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.

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.

Rhabdomyolysis following single administration of pembrolizumab: Is severe immune-reaction a marker for durable treatment response?

•Immune checkpoint inhibitors are approved for all mismatch repair deficient tumors.•Although rare, autoimmune myositis complicating pembrolizumab therapy may be fatal.•In this case, pembrolizumab caused rhabdomyolysis but also a durable response.•Severe autoimmune reaction may be associated with durable treatment response.

Non-prescription cannabis use for symptom management amongst women with gynecologic malignancies.

OBJECTIVES: To evaluate interest in and patterns of use of non-prescription cannabis products for symptom management amongst gynecologic cancer patients living in states with legal access to medical and recreational marijuana. METHODS: Cross-sectional study using a novel 35-question survey distributed to women diagnosed with gynecologic cancer within two academic centers in California and Colorado. The survey queries demographic and disease traits, and both objective and subjective issues surrounding use of cannabis products for symptom management. Surveys were distributed to patients actively receiving treatment or under surveillance. RESULTS: Enrollment began July 16, 2018 and was completed December 1, 2018. Survey return rate was 52.7%. A total of 225 participants met inclusion criteria.Sixty-two percent reported that they have used or would be interested in using cannabis products for symptom management; 60 (26.7%) are using non-prescription cannabis for treatment of cancer related symptoms, and 80 (35.6%) are interested in using cannabis derivatives under direction of their oncologist. Reasons cited for use of cannabis included: pain control (n = 41, 68.3), insomnia (n = 33, 55.0%), anxiety (n = 29, 48.3%), nausea (n = 26, 43.3%), and appetite stimulation (n = 21, 35.0%). Of the women using cannabis products, almost half report decreased prescription narcotic use after initiation of cannabis products (n = 27, 45.0%). CONCLUSIONS: Women with gynecologic cancer report a strong interest in the use of non-prescription cannabis products for management of cancer-related symptoms. Practitioners in the field of gynecologic oncology should be aware of the frequency of use of non-prescription cannabis amongst their patients as well as the growing desire for guidance about the use of cannabis derivatives. A substantial number of patients report decreased reliance on opioids when using cannabis derivatives for pain control.

Tumor characteristics and outcome of uterine carcinosarcoma in women aged ≥80 years.

OBJECTIVE: To examine clinico-pathological characteristics and outcomes of uterine carcinosarcoma (UCS) in women aged ≥80 years. METHODS: This is a secondary analysis of a previous multicenter retrospective study examining 906 women with stage I-IV UCS who underwent primary hysterectomy. Patient demographics, treatment types, tumor characteristics, and survival were examined across aged ≥80 (n = 82 [9.1%]), aged 60-79, (n = 526 [58.1%]), and aged <60 (n = 298 [32.9%]). RESULTS: Women in the aged ≥80 group were more likely to be Caucasian, undergo simple hysterectomy without lymphadenectomy, and receive no postoperative therapy (all, P < 0.05). Tumors in the aged ≥80 group were more likely to have high-grade carcinoma, heterologous sarcoma, and sarcoma dominance but less likely to have lympho-vascular space invasion (all, P < 0.05). Lymphadenectomy did not improve survival in the aged ≥80 group (P > 0.05), whereas lymphadenectomy was protective for survival in the younger groups (both, P < 0.05). Postoperative chemotherapy was associated with improved progression-free survival (PFS) in the aged ≥80 group (hazard ratio [HR] 0.44, 95% confidence interval [CI] 0.22-0.89, P = 0.021). With chemotherapy treatment, women in the aged ≥80 group had PFS similar to those in the aged 60-79 group (HR 0.97, 95%CI 0.51-1.83, P = 0.92). In contrast, without chemotherapy treatment, women in the aged ≥80 group had significantly decreased PFS compared to the aged 60-79 group (HR 1.62, 95%CI 1.09-2.40, P = 0.016). Similar associations were observed for postoperative radiotherapy. CONCLUSION: Nearly 10% of women with UCS are aged ≥80 that are characterized by aggressive tumor factors. Postoperative therapy but not extensive surgery may improve survival in this age group.

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.

Characterizing sarcoma dominance pattern in uterine carcinosarcoma: Homologous versus heterologous element.

OBJECTIVE: To examine significance of sarcoma dominance (SD) patterns in uterine carcinosarcoma (UCS). METHODS: This is a secondary analysis of multicenter retrospective study examining women with stages I-IV UCS who underwent primary surgery. SD was defined as >50% of sarcoma component in uterine tumor. SD patterns were grouped as homologous sarcoma without SD (homo/non-dominance, n = 351), heterologous sarcoma without SD (hetero/non-dominance, n = 174), homologous sarcoma with SD (homo/dominance, n = 175), and heterologous sarcoma with SD (hetero/dominance, n = 189), and correlated to tumor characteristics and survival. RESULTS: SD patterns were significantly associated with age, body habitus, carcinoma type, tumor size, depth of myometrial invasion, and nodal metastasis (all, P < 0.05). On univariate analysis, SD was associated with decreased progression-free survival (PFS) and cause-specific survival (CSS) in homologous cases (both, P < 0.05) but not in heterologous cases. On multivariate models, both homologous and heterologous SD patterns remained independent prognostic factors for decreased PFS (adjusted-hazard ratio [HR] ranges: homo/dominance 1.35-1.69, and hetero/dominance 1.47-1.64) and CSS (adjusted-HR ranges: 1.52-1.84 and 1.66-1.81, respectively) compared to homo/non-dominance (all, P < 0.05). Among stage I-III disease, when tumors had SD, adding radiotherapy to chemotherapy was significantly associated with improved PFS (adjusted-HR: homo/dominance 0.49, and hetero/dominance 0.45) and CSS (0.36 and 0.31, respectively) compared to chemotherapy alone (all, P < 0.05); contrary, this association was not observed with absence of SD (all, P > 0.05). CONCLUSION: In UCS, SD impacts survival in homologous but not in heterologous type. Regardless of sarcoma types, SD was associated with decreased survival in UCS; adding radiotherapy to chemotherapy may be an effective postoperative strategy.

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.

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.

Trends and outcomes of women with synchronous endometrial and ovarian cancer.

This retrospective observational study examined trends, characteristics, and survival of women with synchronous endometrial and ovarian cancer (SEOC) in the Surveillance, Epidemiology, and End Results Program between 1973 and 2013. Among 235,454 women with primary endometrial cancer, synchronous ovarian cancer was seen in 4,082 (1.7%) women with the proportion being decreased from 2.0% to 1.6% between 1983 and 2013 (P=0.049); and the proportion of concurrent endometrioid tumors in the two cancer sites has increased from 24.2% to 49.9% among SEOC women (P<0.001). When compared to endometrial cancer without synchronous ovarian cancer, endometrioid histology in the two cancer sites was associated with improved cause-specific survival while non-endometrioid histology in the ovarian cancer was associated with decreased cause-specific survival (adjusted-P<0.01). Among 110,063 women with primary epithelial ovarian cancer, synchronous endometrial cancer was seen in 3,940 (3.6%) women with the proportion being increased from 2.2% to 4.4% between 1973 and 2013 (P<0.001); and the proportion of concurrent endometrioid tumors in the two cancer sites had increased from 24.3% to 50.2% among SEOC women (P<0.001). When compared to primary epithelial ovarian cancer without synchronous endometrial cancer, SEOC was associated with better cause-specific survival if ovarian cancer is endometrioid type or if endometrial cancer is endometrioid type (adjusted-P<0.001). Across the two cohorts, the proportion of SEOC reached to the peak in the late-40 years of age and then decreased significantly (P<0.001). In conclusion, our study suggests that synchronous ovarian cancer has decreased among endometrial cancer whereas synchronous endometrial cancer has increased among 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.

Nivolumab use for BRCA gene mutation carriers with recurrent epithelial ovarian cancer: A case series.

Tumors deficient in DNA mismatch repair are known to display increased susceptibility to immune checkpoint inhibitors due to accumulation of DNA damage and increased neoantigen load. This suggests that deficiency in the BRCA-related DNA repair mechanism may also be a surrogate marker for immunotherapy response. The aim of this study was to examine the efficacy of the immune checkpoint inhibitor, nivolumab, in women with BRCA gene mutations and recurrent müllerian cancer. This retrospective case series followed six BRCA carriers who received nivolumab monotherapy (3.0 mg/kg, intravenous, day 1 and 15, every 4 weeks) as salvage therapy for recurrent epithelial ovarian (n = 5) and fallopian tubal (n = 1) cancers. Toxicity, treatment response, and survival were examined. Median age was 57 (range 51-64). BRCA1 and 2 mutations were equally distributed. All had high-grade serous histology, and all but one had advanced-stage disease at initial diagnosis. The majority had platinum-resistant disease (n = 4). All received salvage therapy prior to nivolumab therapy (median 3 lines), including PARP inhibitors (n = 3). The median number of nivolumab treatment cycles was 9, including 2 women receiving 18 cycles. Three women developed nivolumab-related toxicities, most commonly grade 2 hypothyroidism (n = 2). Median follow-up time was 13.4 months, and there were 3 complete responses, 1 partial response, and 2 patients with progressive disease. Objective response rate was 67% (4 out of 6). In conclusion, our study suggests that nivolumab monotherapy is well-tolerated and may be an effective salvage therapy for BRCA mutation carriers with recurrent epithelial ovarian, fallopian tubal, and primary peritoneal cancers.

Teenage pregnancy complicated by primary invasive ovarian cancer: association for oncologic outcome.

OBJECTIVE: To examine survival of teenage women with pregnancies complicated by primary ovarian cancer. METHODS: This is a secondary analysis of a previously organized systematic literature review of primary ovarian cancer diagnosed during pregnancy. Cases eligible for analysis were patients whose age at cancer diagnosis and survival outcome were known (n=201). Pregnancy and oncologic outcome were then examined based on patient age. RESULTS: These were comprised of 95 (47.3%) epithelial ovarian cancers (EOCs), 82 (40.8%) malignant germ cell tumors (MGCTs), and 24 (11.9%) sex-cord stromal tumors (SCSTs). Teenage pregnancy was seen in 21 (10%) cases, and was highest among the SCST group compared to the other cancer types (EOC, 1.1%; MGCT, 14.6%; and SCST, 29.2%, p<0.001). Live birth rates, neonatal weight, full term delivery rates, and Cesarean section rates were similar between the teenage group and the non-teenage group (all, p>0.05); however, teenage pregnancy was significantly associated with an increased risk of serious maternal/neonatal adverse events (50% vs. 22.7%, p=0.013). On univariable analysis, teenage pregnancy was significantly associated with decreased ovarian cancer-specific survival (5-year rate: age ≥30, 79.6%; age 20-29, 87.2%; and age <20, 41.6%; p<0.001). On multivariable analysis controlling for calendar year, cancer type, cancer stage, and gestational age at ovarian cancer diagnosis, teenage pregnancy remained an independent prognostic factor for decreased ovarian cancer-specific survival compared to women aged ≥30 (adjusted-hazard ratio=4.71; 95% confidence interval=1.17-18.9; p=0.029). CONCLUSION: Teenage women with pregnancies complicated by primary ovarian cancer may be at increased risk of poor survival from ovarian cancer.

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.

Trends of uterine carcinosarcoma in the United States.

OBJECTIVE: Uterine carcinosarcoma (UCS) is a rare type of high-grade endometrial cancer (EC) that has been understudied with population-based statistics due to its rarity. This study examined temporal trends in the proportion of UCS among women with EC. METHODS: This is a retrospective observational study examining The Surveillance, Epidemiology, and End Results program between 1973-2013. Primary EC cases were eligible for analysis, and a time-specific proportion of UCS was examined during the study period. RESULTS: UCS was seen in 11,000 (4.7%) women among 235,849 primary EC cases. Mean age at UCS diagnosis increased from 65.9 to 71.7 years between 1973-1989 and then decreased from 71.7 to 67.0 years between 1989-2013 (both, p<0.001). Proportion of Black women significantly increased during the study period (11.9%-20.0%, p<0.001), whereas the proportion of White women decreased from 86.0% to 60.5% between 1987-2013 (p<0.001). There was a significant increase in the proportion of UCS among primary EC from 1.7% to 5.6% between 1973-2013 (p<0.001). Among type II ECs (n=76,118), the proportion of UCS also increased significantly from 6.0% to 17.5% between 1973-2013 (p<0.001). An increasing proportion of UCS was seen in both young and older women but the magnitude of interval increase was larger in the older age group between 1973-2013 (<60 years, from 1.3% to 3.3%. p<0.001; and ≥60 years, from 2.6% to 7.0%, p<0.001). CONCLUSION: Our study demonstrated that the proportion of UCS has significantly increased among EC, accounting for more than 5% in recent years.

Trends in single women with malignancy of the uterine cervix in United States.

OBJECTIVE: To examine trends and characteristics of single women with malignancy of the uterine cervix. METHODS: This is a retrospective observational study examining the United States population-based tumor registry (the Surveillance, Epidemiology, and End Results program). Time-specific trends in single marital status were examined in 3,294,208 women among 12 common female malignancies including 87,151 women with uterine cervical malignancy between 1973 and 2013. RESULTS: While the proportion of single women in the majority of malignancies increased during the study time, the proportion of single women with cervical malignancy significantly increased more than in other malignancies (29.3% in 2013 from 6.3% in 1973). There was a surge in the proportion of single women with cervical malignancy starting in the early 1990s, exhibiting the largest annual percentage rate change (APC) among all examined malignancies (1.8%; 95% confidence interval [CI]=1.6, 2.0; p<0.001). There was a significant decrease in the proportion of women aged <40 years with cervical malignancy between 1989 and 2013 (APC, -1.2%; 95% CI=-1.4, -1.0; p<0.001). However, when stratified by age, the proportion of single women aged ≥40 years increased significantly during the time (APC, 2.7%; 95% CI=2.3, 3.2; p<0.001) but did not in those who were <40 years (APC, 0.1%; 95% CI=-0.7, 0.6; p=0.850). CONCLUSION: The proportion of single women with malignancy of the uterine cervix has significantly increased in the past 4 decades. This increase was most dramatic in single women aged ≥40 years. Improving screening strategies in single women aged ≥40 years may help reduce the incidence of this malignancy.

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.