Associations between race and ethnicity and treatment setting among gynecologic cancer patients.

INTRODUCTION: Racial and ethnic disparities in gynecologic cancer care have been documented. Treatment at academic facilities is associated with improved survival, yet no study has examined independent associations between race and ethnicity with facility type among gynecologic cancer patients. MATERIALS & METHODS: We used the National Cancer Database and identified 484,455 gynecologic cancer (cervix, ovarian, uterine) patients diagnosed between 2004 and 2020. Facility type was dichotomized as academic vs. non-academic, and we used logistic regression to estimate multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) between race and ethnicity and facility type. Secondarily, we examined joint effects of race and ethnicity and facility type on overall survival using Cox proportional hazards regression. RESULTS: We observed higher odds of treatment at academic (vs. non-academic) facilities among American Indian/Alaska Native (OR = 1.42, 95% CI = 1.28-1.57), Asian (OR = 1.64, 95% CI = 1.59-1.70), Black (OR = 1.69, 95% CI = 1.65-1.72), Hispanic (OR = 1.70, 95% CI = 1.66-1.75), Native Hawaiian/Pacific Islander (OR = 1.74, 95% CI = 1.57-1.93), and other race (OR = 1.29, 95% CI = 1.20-1.40) patients compared with White patients. In the joint effects survival analysis with White, academic facility-treated patients as the reference group, Asian, Hispanic, and other race patients treated at academic or non-academic facilities had improved overall survival. Conversely, Black patients treated at academic facilities [Hazard Ratio (HR) = 1.10, 95% CI = 1.07-1.12] or non-academic facilities (HR = 1.19, 95% CI = 1.16-1.21) had worse survival. DISCUSSION: Minoritized gynecologic cancer patients were more likely than White patients to receive treatment at academic facilities. Importantly, survival outcomes among patients receiving care at academic institutions differed by race, requiring research to investigate intra-facility survival disparities.

Social determinants of health and depressive symptoms before and after cancer diagnosis.

Despite frequent reports of mental health needs among older women with cancer, depressive symptoms often go unrecognized and untreated, particularly in socially vulnerable survivors. Here, we examined associations of sociodemographic factors and social limitations with depressive symptoms from pre-diagnosis to post-diagnosis in older women diagnosed with breast or gynecological cancer. Using the Surveillance, Epidemiology, and End Results-Medicare Health Outcomes Survey (SEER-MHOS) linked dataset, we used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between sociodemographic factors (race, ethnicity, marital status, rurality) and social limitations (i.e., health interfering with social activities) on depressive symptoms in women aged ≥65 years with breast or gynecologic cancer (n = 1,353). Most participants had breast cancer (82.0%), stage I-II cancer (85.8%), received surgery for their cancer (94.8%), and radiation treatment (50.6%). Prior to diagnosis, 11.8% reported depressive symptoms, which nearly doubled to 22.4% at follow-up. Participants were 2.7 times more likely of reporting depressive symptoms after cancer diagnosis compared with pre-cancer diagnosis (95%CI: 2.10-3.48). Race, ethnicity, rurality, marital status, and social interference were significantly associated with an increased risk of depressive symptoms after cancer diagnosis than before their cancer diagnosis (p < 0.05). In summary, depressive symptoms increased following a cancer diagnosis. Our results suggest potential avenues for intervention that could lead to reduced depressive symptoms among older female cancer survivors.

The microbiome and gynecologic cancer: cellular mechanisms and clinical applications.

The microbiome plays a vital function in maintaining human health and homeostasis. Each microbiota has unique characteristics, including those of the gastrointestinal and female reproductive tract. Dysbiosis, or alterations to the composition of the microbial communities, impacts the microbiota-host relationship and is linked to diseases, including cancer. In addition, studies have demonstrated that the microbiota can contribute to a pro-carcinogenic state through altered host immunologic response, modulation of cell proliferation, signaling, gene expression, and dysregulated metabolism of nutrients and hormones.In recent years, the microbiota of the gut and female reproductive tracts have been linked to many diseases, including gynecologic cancers. Numerous pre-clinical and clinical studies have demonstrated that specific bacteria or microbial communities may contribute to the development of gynecologic cancers. Further, the microbiota may also impact the toxicity and efficacy of cancer therapies, including chemotherapy, immunotherapy, and radiation therapy in women with gynecologic malignancies. The microbiota is highly dynamic and may be altered through various mechanisms, including diet, exercise, medications, and fecal microbiota transplantation. This review provides an overview of the current literature detailing the relationship between gynecologic cancers and the microbiota of the female reproductive and gastrointestinal tracts, focusing on mechanisms of carcinogenesis and strategies for modulating the microbiota for cancer prevention and treatment. Advancing our understanding of the complex relationship between the microbiota and gynecologic cancer will provide a novel approach for prevention and therapeutic modulation in the future.

Activation of TnSmu1, an integrative and conjugative element, by an ImmR-like transcriptional regulator in Streptococcus mutans.

Integrative and conjugative elements (ICEs) are chromosomally encoded mobile genetic elements that can transfer DNA between bacterial strains. Recently, as part of efforts to determine hypothetical gene functions, we have discovered an important regulatory module encoded on an ICE known as TnSmu1 on the Streptococcus mutans chromosome. The regulatory module consists of a cI-like repressor with a helix-turn-helix DNA binding domain immR Smu (immunity repressor) and a metalloprotease immA Smu (anti-repressor). It is not possible to create an in-frame deletion mutant of immR Smu and repression of immR Smu with CRISPRi (CRISPR interference) causes substantial cell defects. We used a bypass of essentiality (BoE) screen to discover genes that allow deletion of the regulatory module. This revealed that conjugation genes, located within TnSmu1, can restore the viability of an immR Smu mutant. Deletion of immR Smu also leads to production of a circular intermediate form of TnSmu1, which is also inducible by the genotoxic agent mitomycin C. To gain further insights into potential regulation of TnSmu1 by ImmRSmu and broader effects on S. mutans UA159 physiology, we used CRISPRi and RNA-seq. Strongly induced genes included all the TnSmu1 mobile element, genes involved in amino acid metabolism, transport systems and a type I-C CRISPR-Cas system. Lastly, bioinformatic analysis shows that the TnSmu1 mobile element and its associated genes are well distributed across S. mutans isolates. Taken together, our results show that activation of TnSmu1 is controlled by the immRA Smu module, and that activation is deleterious to S. mutans, highlighting the complex interplay between mobile elements and their host.

Does the addition of radiation improve survival compared to chemotherapy alone in women with stage IV endometrial carcinoma? Analysis of the NCDB and SEER databases.

OBJECTIVE: To evaluate whether the addition of radiation to adjuvant chemotherapy is associated with improved survival in women with stage IV endometrial cancer following surgery. METHODS: The National Cancer Database (NCDB) and Surveillance, Epidemiology, and End Results Program (SEER) registries were queried for patients with stage IV endometrial cancer from 2004 to 2017. Treatment was categorized as chemotherapy alone, chemotherapy with external beam radiation therapy (EBRT), chemotherapy with vaginal brachytherapy (VBT), or chemotherapy with EBRT+VBT. Multivariable Cox regression models assessed associations between treatment modality and overall survival (OS). RESULTS: This analysis included 17,890 (NCDB: 12,812, SEER: 5078) women with stage IV endometrial cancer, including 1757 (9.8%) with IVA disease and 16,133 (90.2%) with IVB. The majority of stage IV patients received chemotherapy alone (NCDB 78.8%, SEER 77.0%). When radiation was utilized in addition to chemotherapy, EBRT was most common (NCDB 15.8%, SEER: 15.4%). In both databases, use of any radiation in addition to chemotherapy was associated with improved OS. Stage IV patients treated with chemotherapy plus EBRT had better survival than those receiving chemotherapy alone [NCDB: HR 0.75 (95% CI 0.70, 0.79), SEER: HR 0.85 (95% CI 0.77, 0.94)]. This benefit was more pronounced in patients with IVA disease [NCDB: HR 0.66 (95% CI 0.55, 0.79), SEER: HR 0.63 (95% CI 0.46, 0.85)]. In histology-stratified analyses, the addition of radiation to chemotherapy was associated with improved OS in all histologies, except clear cell. CONCLUSIONS: In this analysis of the NCDB and SEER registries, the use of multimodality treatment with radiation and chemotherapy was associated with improved OS compared to chemotherapy alone in women with stage IVA and IVB endometrial cancer.

Predicting sperm production of young dairy bulls using collection history and management factors.

Selection of elite young dairy bulls by using genomic data shortened the generation interval and increased pressure to collect and market germplasm at an early age. The objectives of this study were (1) develop prediction models for daily, weekly, and monthly total sperm (TSp) production from collection history, health status, and management factors, and (2) assess the ability of these models to forecast future TSp production, as well as differences in prediction accuracy by seasonality or age of bull. Data consisted of 43,918 daily processing records from 1,037 Holstein and Jersey bulls between 10 and 28 mo of age at collection. Potential explanatory variables included year and season of collection, barn location, collection frequency, breed, scrotal circumference, TSp in previous months, health events, and age at arrival, first collection, and current collection. Linear regression, random forest (RF), Bayesian regularized neural network, model tree, multilayer perceptron neural network with multiple layers, and extreme learning machine were used to predict daily, weekly, and monthly TSp (R v3.5.1, https://www.r-project.org/). In the additive approach, all prior data were used for training; however, in the fixed-window approach, records from 3 previous months were used for age-based prediction, records from 4 previous months or 1 yr were used for the monthly date-based analyses, and records from 1 previous month or year were used for the weekly date-based analyses. Model performance was measured by root mean squared error (RMSE) and the correlation (r) between actual and predicted TSp in testing sets. In monthly analyses, RF with additive training performed best in age-based (RMSE = 13.6 billion cells, r = 0.93) and date-based (RMSE = 11.9, r = 0.94) prediction, compared with linear regression (age-based RMSE = 16.6, r = 0.89; date-based RMSE = 15.5, r = 0.90) and Bayesian regularized neural network (age-based RMSE = 14.1, r = 0.92). On average, RMSE was 0.93 or 0.14 billion cells greater with fixed 4-mo or 1-yr training windows, respectively, than in the additive analyses. The most important management variables affecting TSp were collection frequency, TSp in previous months, and age at collection. Results indicate RF models with additive training can predict TSp output of individual bulls with ≥85% accuracy up to 4 mo into the future. Spikes in accuracy were associated with sire summary times and company processing changes, and accuracy tended to stabilize when bulls reached 19 to 20 mo of age.

Guideline-concordant treatment is associated with improved survival among women with non-endometrioid endometrial cancer.

BACKGROUND: Among women diagnosed with non-endometrioid endometrial carcinoma (EC), we investigated associations between race/ethnicity and receipt of guideline-concordant treatment (GCT), as well as relationships between GCT and survival. METHODS: We used the National Cancer Database and identified 21,177 non-Hispanic White (NHW), 6657 non-Hispanic Black (NHB), 1689 Hispanic, and 903 Asian/Pacific Islander (AS/PI) women diagnosed with non-endometrioid EC between 2004 and 2014. Year-specific National Comprehensive Cancer Network (NCCN) guidelines were used to classify GCT. We used multivariable logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between race/ethnicity and GCT receipt. Multivariable-adjusted Cox proportional hazards models were used to estimate hazards ratios (HRs) and 95% CIs for relationships between GCT and overall survival in the total study population and stratified by race/ethnicity. RESULTS: Overall, 43.8% of women with non-endometrioid EC received GCT. Compared to NHW women, NHB (OR = 1.01, 95% CI = 0.95-1.07), Hispanic (OR = 1.01, 95% CI = 0.91-1.12) and AS/PI women (OR = 1.10, 95% CI = 0.96-1.26) did not have significantly different odds of receiving GCT. GCT was significantly associated with improved survival among NHW (HR = 0.84, 95% CI = 0.80-0.87), NHB (HR = 0.85, 95% CI = 0.80-0.91), and Hispanic women (HR = 0.84, 95% CI = 0.72-0.98) but not among AS/PI women (HR = 0.97, 95% CI = 0.78-1.19). CONCLUSIONS: While more than half of women with non-endometrioid EC did not receive GCT, no difference in GCT receipt by race/ethnicity was observed. When received, GCT was associated with improved survival in almost all racial groups. Interventions to improve GCT adherence may improve survival for most women with non-endometrioid EC.

Black and Hispanic women are less likely than white women to receive guideline-concordant endometrial cancer treatment.

BACKGROUND: Differences in receipt of guideline-concordant treatment might underlie well-established racial disparities in endometrial cancer mortality. OBJECTIVE: Using the National Cancer Database, we assessed the hypothesis that among women with endometrioid endometrial cancer, racial/ethnic minority women would have lower odds of receiving guideline-concordant treatment than white women. In addition, we hypothesized that lack of guideline-concordant treatment was linked with worse survival. STUDY DESIGN: We defined receipt of guideline-concordant treatment using the National Comprehensive Cancer Network guidelines. Multivariable logistic regression models were used to compute odds ratios and 95% confidence intervals for associations between race and guideline-concordant treatment. We used multivariable Cox proportional hazards regression models to estimate hazards ratios and 95% confidence intervals for relationships between guideline-concordant treatment and overall survival in the overall study population and stratified by race/ethnicity. RESULTS: This analysis was restricted to the 89,319 women diagnosed with an invasive, endometrioid endometrial cancer between 2004 and 2014. Overall, 74.7% of the cohort received guideline-concordant treatment (n = 66,699). Analyses stratified by race showed that 75.3% of non-Hispanic white (n = 57,442), 70.1% of non-Hispanic black (n = 4334), 71.0% of Hispanic (n = 3263), and 72.5% of Asian/Pacific Islander patients (n = 1660) received treatment in concordance with guidelines. In multivariable-adjusted models, non-Hispanic black (odds ratio, 0.92, 95% confidence interval, 0.86-0.98) and Hispanic women (odds ratio, 0.90, 95% confidence internal, 0.83-0.97) had lower odds of receiving guideline-concordant treatment compared with non-Hispanic white women, while Asian/Pacific Islander women had a higher odds of receiving guideline-concordant treatment (odds ratio, 1.11, 95% confidence interval, 1.00-1.23). Lack of guideline-concordant treatment was associated with lower overall survival in the overall study population (hazard ratio, 1.12, 95% confidence interval, 1.08-1.15) but was not significantly associated with overall survival among non-Hispanic black (hazard ratio, 1.09, 95% confidence interval, 0.98-1.21), Hispanic (hazard ratio, 0.92, 95% confidence interval=0.78-1.09), or Asian/Pacific Islander (hazard ratio, 0.90, 95% confidence interval, 0.70-1.16) women. CONCLUSION: Non-Hispanic black and Hispanic women were less likely than non-Hispanic white women to receive guideline-concordant treatment, while Asian/Pacific Islander women more commonly received treatment in line with guidelines. Furthermore, in the overall study population, overall survival was worse among those not receiving guideline-concordant treatment, although low power may have had an impact on the race-stratified models. Future studies should evaluate reasons underlying disparate endometrial cancer treatment.

Cervical Cancer Among Older Women: Analyses of Surveillance, Epidemiology and End Results Program Data.

OBJECTIVE: To describe age-specific cervical cancer incidence rates based on demographic and clinical characteristics. METHODS: Women with cervical cancer in the SEER program were grouped into 3 age categories. Demographics, clinical characteristics, and incidence rates were obtained for each age group. RESULTS: Older women (≥65 years) had higher incidence rates of cervical cancer than women <65 years with the highest rates in black women ≥75 years. Older black women had more adverse factors at diagnosis than similarly aged white and younger black women. There was a higher incidence rate of cervical cancer in women with lower socioeconomic status (SES), with the highest rates in older black women. However, the incidence rates were similar for older black women regardless of SES. CONCLUSION: Older black have the highest cervical cancer incidence rates, regardless of SES, suggesting an age and race disparity when compared to younger and white women.

Fractional CO2 laser therapy for genitourinary syndrome of menopause for breast cancer survivors.

PURPOSE: Fractional CO2 laser therapy is an emerging treatment for genitourinary syndrome of menopause (GSM). The objective of this study was to determine the feasibility and preliminary efficacy of fractional CO2 laser therapy in breast cancer survivors. METHODS: This was a single arm feasibility study of breast cancer survivors with dyspareunia and/or vaginal dryness. Participants received three treatments of fractional CO2 laser therapy at 30-day intervals and returned for a 1-month follow-up. Feasibility was defined as treatment completion without serious adverse events (SAE) in 80% of patients. We collected data on the Vaginal Assessment Scale (VAS), the Female Sexual Function Index (FSFI), the Urinary Distress Index (UDI), and SAE. RESULTS: A total of 64 patients participated in the study. The majority of women had Estrogen receptor/Progesterone receptor (ER/PR) positive/Her2neu negative (n = 37; 63%), stage I (n = 32, 54%) or II (n = 19, 32%) breast cancer. Most were receiving endocrine therapy (n = 54, 92%), most commonly aromatase inhibitors (AI; n = 40, 68%). Fifty-nine (88.1%) of those enrolled completed all treatments according to protocol with no reported SAE. No patient withdrew due to SAE. The scores of the VAS (mean Δ - 0.99; 95% CI [- 1.19, - 0.79], p < 0.001)), FSFI (mean Δ 9.67; 95% CI [7.27, 12.1], p < 0.001), and UDI (mean Δ - 8.85; 95% CI [- 12.75, - 4.75], p < 0.001)) improved from baseline to follow-up. CONCLUSION: Fractional CO2 laser treatment for breast cancer survivors is feasible and appears to reduce GSM symptoms across treatment and follow-up.

Genomic analysis of bovine respiratory disease and lung consolidation in preweaned Holstein calves using clinical scoring and lung ultrasound.

Bovine respiratory disease (BRD) is a leading cause of morbidity and mortality in dairy calves, with detrimental long-term effects that include stunted growth, increased age at first calving, and decreased milk production in first lactation. The objectives of this study were to establish a protocol for objective and efficient assessment of BRD phenotypes in preweaned dairy calves, develop a genomic reference population with well-defined clinical and subclinical phenotypes, identify chromosomal regions associated with BRD in a genome-wide association study, estimate genetic parameters of BRD, and predict genomic breeding values of dairy calves. A total of 1,107 Holstein calves from 6 dairy farms in southern Wisconsin were examined using clinical respiratory scoring and lung ultrasound at 3 and 6 wk of age. The clinical respiratory score was based on visual appraisal of eyes, nose, ears, cough, and temperature. Lung ultrasound scores were assigned based on the amount of consolidation present. Calves were genotyped with a commercially available SNP array and after quality control and imputation to higher density, 690,291 SNP markers and 1,014 individuals remained. Single-step genome-wide association study and single-step genomic best linear unbiased prediction were applied to binary 3- and 6-wk phenotypes considered as overall respiratory healthy versus affected (RESP3, RESP6) or as presence or absence of lung consolidation (CON3, CON6). Lung ultrasound combined with a clinical scoring system allowed for efficient and objective assessment for the prevalence of BRD. Proportions of variance attributed to 1-Mb non-overlapping windows suggested genomic regions that may contain putative candidate genes, most notably regions on Bos taurus autosomes 1, 6, 7, 10, 11, 12, 15, 17, 18, 27, and 28 that explained 0.70 to 1.45% of the genetic variance. Heritability estimates were higher at 3 wk (0.214 and 0.241 for CON3 and RESP3, respectively) than 6 wk (0.084 and 0.111 for CON6 and RESP6, respectively), and mean reliabilities of genomic estimated breeding vales for calves with genotypes and phenotypes ranged from 0.12 for CON6 to 0.30 for RESP3.

Heterogeneity in Outcomes of Pathologic T1-2N1 Breast Cancer After Mastectomy: Looking Beyond Locoregional Failure Rates.

PURPOSE: A meta-analysis of 22 randomized trials accrued from 1964 to 1986 demonstrated significantly higher rates of locoregional failure (LRF) and breast-cancer mortality in women with 1-3 positive nodes without postmastectomy radiotherapy (PMRT) after mastectomy (mast.). Recent data demonstrate that PMRT reduces distant metastases (DM) in women with pN1 disease. The challenge today is whether all patients with pathologic T1-2pN1 disease have similar substantial LRF/DM risk that routinely warrants PMRT. METHODS: We reviewed patients with pT1-2N1 breast cancer treated with mast. ± adjuvant systemic therapy without PMRT from 2000 to 2013. The endpoints were LRF and DM rates, estimated by cumulative incidence method. RESULTS: We identified 468 patients with median follow-up of 6.3 years. Most (71%) were estrogen receptor/progesterone receptor + human epidermal growth factor receptor 2 (HER2). There were 269 patients with 1+ node, 140 patients with 2+ nodes, and 59 patients with 3+ nodes. The 6-year LRF/DM rates were 4.1%/8.4%. Patients with 1+, 2+, and 3+ nodes had 6-year LRF of 2.3, 5.1 and 8.9%, respectively (p = 0.13). The 6-year DM rate was higher in patients with 3+ nodes versus 1-2+ nodes: 15.7% versus 7.4% (p = 0.02). Several subgroups had low 6-year LRF and DM rates, including T1/1+ node (0.8%/4.1% LRF/DM) and micrometastases (0%/5.8% LRF/DM). CONCLUSIONS: Patients with pT1-2pN1 represent a heterogeneous group with a wide range of LRF/DM rates. In particular, patients with pT1 tumors and 1 + LN, and patients with micrometastases, had low event rates. These groups would derive small absolute reductions in LRF and DM with addition of PMRT, underscoring the importance of patient selection for PMRT in pT1-2pN1 breast cancer.

Associations of Demographic and Social Factors on Health-Related Quality-of-Life Changes Among Older Women With Breast or Gynecologic Cancer.

OBJECTIVES: To examine associations of sociodemographic factors and social limitations with health-related quality of life (HRQOL) from pre- to postdiagnosis in older female cancer survivors. SAMPLE & SETTING: 9,807 women aged 65 years or older with breast or gynecologic cancer from the Surveillance, Epidemiology, and End Results-Medicare Health Outcomes Survey. METHODS & VARIABLES: Physical and mental HRQOL were assessed using the physical component summary (PCS) and mental component summary (MCS) of the Veterans RAND 12-Item Health Survey. Descriptive statistics and mixed-effects models for repeated measures were used. RESULTS: Social limitations were the only significant factor associated with changes in MCS scores. Race and ethnicity, rurality, and social interference were associated with significant decreases in PCS scores. IMPLICATIONS FOR NURSING: Nurses can assess mental and physical HRQOL after diagnosis and advocate for appropriate referrals. Oncology care should be tailored to cultural considerations, including race and ethnicity, rurality, and social support.

FIGO IVB vaginal cancer with non-contiguous rectal metastasis treated with definitive chemoradiation: A case report.

•Noncontiguous rectal metastasis of vaginal squamous cell carcinoma.•Definitive treatment of vaginal cancer with rectal metastasis.•Chemoradiation and brachytherapy for vaginal SCC with local metastasis.

Changes in physical function in older women with endometrial cancer with or without adjuvant therapy.

OBJECTIVE: To evaluate changes in physical function (PF) for older women with endometrial cancer (EC) + / - adjuvant therapy in the Women's Health Initiative Life and Longevity after Cancer cohort. MATERIALS AND METHODS: This study examined women ≥ 70 years of age with EC with available treatment records. Change in PF was measured using the RAND-36 and compared between groups using Wilcoxon rank-sum tests. Multivariable median regression was used to compare the changes in scores while adjusting for confounding variables. RESULTS: Included in the study were 287 women, 150 (52.3%) women who did not receive adjuvant therapy and 137 (47.7%) who received adjuvant therapy. When comparing PF scores, there was a statistically significant difference in the median percent change in functional decline, with a greater decline in those who received adjuvant therapy (- 5.9% [- 23.5 to 0%]) compared to those who did not (0 [- 18.8 to + 6.7%]), p = 0.02). Results were not statistically significant after multivariable adjustment, but women who underwent chemotherapy had a greater percent change (median ∆ - 13.8% [- 35.5 to 0%]) compared to those who received radiation alone (median ∆ - 5.9% [- 31.3 to 0%]) or chemotherapy and radiation (median ∆ - 6.5% [- 25.8 to + 5.7%]. CONCLUSIONS: Older women with EC who received adjuvant therapy experienced greater change in PF than those who did not receive adjuvant therapy, particularly women who received chemotherapy. These results were not statistically significant on multivariate analysis. IMPLICATIONS FOR CANCER SURVIVORS: EC survivors may experience changes in PF because of chemotherapy and/or radiation therapy. Additional supportive care may need to be provided to older women to mitigate functional decline.

Primary radiation therapy for medically inoperable patients with clinical stage I and II endometrial carcinoma.

OBJECTIVE: To determine the outcomes associated with primary radiation therapy for medically inoperable, clinical stage I and II, endometrial adenocarcinoma (EAC). METHODS: A multi-institution, retrospective chart review from January 1997 to January 2009 was performed. Overall survival (OS), disease-specific survival (DSS), progression-free survival (PFS) and time to progression (TTP) were assessed using the Kaplan-Meier method. Disease-specific survival was analyzed using a competing risks approach. RESULTS: Seventy-four patients were evaluable. The median age and BMI were 65 years (range 36-92 years) and 46 kg/m(2) (range 23-111 kg/m(2)), respectively. 85.1% had severe systemic disease, most frequently cardiopulmonary risk and morbid obesity. With a mean follow-up of 31 months, 13 patients (17.6%) experienced a recurrence. The median PFS and OS were 43.5 months and 47.2 months, respectively. Overall, 35 women died, including 4 women who died of unknown cause. Of the remaining 31 women, 7 patients (9.5%) died of disease, while 24 died of other causes (32.4%). The hazard ratio comparing the risk of death due to other causes to the risk of death due to disease was 3.4 (95% CI 1.4-9.4, p=0.003). Among patients who are alive three years after diagnosis, 14% recurred and the conditional recurrence estimate did not exceed 16%. CONCLUSIONS: Primary radiation therapy for clinical stage I and II EAC is a feasible option for medically inoperable patients and provides disease control, with fewer than 16% of surviving patients experiencing recurrence.

Sexual function after intracavitary vaginal brachytherapy for early-stage endometrial carcinoma.

OBJECTIVE: To describe the effects of intracavitary brachytherapy (IVB) on sexual function and quality of life of women with early-stage endometrial cancer. METHODS: Women with International Federation of Gynecology and Obstetrics stage I to stage II endometrial cancer treated surgically with or without IVB were identified and mailed questionnaires. Quality of life and sexual function were measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and the cervical cancer disease-specific module. Pertinent data from prior surgery and radiation treatments were abstracted retrospectively. Linear transformation of the survey subscale scores was conducted per European Organization for Research and Treatment of Cancer guidelines. RESULTS: Sixteen women in the IVB arm and 53 in the surgery-alone group completed the survey. Of the sexually active patients, 33% of the IVB patients and 42% of the surgery-alone patients felt their vagina was dry during sexual activity (P = 0.804) and 17% versus 20% felt their vagina was short (P = 0.884). Seventeen percent of patients in the IVB group felt their vagina was tight compared to 29% in the surgery-alone group (P = 0.891) and 0% versus 14% of patients reported pain during intercourse (P = 0.808). There was no statistically significant difference in sexual/vaginal functioning, sexual worry, or sexual enjoyment between the 2 groups. CONCLUSIONS: Although both groups report vaginal changes that may affect sexual function, the patients treated with IVB reported similar outcomes on a sexual function questionnaire compared to patients treated with surgery alone.

Long-Term Follow-Up of Fractional CO2 Laser Therapy for Genitourinary Syndrome of Menopause in Breast Cancer Survivors.

(1) Background: The objective of this study was to determine the long-term efficacy of fractional CO2 laser therapy in breast cancer survivors. (2) Methods: This was a single-arm study of breast cancer survivors. Participants received three treatments of fractional CO2 laser therapy and returned for a 4 week follow-up. Participants were contacted for follow-up at annual intervals. The Vaginal Assessment Scale (VAS), the Female Sexual Function Index (FSFI), the Female Sexual Distress Scare Revised (FSDS-R), the Urinary Distress Inventory (UDI), and adverse events were collected and reported for the two-year follow-up. The changes in scores were compared between the four-week and two-year and the one-year and two-year follow-ups using paired t-tests. (3) Results: In total, 67 BC survivors were enrolled, 59 completed treatments and the four week follow-up, 39 participated in the one-year follow-up, and 33 participated in the two-year follow-up. After initial improvement in the VAS from baseline to the four week follow-up, there was no statistically significant difference in the VAS score (mean Δ 0.23; 95% CI [-0.05, 0.51], p = 0.150) between the four week follow-up and the two-year follow-up. At the two-year follow-up, the FSFI and FSDS-R scores remained improved from baseline and there was no statistically significant change in the FSFI score (mean Δ -0.83; 95% CI [-3.07, 2.38] p = 0.794) or the FSDS-R score (mean Δ -2.85; 95% CI [-1.88, 7.59] p = 0.227) from the one to two-year follow-up. The UDI scores approached baseline at the two-year follow-up; however, the change between the one- and two-year follow-ups was not statistically significant (mean Δ 4.76; 95% CI [-1.89, 11.41], p = 0.15). (4) Conclusions: Breast cancer survivors treated with fractional CO2 laser therapy have sustained improvement in sexual function two years after treatment completion, suggesting potential long-term benefit.

Clinical outcomes of distal vaginal and vulvar cancer treated with image-guided brachytherapy.

PURPOSE: To evaluate treatment outcomes with image-guided brachytherapy (IGBT) for distal vaginal and vulvar cancers. MATERIAL AND METHODS: Women treated for distal vaginal or vulvar malignancies utilizing IGBT were retrospectively reviewed, and acute and late toxicities were retrospectively graded. Descriptive statistical analysis was performed. RESULTS: Eighteen patients were included, out of which, twelve patients (66.7%) were with primary disease of the distal vagina and vulva, most commonly squamous cell carcinoma of the vulva (n = 8, 66.7%), and six with recurrent disease, most commonly recurrent endometrial carcinoma (n = 5, 83.3%). All patients received external beam radiation (EBRT) to a median dose of 45 Gy in 25 fractions, followed by IGBT (range of 15 to 27.5 Gy in 3 to 5 fractions). Mean follow-up was 20.6 months. Mean dose to high-risk clinical target volume (HR-CTV) D90 was 72.4 Gy. Mean D2cc for the rectum, bladder, and urethra were 50 Gy, 50.6 Gy, and 62.9 Gy, respectively. Five patients (27.8%) recurred. Three patients (16.7%) had local recurrence, 1 patient (5.6%) had distant recurrence only, and 1 patient (5.6%) had simultaneous regional and distant recurrence. Grade 3 acute toxicities included 1 (5.6%) vaginal stenosis, 6 (33.3%) dermatitis/mucositis, 2 (11.1%) vaginal pain, and 1 (5.6%) vaginal/vulvar infection. Grade 3 late toxicities comprised 3 (17.7%) cases of vaginal pain and 1 (5.9%) skin/vaginal necrosis. There were no grade 4 or higher toxicities. CONCLUSIONS: Definitive radiation therapy in the form of EBRT and IGBT provides meaningful loco-regional control in women with distal vaginal and vulvar cancers, with mainly skin and vaginal toxicity.

Toxicity and outcomes associated with high-dose rate brachytherapy for medically inoperable endometrial cancer.

PURPOSE: To evaluate toxicity in inoperable endometrial cancer (EC) treated with definitive radiation therapy (RT). MATERIALS AND METHODS: Patients treated with definitive RT for EC were retrospectively reviewed. EQD2 values were calculated for bladder, rectum, and sigmoid. Acute and late toxicities were retrospectively graded. Descriptive statistical analysis was performed. RESULTS: Fifty-one patients were included. The majority of patients had endometrioid histology (N = 46, 90.2%) and Grade 1 disease (N = 32, 62.75%). Thirty-seven patients (72.5%) were treated with image-guided BT (IGBT) and 14 (27.5%) with two-dimensional BT. Forty patients (78.4%) received EBRT + BT and 11 (21.57%) received BT alone. No grade 2 (G2) or higher toxicities were reported with BT alone. G2 or higher acute toxicities with EBRT + BT were G2 proctitis (N = 2, 5.0%) and G3 proctitis (N = 1, 2.5%). Late toxicities included G3 vaginal stenosis (N = 1, 2.5%), proctitis (N = 1, 2.5%), enteritis (N = 1, 2.5%), and one G4 gastrointestinal bleed. One- and 2-year local control were 100% with BT alone and 93% and 89%, respectively, with EBRT + BT. One- and 2-year locoregional control were 100% with BT and 97% and 93%, respectively, with EBRT + BT. Recurrence-free survival was 89% at 1 and 2 years with BT alone compared to 87% and 80% with EBRT + BT. One- and 2-year overall survival were 88% and 72% with BT alone compared to 94% and 84% with EBRT + BT. There were no statistically significant differences in cancer control between the two groups. CONCLUSIONS: Women with inoperable EC treated with definitive RT have low toxicity rates and durable local control.