Adjuvant radiation therapy and health-related quality of life among older women with early-stage endometrial cancer: an analysis using the SEER-MHOS linkage.

PURPOSE: Radiation therapy (RT) has been associated with decreased health-related quality of life (HRQOL) in clinical trials of early-stage endometrial cancer (EC), but few studies have examined the association in real-world settings. We assessed HRQOL associated with adjuvant RT for older women with early-stage EC within a large U.S. population-based registry resource. METHODS: The Surveillance Epidemiology and End Results and the Medicare Health Outcomes Survey linkage (1998-2017) was used to identify women with early-stage EC aged ≥ 65 years at survey who received surgery and were diagnosed ≥ 1-year prior (n = 1,140). HRQOL was evaluated with the 36-item Short-Form Health Survey (SF-36) until 2006 and the Veterans RAND 12-Item Health Survey (VR-12) post 2006. Ordinary least squares regression was used to estimate mean difference (MD) in T scores and 95% confidence intervals (CIs) comparing treatment groups (surgery alone, adjuvant external beam radiation therapy [EBRT], or adjuvant vaginal brachytherapy [VBT]) after accounting for confounders using propensity score weighting. RESULTS: Overall, RT was not associated with physical health (MD = 0.97; 95% CI = - 1.13, 3.07) or mental health (MD = - 0.78; 95% CI = - 2.60, 1.05) relative to surgery alone. In analyses by RT type, adjuvant VBT was associated with better general health on the SF-36/VR-12 subscale (MD = 3.59; 95% CI = 0.56, 6.62) relative to surgery alone. No statistically significant associations were observed for adjuvant VBT and physical or mental health, or for adjuvant EBRT and any HRQOL domain. CONCLUSION: Older women with early-stage EC treated with adjuvant RT did not report worse physical and mental HRQOL scores compared to those treated with surgery alone, though relevant symptoms should be evaluated further to fully understand the disease and treatment specific aspects of the HRQOL.

Epigenome-wide methylation and progression to high-grade cervical intraepithelial neoplasia (CIN2+): a prospective cohort study in the United States.

BACKGROUND: Methylation levels may be associated with and serve as markers to predict risk of progression of precancerous cervical lesions. We conducted an epigenome-wide association study (EWAS) of CpG methylation and progression to high-grade cervical intraepithelial neoplasia (CIN2 +) following an abnormal screening test. METHODS: A prospective US cohort of 289 colposcopy patients with normal or CIN1 enrollment histology was assessed. Baseline cervical sample DNA was analyzed using Illumina HumanMethylation 450K (n = 76) or EPIC 850K (n = 213) arrays. Participants returned at provider-recommended intervals and were followed up to 5 years via medical records. We assessed continuous CpG M values for 9 cervical cancer-associated genes and time-to-progression to CIN2+. We estimated CpG-specific time-to-event ratios (TTER) and hazard ratios using adjusted, interval-censored Weibull accelerated failure time models. We also conducted an exploratory EWAS to identify novel CpGs with false discovery rate (FDR) < 0.05. RESULTS: At enrollment, median age was 29.2 years; 64.0% were high-risk HPV-positive, and 54.3% were non-white. During follow-up (median 24.4 months), 15 participants progressed to CIN2+. Greater methylation levels were associated with a shorter time-to-CIN2+ for CADM1 cg03505501 (TTER = 0.28; 95%CI 0.12, 0.63; FDR = 0.03) and RARB Cluster 1 (TTER = 0.46; 95% CI 0.29, 0.71; FDR = 0.01). There was evidence of similar trends for DAPK1 cg14286732, PAX1 cg07213060, and PAX1 Cluster 1. The EWAS detected 336 novel progression-associated CpGs, including those located in CpG islands associated with genes FGF22, TOX, COL18A1, GPM6A, XAB2, TIMP2, GSPT1, NR4A2, and APBB1IP. CONCLUSIONS: Using prospective time-to-event data, we detected associations between CADM1-, DAPK1-, PAX1-, and RARB-related CpGs and cervical disease progression, and we identified novel progression-associated CpGs. IMPACT: Methylation levels at novel CpG sites may help identify individuals with ≤CIN1 histology at higher risk of progression to CIN2+ and inform risk-based cervical cancer screening guidelines.

Gastrointestinal outcomes among older women with endometrial cancer.

OBJECTIVE: Treatment for endometrial cancer may contribute to bowel dysfunction and other gastrointestinal outcomes. We investigated the risk of several gastrointestinal diagnoses among older women with endometrial cancer and matched women without a history of cancer. METHODS: Women aged 66 years and older diagnosed with endometrial cancer during 2004-2017 (N = 44,386) and matched women without a known cancer history (N = 221,219) were identified in the SEER-Medicare linked data. An index date was defined as the endometrial cancer diagnosis date in that matched set. ICD-9 and -10 diagnosis codes were used to define gastrointestinal outcomes, including constipation, abdominal pain, IBS, fecal incontinence, bowel obstruction, ileus, radiation enteritis or proctitis, colonic stricture, and vascular insufficiency of the bowel in the Medicare claims. Hazard ratios (HRs) for incident gastrointestinal diagnoses were estimated using multivariable Cox proportional hazards regression models. RESULTS: Compared to women without cancer, women with endometrial cancer had an increased risk of gastrointestinal symptoms after the index date, including constipation (HR = 2.27; 95% CI: 2.22-2.32), abdominal pain (HR = 2.94; 95% CI: 2.89-2.99), and fecal incontinence (HR = 1.96; 95% CI: 1.83-2.10). The risk of other gastrointestinal diagnoses was also higher among women with endometrial cancer (e.g., bowel obstruction: HR = 5.72; 95% CI: 5.47-5.98; ileus: HR = 7.22; 95% CI: 6.89-7.57). These associations were also apparent in sensitivity analyses limited to 1+ and 5+ years after the index date. CONCLUSIONS: Older women with endometrial cancer experience an excess risk of gastrointestinal diagnoses that may persist long after cancer diagnosis. Surveillance for these conditions may be a critical part of survivorship care.

Cardiovascular disease diagnoses among older women with endometrial cancer.

BACKGROUND: Endometrial cancer (EC) shares risk factors (e.g. obesity) with cardiovascular disease (CVD), yet little research has investigated CVD diagnoses among EC survivors. We aimed to describe the burden of CVD diagnoses among older women with EC compared to women without a cancer history. METHODS: Women aged 66+ years with an EC diagnosis during 2004-2017 (N = 44,386) and matched women without cancer (N = 221,219) were identified in the SEER-Medicare linked data. An index date was defined as the cancer diagnosis date of the EC case in that matched set. ICD-9/10 diagnosis codes were used to define CVD outcomes in the Medicare claims. Prevalent CVD was identified using diagnosis codes in the year before the index date. Hazard ratios (HRs) for incident CVD diagnoses after the index date were estimated using multivariable Cox proportional hazards regression. Women with a prevalent CVD were excluded from incidence analyses for that outcome. RESULTS: Compared to women without cancer, women with EC had a higher prevalence of CVD diagnoses at the index date. In analyses beginning follow-up at 1 year post-index date, EC survivors had an increased risk of incident CVD diagnoses including ischemic heart diseases (HR = 1.73; 95% CI: 1.69-1.78), pulmonary heart disease (HR = 1.95; 95% CI: 1.88-2.02), and diseases of the veins and lymphatics (HR = 2.71; 95% CI: 95% CI: 2.64-2.78). Risk of CVD diagnoses among women with EC was also elevated within the first year post-index date. CONCLUSIONS: Management of pre-existing CVD and monitoring for incident CVD may be critical during EC treatment and throughout long-term survivorship.

Differences in the microbial profiles of early stage endometrial cancers between Black and White women.

OBJECTIVE: Black women suffer a higher mortality from endometrial cancer (EC) than White women. Potential biological causes for this disparity include a higher prevalence of obesity and more lethal histologic/molecular subtypes. We hypothesize that another biological factor driving this racial disparity could be the EC microbiome. METHODS: Banked tumor specimens of postmenopausal, Black and White women undergoing hysterectomy for early stage endometrioid EC were identified. The microbiota of the tumors were characterized by bacterial 16S rRNA sequencing. The microbial component of endometrioid ECs in The Cancer Genome Atlas (TCGA) database were assessed for comparison. RESULTS: 95 early stage ECs were evaluated: 23 Black (24%) and 72 White (76%). Microbial diversity was increased (p < 0.001), and Firmicutes, Cyanobacteria and OD1 phyla abundance was higher in tumors from Black versus White women (p < 0.001). Genus level abundance of Dietzia and Geobacillus were found to be lower in tumors of obese Black versus obese White women (p < 0.001). Analysis of early stage ECs in TCGA found that microbial diversity was higher in ECs from Black versus White women (p < 0.05). When comparing ECs from obese Black versus obese White women, 5 bacteria distributions were distinct, with higher abundance of Lactobacillus acidophilus in ECs from Black women being the most striking difference. Similarly in TCGA, Dietzia and Geobacillus were more common in ECs from White women compared to Black. CONCLUSION: Increased microbial diversity and the distinct microbial profiles between ECs of obese Black versus obese White women suggests that intra-tumoral bacteria may contribute to EC disparities and pathogenesis.

Falls, walking or balance problems, and limitations in activities of daily living (ADLs) among older endometrial cancer survivors.

PURPOSE: Functional status deficits are important quality of life concerns for older cancer survivors. We examined the prevalence of falls, walking/balance problems, and limitations in activities of daily living (ADLs) among older women with a history of endometrial cancer. METHODS: Cancer registry records from the Surveillance, Epidemiology, and End Results (SEER) program linked with Medicare Health Outcomes Survey (MHOS) data were used to identify endometrial cancer survivors aged ≥ 65 years who completed a survey ≥ 1 year after their cancer diagnosis (N = 3766), as well as an age- and race-matched group of women without a cancer history (N = 3766). We estimated prevalence ratios (PRs) to compare the prevalence of falls, walking or balance problems, and limitations in ADLs (bathing, dressing, eating, getting in/out of chairs, walking, using the toilet) between groups. RESULTS: Difficulty with walking or balance was more common among survivors than the noncancer group (43% vs 36%; PR = 1.19; 95% CI: 1.10-1.27). Fall prevalence was similar between groups (endometrial cancer: 25%; noncancer: 26%; PR = 0.98; 95% CI: 0.89-1.08). Nearly half of endometrial cancer survivors (47%) reported at least one ADL limitation, with several activities (getting in/out of a chair, walking, bathing, using the toilet) more often limited among survivors than among women without cancer. CONCLUSION: Functional impairments, especially problems with walking and/or balance, are common among older endometrial cancer survivors. Our results highlight the importance of addressing functional problems during the ongoing survivorship care of women with a history of endometrial cancer, with referral to rehabilitation or other relevant services when indicated.

Simple Adnexal Cysts: SRU Consensus Conference Update on Follow-up and Reporting.

This multidisciplinary consensus update aligns prior Society of Radiologists in Ultrasound (SRU) guidelines on simple adnexal cysts with recent large studies showing exceptionally low risk of cancer associated with simple adnexal cysts. Most small simple cysts do not require follow-up. For larger simple cysts or less well-characterized cysts, follow-up or second opinion US help to ensure that solid elements are not missed and are also useful for assessing growth of benign tumors. In postmenopausal women, reporting of simple cysts greater than 1 cm should be done to document their presence in the medical record, but such findings are common and follow-up is recommended only for simple cysts greater than 3-5 cm, with the higher 5-cm threshold reserved for simple cysts with excellent imaging characterization and documentation. For simple cysts in premenopausal women, these thresholds are 3 cm for reporting and greater than 5-7 cm for follow-up imaging. If a cyst is at least 10%-15% smaller at any time, then further follow-up is unnecessary. Stable simple cysts at initial follow-up may benefit from a follow-up at 2 years due to measurement variability that could mask growth. Simple cysts that grow are likely cystadenomas. If a previously suspected simple cyst demonstrates papillary projections or solid areas at follow-up, then the cyst should be described by using standardized terminology. These updated SRU consensus recommendations apply to asymptomatic patients and to those whose symptoms are not clearly attributable to the cyst. These recommendations can reassure physicians and patients regarding the benign nature of simple adnexal cysts after a diagnostic-quality US examination that allows for confident diagnosis of a simple cyst. Patients will benefit from less costly follow-up, less anxiety related to these simple cysts, and less surgery for benign lesions.

Evaluating the urban-rural paradox: The complicated relationship between distance and the receipt of guideline-concordant care among cervical cancer patients.

OBJECTIVE: Urban-rural health disparities are often attributed to the longer distances rural patients travel to receive care. However, a recent study suggests that distance to care may affect urban and rural cancer patients differentially. We examined whether this urban-rural paradox exists among patients with cervical cancer. METHODS: We identified individuals diagnosed with cervical cancer from 2004 to 2013 using a statewide cancer registry linked to multi-payer, insurance claims. Our primary outcome was receipt of guideline-concordant care: surgery for stages IA1-IB1; external beam radiation therapy (EBRT), concomitant chemotherapy, and brachytherapy for stages IB2-IVA. We estimated risk ratios (RR) using modified Poisson regressions, stratified by urban/rural location, to examine the association between distance to nearest facility and receipt of treatment. RESULTS: 62% of 999 cervical cancer patients received guideline-concordant care. The association between distance and receipt of care differed by type of treatment. In urban areas, cancer patients who lived ≥15 miles from the nearest surgical facility were less likely to receive primary surgical management compared to those <5 miles from the nearest surgical facility (RR: 0.77, 95% CI: 0.60-0.98). In rural areas, patients living ≥15 miles from the nearest brachytherapy facility were more likely to receive treatment compared to those <5 miles from the nearest brachytherapy facility (RR: 1.71, 95% CI: 1.14-2.58). Distance was not associated with the receipt of chemotherapy or EBRT. CONCLUSIONS: Among cervical cancer patients, there is evidence supporting the urban-rural paradox, i.e., geographic distance to cancer care facilities is not consistently associated with treatment receipt in expected or consistent ways. Healthcare systems must consider the diverse and differential barriers encountered by urban and rural residents to improve access to high quality cancer care.

DNA methylation of imprinted gene control regions in the regression of low-grade cervical lesions.

The role of host epigenetic mechanisms in the natural history of low-grade cervical intraepithelial neoplasia (CIN1) is not well characterized. We explored differential methylation of imprinted gene regulatory regions as predictors of the risk of CIN1 regression. A total of 164 patients with CIN1 were recruited from 10 Duke University clinics for the CIN Cohort Study. Participants had colposcopies at enrollment and up to five follow-up visits over 3 years. DNA was extracted from exfoliated cervical cells for methylation quantitation at CpG (cytosine-phosphate-guanine) sites and human papillomavirus (HPV) genotyping. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox regression to quantify the effect of methylation on CIN1 regression over two consecutive visits, compared to non-regression (persistent CIN1; progression to CIN2+; or CIN1 regression at a single time-point), adjusting for age, race, high-risk HPV (hrHPV), parity, oral contraceptive and smoking status. Median participant age was 26.6 years (range: 21.0-64.4 years), 39% were African-American, and 11% were current smokers. Most participants were hrHPV-positive at enrollment (80.5%). Over one-third of cases regressed (n = 53, 35.1%). Median time-to-regression was 12.6 months (range: 4.5-24.0 months). Probability of CIN1 regression was negatively correlated with methylation at IGF2AS CpG 5 (HR = 0.41; 95% CI = 0.23-0.77) and PEG10 DMR (HR = 0.80; 95% CI = 0.65-0.98). Altered methylation of imprinted IGF2AS and PEG10 DMRs may play a role in the natural history of CIN1. If confirmed in larger studies, further research on imprinted gene DMR methylation is warranted to determine its efficacy as a biomarker for cervical cancer screening.

For U.S. Black women, shift of hysterectomy to outpatient settings may have lagged behind White women: a claims-based analysis, 2011-2013.

BACKGROUND: Hysterectomy is among the most common surgeries performed on U.S. women. For benign conditions, minimally invasive hysterectomy is recommended, whenever permitted by clinical indication and previous surgery history. No study has examined whether the use of less invasive hysterectomy spread more slowly for Black women. METHODS: We used the hysterectomy that occurs in outpatient settings as a proxy for minimally invasive hysterectomy. Using claims-based surgery data and census denominators, we calculated age-standardized rates of all hysterectomies in North Carolina from 2011 to 2013. Study participants were 41,899 women (64.6% non-Hispanic White, 28.3% non-Hispanic Black) who underwent hysterectomy for non-malignant indications. We fit Poisson models to determine whether changes in outpatient hysterectomy rates differed by Black-White race. We employed a difference-in-difference approach to control for racial differences in the severity of clinical indication. Further, we restricted to one state to minimize confounding from geographic differences in where Black and White women live. RESULTS: From 2011 to 2013, the overall hysterectomy rate decreased from 42.3 per 10,000 women (n = 14,648) to 37.9 per 10,000 (n = 13,241) (p < 0.0001). Most hysterectomy (67.6%) occurred in outpatient settings. The inpatient rate decreased 35.2% (p < 0.0001), to 10.3 per 10,000, while the outpatient rate increased 4.6% (p < 0.01), to 27.5 per 10,000. From 2011 to 2013, Black women's outpatient rate increased 22% (p < 0.0001): from 25.8 per 10,000 to 31.5. In contrast, among White women, outpatient rates remained stable (p = 0.79): at 28.3 per 10,000 in 2013. CONCLUSIONS: Rapid increases in outpatient hysterectomy among Black women compared to stable rates among White women indicate a race-specific catch-up phenomenon in the spread of minimally invasive hysterectomy. These results are consistent with the hypothesis that minimally invasive hysterectomy may have been adopted more slowly for Black women than their White counterparts after its introduction in the early 2000s. The persistently high rates of hysterectomy among young Black women and potentially slower adoption of minimally invasive procedures among these women highlight a potential racial disparity in women's healthcare.

Referral patterns between high- and low-volume centers and associations with uterine cancer treatment and survival: a population-based study of Medicare, Medicaid, and privately insured women.

BACKGROUND: High-volume center surgery and gynecologic oncology care are associated with improved outcomes for women with uterine cancer. Referral patterns, from biopsy through to chemotherapy, may have patients interacting with high-volume centers for all, a portion, or none of their care. The relative frequency, the underlying factors that contribute to referral, and the potential impact of these referral patterns on treatment outcomes are unknown. OBJECTIVE: We sought to analyze the referral patterns and subsequent impact of care sites on treatment for women with high- and low-risk uterine cancer. STUDY DESIGN: This is a population-based retrospective cohort study of uterine cancer cases from 2004 through 2009 in North Carolina. Using state cancer registry files linked to Medicare, Medicaid, and private payer insurance claims, we analyzed referral and treatment patterns by annual surgical volume (high ≥12/y). We examined clinical and demographic factors associated with referral and used modified Poisson regression to evaluate risk of referral, lymphadenectomy, and chemotherapy. Stratified Kaplan-Meier plots and Cox proportional hazard models were used to examine survival. RESULTS: A total of 2053 women were analyzed, including 34% (n = 677) with grade 3 histology. Of 1630 (80%) women with preoperative biopsies, referral patterns (biopsy to surgery) were: low volume to high volume (n = 652, 40%), followed by high volume to high volume (n = 605, 37%), then low volume to low volume (n = 318, 20%), and the rare high volume to low volume (n = 50, 3%). Women retained in low-volume centers after biopsy were older, were less likely to have private insurance, and had more comorbidities. High-risk histology (aRR, 1.14; 95% confidence interval, 1.04-1.25) was positively associated with referral, while Medicaid insurance was negatively associated with referral (aRR, 0.64; 95% confidence interval, 0.42-0.96). Most women (74%, n = 1557) had surgery at high-volume centers. Lymphadenectomy was less likely at low-volume centers (aRR, 0.71; 95% confidence interval, 0.64-0.77). Similarly, for high-risk patients, the relationship between low-volume center surgery and subsequent chemotherapy was aRR, 0.71 (95% confidence interval, 0.48-1.02). Of 290 women who received chemotherapy, the referral patterns (surgery to chemotherapy) were: high volume-all (high volume to high volume), high volume-hybrid (high volume to low volume, or low volume to high volume), and high volume-none (low volume to low volume). In all, 36% (n = 104/290) received chemotherapy at a low-volume center, the majority (68%, n = 71/104) of whom were referred from high-volume centers after surgery. Crude, unadjusted mortality risk of chemotherapy recipients differed by referral pattern (surgery to chemotherapy): high volume-all patients (hazard ratio, 1.0; referent), followed by high volume-hybrid (hazard ratio, 1.33; 95% confidence interval, 0.93-1.91) then high volume-none patients (RR, 1.95; 95% confidence interval, 1.24-3.08). CONCLUSION: Most women with uterine cancer treated at high-volume centers arrive through referral, which is affected by age and type of insurance, in addition to histology. For high-risk women who require chemotherapy, survival may be related to the extent of treatment received at high-volume centers.

Gynecologic cancer outcomes in the elderly poor: A population-based study.

BACKGROUND: Adults aged ≥65 years who are dually enrolled in Medicare and Medicaid are an at-risk group in health care. However, to the best of the authors' knowledge, the outcomes of women with gynecologic cancers in this population are unknown. METHODS: The current study was a population-based cohort study of North Carolina state cancer registry cases of uterine, ovarian, cervical, and vulvar/vaginal cancers (2003-2009), with linked enrollment in Medicare and state Medicaid. Outcomes of all-cause mortality and stage of disease at the time of diagnosis were analyzed as a function of enrollment status using multivariate analysis and survival curves. RESULTS: Of 4522 women aged ≥65 years (3702 of whom were enrolled in Medicare [82%] and 820 of whom were dually enrolled [18%]), there were 2286 cases of uterine (51%), 1587 cases of ovarian (35%), 302 cases of cervical (7%), and 347 cases of vulvar/vaginal (8%) cancers. Dual enrollees had increased all-cause mortality overall (adjusted hazard ratio [aHR], 1.34; 95% confidence interval [95% CI], 1.19-1.49), and within each cancer site (uterine: aHR, 1.22 [95% CI, 1.02-1.47]; ovarian: aHR, 1.25 [95% CI, 1.05-1.49]; cervical: aHR, 1.34 [95% CI, 0.96-1.87]; and vulvar/vaginal: aHR, 1.93 [95% CI, 1.36-2.72]). Increased odds of advanced-stage disease at the time of diagnosis among dual enrollees was only present in patients with uterine cancer (adjusted odds ratio, 1.38; 95% CI, 1.06-1.79). Stratified survival curves demonstrated the strongest disparities among women with early-stage uterine and early-stage vulvar/vaginal cancers. CONCLUSIONS: Women aged ≥65 years who were dually enrolled in Medicare and Medicaid were found to have an overall 34% increase in all-cause mortality after diagnosis with a gynecologic cancer compared with the non-dually enrolled Medicare population. Women with early-stage uterine and vulvar/vaginal cancers appeared to have the most disparate outcomes. Because these malignancies are generally curable, they have the most potential for benefit from targeted interventions.

Translational studies of phenotypic probes for the mononuclear phagocyte system and liposomal pharmacology.

As nanoparticles (NPs) are cleared via phagocytes of the mononuclear phagocyte system (MPS), we hypothesized that the function of circulating monocytes and dendritic cells (MO/DC) in blood can predict NP clearance (CL). We measured MO/DC phagocytosis and reactive oxygen species (ROS) production in mice, rats, dogs, and patients with refractory solid tumors. Pharmacokinetic studies of polyethylene glycol (PEG)-encapsulated liposomal doxorubicin (PEGylated liposomal doxirubicin [PLD]), CKD-602 (S-CKD602), and cisplatin (SPI-077) were performed at the maximum tolerated dose. MO/DC function was also evaluated in patients with recurrent epithelial ovarian cancer (EOC) administered PLD. Across species, a positive association was observed between cell function and CL of PEGylated liposomes. In patients with EOC, associations were observed between PLD CL and phagocytosis (R(2) = 0.43, P = 0.04) and ROS production (R(2) = 0.61, P = 0.008) in blood MO/DC. These findings suggest that probes of MPS function may help predict PEGylated liposome CL across species and PLD CL in patients with EOC.

Did GOG99 and PORTEC1 change clinical practice in the United States?

OBJECTIVE: To assess the practice of adjuvant radiation (RT) for endometrial cancer in the United States following the publication of the Post Operative Radiation Therapy in Endometrial Carcinoma (PORTEC1), and Gynecologic Oncology Group-Adjuvant Radiation for Intermediate Risk Endometrial Cancers (GOG99). METHODS: A retrospective cohort study using the NCI SEER database compared the use of RT pre and post publication of PORTEC1 (1996-99 v 2000-03) and GOG 99 (2000-03 v 2004-07). Criteria for intermediate (IR) and high-intermediate (HIR) risk categories as defined by PORTEC1 and GOG99 were applied. Chi-squared statistics and adjusted multivariable Poisson models were used. RESULTS: RT did not increase for HIR (RR 1.05, 95%CI 0.99, 1.11) or IR groups (RR 1.0, 95% CI 0.95, 1.05) following GOG99 publication, or for HIR (RR 1.01, 95% CI 0.86, 1.19) or IR groups (RR 0.88, 95% CI 0.77-1.00) following PORTEC1 publication. Radiation rates changed heterogeneously across the country without a discernible pattern of cause. Among radiated patients, brachytherapy use increased, whereas external beam use decreased after GOG99 publication. CONCLUSIONS: As the debate regarding the utility of adjuvant radiation in early stage endometrial cancer continues, we found that overall, clinicians had not adopted GOG99 or PORTEC1 results into their clinical practice in the years immediately after publication. However, we did identify significant variation in practice by geographic location. Given that barely half the women deemed highest risk for recurrence received radiation, these findings illustrate that clinical practice reflects the continued controversy surrounding adjuvant radiation in the treatment of endometrial cancer.

Outpatient end of life discussions shorten hospital admissions in gynecologic oncology patients.

OBJECTIVE: The study goal was to determine whether prior outpatient exposure to hospice discussion altered the inpatient course and end-of-life (EOL) care among patients ultimately discharged to hospice. METHODS: Medical records from January 2009 to June 2012 were reviewed and data were abstracted under an IRB-approved protocol. Hospice discussions were identified in the last outpatient clinical encounter prior to admission. Kaplan-Meier was used to estimate overall survival (OS) and the log-rank test was used to test for differences. RESULTS: There were 89 hospitalizations resulting in discharge to hospice care: 41 women with ovarian (46%), 23 with uterine (29%), 19 with cervical (21.3%), and with 6 vulvar/vaginal (6.7%) cancers. 83 patients (93%) had outpatient clinical encounters prior to admission;18% (15/83) were exposed to a hospice discussion (HD) and 82% (68/83) were not (NHD). Median time from last outpatient encounter was 18 days (range 0-371). NHD patients had longer inpatient length of stay (median 7 days vs. 4 days, p=0.008) and were less likely to receive palliative care consults than the HD patients (65% vs. 93%, p=0.03). Median OS for HD patients was 33 days (95% CI 22d-61 d) vs. 60 days (95% CI 49 d-84 d) for NHD patients (p=0.01). There were no differences detected based on race, ethnicity, or insurance status. CONCLUSIONS: HD patients had significantly shorter OS suggesting that providers were accurate in identifying patients nearing the EOL. Patients exposed to outpatient hospice discussions had a shorter length of stay and increased utilization of palliative care resources.

Association between endometriosis and risk of histological subtypes of ovarian cancer: a pooled analysis of case-control studies.

BACKGROUND: Endometriosis is a risk factor for epithelial ovarian cancer; however, whether this risk extends to all invasive histological subtypes or borderline tumours is not clear. We undertook an international collaborative study to assess the association between endometriosis and histological subtypes of ovarian cancer. METHODS: Data from 13 ovarian cancer case-control studies, which were part of the Ovarian Cancer Association Consortium, were pooled and logistic regression analyses were undertaken to assess the association between self-reported endometriosis and risk of ovarian cancer. Analyses of invasive cases were done with respect to histological subtypes, grade, and stage, and analyses of borderline tumours by histological subtype. Age, ethnic origin, study site, parity, and duration of oral contraceptive use were included in all analytical models. FINDINGS: 13 226 controls and 7911 women with invasive ovarian cancer were included in this analysis. 818 and 738, respectively, reported a history of endometriosis. 1907 women with borderline ovarian cancer were also included in the analysis, and 168 of these reported a history of endometriosis. Self-reported endometriosis was associated with a significantly increased risk of clear-cell (136 [20·2%] of 674 cases vs 818 [6·2%] of 13 226 controls, odds ratio 3·05, 95% CI 2·43-3·84, p<0·0001), low-grade serous (31 [9·2%] of 336 cases, 2·11, 1·39-3·20, p<0·0001), and endometrioid invasive ovarian cancers (169 [13·9%] of 1220 cases, 2·04, 1·67-2·48, p<0·0001). No association was noted between endometriosis and risk of mucinous (31 [6·0%] of 516 cases, 1·02, 0·69-1·50, p=0·93) or high-grade serous invasive ovarian cancer (261 [7·1%] of 3659 cases, 1·13, 0·97-1·32, p=0·13), or borderline tumours of either subtype (serous 103 [9·0%] of 1140 cases, 1·20, 0·95-1·52, p=0·12, and mucinous 65 [8·5%] of 767 cases, 1·12, 0·84-1·48, p=0·45). INTERPRETATION: Clinicians should be aware of the increased risk of specific subtypes of ovarian cancer in women with endometriosis. Future efforts should focus on understanding the mechanisms that might lead to malignant transformation of endometriosis so as to help identify subsets of women at increased risk of ovarian cancer. FUNDING: Ovarian Cancer Research Fund, National Institutes of Health, California Cancer Research Program, California Department of Health Services, Lon V Smith Foundation, European Community's Seventh Framework Programme, German Federal Ministry of Education and Research of Germany, Programme of Clinical Biomedical Research, German Cancer Research Centre, Eve Appeal, Oak Foundation, UK National Institute of Health Research, National Health and Medical Research Council of Australia, US Army Medical Research and Materiel Command, Cancer Council Tasmania, Cancer Foundation of Western Australia, Mermaid 1, Danish Cancer Society, and Roswell Park Alliance Foundation.

Patient characteristics and health system factors associated with adjuvant radiation therapy receipt in older women with early-stage endometrial cancer.

INTRODUCTION: Among women with early-stage endometrial cancer (EC), age, stage, grade, and histology are used to determine fitness for adjuvant radiation therapy (RT) administration. We examined non-cancer factors associated with adjuvant RT receipt in older women with early-stage EC. MATERIALS & METHODS: Using data from the Surveillance Epidemiology and End Results cancer registry program linked with Medicare claims, we identified 25,654 women (aged ≥66 years) diagnosed with first primary stage I-II EC during 2004-2017 who underwent a hysterectomy. Diagnosis and procedure codes were used to identify adjuvant RT claims filed for the seven-month period post-hysterectomy. Multivariable log-binomial regression was used to estimate adjuvant RT prevalence associated with patient characteristics and health system factors after adjustment for age, frailty, and endometrial factors. RESULTS: Adjuvant RT was less commonly administered to Asian American and Pacific Islander patients than non-Hispanic White patients (Prevalence ratio [PR], 0.84; 95% confidence interval [CI], 0.73 to 0.97). Compared to women treated in the Northeast region, women treated other regions of the US were less likely to undergo adjuvant RT (PR, 0.75; 95% CI, 0.71 to 0.79). Residing in rural or high neighborhood-poverty counties was associated with lower adjuvant RT administration. Higher comorbidity score was not associated with reduced prevalence of adjuvant RT receipt; however, women with high probability of predicted probability of frailty were less likely to undergo adjuvant RT (PR, 0.67; 95% CI, 0.55 to 0.81) compared to women with low probability of frailty. Women who received lymph node assessment were more likely to undergo adjuvant RT compared to women who did not (PR, 1.43; 95% CI, 1.34 to 1.51). Women treated by a gynecologic oncologist were more likely to undergo adjuvant RT compared to women treated by a non-gynecologic oncologist (PR 1.09; 95% CI, 1.04 to 1.14). Adjuvant RT was more commonly administered to women treated in larger academic hospitals. DISCUSSION: Findings suggest that various non-cancer factors affect the delivery of adjuvant RT to older women with early-stage EC in real-world oncology practice. Advancing our understanding of factors associated with adjuvant RT administration may help expand equitable access to RT.

Discussion: 'Surgical staging in early ovarian carcinoma' by Garcia-Soto et al.

In the roundtable that follows, clinicians discuss a study published in this issue of the Journal in light of its methodology, relevance to practice, and implications for future research.