IV). In a multivariate adjusted model, women with tumors greater than 4 cm and advanced disease had elevated risks of mortality (hazard ratios 1.71 and 4.67, respectively). Compared with women with squamous cell carcinomas, patients with vaginal melanoma had a 1.51-fold (95% confidence interval 1.07-2.41) increased risk of mortality. Surgery alone as a treatment modality had the lowest risk of mortality. The risk of mortality has decreased over time, as women diagnosed after 2000 had an adjusted 17% decrease in their risk of death compared with women from 1990-1994.
Stage, tumor size, histology, and treatment modality significantly affect a woman's risk of mortality from vaginal cancer. There seems to be a survival advantage that is temporally related to the advent of chemoradiation.
Obstetrics and Gynecology 06/2009; 113(5):1038-45. DOI:10.1097/AOG.0b013e31819fe844 · 4.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate if serum levels of candidate ovarian cancer biomarkers vary with individual characteristics of healthy women who are likely candidates for an ovarian cancer screening program.
We analyzed serum CA125, mesothelin, and HE4 levels in a sample of 155 healthy postmenopausal women at increased risk for developing ovarian cancer based on personal and family cancer history. Information on reproductive, family and medical histories, lifestyle factors, and anthropometry was collected by self-report. Twenty-two factors were examined using univariate and multiple linear regression models for the three biomarker levels.
In the multivariate models, CA125 levels were significantly higher in women who had used talcum powder (P = 0.02) and were lower in women who were parous (P = 0.05). Mesothelin levels were significantly higher in older women (P = 0.01) and lower in heavier women (P = 0.03). HE4 levels were higher in older women (P = 0.001) and in women who began menstruating at an older age (P = 0.03).
CA125, mesothelin, and HE4 levels in healthy, postmenopausal women at increased risk for ovarian cancer are significantly associated with a few ovarian cancer risk factors. Since the effects of these personal characteristics on these serum markers are not large, their incorporation in screening algorithms may be unnecessary. This is true especially if a longitudinal algorithm is used because the marker level at the previous screen reflects personal characteristics such as age, body mass index, and age of menarche. Understanding the influence of personal factors on levels of novel early detection markers in healthy, unaffected women may have clinical utility in interpreting biomarker levels.
[Show abstract][Hide abstract] ABSTRACT: The objective of the study was to evaluate outcomes during the first year of a robotic surgery program in gynecologic oncology.
We studied the initiation of a robotic surgery program with prospective data collection, including intraoperative times, estimated blood loss (EBL), length of stay (LOS), lymph node yields, and complications. Patients were compared with historical and contemporary open staging surgery for endometrial cancer.
One hundred eighteen patients underwent robotic surgery (mean age 52.5 years, body mass index of 26.3 kg/m(2), hospital stay of 32.4 hours), with 8 major and 13 minor complications. Compared with open endometrial staging (n = 131), the robotic procedure (n = 25) was longer (283 vs 139 minutes, P < .0001), had less blood loss (66.6 vs 197.6 mL, P < .0001), and had shorter length of stay (40.3 vs 127 hours, P < .0001) with comparable node yields (17.5 vs 13.1, P = .1109).
Robotic surgery is feasible in gynecologic oncology and facilitated a dramatic expansion in our minimally invasive surgical practice. Despite longer operative times, EBL and LOS are reduced and lymph node yields are comparable.
American journal of obstetrics and gynecology 07/2008; 198(6):679.e1-9; discussion 679.e9-10. DOI:10.1016/j.ajog.2008.03.032 · 3.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess prior cervical cancer screening, stage at time of diagnosis and outcome in women sixty years of age and over with cervical cancer.
A retrospective review of cervical cancer patients evaluated at the University of Washington identified a cohort of women age sixty and older with cervical cancer diagnosed between January 1, 1993 and December 31, 2003. Electronic medical records and the University of Washington Tumor Registry were reviewed for age, ethnicity, cervical cancer risk factors, pathology, treatment, and outcome.
Six hundred forty-five women with cervical cancer were identified. One hundred (15.5%) women were age 60 or older with a median age of 64 years. At time of diagnosis, 41 were early stage (1A1-1B1) and 59 were advanced stage (1B2-4B). Length of time from last Pap smear significantly correlated with stage. Radical hysterectomy was performed on 29 patients, and 15 received adjuvant treatment. Forty-nine women received primary chemo-radiation, and 22 were treated with primary radiation. Lymph node metastases were identified in 65% of women with locally advanced cervical cancer. At conclusion of the study period, 80% were alive. Stage and time since last Pap smear correlated with overall outcome.
Women 60 and older make up a significant proportion of cervical cancer patients, often fail to receive screening, present with locally advanced disease, and tolerate standard treatment protocols. Careful consideration of these findings should be made when establishing Pap smear screening guidelines for this population of women.
[Show abstract][Hide abstract] ABSTRACT: Forty percent of women with ovarian cancer have circulating free tumor DNA. We sought to determine if the tumor immune infiltrate varied based on tumor p53 mutation status or presence of circulating tumor DNA.
We performed immunohistochemistry on 119 ovarian cancer specimens with CD3 and CD8 (Intratumoral T cells (TILs)), CD68 (tumor-associated macrophages (TAMs)), and FoxP3 (T regulatory cells (Tregs)). Tumors had been previously sequenced for mutations in exons 4-10 of p53, and plasma from women characterized for free tumor DNA.
TIL and TAM levels were positively correlated (P<0.0001). High levels of TILs were identified in 54 of 119 tumors (45.4%). No survival difference was identified according to the presence of TILs or TAMs. Patients with greater TILs were more likely to be optimally cytoreduced (P=0.005). p53 mutations were associated with more TILs (P=0.008). The presence of circulating tumor DNA did not correlate with TILs, TAMs, or Tregs. In the subgroup with a low host antitumor immune response, the intermediate response Tregs group did have a survival advantage (P=0.049).
p53 mutations are associated with higher levels of TILs. The ratio of Tregs to TILS may be more important than absolute levels. A brisk T cell response within the tumor predicts adequacy of cytoreduction, suggesting successful cytoreduction may be partially due to underlying tumor biology and host response.
[Show abstract][Hide abstract] ABSTRACT: Malignant transformation of endometriosis is an infrequent complication of endometriosis. Extragonadal disease is uncommon.
55-year-old female presented with postmenopausal bleeding. Physical examination revealed a 2-cm polypoid lesion at the posterior vaginal apex, which was found to be a moderately differentiated invasive adenocarcinoma. Final pathology at the time of definitive surgery demonstrated a clear cell adenocarcinoma of the vagina arising in vaginal endometriosis.
Vaginal endometriosis may lead to the development of cancer. Malignancy arising in endometriotic foci is rare, but most commonly occurs in the ovary. We report a case of clear cell malignancy arising in vaginal endometriosis, adding to only seven cases previously reported. Risk factors include unopposed estrogen and obesity, but it may occur in the absence of either.
[Show abstract][Hide abstract] ABSTRACT: To determine whether tumor size or morphology is predictive of extrauterine disease and/or recurrence risk in endometrial cancer and therefore guide decisions about the necessity of complete surgical staging and adjuvant therapy.
All women with surgically treated endometrial carcinoma between 1 January 1990 and 1 January 2000 were eligible. 345 patients were eligible for retrospective chart review. Univariate and multivariate logistic regression models were used to determine the predictors of nodal metastasis and recurrence.
As tumor size increased, the risk of nodal metastasis increased. However, a risk of nodal metastasis remained even with small lesions less than or equal to 2 cm (6.3% risk). Patients with tumor size greater than 2 cm had a 26.3% incidence of nodal metastasis. In univariate analysis, the odds ratio (OR) for tumor size as a predictor of extrauterine disease was 1.4 (95% CI 1.2-1.6). In multivariate analysis, tumor size was not statistically significant. Only the lesions greater than or equal to 8 cm confer a risk that approaches previously identified well-known predictors. Tumor size was not found to be a statistically significant predictor of recurrence OR 1.3 (1.0-1.8).
Tumor size correlates with extrauterine disease, but it is not an independent prognostic variable. Although the risk of extrauterine disease increases with tumor size, the risk of nodal metastases remains even for those patients with very small tumors, underscoring the need for routine complete surgical staging. Tumor size does not appear to be an independent predictor of recurrence.