A proteome-wide analysis unveils a core Epstein-Barr virus antibody signature of classic Hodgkin lymphoma across ethnically diverse populations.

Epstein-Barr virus (EBV) is an oncogenic virus associated with various malignancies, including classical Hodgkin lymphoma (cHL). Despite its known association, the specific role of humoral immune response to EBV remains poorly characterized in cHL. To address this, we conducted a study using a custom protein microarray to measure the antibody responses in cHL patients and matched healthy controls recruited from an East-Asian hospital-based case-control study. We identified 16 IgG antibodies significantly elevated in EBV-positive cHL compared with controls, defining an "East-Asian antibody signature of EBV-positive cHL." We evaluated responses against these 16 antibodies in a distinct European population, leveraging data from our previous European cHL case-control study from the UK, Denmark, and Sweden. A subset of antibodies (14/16, 87.5%) from the "East-Asian antibody signature of EBV-positive cHL" exhibited significant associations with cHL in the European population. Conversely, we assessed the "European antibody signature of EBV-positive cHL" identified in our prior study which consisted of 18 EBV antibodies (2 IgA, 16 IgG), in the East-Asian population. A subset of these antibodies (15/18, 83.3%) maintained significant associations with cHL in the East-Asian population. This cross-comparison of antibody signatures underscores the robust generalizability of EBV antibodies across populations. Five anti-EBV IgG antibodies (LMP-1, TK, BALF2, BDLF3, and BBLF1), found in both population-specific antibody signatures, represent a "core signature of EBV-positive cHL." Our findings suggest that the antibody responses targeting these core EBV proteins reflect a specific EBV gene expression pattern, serving as potential biomarkers for EBV-positive cHL independent of population-specific factors.

Fifth Edition of the World Health Organization Classification of Tumors of the Hematopoietic and Lymphoid Tissues: Mature T-Cell, NK-Cell, and Stroma-Derived Neoplasms of Lymphoid Tissues.

This review focuses on mature T cells, natural killer (NK) cells, and stroma-derived neoplasms in the fifth edition of the World Health Organization classification of hematolymphoid tumors, including changes from the revised fourth edition. Overall, information has expanded, primarily due to advancements in genomic understanding. The updated classification adopts a hierarchical format. The updated classification relies on a multidisciplinary approach, incorporating insights from a diverse group of pathologists, clinicians, and geneticists. Indolent NK-cell lymphoproliferative disorder of the gastrointestinal tract, Epstein-Barr virus-positive nodal T- and NK-cell lymphoma, and several stroma-derived neoplasms of lymphoid tissues have been newly introduced or included. The review also provides guidance on how the fifth edition of the World Health Organization classification of hematolymphoid tumors can be applied in routine clinical practice.

Exploring U.S. Hispanic origin groups diagnosed with uterine cancer - Are there disparities?

OBJECTIVE: To evaluate patterns and trends of uterine cancer among Hispanic subgroups. METHODS: The United States Cancer Statistics (USCS), National Cancer Database (NCDB), and World Population Review were used to obtain data on incidence, demographic characteristics, and cancer histology. Joinpoint regression program was used for statistical analysis. RESULTS: Based on 2001-2017 USCS data, the overall incidence of uterine cancer was 27.46 vs. 23.29/100,000 in Hispanics vs. non-Hispanic Whites. There was an over 2-fold higher annual increase in the incidence in Hispanics (1.94%; p < 0.001) vs. Whites (0.85%; p < 0.001), particularly in local stage disease. There was an increase in grade 1 endometrioid carcinoma (1.48%; p < 0.001 vs. -0.52%; p = 0.1) and aggressive histologic subtypes (4.04% p = 0.000 vs. 2.53% p = 0.000) in Hispanics vs. Whites. Using the NCDB (2004-2015), we analyzed 17,351 Hispanics by subgroup (Mexican, South/Central American, Puerto Rican, Cuban, and Dominican). Over the 12 years, there was an increase in the proportion of uterine cancer diagnoses in all Hispanics (5.2% to 11.0%; p < 0.0001). Dominican patients experienced the largest increase in diagnosis (2.6% to 14.9%; p < 0.0001), the highest proportion of advanced disease at 28.0% (p < 0.0001), and the highest incidence of non-endometrioid histologies at 37.1% (p < 0.0001). World Population Review 2023 revealed the highest female obesity rates in Puerto Rico (51.4%), the Dominican Republic (34.1%), and Mexico (32.8%). CONCLUSION: Uterine cancer incidence is increased in Hispanics, with the largest increase in Dominican women with more advanced stages and high-risk histologic subtypes. The impact of obesity on cancer risk, especially in Puerto Ricans, Dominicans, and Mexicans, warrants further investigation.

Uterine cancer among Asian Americans - Disparities & clinical characteristics.

OBJECTIVE: To evaluate the patterns and trends of uterine cancer among Asian subgroups living in the U.S. METHODS: Data were obtained from United States Cancer Statistics (2001-2017), National Cancer Database (2004-2015), and World Population Review (2023). SEER*Stat version 8.3.9.2, Joinpoint regression program 4.9.0.0, and SAS v 9.4 were employed for statistical analysis. RESULTS: Based on data from 778,891 women in the United States Cancer Statistics database, Asians had a 3.4-fold higher rate of incident uterine cancer compared to White populations (2.14% vs. 0.63%; p < 0.001). Using the National Cancer Database, 7,641 Asian women from six subgroups were analyzed: Filipino, Korean, Indian/Pakistani, Vietnamese, Chinese, and Japanese. Indian and Pakistani women had the greatest increase in the proportion of cancer diagnoses (5.0% to 14.4%; p = 0.0003). Additionally, Indian and Pakistani patients had higher comorbidity scores while Koreans had the lowest (22.7% vs. 10.7%, p < 0.0001). Regarding stage of disease, 25.3% of Filipinos presented with advanced stage disease compared to 19.2% of Indians and Pakistanis (p = 0.0001). Furthermore, Filipinos had the highest proportion of non-endometrioid cancers at 18.4% compared to other subgroups (p = 0.0003). Using the World Population Review, female obesity was highest in Pakistan (8.6%) and the Philippines (7.5%) and lowest in Vietnam (2.6%). CONCLUSION: Uterine cancer incidence increased at higher rates among Asians compared to White populations. Specifically, Indian and Pakistani uterine cancer patients were more likely to have higher comorbidity rates and Filipino patients had more advanced stage cancer with non-endometrioid histologies than other Asian subgroups. Further research is warranted to better understand these trends.

Preoperative and pre-chemotherapy CA-125 levels in high-risk early-stage ovarian cancer - An NRG/GOG study.

OBJECTIVES: To determine clinical significance of preoperative and pre-chemotherapy CA-125 in high-risk early-stage epithelial ovarian cancer patients. METHODS: All patients with stage IA/IB and grade 3, stage IC, clear cell, or completed resected stage II cancer were enrolled in a phase III trial and treated with chemotherapy. Kaplan-Meier method and Cox proportional hazards model were used for statistical analyses. RESULTS: 427 patients with high-risk early-stage ovarian cancer were enrolled. Of 213 patients with preoperative CA-125 data, 79% had elevated CA-125. Median preoperative CA-125 level was 103 U/mL. Patients with ≤10, 11-15, and > 15 cm tumors had median preoperative CA-125 levels of 62, 131 and 158 U/mL, respectively (p = 0.002). For the 350 patients with data for pre-chemotherapy CA-125 level, 69% had elevated pre-chemotherapy CA-125 above 35 U/mL with median value of 65 U/mL. However, age, race, stage, cell type and grade of disease were not correlated with CA-125 levels before and after surgery. On multivariate analysis, elevated pre-chemotherapy CA-125 independently predicted worse recurrence-free survival (HR = 2.13, 95% CI: 1.23-3.69; p = 0.007) and overall survival (HR = 1.99, 95% CI: 1.10-3.59; p = 0.022) after adjusting for age, stage, cell type and grade of disease. Compared to those with normal CA-125, patients with elevated pre-chemotherapy CA-125 had lower recurrence-free survival (RFS, 87% vs. 75%; p = 0.007) and overall survival (OS, 88% vs. 82%; p = 0.02). However, preoperative CA-125 was not prognostic of RFS (p = 0.699) or OS (p = 0.701). CONCLUSIONS: Preoperative CA-125 was elevated in nearly 80% of high-risk early-stage ovarian cancer patients. Pre-chemotherapy CA-125 was associated with recurrence-free and overall survival; however, preoperative CA-125 was not prognostic.

Underrepresentation of racial and ethnic minority groups in gynecologic oncology: An analysis of over 250 trials.

OBJECTIVE: To describe the participation of racial and ethnic minority groups (REMGs) in gynecologic oncology trials. METHODS: Gynecologic oncology studies registered on ClinicalTrials.gov between 2007 and 2020 were identified. Trials with published results were analyzed based on reporting of race/ethnicity in relation to disease site and trial characteristics. Expected enrollment by race/ethnicity was calculated and compared to actual enrollment, adjusted for 2010 US Census population data. RESULTS: 2146 gynecologic oncology trials were identified. Of published trials (n = 252), 99 (39.3%) reported race/ethnicity data. Recent trials were more likely to report these data (36% from 2007 to 2009; 51% 2013-2015; and 53% from 2016 to 2018, p = 0.01). Of all trials, ovarian cancer trials were least likely to report race/ethnicity data (32.1% vs 39.3%, p = 0.011). Population-adjusted under-enrollment for Blacks was 7-fold in ovarian cancer, Latinx 10-fold for ovarian and 6-fold in uterine cancer trials, Asians 2.5-fold in uterine cancer trials, and American Indian and Alaska Native individuals 6-fold in ovarian trials. Trials for most disease sites have enrolled more REMGs in recent years - REMGs made up 19.6% of trial participants in 2007-2009 compared to 38.1% in 2016-2018 (p < 0.0001). CONCLUSION: Less than half of trials that published results reported race/ethnicity data. Available data reveals that enrollment of REMGs is significantly below expected rates based on national census data. These disparities persisted even after additionally adjusting for population size. Despite improvement in recent years, additional recruitment of REMGs is needed to achieve more representative and equitable participation in gynecologic cancer clinical trials.

Racial, ethnic and country of origin disparities in aggressive endometrial cancer histologic subtypes.

OBJECTIVE: This study investigated the risk of an aggressive endometrial cancer (EC) diagnosis by race, ethnicity, and country of origin to further elucidate histologic disparities in non-Hispanic Black (NHB), Hispanic, Asian/Pacific Islander (API), American Indian/Alaskan Native (AIAN) vs. non-Hispanic White (NHW) patients, particularly in Hispanic or API subgroups. METHODS: Patient diagnosed between 2004 and 2020 with low grade (LG)-endometrioid endometrial cancer (ECC) or an aggressive EC including grade 3 EEC, serous carcinoma, clear cell carcinoma, mixed epithelial carcinoma, or carcinosarcoma in the National Cancer Database were studied. The odds ratio (OR) and 95% confidence interval (CI) for diagnosis of an aggressive EC histology was estimated using logistic modeling. RESULTS: There were 343,868 NHW, 48,897 NHB, 30,013 Hispanic, 15,015 API and 1646 AIAN patients. The OR (95% CI) for an aggressive EC diagnosis was 3.07 (3.01-3.13) for NHB, 1.08 (1.06-1.11) for Hispanic, 1.17 (1.13-1.21) for API and 1.07 (0.96-1.19) for AIAN, relative to NHW patients. Subset analyses by country of origin illustrated the diversity in the OR for an aggressive EC diagnosis among Hispanic (1.18 for Mexican to 1.87 for Dominican), Asian (1.14 Asian Indian-Pakistani to 1.48 Korean) and Pacific Islander (1.00 for Hawaiian to 1.33 for Samoan) descendants. Hispanic, API and AIAN patients were diagnosed 5-years younger that NHW patients, and the risk for an aggressive EC histology were all significantly higher than NHW patients after correcting for age. Insurance status was another independent risk factor for aggressive histology. CONCLUSIONS: Risk of an aggressive EC diagnosis varied by race, ethnicity, and country of origin. NHB patients had the highest risk, followed by Dominican, South/Central American, Cuban, Korean, Thai, Vietnamese, and Filipino descendants.

Survival disparities in non-Hispanic Black and White cervical cancer patients vary by histology and are largely explained by modifiable factors.

PURPOSE: We investigated racial disparities in survival by histology in cervical cancer and examined the factors contributing to these disparities. METHODS: Non-Hispanic Black and non-Hispanic White (hereafter known as Black and White) patients with stage I-IV cervical carcinoma diagnosed between 2004 and 2017 in the National Cancer Database were studied. Survival differences were compared using Cox modeling to estimate hazard ratio (HR) or adjusted HR (AHR) and 95% confidence interval (CI). The contribution of demographic, socioeconomic and clinical factors to the Black vs White differences in survival was estimated after applying propensity score weighting in patients with squamous cell carcinoma (SCC) or adenocarcinoma (AC). RESULTS: This study included 10,111 Black and 43,252 White patients with cervical cancer. Black patients had worse survival than White cervical cancer patients (HR = 1.40, 95% CI = 1.35-1.45). Survival disparities between Black and White patients varied significantly by histology (HR = 1.20, 95% CI = 1.15-1.24 for SCC; HR = 2.32, 95% CI = 2.12-2.54 for AC, interaction p < 0.0001). After balancing the selected demographic, socioeconomic and clinical factors, survival in Black vs. White patients was no longer different in those with SCC (AHR = 1.01, 95% CI 0.97-1.06) or AC (AHR = 1.09, 95% CI = 0.96-1.24). In SCC, the largest contributors to survival disparities were neighborhood income and insurance. In AC, age was the most significant contributor followed by neighborhood income, insurance, and stage. Diagnosis of AC (but not SCC) at ≥65 years old was more common in Black vs. White patients (26% vs. 13%, respectively). CONCLUSIONS: Histology matters in survival disparities and diagnosis at ≥65 years old between Black and White cervical cancer patients. These disparities were largely explained by modifiable factors.

Disease progression, survival, and molecular disparities in Black and White patients with endometrioid endometrial carcinoma in real-world registries and GOG/NRG oncology randomized phase III clinical trials.

OBJECTIVE: Investigate racial disparities in outcomes and molecular features in Black and White patients with endometrioid endometrial carcinoma (EEC). METHODS: Black and White patients diagnosed with EEC who underwent hysterectomy ± adjuvant treatment in SEER, National Cancer Database (NCDB), the Genomics Evidence Neoplasia Information Exchange (GENIE) project (v.13.0), and eight NCI-sponsored randomized phase III clinical trials (RCTs) were studied. Hazard ratio (HR) and 95% confidence interval (CI) were estimated for cancer-related death (CRD), non-cancer death (NCD), and all-cause death. RESULTS: Black (n = 4397) vs. White (n = 47,959) patients in SEER had a HR (95% CI) of 2.04 (1.87-2.23) for CRD and 1.22 (1.09-1.36) for NCD. In NCDB, the HR (95% CI) for death in Black (n = 13,468) vs. White (n = 155,706) patients was 1.52 (1.46-1.58) dropping to 1.29 (1.23-1.36) after propensity-score matching for age, comorbidity, income, insurance, grade, stage, LVSI, and treatment. In GENIE, Black (n = 109) vs. White (n = 1780) patients had fewer PTEN, PIK3R1, FBXW7, NF1, mTOR, CCND1, and PI3K-pathway-related gene mutations. In contrast, TP53 and DNA-repair-related gene mutation frequency as well as tumor mutational burden-high status were similar in Black and White patients. In RCTs, Black (n = 187) vs. White (n = 2877) patients were more likely to have advanced or recurrent disease, higher grade, worse performance status and progressive disease. Risk of death in Black vs. White patients in RCTs was 2.19 (1.77-2.71) persisting to 1.32 (1.09-1.61) after matching for grade, stage, and treatment arm while balancing age and performance status. CONCLUSIONS: Differences exist in clinical presentation, outcomes, and molecular features in Black vs. White patients with EEC in real-world registries and RCTs. Targeted-drug development, strategies to modify social determinants, and diverse inclusion in RCTs are approaches to reduce disparities.

Real-world use of immune checkpoint inhibitors in advanced or recurrent endometrial cancer.

OBJECTIVE: The aim of this study was to describe real-world use of immune checkpoint inhibitors for women with advanced or recurrent endometrial cancer. METHODS: Adult women with advanced or recurrent endometrial cancer who received at least one line of systemic treatment between January 1, 2014 and November 1, 2020, then followed to May 31, 2021 in a nationwide electronic health record-derived de-identified database. Chi-Squared test or Welch's 2-sample t-tests were used to compare patient and clinical factors associated with immune checkpoint inhibitor treatment. Time to next treatment analyses were performed based on the treatment line of the immune checkpoint inhibitor. Sankey plots depicted patient-level temporal systemic treatment. RESULTS: During our study period, 326 women received their first immune checkpoint inhibitor treatment, increasing from 12 patients in 2016 to 148 in 2020. Factors associated with ever receiving immune checkpoint inhibitors included disease stage (p=0.002), mismatch repair (MMR)/microsatellite instability (MSI) status (p<0.001), performance status (p=0.001), and prior radiation receipt (p<0.001) and modality (p=0.003). The most common immune checkpoint inhibitor regimen was pembrolizumab (47.9%) followed by pembrolizumab and lenvatinib (34.7%). Immune checkpoint inhibitors were given as first, second, and third or greater lines of therapy in 24.5%, 41.7%, and 46.1% of evaluable patients. The median time to next treatment was significantly longer if given as an earlier line of treatment (p=0.008). There were significant differences in treatment line of immune checkpoint inhibitor by region (p=0.004), stage (p<0.001), and prior radiation receipt (p=0.014) and modality (p=0.009). Among 326 patients who received immune checkpoint inhibitors, 114 (34.9%) received subsequent treatment including chemotherapy (43.9%), additional immune checkpoint inhibitors (29.8%), and other (26.3%) with no differences in demographic or clinical characteristics based on the type of post-immune checkpoint inhibitor treatment. CONCLUSION: In an observational retrospective real-world database study, immune checkpoint inhibitors were used in 14.7% of patients with advanced or recurrent endometrial cancer across multiple lines of treatment, including after initial immune checkpoint inhibitor treatment.

Sequential Targeted Therapy for Advanced, Metastatic, and Recurrent Cervical Cancer: A Cost-Effectiveness Analysis of the Patient Journey.

OBJECTIVES: To evaluate outcomes and cost-effectiveness of targeted therapy sequencing for metastatic and recurrent cervical cancer. METHOD: Models were simulated based on phase II and III trials on bevacizumab (bev) from GOG-240, cemiplimab (cemi) from GOG 3016, pembrolizumab (pembro) from KEYNOTE-826, and tisotumab vedotin (tiso) from GOG 3023. Costs were based on IBM Micromedex RED BOOK™ and company listed costs. RESULTS: For [chemo + bev → chemo], total cost was $125,918.04, with median overall survival (mOS) of 21.8 months, and cost-effectiveness ratio (CER) of $119,835.79. For [chemo + bev → cemi], total cost was $187,562.99 with mOS of 28.5 months and CER of $162,039.16. For [chemo + bev + pembro → chemo], total cost was $319,963.78 with mOS 32.9 months and CER of $249,930.10. For [chemo + bev + pembro → tiso], total cost was $455,204.45, with mOS 36.5 months and CER of $320,072.99. CONCLUSION: The combination of immunotherapies and biologics have significantly increased overall survival, but with associated higher costs, primarily related to drug costs.

Trends in Incidence of Cancers Associated With Obesity and Other Modifiable Risk Factors Among Women, 2001-2018.

We used data from the US Cancer Statistics database to determine trends in cancer incidence, stratified by age, race, and ethnicity, among women aged 20 years or older during an 18-year study period (2001-2018). We limited analysis to cancers associated with 5 modifiable risk factors: tobacco use, excess body fat, alcohol consumption, insufficient physical activity, and human papillomavirus infection. The incidence of cancers associated with obesity have risen, particularly among women aged 20 to 49 years (vs ≥50 y) and among Hispanic women. Strategies that address obesity rates in these populations may help decrease cancer risk.

Secondary Surgical Cytoreduction for Recurrent Ovarian Cancer.

BACKGROUND: Secondary surgical cytoreduction in women with platinum-sensitive, recurrent epithelial ovarian, primary peritoneal, or fallopian-tube ("ovarian") cancer is widely practiced but has not been evaluated in phase 3 investigation. METHODS: We randomly assigned patients with recurrent ovarian cancer who had received one previous therapy, had an interval during which no platinum-based chemotherapy was used (platinum-free interval) of 6 months or more, and had investigator-determined resectable disease (to no macroscopic residual disease) to undergo secondary surgical cytoreduction and then receive platinum-based chemotherapy or to receive platinum-based chemotherapy alone. Adjuvant chemotherapy (paclitaxel-carboplatin or gemcitabine-carboplatin) and use of bevacizumab were at the discretion of the investigator. The primary end point was overall survival. RESULTS: A total of 485 patients underwent randomization, 240 to secondary cytoreduction before chemotherapy and 245 to chemotherapy alone. The median follow-up was 48.1 months. Complete gross resection was achieved in 67% of the patients assigned to surgery who underwent the procedure. Platinum-based chemotherapy with bevacizumab followed by bevacizumab maintenance was administered to 84% of the patients overall and was equally distributed between the two groups. The hazard ratio for death (surgery vs. no surgery) was 1.29 (95% confidence interval [CI], 0.97 to 1.72; P = 0.08), which corresponded to a median overall survival of 50.6 months and 64.7 months, respectively. Adjustment for platinum-free interval and chemotherapy choice did not alter the effect. The hazard ratio for disease progression or death (surgery vs. no surgery) was 0.82 (95% CI, 0.66 to 1.01; median progression-free survival, 18.9 months and 16.2 months, respectively). Surgical morbidity at 30 days was 9%; 1 patient (0.4%) died from postoperative complications. Patient-reported quality of life decreased significantly after surgery but did not differ significantly between the two groups after recovery. CONCLUSIONS: In this trial involving patients with platinum-sensitive, recurrent ovarian cancer, secondary surgical cytoreduction followed by chemotherapy did not result in longer overall survival than chemotherapy alone. (Funded by the National Cancer Institute and others; GOG-0213 ClinicalTrials.gov number, NCT00565851.).

Clinical calculator redefines prognosis for high-risk early-stage ovarian cancers and potential to guide treatment in the adjuvant setting.

OBJECTIVE: To determine the utility of a clinical calculator to redefine prognosis and need for chemotherapy among patients with early-stage high-risk epithelial ovarian cancer. METHODS: Data were abstracted for stage I-II, high-risk ovarian cancer from the National Cancer Database from years 2005 to 2015. Based on demographic, pathologic, surgical, and laboratory characteristics, a clinical score was developed using Cox regression. Propensity score weighting was used to adjust for differences between patients who did and did not receive chemotherapy. RESULTS: Of 8188 patients with early-stage high-risk ovarian cancer, 6915 (84%) did and 1273 (16%) did not receive chemotherapy. A clinical calculator was created utilizing age, stage, histology, grade, tumor size, number of pelvic and paraaortic lymph nodes examined, the presence of malignant ascites, and CA125. The calculator divided patients into low, moderate, and high-risk groups with 5-year OS (overall survival) of 92%, 82%, and 66%, and 10-year OS of 85%, 67%, and 44%, respectively. Chemotherapy improved 5-year OS and 10-year OS in the high-risk group (56% to 73%; p < 0.001, 34% to 48%; p < 0.001). The moderate risk group had improved 5-year OS (80% to 85%; p = 0.01) but not 10-year OS (66% to 66%; p = 0.13). Chemotherapy did not improve 5-year or 10-year OS in low-risk patients (93% to 92%, p = 1.0, 86% to 84%, p = 0.99). CONCLUSIONS: The prognosis among high-risk early-stage ovarian cancer patients is heterogeneous. This calculator may aid in patient-centered counseling regarding potential treatment benefits.

Conditional estimates for uterine serous cancer: Tools for survivorship counseling and planning.

OBJECTIVES: Develop conditional survival and risk-assessment estimates for uterine serous carcinoma (USC) overall and stratified by stage as tools for annual survivorship counseling and care planning. METHODS: Patients in the National Cancer Data Base diagnosed between 2004 and 2014 with stage I-IV USC were eligible. Individuals missing stage or survival data or with multiple malignancies were excluded. Five-year conditional survival was estimated using the stage-stratified Kaplan-Meier method annually during follow-up. A standardized mortality ratio (SMR) estimated the proportion of observed to expected deaths in the U.S. adjusted for year, age, and race. The relationships between prognostic factors and survival were studied using multivariate Cox modeling at diagnosis and conditioned on surviving 5-years. RESULTS: There were 14,575 participants, including 43% with stage I, 8% with stage II, 29% with stage III, and 20% with stage IV USC. Five-year survival at diagnosis vs. after surviving 5-years was 52% vs. 75% overall, 77% vs. 81% for stage I, 57% vs. 72% for stage II, 40% vs. 66% for stage III, and 17% vs. 60% for stage IV USC, respectively (P < 0.0001). Incremental improvements in 5-year conditional survival and reductions in SMR tracked with annual follow-up and higher stage. The adjusted risk of death at diagnosis vs. after surviving 5-years was 1.15 vs. 1.40 per 5-year increase of age, 1.26 vs. 1.68 for Medicaid insurance, 3.92 vs. 2.48 for stage III disease, and 6.65 vs. 2.79 for stage IV disease, respectively (P < 0.0001). CONCLUSION: In USC, the evolution of conditional survival permits annual reassessments of prognosis to tailor survivorship counseling and care planning.

The clinical and prognostic significance of pre-chemotherapy serum CA-125 in high-risk early stage ovarian cancer: An NRG/GOG ancillary study.

OBJECTIVES: To determine the clinical and prognostic significance of CA-125 trends prior to, during, and after chemotherapy in high-risk early-stage epithelial ovarian cancer patients. METHODS: All patients were enrolled in a phase III randomized trial (GOG 157) following upfront surgery for grade 3 stage IA/IB, stage IC, or stage II disease, and had been treated with either three or six cycles of carboplatin/paclitaxel. Kaplan-Meier method and Cox proportional hazards model were used to evaluate recurrence-free survival (RFS) and overall survival (OS). RESULTS: Of 350 patients, the median pre-chemotherapy CA-125 was 65 (IQR: 31-129). 71% of Whites had an elevated CA-125 compared to 47% of non-Whites (p = 0.006). Following the first cycle of chemotherapy, 74% of those with elevated CA-125 had normalization. Those who had normalization of CA-125 after 1 cycle had significantly better 5-year RFS (81% vs. 65%, p = 0.003) and OS (87% vs. 75%, p = 0.009) compared to those who did not normalize (defined as ≤35 U/mL). The pattern of CA-125 change following chemotherapy cycle 1, from normal to normal vs. elevated to normal vs. elevated to elevated had corresponding RFS of 87% vs. 80% vs. 68% (p = 0.013), and OS of 92% vs. 88% vs. 77% (p = 0.009). However, the percent decline (p = 0.993) and absolute nadir normal value of CA-125 (0-10 vs. 11-35 U/mL) were not predictive of outcome (p = 0.4). CONCLUSIONS: Normal baseline CA125 and normalization of this biomarker after the first cycle of chemotherapy were associated with better survival in high-risk early-stage epithelial ovarian cancer patients.

Impact of veliparib, paclitaxel dosing regimen, and germline BRCA status on the primary treatment of serous ovarian cancer - an ancillary data analysis of the VELIA trial.

OBJECTIVE: In the Phase 3 VELIA trial (NCT02470585), veliparib added to carboplatin plus paclitaxel concomitantly and as maintenance for women with newly-diagnosed advanced ovarian cancer significantly improved progression-free survival (PFS) versus chemotherapy alone. Here we present exploratory analyses by paclitaxel dosing schedule and germline BRCA (gBRCA) status. METHODS: Women with untreated ovarian carcinoma were randomized (1:1:1) to: veliparib during chemotherapy and maintenance (veliparib-throughout), veliparib during chemotherapy followed by placebo maintenance (veliparib-combination only), or placebo during chemotherapy and maintenance (control). Chemotherapy included carboplatin plus dose-dense (DD; weekly) or every-3-week (Q3W) paclitaxel (a stratification factor at randomization), selected at the investigator's discretion pre-randomization. PFS was assessed by paclitaxel dosing schedule using a Cox proportional hazard model adjusted by treatment arm and stratification factors; safety was analyzed based on paclitaxel dosing schedule and gBRCA status. RESULTS: 1132 patients were analyzed by paclitaxel schedule. Pooled treatment arms demonstrated longer median PFS with DD (n = 586) versus Q3W (n = 546) paclitaxel (ITT: 20.5 vs 15.7 months, hazard ratio [HR] 0.77; homologous recombination proficient cancer: 15.1 vs 11.8 months, HR 0.64; BRCAwt: 18.0 vs 12.9 months, HR 0.70). Comparison between arms favored veliparib-throughout versus control in both DD (PFS, 24.2 vs 18.3 months, hazard ratio 0.67) and Q3W (19.3 vs 14.6, hazard ratio 0.69) subgroups. DD paclitaxel was associated with higher incidence of Grade 3/4 neutropenia, fatigue, and anemia versus Q3W. There were no differences in toxicity between gBRCAm (n = 211) and gBRCAwt (n = 902) subgroups. CONCLUSIONS: DD paclitaxel was tolerable and associated with longer PFS in the HR proficient and gBRCAwt groups, versus Q3W. gBRCA status did not impact safety.

What proportion of patients with stage 3 ovarian cancer are potentially cured following intraperitoneal chemotherapy? Analysis of the long term (≥10 years) survivors in NRG/GOG randomized clinical trials of intraperitoneal and intravenous chemotherapy in stage III ovarian cancer.

OBJECTIVE: Patients with advanced epithelial ovarian cancer (EOC) alive without progression at a landmark time-point of 10 years from diagnosis are likely cured. We report the proportion of patients with Stage III EOC who were long-term disease-free survivors (LTDFS≥10 years) following either intraperitoneal (IP) or intravenous (IV) chemotherapy as well as the predictors of LTDFS. METHODS: Data from 3 mature NRG/GOG trials (104, 114, 172) were analyzed and included demographics, clinicopathologic details, route of administration, and survival outcomes of patients living ≥10 years assessed according to the Kaplan-Meier method. Cox regression survival analysis was performed to evaluate independent prognostic predictors of LTDFS. RESULTS: Of 1174 patients randomized, 10-year overall survival (OS) was 26% (95% CI, 23-28%) and LTDFS ≥10 years was 18% (95% CI, 16-20%). Patients with LTDFS ≥10 years had a median age of 54.6 years (p < 0.001). Younger age (p < 0.001) was the only independent prognostic factor for LTDFS≥10 years on multivariate Cox analysis. CONCLUSIONS: Approximately 18% of patients were LTDFS ≥10 years. They form the tail end of the survival curve and are likely cured. Our results provide a comparative benchmark to evaluate the impact of PARP inhibitors in 1st line maintenance trials on survival outcomes.

The increasing incidence of stage IV cervical cancer in the USA: what factors are related?

OBJECTIVE: Cervical cancer (International Federation of Gynecology and Obstetrics (FIGO)) stage IVA-B (distant stage) is a rare diagnosis with an approximate 5 year survival rate of 17% and with limited treatment options. The objective of this study was to determine the trends in distant stage cervical cancer in the USA and identify possible factors related to these trends. METHODS: Data were obtained from the United States Cancer Statistics program from 2001 to 2018. Rates of cervical cancer screening and vaccination were evaluated using the Behavioral Risk Factor Surveillance System and TeenVaxView. SEER*Stat 8.3.8.9.2 and Joinpoint regression program 4.9.0.0 were used to calculate incidence trends. RESULTS: Over the last 18 years, 29 715 women were diagnosed with distant stage cervical carcinoma. Black women have disproportionately higher rates at 1.55/100 000 versus 0.92/100 000 in White women (p<0.001). When examining the trends over time, there has been an annual increase in distant stage cervical cancer at a rate of 1.3% per year (p<0.001). The largest increase is seen in cervical adenocarcinoma with an average annual percent change of 2.9% (p<0.001). When performing an intersection analysis of race, region and age, White women in the South aged 40-44 have the highest rise in distant cervical cancer at a rate of 4.5% annually (p<0.001). Using the Behavioral Risk Factor Surveillance System and TeenVax data, compared with Black women, we found that White women have a nearly two-fold higher rate of missed or lack of guideline screening, 26.6% vs 13.8%. White teenagers (13-17 years) have the lowest human papillomavirus vaccination rate at 66.1% compared with others at 75.3%. CONCLUSIONS: Black women have a higher incidence of distant stage disease compared with White women. However, White women have a greater annual increase, particularly in adenocarcinomas. Compared with Black women, White women also have lower rates of guideline screening and vaccination.

Diagnostic Value of MAML2 Rearrangements in Mucoepidermoid Carcinoma.

Mucoepidermoid carcinoma (MEC) is often seen in salivary glands and can harbor MAML2 translocations (MAML2+). The translocation status has diagnostic utility as an objective confirmation of the MEC diagnosis, for example, when distinction from the more aggressive adenosquamous carcinoma (ASC) is not straightforward. To assess the diagnostic relevance of MAML2, we examined our 5-year experience in prospective testing of 8106 solid tumors using RNA-seq panel testing in combinations with a two-round Delphi-based scenario survey. The prevalence of MAML2+ across all tumors was 0.28% (n = 23/8106) and the majority of MAML2+ cases were found in head and neck tumors (78.3%), where the overall prevalence was 5.9% (n = 18/307). The sensitivity of MAML2 for MEC was 60% and most cases (80%) were submitted for diagnostic confirmation; in 24% of cases, the MAML2 results changed the working diagnosis. An independent survey of 15 experts showed relative importance indexes of 0.8 and 0.65 for "confirmatory MAML2 testing" in suspected MEC and ASC, respectively. Real-world evidence confirmed that the added value of MAML2 is a composite of an imperfect confirmation test for MEC and a highly specific exclusion tool for the diagnosis of ASC. Real-world evidence can help move a rare molecular-genetic biomarker from an emerging tool to the clinic.