Clinical analysis of pathologic complete responders in advanced-stage ovarian cancer.

OBJECTIVE: To determine the clinical characteristics of patients who attained pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) and to identify specific predictive or prognostic factors associated with pCR. METHODS: Two distinct populations of patients who underwent NACT followed by interval tumor reductive surgery (TRS) were used in this retrospective study. The first contained 472 patients from a single institution. The second contained only pCR patients (67); those identified from population one, plus 44 obtained through collaborative institutions. Cox analysis and log-rank tests were performed to assess associations between clinical characteristics and pCR outcome, recurrence-free survival (RFS), and overall survival (OS). RESULTS: The median RFS and OS in our pCR-only population was 24.2 and 80.8 months, respectively, with a median follow-up time of 32.4 months. In our single institution population, 23 patients attained pCR (4.9%) and had longer RFS compared to non-pCR patients with viable microscopic, optimal, or suboptimal residual disease (24.3 vs. 12.1 vs. 11.6 vs. 9.6 months, p = 0.025, 0.012, 0.008, respectively), and longer OS compared to those with optimal or suboptimal residual disease (54.5 vs. 29.4 vs. 25.7 months, p = 0.027, 0.007, respectively). Patients were more than three-fold likely to attain pCR if their CA125 value was normal at the time of surgery (OR 3.54, 95% CI: 1.14-11.05, p = 0.029). CONCLUSIONS: Women with pCR after NACT have significantly longer RFS compared to those with residual viable tumor at the time of interval tumor-reductive surgery, and CA125 is plausible biomarker for identifying these extreme responders preoperatively.

Immunohistochemical analysis of glassy cell carcinoma of the cervix reveals robust lymphocyte infiltrate and the expression of targetable inhibitory immune checkpoints.

OBJECTIVE: To validate our previous findings of high-level EGFR expression in GCCC using an expanded cohort of specimens and to further examine the molecular and cellular features of this aggressive malignancy to identify potentially actionable therapeutic targets. METHODS: The SEER database was queried to obtain the epidemiological data regarding the current national survival trends for GCCC. Immunohistochemistry (IHC) was used to examine the expression of EGFR, PD-1, and PD-L1. CiberSort analysis was used to analyze a previously published RNA-sequencing dataset obtained from a single patient diagnosed with GCCC. RESULTS: In comparison to squamous cell carcinomas and adenocarcinoma/adenosquamous carcinomas, GCCC was observed in younger patients (p < 0.001) and demonstrated inferior survival (p < 0.001). All (100%) of the specimens (8/8) exhibited immunoreactivity when stained for CD3ε (T-cell marker), EGFR, PD-1, and PD-L1 whereas CTLA4 expression was not detected. Analysis of RNA-sequencing data revealed that cetuximab and erlotinib altered the chemokine profile, lymphocyte abundance, and expression of inhibitory immune checkpoints in a single patient when combined with cytotoxic chemotherapy in a single patient. CONCLUSIONS: The data from this descriptive study suggests that immune checkpoint blockade, whether single agent or in combination, may be a suitable therapeutic option for a disease for which targeted approaches do not currently exist.

Utero-ovarian preservation and overall survival of young women with early-stage borderline ovarian tumors.

PURPOSE: To examine survival of women who had uterine and ovarian preservation during surgical treatment for early-stage borderline ovarian tumors (BOTs). METHODS: The Surveillance, Epidemiology, and End Results Program was used to identify women aged < 50 years with stage I BOTs who underwent ovarian conservation at surgical treatment between 1988 and 2003. Survival outcomes were examined based on the use of concurrent hysterectomy at surgery. RESULTS: Among 6379 cases of BOT, there were 1065 women who had utero-ovarian preservation at surgery, and there were 52 women who had hysterectomy with ovarian preservation alone. Women who had uterine preservation were more likely to be single and diagnosed in recent years (both, P < 0.05). On univariable analysis, women who had utero-ovarian preservation had cause-specific survival similar to those who had ovarian preservation alone without uterine preservation (10-year rates: 99.2% versus 98.1%, P = 0.42); however, overall survival was higher in the utero-ovarian preservation group compared to the hysterectomy group (95.8% versus 87.6%, P < 0.001). On multivariable analysis, utero-ovarian preservation remained an independent prognostic factor for improved overall survival (adjusted hazard ratio 0.35, 95% confidence interval 0.15-0.79, P = 0.012). Cardiovascular disease mortality was lower in the utero-ovarian preservation group compared to the hysterectomy group, but it did not reach statistical significance (20-year cumulative rate, 0.8% versus 3.0%, P = 0.29). CONCLUSION: Our study suggests that utero-ovarian preservation for young women with early-stage BOTs may be associated with improved overall survival compared to ovarian preservation alone without affecting BOT-related survival outcome.

Efficacy of pegylated liposomal doxorubicin maintenance therapy in platinum-sensitive recurrent epithelial ovarian cancer: a retrospective study.

OBJECTIVE: To examine the effectiveness of pegylated liposomal doxorubicin (PLD) maintenance therapy (intravenous administration at dose 40 mg/m2 on day 1, repeated every 4 weeks) after first-line salvage chemotherapy for platinum-sensitive recurrent epithelial ovarian cancer. METHODS: This retrospective cohort study examined women with a first recurrence of platinum-sensitive epithelial ovarian cancer diagnosed between 2005 and 2015. Eligible cases had PLD maintenance following the first-line salvage chemotherapy (n = 28). Outcomes of interest included adverse events related to PLD maintenance therapy and survival outcome after the first recurrence. RESULTS: The median number of PLD maintenance cycles was 7.5 (range 2-26), and 11 (40%) women received ≥ 12 cycles. The median cumulative dose of PLD was 432.5 mg/m2 (range 120-1200 mg/m2). No women developed cardiotoxicity or secondary malignancies. There were 16 (57%) women who developed any grade of adverse events, including 3 (11%) women who developed grade 3 adverse events. There were no grade 4 adverse events. The most common adverse event was mucositis (n = 7, 25%). Dose reduction due to adverse events occurred in 14 (50%) women including 3 (11%) women with discontinuation due to toxicity. Median progression-free survival and overall survival after the initiation of PLD maintenance was 14.5 months (2-year rate 21.1%) and 51.2 months (5-year rate 43.4%), respectively. CONCLUSION: Our study suggests that PLD maintenance therapy for platinum-sensitive recurrent ovarian cancer is relatively well tolerated with the use of dose reduction to manage toxicity. Our study suggests that PLD maintenance therapy may be effective for women with platinum-sensitive recurrent epithelial ovarian cancer.

Significance of Lymphovascular Space Invasion by the Sarcomatous Component in Uterine Carcinosarcoma.

OBJECTIVE: The aim of this study was to examine the significance of lymphovascular space invasion (LVSI) with a sarcomatous component on the tumor characteristics and clinical outcomes of women with uterine carcinosarcoma (UCS). METHODS: This was a secondary analysis of a prior multicenter retrospective study that examined women with stage I-IV UCS who underwent primary hysterectomy. Archived histopathology slides were reviewed and LVSI was scored as follows: LVSI with a carcinomatous component alone (LVSI-carcinoma; n = 375, 76.8%) or LVSI containing a sarcomatous component with or without a carcinomatous component (LVSI-sarcoma; n = 113, 23.2%). Qualitative metrics of LVSI were correlated to clinicopathological factors and survival outcome. RESULTS: Tumors in the LVSI-sarcoma group were more likely to have sarcoma dominance (82.1 vs. 26.4%) heterologous sarcomatous component (51.3 vs. 37.9%), low-grade carcinoma (42.5 vs. 22.4%), and large tumor size (81.0 vs. 70.2%) in the primary tumor site compared with tumors in the LVSI-carcinoma group (all p < 0.05). On multivariate analysis, LVSI-sarcoma was independently associated with decreased progression-free survival (5-year rates: 34.9 vs. 40.8%, adjusted hazard ratio [HR] 1.84, 95% confidence interval [CI] 1.36-2.50, p < 0.001), and cause-specific survival (5-year rates: 41.8 vs. 55.9%, adjusted HR 1.95, 95% CI 1.39-2.75, p < 0.001) compared with LVSI-carcinoma. Postoperative radiotherapy for women with LVSI-sarcoma had a higher reduction rate of recurrence/progression of disease (54% reduction, p = 0.04) compared with postoperative radiotherapy for women with LVSI-carcinoma (26% reduction, p = 0.08). CONCLUSION: In UCS, the presence of a sarcomatous component in LVSI is particularly prevalent when a tumor has sarcoma dominance. Our study suggests that LVSI containing a sarcomatous component may be a predictor of decreased survival for women with UCS.

Proposal for a Risk-Based Categorization of Uterine Carcinosarcoma.

PURPOSE: To propose a categorization model of uterine carcinosarcoma (UCS) based on tumor cell types (carcinoma and sarcoma) and sarcoma dominance. METHODS: This secondary analysis of a prior multicenter retrospective study examined 889 cases of UCS with available histologic evaluation. Based on survival outcome, cases were clustered into three groups: low-grade carcinoma with nondominant homologous sarcoma [type A, n = 96 (10.8%)], (1) low-grade carcinoma with heterologous sarcoma or any sarcoma dominance and (2) high-grade carcinoma with nondominant homologous sarcoma [type B, n = 412 (46.3%)], and high-grade carcinoma with heterologous sarcoma or any sarcoma dominance [type C, n = 381 (42.9%)]. Tumor characteristics and outcome were examined based on the categorization. RESULTS: Women in type C category were more likely to be older, obese, and Caucasian, whereas those in type A category were younger, less obese, Asian, and nulligravid (all P < 0.01). Type C tumors were more likely to have metastatic implants, large tumor size, lymphovascular space invasion with sarcoma cells, and higher lymph node ratio, whereas type A tumors were more likely to be early-stage disease and small (all P < 0.05). On multivariate analysis, tumor categorization was independently associated with progression-free survival (5-year rates: 70.1% for type A, 48.3% for type B, and 35.9% for type C, adjusted P < 0.01) and cause-specific survival (5-year rates: 82.8% for type A, 63.0% for type B, and 47.1% for type C, adjusted P < 0.01). CONCLUSION: Characteristic differences in clinicopathological factors and outcomes in UCS imply that different underlying etiologies and biological behaviors may be present, supporting a new classification system.

Aspirin use and endometrial cancer risk and survival.

The role of acetylsalicylic acid (aspirin) as a chemo-preventive and adjuvant therapeutic agent for cancers is generating attention. Mounting evidence indicates that aspirin reduces the incidence and mortality of certain obesity-related cancers, particularly colorectal cancer. In endometrial cancer, previous studies examining the effect of aspirin remain inconsistent as to the reduction in the risk of endometrial cancer. While some evidence indicates protective effects in obese women, other studies have showed a potential deleterious effect of these medications on endometrial cancer outcomes. However, exposure measurement across studies has been inconsistent in recording dose, duration, and frequency of use; thus making comparisons difficult. In this article, we review the evidence for the association between endometrial cancer and obesity, the pharmacological differences between regular- and low-dose aspirin, as well as the potential anti-tumor mechanism of aspirin, supporting a possible therapeutic effect on endometrial cancer. A proposed mechanism behind decreased cancer mortality in endometrial cancer may be a result of inhibition of metastasis via platelet inactivation and possible prostaglandin E2 suppression by aspirin. Additionally, aspirin use in particular may have a secondary benefit for obesity-related comorbidities including cardiovascular disease in women with endometrial cancer. Although aspirin-related bleeding needs to be considered as a possible adverse effect, the benefits of aspirin therapy may exceed the potential risk in women with endometrial cancer. The current evidence reviewed herein has resulted in conflicting findings regarding the potential effect on endometrial cancer outcomes, thus indicating that future studies in this area are needed to resolve the effects of aspirin on endometrial cancer survival, particularly to identify specific populations that might benefit from aspirin use.

Incidences and risk factors of metachronous vulvar, vaginal, and anal cancers after cervical cancer diagnosis.

OBJECTIVE: To examine incidences and risk factors for metachronous vulvar, vaginal, and anal malignancies after a cervical cancer diagnosis. METHODS: This is a retrospective study examining data from the Surveillance, Epidemiology, and End Result Program between 1973 and 2013. Cumulative incidences of vulvar, vaginal, and anal cancers after the diagnosis of cervical cancer were assessed (n = 79,050). Multivariable analysis was performed to determine independent risk factors for these metachronous cancers. RESULTS: Vaginal cancer (20-year cumulative incidence, 0.57%) was the most common type of metachronous malignancy, followed by vulvar cancer (0.33%), and anal cancer (0.16%, P < 0.001). Median time to diagnosis was 5.4 years for vaginal cancer, 6.5 years for vulvar cancer, and 13.5 years for anal cancer. On multivariable analysis, metachronous vulvar cancer was associated with older age (hazard ratio [HR] per year 1.04, 95% confidence interval [CI] 1.02-1.05, P < 0.001), squamous histology (HR 2.64, 95%CI 1.38-5.05, P = 0.003), and radiotherapy use (HR 2.52, 95%CI 1.66-3.84, P < 0.001); metachronous vaginal cancer was associated with older age (HR per year 1.03, 95%CI 1.02-1.04, P < 0.001) and Black race (HR 1.73, 95%CI 1.20-2.48, P = 0.003); and metachronous anal cancer was associated with older age (HR 1.03, 95%CI 1.01-1.05, P = 0.017). Overall survival of metachronous cancer was poor (5-year rates: 46.3% for vulvar, 43.0% for vaginal, and 47.5% for anal cancer, respectively). CONCLUSION: Although rare, the rate of ano-genital cancers continues to increase over time after a cervical cancer diagnosis. Long-term follow-up and surveillance after cervical cancer treatment is therefore reasonable to detect these metachronous malignancies, particularly in those with risk factors.

Significance of venous thromboembolism in women with uterine carcinosarcoma.

OBJECTIVE: To identify risk factors for venous thromboembolism (VTE) and to examine the association of VTE and survival in women with uterine carcinosarcoma. METHODS: This multicenter retrospective study examined 906 women who underwent primary surgical treatment for stage I-IV uterine carcinosarcoma. Time-dependent analyses were performed for cumulative incidence of VTE after surgery on multivariate models. RESULTS: There were 72 (7.9%) women who developed VTE after surgery with 1-, 2-, and 5-year cumulative incidences being 5.1%, 7.3%, and 10.2%, respectively. On multivariate analysis, older age (hazard ratio [HR] per year 1.03, P=0.012), non-Asian race (HR 6.28, P<0.001), large body habitus (HR per kg/m2 1.04, P=0.014), residual disease at surgery (HR 3.04, P=0.003), tumor size ≥5cm (HR 2.73, P=0.003), and stage IV disease (HR 2.12, P=0.025) were independently associated with increased risk of developing VTE. A risk pattern analysis identified that obese Non-Asian women with large tumors (13.7% of population) had the highest incidence of VTE (2-year cumulative rate, 26.1%) whereas Asian women with no residual disease (47.1% of population) had the lowest (2-year cumulative rate, 1.6%) (P<0.001). Presence of carcinoma/sarcoma in metastatic sites was significantly associated with increased risk of VTE compared to carcinoma alone (2-year rates, 31.2% versus 8.4%, P=0.049). VTE was independently associated with decreased progression-free survival on multivariate models (5-year rates, 24.9% versus 47.2%, HR 1.46, 95%CI 1.05-2.04, P=0.026). CONCLUSION: Our study suggests that VTE represents a surrogate marker of aggressive tumor behavior and diminished patient condition in uterine carcinosarcoma; obese Non-Asian women with large tumors carry a disproportionally high risk of VTE, suggesting that long-term prophylaxis may benefit this population.

Impact of lympho-vascular space invasion on tumor characteristics and survival outcome of women with low-grade serous ovarian carcinoma.

BACKGROUND AND OBJECTIVES: To examine association of lympho-vascular space invasion (LVSI) with clinico-pathological factors and to evaluate survival of women with low-grade serous ovarian carcinoma containing areas of LVSI. METHODS: This is a multicenter retrospective study examining consecutive cases of surgically treated stage I-IV low-grade serous ovarian carcinoma (n = 178). Archived histopathology slides for the ovarian tumors were reviewed, and LVSI was scored as present or absent. LVSI status was correlated to clinico-pathological findings and survival outcome. RESULTS: LVSI was seen in 79 cases (44.4%, 95% confidence interval [CI] 37.1-51.7). LVSI was associated with increased risk of omental metastasis (87.0% vs 64.9%, odds ratio [OR] 3.62, P = 0.001), high pelvic lymph node ratio (median 12.9% vs 0%, P = 0.012), and malignant ascites (49.3% vs 32.6%, OR 2.01, P = 0.035). On multivariable analysis, controlling for age, stage, and cytoreductive status, presence of LVSI in the ovarian tumor remained an independent predictor for decreased progression-free survival (5-year rates 21.0% vs 35.7%, adjusted-hazard ratio 1.57, 95%CI 1.06-2.34, P = 0.026). LVSI was significantly associated with increased risk of recurrence in lymph nodes (OR 2.62, 95%CI 1.08-6.35, P = 0.047). CONCLUSION: LVSI in the ovarian tumor is associated with adverse clinico-pathological characteristics and decreased progression-free survival in women with low-grade serous ovarian carcinoma.

Survival outcome of women with stage IV uterine carcinosarcoma who received neoadjuvant chemotherapy followed by surgery.

BACKGROUND AND OBJECTIVES: To examine survival of women with stage IV uterine carcinosarcoma (UCS) who received neoadjuvant chemotherapy followed by hysterectomy. METHODS: This is a nested case-control study within a retrospective cohort of 1192 UCS cases. Women who received neoadjuvant chemotherapy followed by hysterectomy based-surgery for stage IV UCS (n = 26) were compared to those who had primary hysterectomy-based surgery without neoadjuvant chemotherapy for stage IV UCS (n = 120). Progression-free survival (PFS) and cause-specific survival (CSS) were examined. RESULTS: The most common regimen for neoadjuvant chemotherapy was carboplatin/paclitaxel (53.8%). Median number of neoadjuvant chemotherapy cycles was 4. PFS was similar between the neoadjuvant chemotherapy group and the primary surgery group (unadjusted-hazard ratio [HR] 1.19, 95% confidence interval [CI] 0.75-1.89, P = 0.45). Similarly, CSS was comparable between the two groups (unadjusted-HR 1.13, 95%CI 0.68-1.90, P = 0.64). When the types of neoadjuvant chemotherapy regimens were compared, women who received a carboplatin/paclitaxel regimen had better survival outcomes compared to those who received other regimens: PFS, unadjusted-HR 0.38, 95%CI 0.15-0.93, P = 0.027; and CSS, unadjusted-HR 0.21, 95%CI 0.07-0.61, P = 0.002. CONCLUSION: Our study found that there is no statistically significant difference in survival between women with stage IV UCS who are tolerated neoadjuvant chemotherapy and those who undergo primary surgery.

Radiation therapy is not an independent risk factor for decreased sexual function in women with gynecologic cancers.

AIM: To evaluate the associations of external beam radiation therapy (EBRT) and intracavitary brachytherapy (IB) with decreased sexual function. BACKGROUND: There's inconsistent evidence on whether radiation for gynecologic cancers has an impact on sexual health. IB, an underutilized treatment modality, is thought to have less adverse effects than EBRT. MATERIALS AND METHODS: A cross-sectional study examining decreased sexual function following radiation for gynecologic cancers. A decrease in sexual function was measured as a change in the Female Sexual Function Index (FSFI) from before to after treatment, with a significant decrease determined by Reliable Change Index Statistic (RCIS). Chi-square and t-tests were employed. RESULTS: 171 women completed the survey; 35% (n = 60) received radiation, of whom 29 received EBRT and IB (48%), 15 EBRT alone (25%), 16 IB alone (27%). Women who received radiation had similar rates of decreased sexual function as women who did not (47% vs. 38%, P = 0.262). EBRT and IB had similar rates of decreased sexual function compared to women with no radiation (50% vs. 38% P = 0.166 and 47% vs. 38% P = 0.309). Women experiencing decreased sexual function were more likely to be under 50 years old (OR 5.4, 95%CI 1.6-18.1), have received chemotherapy (OR 5.7, 95%CI 1.4-22.9), and have cervical cancer (OR 7.8, 95%CI 2.1-28.8). CONCLUSIONS: Treatment with EBRT or IB does not appear to impair sexual function in women with gynecologic cancer. Age less than 50, concurrent chemotherapy, and cervical cancer may place women with gynecologic cancer at higher risk for decreased sexual function following radiation.

Impact of adjuvant therapy on recurrence patterns in stage I uterine carcinosarcoma.

BACKGROUND: To examine recurrence patterns in women with stage I uterine carcinosarcoma (UCS) stratified by adjuvant therapy pattern. METHODS: We examined 443 cases of stage I UCS derived from a retrospective cohort of 1192 UCS cases from 26 institutions. Adjuvant therapy patterns after primary hysterectomy-based surgery were correlated to recurrence patterns. RESULTS: The most common adjuvant therapy was chemotherapy alone (41.5%) followed by chemotherapy/radiotherapy (15.8%) and radiotherapy alone (8.4%). Distant-recurrence was the most common recurrence pattern (5-year cumulative rate, 28.1%) followed by local-recurrence (13.3%). On multivariate analysis, chemotherapy but not radiotherapy remained an independent prognostic factor for decreased risk of local-recurrence (5-year cumulative rates 8.7% versus 19.8%, adjusted-hazard ratio [HR] 0.46, 95% confidence interval [CI] 0.25-0.83, P=0.01) and distant-recurrence (21.2% versus 38.0%, adjusted-HR 0.41, 95%CI 0.27-0.62, P<0.001). The chemotherapy/radiotherapy group had a lower 5-year cumulative local-recurrence rate compared to the chemotherapy alone group but it did not reach statistical significance (5.1% versus 10.1%, adjusted-HR 0.46, 95%CI 0.13-1.58, P=0.22). Radiotherapy significantly decreased local-recurrence when tumors had high-grade carcinoma, sarcoma component dominance, and deep myometrial tumor invasion (all, P<0.05); and combining radiotherapy with chemotherapy was significantly associated with decreased local-recurrence compared to chemotherapy alone in the presence of multiple risk factors (5-year cumulative rates, 2.5% versus 21.8%, HR 0.12, 95%CI 0.02-0.90; P=0.013) but not in none/single factor (P=0.36). CONCLUSION: Adjuvant chemotherapy appears to be effective to control both local- and distant-recurrences in stage I UCS; adding radiotherapy to chemotherapy may be effective to control local-recurrence when the tumor exhibits multiple risk factors.

Salvage chemotherapy with taxane and platinum for women with recurrent uterine carcinosarcoma.

OBJECTIVE: To examine survival after recurrence (SAR) among women with recurrent uterine carcinosarcoma who received a taxane/platinum doublet as the first-line salvage chemotherapy. METHODS: We retrospectively examined 148 women with recurrent uterine carcinosarcoma who received salvage chemotherapy within a cohort of 906 uterine carcinosarcomas. An independent association of salvage chemotherapy type and SAR was examined with multivariate analysis. RESULTS: There were 71 (48.0%) women who received a taxane/platinum regimen. On univariate analysis, women who received a taxane/platinum doublet had a higher 2-year SAR rate compared to women who received non-taxane/platinum regimens (55.5% versus 34.8%, P<0.001). On multivariate analysis, use of taxane/platinum regimen was independently associated with improved SAR compared to the non-taxane/platinum regimens (adjusted-hazard ratio [HR] 0.56, 95% confidence interval [CI] 0.35 to 0.91, P=0.02). When stratified by disease-free interval, women with a disease-free interval ≥6months who received a taxane/platinum doublet had a higher 2-year SAR rate compared to those who received non-taxane/platinum regimens (61.9% versus 40.0%, HR 0.46, 95% CI 0.28 to 0.75, P=0.002); conversely, in women with a disease-free interval <6months, 2-year SAR rates were similar between the two groups (20.5% versus 18.4%, HR 0.80, 95% CI 0.33 to 1.90, P=0.61). Among women who received a taxane/platinum doublet as adjuvant chemotherapy, re-treatment with taxane/platinum doublet as salvage chemotherapy remained beneficial (2-year SAR rate, 62.1% versus 39.7%, HR 0.40, 95% CI 0.18 to 0.86, P=0.019). CONCLUSION: Our study suggests that taxane/platinum doublet may be a more effective chemotherapy regimen compared to other regimens among women with recurrent uterine carcinosarcoma, especially for those who had a disease-free interval of ≥6months.

Tumor characteristics and survival outcomes of women with tamoxifen-related uterine carcinosarcoma.

OBJECTIVE: To examine tumor characteristics and survival outcome of women with uterine carcinosarcoma who had a history of tamoxifen use. METHODS: This is a multicenter retrospective study examining stage I-IV uterine carcinosarcoma cases based on history of tamoxifen use. Patient demographics, tumor characteristics, treatment pattern, and survival outcomes were compared between tamoxifen users and non-users. RESULTS: Sixty-six cases of tamoxifen-related uterine carcinosarcoma were compared to 1009 cases with no history of tamoxifen use. Tamoxifen users were more likely to be older (mean age, 69 versus 64, P<0.001) and had a past history of malignancy (100% versus 12.7%, P<0.001). Tamoxifen-related uterine carcinosarcoma was significantly associated with a higher proportion of stage IA disease (48.4% versus 29.9%) and a lower risk of stage IVB disease (7.8% versus 16.0%) compared to tamoxifen-unrelated carcinosarcoma (P=0.034). Deep myometrial tumor invasion was less common in uterine carcinosarcoma related to tamoxifen use (28.3% versus 48.8%, P=0.002). On univariate analysis, tamoxifen use was not associated with progression-free survival (5-year rates 44.5% versus 46.8%, P=0.48) and disease-specific survival (64.0% versus 59.1%, P=0.39). After adjusting for age, past history of malignancy, stage, residual disease status at surgery, and postoperative treatment patterns, tamoxifen use was not associated with progression-free survival (adjusted-hazard ratio 0.86, 95% confidence interval 0.50 to 1.50, P=0.60) and disease-specific survival (adjusted-hazard ratio 0.68, 95% confidence interval 0.36 to 1.29, P=0.24). CONCLUSION: Our study suggests that tamoxifen-related uterine carcinosarcoma may have favorable tumor characteristics but have comparable stage-specific survival outcomes compared to tamoxifen-unrelated uterine carcinosarcoma.

Fascin Is Associated With Aggressive Behavior and Poor Outcome in Uterine Carcinosarcoma.

OBJECTIVE: The mechanisms underlying the histogenesis and aggressiveness of uterine carcinosarcoma (UCS) are poorly understood; however, previous studies implicate epithelial-mesenchymal transition (EMT). Fascin is a proinvasive, actin-bundling protein and an important component of EMT. It is associated with poor outcomes in human carcinoma, especially in estrogen receptor (ER)-negative tumors arising in organs normally expressing ER. We sought to evaluate fascin expression in UCS and its relationship to ER status, clinicopathologic indicators of tumor aggressiveness, and survival outcomes. METHOD: Forty-four surgically staged cases of UCS were immunohistochemically evaluated for fascin and estrogen receptor-α expression and correlated with clinicopathologic parameters derived from electronic medical records and pathology reports. RESULTS: Fascin was only expressed in malignant epithelium and mesenchyma and was uniformly absent in background benign counterparts. Increased expression was associated with extrapelvic disease (P = 0.028), higher stage (P = 0.021), larger tumor size (P = 0.032), shorter progression-free interval (P = 0.035), and reduced estrogen receptor-α expression (P = 0.04). CONCLUSION: Fascin is aberrantly expressed in both elements of UCS and is associated with aggressive behavior and worse outcome. As a component of EMT and mediator of invasion, fascin may serve as a target in future therapies.

Single Marital Status and Infectious Mortality in Women With Cervical Cancer in the United States.

OBJECTIVE: Unmarried status including single marital status is associated with increased mortality in women bearing malignancy. Infectious disease weights a significant proportion of mortality in patients with malignancy. Here, we examined an association of single marital status and infectious mortality in cervical cancer. METHODS: This is a retrospective observational study examining 86,555 women with invasive cervical cancer identified in the Surveillance, Epidemiology, and End Results Program between 1973 and 2013. Characteristics of 18,324 single women were compared with 38,713 married women in multivariable binary logistic regression models. Propensity score matching was performed to examine cumulative risk of all-cause and infectious mortality between the 2 groups. RESULTS: Single marital status was significantly associated with young age, black/Hispanic ethnicity, Western US residents, uninsured status, high-grade tumor, squamous histology, and advanced-stage disease on multivariable analysis (all, P < 0.05). In a prematched model, single marital status was significantly associated with increased cumulative risk of all-cause mortality (5-year rate: 32.9% vs 29.7%, P < 0.001) and infectious mortality (0.5% vs 0.3%, P < 0.001) compared with the married status. After propensity score matching, single marital status remained an independent prognostic factor for increased cumulative risk of all-cause mortality (adjusted hazards ratio [HR], 1.15; 95% confidence interval [CI], 1.11-1.20; P < 0.001) and those of infectious mortality on multivariable analysis (adjusted HR, 1.71; 95% CI, 1.27-2.32; P < 0.001). In a sensitivity analysis for stage I disease, single marital status remained significantly increased risk of infectious mortality after propensity score matching (adjusted HR, 2.24; 95% CI, 1.34-3.73; P = 0.002). CONCLUSIONS: Single marital status was associated with increased infectious mortality in women with invasive cervical cancer.

Factors Impacting Use of Robotic Surgery for Treatment of Endometrial Cancer in the United States.

OBJECTIVE: This study was designed to examine the impact of patient socioeconomic, clinical, and hospital characteristics on the utilization of robotics in the surgical staging of endometrial cancer. METHODS: Patients surgically treated for endometrial cancer at facilities that offered robotic and open approaches were identified from the National Inpatient Sample Database from 2008 to 2012. The groups were compared for socioeconomic, clinical, and hospital differences. Medical comorbidity scores were calculated using the Charlson comorbidity index. T tests and χ (2) were used to compare groups. Multivariable analyses were used to determine factors that were independently associated with a robotic approach. RESULTS: A total of 18,284 patients were included (robotic, n = 7169; laparotomy, n = 11,115). Significant differences were noted in all patient clinical and socioeconomic characteristics and all hospital characteristics. Multivariable analyses identified factors that independently predicted patients undergoing robotic surgery. These patients were older [adjusted odds ratio (aOR) 1.008; 95 % confidence interval (CI) 1.004-1.011], white (aOR 1.38; 95 % CI 1.27-1.50), and privately insured (aOR 1.16; 95 % CI 1.07-1.26). Clinically, these women were more likely to be obese (aOR 1.20; 95 % CI 1.11-1.30) and to be undergoing an elective case (aOR 1.25; 95 % CI 1.11-1.40). Hospitals were more likely to be under private control (aOR 1.55, 95 % CI 1.39-1.71) but less likely to be located in the south (aOR 0.87; 0.81-0.93), quantified as large or medium (aOR 0.57; 95 %CI 0.50-0.67), or teaching hospitals (aOR 0.68; 95 % CI 0.63-0.74). CONCLUSIONS: Socioeconomic status and hospital characteristics are factors that independently predict robotic utilization in the United States. These racial, socioeconomic, and geographic disparities warrant further study regarding the utilization of this important technology.

Feto-maternal outcomes of pregnancy complicated by Krukenberg tumor: a systematic review of literature.

PURPOSE: Krukenberg tumor is a rare type of ovarian cancer with a poor prognosis, and little is known about its behavior during pregnancy. METHODS: A systematic review was conducted to identify pregnancies complicated by Krukenberg tumor, correlated to oncologic and neonatal outcomes (n = 35). RESULTS: Mean age of cases was 30.4 years, and the most common origin of primary cancer was the stomach (68.6 %) followed by the colon (14.3 %). The two most common presenting symptoms were abdominal/pelvic pain (51.4 %) and nausea/vomiting (48.6 %). Two-thirds of tumors were bilateral (65.7 %) and the average size was 16.7 cm. Ascites (45.7 %), carcinomatosis (25.7 %) and non-ovarian distant metastases (14.3 %) were found at the time of surgery. Chemotherapy was administered in 20 cases, with fetal exposure in two of these. The ovarian tumor was identified prior to the primary cancer diagnosis in all 28 cases. The overall number of live births was 27 (81.8 %). The median survival was 6 months after Krukenberg tumor diagnosis. In univariate analysis, decreased overall survival was associated with dyspnea, ascites, carcinomatosis, non-radical surgery for the primary cancer, and residual disease at surgery (all, p < 0.05). On multivariate analysis, dyspnea and carcinomatosis remained independent prognostic factors for decreased overall survival after Krukenberg tumor diagnosis (2-year overall survival rates, dyspnea 0 vs. 56.6 %, adjusted-hazard ratio [HR] 9.74, 95 % confidence interval [CI] 2.04-46.2, p < 0.01; and carcinomatosis, 0 vs. 58.1 %, adjusted-HR 7.95, 95 % CI 1.76-36.0, p < 0.01). CONCLUSIONS: Our results showed that prognosis of Krukenberg tumor complicated pregnancies is extremely poor, however it may be improved if radical surgery is achievable.

Tumor lysis syndrome in advanced and high-grade endometrial cancers: A case report and review of the literature.

•Tumor lysis syndrome is a rare but deadly complication of solid tumors.•We suggest that tumor lysis syndrome is especially deadly when it results from high grade or metastatic endometrial cancers.•Consider prophylactic measures to prevent tumor lysis syndrome in high risk patients before initiating therapy.