bluuebunny/crossref_metadata_2025 huggingface dataset:
Retrospective analysis of ovarian cancer patients treated with PARP inhibitors.
Authors: Liang Connie , Leung Ashley , Lee Chung-Shien , Hernandez Jennifer , Cheng Kit , Stefanov Dimitre C. , John Veena S.
Published: June 2021

e17555

Background: Over the last few years, targeted therapy has become the mainstay maintenance treatment of patients with ovarian cancer including patients with BRCA1 or BRCA2 mutations. Poly ADP ribose polymerase (PARP) inhibitors are effective in the treatment of patients who are in complete or partial remission. PARP inhibitors are known to cause hematological adverse events (AEs), but have not been compared directly to each other. Methods: We conducted a single institution, IRB approved, retrospective study on patients who were treated with PARP inhibitors from December 2016 to October 2020. Patients were stratified according to which PARP inhibitor they received. Our primary objective was to assess the incidence of hematological and non-hematological adverse events associated with the use of PARP inhibitor therapy used in patients with ovarian cancer. Data from absolute neutrophil count, hemoglobin and platelet count during the first 2 cycles were graded for hematologic toxicity according to CTCAE v 5.0. Results: A total of 126 patients received a PARP inhibitor during the study time frame. 34 were excluded and 92 patients were included for analysis. Median age of patients were 64.3 (range, 33.8 to 92.3) years, 66 (71.7%) white, and 84 (91.3%) had an ECOG PS of 0/1. Thirty-one (33.7%) of patients received niraparib and 61 (66.3%) of patients received olaparib. Patients in the niraparib group experienced more hematologic AEs, with 11 (35.5%) (95% CI 19.2-54.6), 20 (64.5%) (95% CI 45.4-80.8), and 18 (58.1%) (95% CI 39.1-75.5) experiencing neutropenia, anemia, thrombocytopenia, respectively. Eight (13.1%) (95% CI 5.8-24.2), 24 (39.3%) (95% CI 27.1-52.7), 16 (26.2%) (95% CI 15.8-39.1) patients in the olaparib group experienced neutropenia, anemia, thrombocytopenia, respectively. Conclusions: This single institution retrospective study outlines the hematological toxicities observed between two PARP inhibitors. Although there are four PARP inhibitors approved by FDA, our data compared only two of the four (as they were the most commonly prescribed PARP inhibitors in our institution). Our results suggested that niraparib tended to be associated with a higher risk for hematologic toxicities than olaparib. Our data showed anemia as the most common hematologic toxicity which was consistent with what has been widely documented in the literature.
Using 3D perfusion bioreactor system to studying cell biology of ovarian cancer.
Authors: Martínez Alba , Buckley Molly , Berry Joel , Arend Rebecca Christian
Published: June 2021

e17558

Background: Epithelial Ovarian Cancer (EOC) is the most common cause of death among gynecological malignancies. This is a result of the high rate of recurrence and chemo-resistance in EOC patients. Therefore, the development of new therapeutics is crucial. A major factor contributing to this is the lack of therapeutic candidates is lack of translational accuracy in preclinical models. Recently, 3-dimensional (3-D) models have aided in accurately recreating tumor biology. We have developed an EOC 3-D perfused bioreactor system that recapitulates EOC tumor biology and incorporates tumor biomechanical regulation. This model allows for us to more accurately predict the clinical response of new drug candidates, which aids in elimination of ineffective candidates prior to clinical trials. Methods: EOC cell lines (luciferase-taggedSKOV-3 and OVCAR-8) were embedded in a relevant extracellular matrix (ECM) and injected into a perfused, polydimethylsiloxane (PDMS) bioreactor. Microchannels were embedded in matrigel so that the cell culture media with or without chemotherapy could flow through the perfused PDMS to provide nutrient delivery and gas exchange enhancing viability and function of surrounding cells. The bioreactors were connected to a peristaltic pump that allowed for the cell culture media to perfuse over a 7-day period. We monitored cell viability using bioluminescence imaging (BLI), immunohistochemistry (IHC), and lactate dehydrogenase (LDH) release in media. Results: BLI showed a linear increase in SKOV-3 and OVCAR-8 cell growth over 7 days. These results were confirmed by IHC measuring the number of nucleated cells per micron2. Graphical representation of the region of interest (ROI) showed a high correlation between IHC staining of nucleated cells and BLI score. IHC analysis of PAX8 staining was positive and proved that the perfusion bioreactor system maintains EOC biology over time. In addition, our results suggest that the bioreactor is a suitable model for drug preclinical testing in both cell lines as well as in patients’ samples. Conclusions: Our preliminary results using the 3D EOC perfused, PDMS bioreactor model showed increased EOC cell growth overtime, while maintaining original EOC histology. Moreover, our results suggest that this model could provide a novel platform to study therapeutic interventions in EOC. Our ultimate goal is to implement ovarian cancer microenvironment components (e.g. immune cells) into bioreactor system to study different drug treatments to better determine drug candidate’s translational efficacy.
Clinicopathologic characteristics of distinct molecular subtypes of endometrial carcinoma in Chinese population.
Authors: Zhang Qing , Ma Xinyue , Cao Wenyu , Wu Huan , Dong Xiaomeng , Sun Chenggong , Song Kun , Kong Beihua
Published: June 2021

e17568

Background: Stratifying endometrial carcinoma (EC) based on molecular profiling is of importance. While, spectrum of molecular subtypes of EC in Chinese population needs to be elucidated. Conventional approaches involve methodologies including Sanger sequencing as well as immunohistochemistry which is highly dependent on experience of pathologists. This study is of first time to display clinical and pathological characters of molecular subtypes of EC which were defined by a simplified NGS panel in Chinese population. Methods: Paraffin-embedded tissues of 135 consented EC patients were retrospectively collected from Qilu Hospital, Shandong Province, China. Genomic DNA was extracted and subjected to a simplified panel covering POLE, TP53 as well as 55 MSI loci for massive parallel sequencing. Mutations annotated as Tier I, II were applied for subtyping. MSI was defined as instability in 22 or more microsatellite loci. Subtypes were stratified as POLE, MSI, TP53-wt or TP53-mut group. Correlations of clinicopathological characters as well as prognosis were further conducted. Results: Histology of collected samples were mostly Endometrioid EC (EEC, 93.33%). Most of samples were at stage I (80%). The fractions of POLE (n=10), MSI (n=29), TP53-wt (n=84) and TP53-mut (n=12) group were 7.41%, 21.48%, 62.22%, and 8.89%, respectively. POLE group was associated with earlier stage (Stage I, 90%), EEC (80%) and less lympho-vascular space invasion (LVSI) (10%). TP53-mutant subtype was correlated to later stage (Stage II-IV, 41.67%), higher grade (G2+G3, 83.33%), serous histology (25%) and higher rate of LVSI (25%). The median follow-up was 74 (1.5-122) months. The 8-year overall (OS) and disease-specific survival (DSS) rate were 100% in POLE group, while only 58.3% and 75% in TP53 mutant cases (P<0.001 for OS, P=0.01 for DSS). Conclusions: Molecular subtypes of EC significantly correlated with clinicopathologic characters, especially with patients’ prognosis. This simplified NGS-panel could accurately delineate different EC subgroups.[Table: see text]
A longitudinal study of the adherence to PORTEC-2 based adjuvant radiotherapy in high-intermediate-risk endometrial adenocarcinoma and associated oncologic outcomes.
Authors: Erfani Hadi , Rezaei Atefeh , Costales Anthony
Published: June 2021

e17570

Background: In 2010, Nout et al. reported on PORTEC-2, which randomized patients with high intermediate risk (HIR) endometrial cancer to adjuvant vaginal brachytherapy or pelvic radiotherapy or observation, and showed that vaginal brachytherapy was non-inferior in terms of locoregional control and was deemed the adjuvant treatment of choice for these patients. We sought to evaluate the adherence to and the oncologic outcomes of the PORTEC-2 regimen. Methods: We utilized the SEER database to identify patients who met PORTEC-2 inclusion criteria. All patients underwent surgery followed by either vaginal brachytherapy (VBT) or whole pelvic radiotherapy (WPRT). Inclusion criteria were patients with the following characteristics: grade 1 with ≥ 50% myometrial invasion (MI), grade 2 with any invasion, and grade 3 with < 50% MI. Patients were excluded if any lymph nodes were examined or involved, if they received any chemotherapy, or had any missing values for any of the variables. HIR endometrial adenocarcinoma was defined as the presence of 2 of the following: age > 60, grade 3, and ≥50% myometrial invasion. Radiation status was extracted from the SEER Radiation/Chemotherapy database. Outcomes were overall death, cancer specific death and total survival months per SEER’s standard definitions. Variables are reported as median and interquartile range (IQR) or number (%). Mean survival was calculated using Kaplan Meier analysis and Mantel-Cox rank test was done to test for statistical significance between the study groups. Cox regression analysis was performed, and hazard ratios (HR) were calculated. Statistical analysis was performed using SPSS v. 22.0. Results: Between 2005- 2015, 571 patients met PORTEC-2 inclusion criteria of whom 349 (61.1%) and 222 (38.9%) received WPRT and VBT, respectively. We showed that the rate of VBT was significantly increased from 85 (27.4%) between 2005-2010 to 137 (52.5%) between 2011-2015 (p < 0.001). There was no difference in grade and myometrial invasion between the study groups. Kaplan Meier analysis showed a 22.5 and 16.3 month improvement in overall and cancer specific survival in subjects who underwent VBT as compared to WPRT, respectively (p < 0.001 for both). Cox regression analysis revealed a 36% and 66% decrease in the hazard of overall and cancer specific death, respectively, in the VBT group as compared to WPRT group (Overall death: HR = 0.64, 95% CI: 0.45-0.91, p = 0.012; Cancer specific death: HR = 0.34, 95% CI: 0.16-0.73, p = 0.006). Conclusions: Administration of vaginal brachytherapy following surgery has become significantly more popular after publication of the PORTEC-2 results in 2010. Our study shows a significant decrease in both overall and cancer related death and an increase in survival with VBT over WPRT in patients with HIR endometrial cancer.
Disparities in adjuvant treatment of high-grade endometrial cancer.
Authors: Corey Logan , Cote Michele L. , Ruterbusch Julie J. , Winer Ira Seth
Published: June 2021

e17572

Background: To examine surgical outcomes, patterns of adjuvant therapy, and survival for non-Hispanic Black (NHB) women compared to non-Hispanic White (NHW) and Hispanic (HS) women who have undergone surgery for high grade endometrial cancer in the Medicare population. Methods: We utilized the SEER-Medicare linked database to identify women who underwent surgery as a primary treatment for uterine grade 3 endometrioid adenocarcinoma, carcinosarcoma, clear cell carcinoma, or serous carcinoma between the years 2000 and 2015. Multinomial logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for receiving a treatment delay or not receiving adjuvant treatment (compared to those who received adjuvant treatment within 12 weeks) adjusted for clinical and demographic characteristics. Overall survival (OS) stratified by race/ethnicity, route of surgery, operative complications, and type and timing of adjuvant therapy were analyzed using the Kaplan-Meier method. Cox Proportional hazards regression was used to estimate hazard of death by race/ethnicity adjusted for known predictors, as well as surgical outcomes and adjuvant therapy patterns. Results: 12, 201 women met study inclusion criteria. NHB patients had a significantly worse five-year overall survival (OS) than HS and NHW patients (30.9 months vs 51.0 months vs 53.6 months, respectively). Approximately 8.6% of patients who received adjuvant treatment experienced a treatment delay (632/7, 282). Delay in treatment of greater than or equal to 12 weeks was significantly different by race/ethnicity (p=0.034), with 12% of HS, 9% of NHB, and 8% of NHW women experiencing a delay. After adjustment for number of complications, age, histology (endometrioid v. non-endometroid), FIGO stage, marital status, comorbidity count, surgical approach, lymph node dissection, and urban-rural code, HS had a 71% increased risk of treatment delay (OR 1.71, CI 1.23-2.38) for all stages of disease. In the same model, NHB race was independently predictive of decreased use of adjuvant treatment for FIGO stage II and higher (OR 1.32, CI 1.04-1.68). NHB race, number of perioperative complications, and non-endometrioid histology were predictive of worse OS in univariate models. Treatment delay was not independently predictive of worse 1- or 5-year survival at any stage. Conclusions: NHB race is predictive of worse 5-year survival across all stages and is also associated with omission of adjuvant treatment in ≥FIGO Stage II high grade endometrial cancers. HS ethnicity was associated with treatment delay across all stages. In unadjusted analyses, patients who experience treatment omission or delay experienced poorer OS, but these factors were not independently associated in multivariate analyses.
ALDH1 expression in primary and recurrent vulvar carcinoma.
Authors: Abdullaeva Nina M. , Verenikina Ekaterina V. , Zlatnik Elena Yu. , Ulianova Elena P. , Novikova Inna A. , Sagakyants Aleksandr B. , Menshenina Anna P. , Adamyan Meri L.
Published: June 2021

e17573

Background: Our aim was to evaluate ALDH1 expression as a stem cell marker in primary and recurrence vulvar squamous cell carcinoma. Methods: 27 patients aged 27-80 years with vulvar squamous cell carcinomas, together with their verified histopathological and clinical data were included in the study. All of them underwent treatment the first stage of which was surgery in National Research Centre for Oncology in 2015-2020. In 10 of them I stage of vulvar squamous cell carcinomas was diagnosed, in 13 – II stage, 4 had relapses after complex treatment and 2-10 years` remission. All paraffin-embedded samples of the primary and recurrent vulvar carcinoma were recruited. The presence of ALDH1 was detected by immunohistochemistry using murine monoclonal antibodies to ALDH1 (clone B-5 Santa Cruz Biotechnology) diluted 1:800 and Reveal Polyvalent HRP-DB Detection System. Positively stained cells were counted among all the tumor cells as well as a part of tumors positive for ALDH1 ( > 10% of cells). Statistics analysis was performed by program STATISTICA 13.0 (StatSoftInc., the USА). Results: By immunohistochemical staining, the expression of ALDH1 was observed in 5 patients with I stage of vulvar squamous cell carcinomas, in 5 patients with II stage and in all the patients with recurrence. Mean values of ALDH1 expression in patients with I stage were 14.1±4.3%, in patients with II stage – 16.0±3.6%, in patients with recurrence – 29.6±3.6%. Maximal ALDH1 accumulation was observed in tumor cells of patients with recurrence, it was 1.9 times higher than in the II stage (p = 0.03) and 2.1 times exceeded ones of the I stage (p = 0.027). All the differences were statistically significant according to Student`s t-test (p < 0.05). The was no statistically significant difference between values of the patients with I and II stages (p = 0.738), but it is noteworthy that ALDH1-expressing cells prevailed in tumor stroma especially in II stage. Conclusions: There is some discrepancy in the assessment of ALDH1 prognostic value in vulvar carcinoma patients as well as in understanding if it is related predominantly to cancer stem cells or to normal stem cells either. Our results though obtained on a few cases of vulvar squamous cell carcinomas show that ALDH1 expression in recurrent carcinomas markedly exceeds that in primary tumors and is related to tumor cells while in primary tumors is related rather to stromal cells.
Impact of ECOG performance status on recurrent/metastatic head and neck squamous cell carcinomas treated with anti-PD1 inhibitors.
Authors: Chalker Cameron , Wu Vicky , Voutsinas Jenna M. , Hwang Victoria , Baik Christina S , Liao Jay Justin , Lee Sylvia , Futran Neal D. , Houlton Jeffrey , Barber Brittany , Parvathaneni Upendra , Laramore George E. , Santana-Davila Rafael , Eaton Keith D. , Martins Renato G. , Rodriguez Cristina P.
Published: June 2021

e18004

Background: Anti-PD1 checkpoint inhibitors (ICI) represent an established standard of care for patients with recurrent/metastatic head & neck squamous cell carcinoma (RMHNSCC). Landmark studies excluded patients with ECOG performance status (PS) ≥ 2; the benefit of ICI in this population is therefore unknown. Methods: We retrospectively reviewed RMHNSCC patients who received at least 1 dose of ICI at our institution. Demographic data and clinical outcomes were obtained; the latter included objective response to ICI (ORR), physician-documented CTCAE grade 2+ toxicity (irAE), and any unplanned hospitalization within 100-days of last ICI dose (UH). Associations between demographic data and clinical outcomes were explored using both uni- and multivariate analysis. Overall survival (OS) was estimated using a Cox proportional hazards model; ORR, irAE, and UH were evaluated with logistic regression. This project was approved by our institutional IRB. Results: We identified 152 RMHNSCC patients who were treated with ICI between 1/2013 and 1/2019. ECOG PS was 0 in 42 (27%), 1 in 75 (50%), 2 in 27 (18%), 3 in 2 (1%), and unknown in 6 (4%) patients. The median age was 61 (range: 25 - 90). 124 (82%) were male, 124 (82%) were white, and 69 (45%) were never-smokers. The most common primary sites were the oropharynx (n = 59, 40%), oral cavity (n = 39, 26%), nasopharynx (n = 11, 7%), and larynx (n = 10, 6%). 54 (36%) were p16+ oropharynx cancers. CPS score was available in 10 (6.6%). Single agent ICI was received by 118 (77%) patients. 66 (44%) had a documented irAE and 54 (36%) had an UH. A multivariate model for OS containing PS, smoking status and HPV status showed a strong association between inferior OS and ECOG 2/3 compared to 0/1 (p < 0.001; HR = 3.30, CI = 2.01-5.41), as well as former (vs. never) smoking status (p < 0.001; HR = 2.17, CI = 1.41-3.35). Current smoking (p = 0.25) did not reach statistical significance. On univariate analysis, poor PS was associated with inferior ORR (p = 0.03; OR = 0.25, CI = 0.06-0.77) and increased UH (p = 0.04; OR = 2.43, CI = 1.05—5.71). There was no significant association between irAE and any patient characteristic. Conclusions: We observed inferior overall survival among ICI-treated RMHNSCC patients with ECOG 2/3 in our single-institution, retrospective series. Our findings help frame discussion of therapeutic options in this poor-risk population. Further study must be done to determine which interventions are of greatest benefit for RMHNSCC patients with declining performance status.
Analysis of outcomes and disposition in hospitalized patients with head and neck cancer over 15 years.
Authors: Guddati Achuta Kumar , Komiya Takefumi
Published: June 2021

e18021

Background: The care of hospitalized head and neck cancer patients often involves a multidisciplinary approach. The trends, outcomes and disposition in hospitalized patients with head and neck cancer in United States for the past two decades has not been well characterized. This retrospective study involves analysis of the demographics, outcomes and disposition of these patients and their trend over 15 years. The presence of medical comorbidities and the relationship to inpatient mortality was also studied. Methods: Hospitalization data from the National Inpatient Sample database was analyzed for the years: 2000 to 2014. Patients with head and neck cancer were identified using ICD-9 codes. Demographic features such as age, gender, race, geographical location, hospital size, hospital location, insurance etc. were analyzed. The trend of mortality was analyzed for the study period of 15 years. A sub-analysis of associated comorbidities was also performed in patients who have died during hospitalization. Univariate analysis was initially performed followed by multivariate analysis and logistic regression to identify risk factors associated with mortality. Results: An estimated 145,262 hospitalizations involving patients with head and neck cancer from 2000 to 2014 were studied and it showed a gradual yearly increment in hospitalization. 41% of the hospitalizations were in the 50-64 years age group. There was a 2:1 male preponderance. Caucasians constituted 60% followed by African Americans at 10%. A majority of the hospitalizations occurred in large sized hospitals and urban teaching hospitals. The mean length of stay was 6.4 days but 38% of the hospitalizations involving 2-5 days of stay. The inpatient mortality rate was 4.6% and it down trended over the past 15 years with statistical significance (p < 0.05). Inpatient mortality was highest in the > 80 years age group. Of note, inpatient mortality was equal between both the genders. Mortality was highest in the groups with a length of stay below 2 days and above 11 days. 58% of the discharges did not need any special services while 21% of the discharges involved home health care. The most common comorbidities were smoking and hypertension while < 1% of morbid obesity was observed. Multivariate analysis showed malnutrition, ESRD, cirrhosis, stroke and CHF were significant risk factors (ORs: 1.6, 1.94, 2.18, 2.2 and 1.78 respectively). Conclusions: Mortality in hospitalized patients with head and neck cancer has improved over the past 15 years. Inpatient mortality was high in the very elderly and in female patients (compared to the male preponderance upon admission). Malnutrition, cardiac/liver/renal dysfunction and stroke were significant risk factors for inpatient mortality. Strategies to mitigate inpatient mortality in these patients need to factor the above risk factors during their in-hospital management.
Survival outcomes in primary angiosarcoma of the head and neck: A systematic review and meta-analysis.
Authors: Zayed Sondos , Lin Cindy , Boldt Gabriel , Lang Pencilla , Read Nancy , Venkatesan Varagur , Sathya Jinka , Kevin Fung , MacNeil Danielle , Mendez Adrian , Yoo John , Warner Andrew , Nichols Anthony C. , Palma David A.
Published: June 2021

e18039

Background: Angiosarcoma of the head and neck (ASHN) is a rare entity and confers substantial morbidity and mortality. Yet, the optimal management of ASHN remains unclear. This study aimed to describe the epidemiology of ASHN and to identify the most favorable treatment approach. Methods: We performed a systematic review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, using the PubMed (Medline), EMBASE, and Cochrane Library databases, queried from 1990 until present. Articles in the English language reporting on survival outcomes of adult primary ASHN treated with curative-intent, were included. All estimates were weighted based on sample size. Analysis of variance (ANOVA) and two-sample t-tests were used as appropriate. This study was registered with PROSPERO, CRD42021220970. Results: A total of 3652 studies were identified, with 14 articles reporting on 2265 ASHN patients, meeting inclusion criteria. Mean ± SD age was 70.6 ± 7.7 years with 1621 (66.6%) men and 812 (33.4%) women. ASHN involved the scalp (n = 176, 57.9%) and the face (n = 128, 42.1%). 249 patients had early stage I-II disease (39.6%) whereas 379 had late stage III-IV disease (60.4%). Most (n = 529, 45.6%) received surgery and radiotherapy (RT), 305 (26.3%) received surgery alone, 210 (18.1%) received definitive RT/chemoradiotherapy (CRT), 75 (6.5%) received surgery and CRT, and 33 (2.8%) received surgery and chemotherapy. Negative margins were achieved in 471 (55.9%) whereas 371 (44.1%) had positive margins. Mean ± SD follow-up was 41.7 ± 15.4 months. Weighted mean, 1-, 5-, and 10-year overall survival (OS) were 26.9 months, 67.3%, 30.6%, and 20.8% respectively. Mean and 5-year disease-specific survival (DSS) were 72.9 months and 50.3% respectively. Mean ± SD local recurrence rate (LRR) was 32.1 ± 11.7%. Median RT dose delivered was 60 Gy (interquartile range: 60-70). Patients who received surgery had a significantly higher mean OS (34.9 vs. 18.7 months, P = 0.04) and 5-year OS (30.1 vs. 14.2%, P = 0.01) compared with those who did not receive surgery. There was no significant difference in mean OS for receiving adjuvant chemotherapy (P = 0.99) or RT (P = 0.51). Conclusions: In the largest ASHN study to date, definitive surgical resection was associated with an improvement in OS. Multimodality treatment did not confer an OS benefit. Randomized trials are needed to establish the optimal treatment approach for ASHN.
A comparison of the burden of thyroid cancer amongst European Union 15+ countries, 1990-2017: Estimates from the Global Burden of Disease Study.
Authors: Schuster-Bruce James , Jani Chinmay , Goodall Richard , Kim Dae , Hughes William , Salciccioli Justin D , Marshall Dominic C , Shalhoub Joseph
Published: June 2021

e18048

Background: The global incidence of thyroid cancer has been increasing rapidly and this has an attendant burden on health-systems. The Global Cancer Observatory reported an estimate of 567,233 new cases of thyroid cancer and 41,071 deaths in 2018. The objective of this study is to observe the trends in mortality, incidence and disability-adjusted life years (DALYs) from thyroid cancer between 1990-2017 in European Union (EU) 15+ nations. Methods: We extracted thyroid cancer mortality data from the Global Burden of Disease Study database based on the International Classification of Diseases versions 10 and 9. Age-standardised incidence rates (ASIR), age-standardised mortality rates (ASMR) and disability-adjusted life years (DALYs) were extracted for individual EU15+ countries per sex for each of the years 1990-2017, inclusive, and mortality-to-incidence indices (MII) were computed. Joinpoint regression analysis was used to describe trends. Results: Between 1990 and 2017, thyroid cancer ASIRs increased in all EU15+ countries for males, and in 15/19 countries for females. We identify ASIR to have plateaued in the majority of nations in the time period covered by the most recent trends. 16/19 countries observed decreasing ASMRs. Australia showed the highest increasing trends in both males (+19.2%) and females (+7.5%). The greatest decreases were seen in Belgium (-63.3%) for females and Austria for males (-34.9%). For both sexes, the MIIs decreased in all EU15+ countries. The smallest reductions were observed in the US (-22.4%) and Denmark (-22.4%) for males, and the US (-30.6%) for females. Variable directions of trends in DALYs were observed. Increasing DALYs for both genders were observed in the US and Australia. In 2017, highest ASIR was seen in Luxembourg for males (5.89/100,000) and Italy for females (8.81/100,000), highest ASMR was seen in Luxembourg for males (0.69/100,000) and females (0.53/100,000), highest MII was observed in Portugal for males (2.60/100,000) and in Finland for females (0.10/100,000) and, highest DALY was observed in Luxembourg for males (17.77/100,000) and Greece for females (16.69/100,000). Conclusions: Overall, we report EU15+ countries to be managing the burden of thyroid cancer, as evidenced by plateauing incidence rates and reductions in mortality and DALYs over the 28-year study period. However, some EU15+ countries, including the United States, demonstrate unfavorable ASMR and DALY trends. Ongoing vigilance is required to ensure changes in clinical practice and risk factor prevalence do not negatively impact on DALYs and mortality.
Characteristics of patients with lymphoma presenting initially as a neck mass referral to otolaryngology.
Authors: Lynch Andrew , Anderson Meredith , Kshirsagar Rijul , Baer David M. , Lo Joan C. , Glide Jason , Wang Kevin H.
Published: June 2021

e18054

Background: Lymphomas that present initially as a neck mass can be challenging to diagnose as their onset is often insidious, frequently without classic symptoms, and fine-needle aspiration has limited utility for diagnosis. Understanding their clinical presentation may facilitate recognition and diagnosis, essential for timely treatment of aggressive lymphoma subtypes. Methods: Using data from a large integrated healthcare delivery system, adults aged 18-89 years without known previous cancer who were referred to Head and Neck Surgery for evaluation of a “neck mass” in 2017 were identified. Among the subset of 205 patients found to have malignancy, 76 had lymphoma (N = 69) or leukemia (N = 7) and 129 had a non-lymphoma/leukemia malignancy. The demographic characteristics of patients with and without lymphoma/leukemia were compared. Among the 69 with lymphoma, tumor histology and stage were examined. Differences between subgroups were compared using Chi-squared, Fisher’s exact, Student’s t-test, F-tests, and Tukey’s range tests for pairwise comparison. Results: Among 205 patients identified with a malignant neck mass, 76 (37%) were diagnosed with lymphoma/leukemia. Patients with lymphoma/leukemia were more likely to be female (47% vs. 27%, p = 0.003) and under age 50 years (36% vs. 13%, p = 0.001). There were no statistically significant differences in race, smoking status, or BMI between the two groups. Among the lymphoma/leukemia subset, 18 (24%) had Diffuse Large B-Cell Lymphoma (DLBCL), 13 (17%) had Follicular Lymphoma (FL), and 25 (33%) had Hodgkin’s Lymphoma (HL). The HL subset was significantly younger than both the FL and DLBCL subsets (mean age 41.6 years vs. 62.2 and 66.6, p < 0.001). A range of findings was seen when examining sex (72%, 44% and 46% male), race/ethnicity (60%, 72% and 69% non-Hispanic White), smoking status (36%, 33% and 62% current/former) and tumor stage at presentation (52%, 50% and 69% late stage (III-IV)) for HL, DLBCL and FL subtypes, respectively, but the differences were not statistically significant in these smaller subsets. Conclusions: Significant differences in baseline characteristics exist between lymphoma and non-lymphoma patients presenting with a malignant neck mass. Notably, the lymphoma subset was younger and, except for those with HL, did not demonstrate a male predominance. Within the lymphoma subset, HL patients were significantly younger than patients with other lymphoma subtypes. Further studies in a larger population identifying demographic differences by cancer subtype may inform efforts to prevent diagnostic delays in head and neck lymphoma. Characterizing the diagnostic pathway is also needed to quantify room for improvement in the treatment approach of patients with neck mass considered at higher risk for lymphoma.
Rural health cancer care: A literature review.
Authors: Swenson Wade T. , Westergard Emily , Swenson Abigail Paige
Published: June 2021

e18500

Background: A recent review of the medical literature of rural health cancer care delivery has not been published. We conducted a preliminary review of the last twenty years of rural health cancer care delivery literature utilizing medical subject headings (MeSH) within the PubMed NCBI) database. Methods: Using PubMed MeSH Major Topic terms “rural population” and “cancer” we identified publications published from 2000 to 2020. We searched PubMed for publications that included the major topic MeSH terms “rural population” and “cancer”. We individually reviewed articles, confirmed the focus of the article, and subcategorized the articles. Results: We identified 580 publications which met the search criteria, the majority were focused on the United States (266), followed by China (56), Australia (54), and India (27). Among the publications focusing on the United States, 76 involved Appalachian States. Kentucky (18) and Georgia (10) were the states most frequently represented. Malignancies most commonly represented were: breast cancer (148), uterine/cervical (84), and colorectal cancers (68). The journals which published the most rural health cancer care delivery were The Journal of Rural Health (42), Asian Pacific Journal of Cancer Prevention (20), Cancer (14), Rural and Remote Health (13), Journal of Cancer Education (13), Australian Journal of Rural Health (12). Conclusions: The rural health cancer care literature in the last two decades focuses primarily on the United States, China, Australia, and India. Within the United States, the research focus is Appalachia. The majority of articles focus on breast cancer, uterine/cervical, and colorectal cancers. The journal which published the majority of rural health cancer care articles was the Journal of Rural Health.
Willingness to travel for CAR-T: A choice-based conjoint analysis.
Authors: Frosch Zachary AK , Namoglu Esin C. , Mitra Nandita , Landsburg Daniel Jeffrey , Nasta Sunita , Shea Judy , Bekelman Justin E. , Guerra Carmen E. , Schapira Marilyn M.
Published: June 2021

e18503

Background: Chimeric antigen receptor T-cell therapy (CAR-T) is a novel therapy only available at specialized centers. Because patients prefer treatment close to home and provider continuity, preferences may result in unequal access. Sharing follow-up (f/u) with a local provider could increase willingness to travel, but its appeal to patients is unknown. Methods: We conducted a choice-based conjoint analysis to determine the clinical and care delivery factors that patients with diffuse-large B cell lymphoma (DLBCL) value when deciding whether to travel for CAR-T. We recruited from 13 sites within an integrated health system and asked participants to make choices between 12 pairs of treatment options that varied on 5 attributes: travel time, oncologist continuity, whether shared f/u was offered, two-year overall survival (OS), and intensive care unit (ICU) admission rate. Preferences for specific attributes were determined using a generalized estimating equation model with treatment choice as the outcome and the attributes as the variables. Each attribute’s coefficient (importance weight [IW]) represented its value to participants: higher IWs indicated greater value; negative IWs indicated undesirable attributes. Results: We invited 489 patients and 303 (62%) responded. IWs ranged from -0.56 to 1.15 (total cohort) and -2.83 to 2.50 (when modeled by race). Treatments at cancer centers ≥60 minutes away were valued less than those 30 minutes away without collaborative f/u; but were desirable if shared f/u care was offered (Table). Black respondents valued treatments ≥60 minutes away less despite shared f/u care. Participants also valued oncologist continuity (IW 1.15 [0.99, 1.32]), greater OS (IW 0.71 [0.63, 0.79] per 5 percentage point increase), and lower ICU admission rates (IW -0.21 [-0.25, -0.17] per 5 percentage point increase). Oncologist continuity was more highly valued by Black than by White respondents (IW 2.50 [1.74, 3.27] vs 1.09 [0.92, 1.25]). Conclusions: Patients with DLBCL are more likely to select CAR-T therapy at distant cancer centers if f/u care is shared locally. This could represent a strategy to expand access to CAR-T. Travel remains a barrier for Black patients despite shared f/u, suggesting the need to investigate targeted strategies that promote equitable access to CAR-T. [Table: see text]
COVID-19 communication to English- and Spanish-speaking cancer patients: A website analysis of seven healthcare systems in north Texas.
Authors: Higashi Robin T. , Sweetenham John W. , Israel Aimee D. , Tiro Jasmin A.
Published: June 2021

e18515

Background: The COVID-19 pandemic created an urgent need for timely and accurate public health information. This is especially true for those with cancer because they face higher morbidity and mortality from COVID-19. At the same time, the disproportionate impact of the pandemic on Latinx populations underscores the need for information to reach Spanish-speakers. Given the large proportion of Spanish-speakers in the U.S., healthcare institutions have a professional and moral obligation to meet this critical need. Methods: We conducted a multi-modal, mixed method document review study to evaluate the equity of online information about COVID and cancer available to English- and Spanish-speakers from seven north Texas healthcare institutions. We sampled 50 websites (33 English, 17 Spanish) over a one-week period in May 2020. Websites included 27 healthcare institutions and 23 external organizations (e.g. CDC). Thematic content was analyzed using a coding conversion process; literacy level was measured using Readability software; accessibility was measured using the Patient Education and Materials Assessment Tool (PEMAT); and video and diversity content were defined and counted. Results: Content on Spanish websites was sub-optimal compared to English. We observed significant differences in thematic content, poor linkage to external Spanish content, and errors in translation. Whether differences were intentional was unclear. Across all sites, content specifically about COVID and cancer was more prevalent in English than Spanish (58% vs. 43%). Three institutions’ websites contained no information about COVID specifically for cancer patients, and three institutions included only a banner link to COVID updates or information from their main oncology page. Only one institution’s website included comprehensive COVID-related information specifically for cancer patients, such as postponing treatment, oral cancer treatments, and extra assurances taken for protection during in-person care; however, this website was available in English only. Spanish websites scored on average at a lower literacy level than English (11th vs. 13th grade). Using the PEMAT, healthcare institutions’ average accessibility of Spanish pages (n = 7) was slightly lower than that of English pages (n = 19) (77% vs. 81%, respectively), due mostly to discrepancies in English-only videos and visual aids; conversely, among external organizations’ websites, the average accessibility score of Spanish pages (n = 10) was higher than that of English pages (n = 13) (86% vs. 83%, respectively). Conclusions: In one region, Spanish-speakers lack equitable access to information about COVID-19 and cancer compared with English-speakers, leaving an already vulnerable patient population at greater risk for poor health outcomes. We offer recommendations for enhancing equity of access to information.
Racial distribution of clinical trial participants in the United States.
Authors: Patel Monaliben , Hess Lisa M. , Su Eric Wen , Li Xiaohong , Bruno Debora S.
Published: June 2021

e18516

Background: Lack of diverse representation in clinical trials negatively impacts the cancer survival of patients and populations unaccounted for in clinical research. Efforts such as the 1993 NIH Revitalization Act have focused on improving the diversity of trial participants in the US. This retrospective study evaluated the racial distribution of oncology clinical trial participants using data published in clinicaltrials.gov from Jan 2010 through Dec 2020. Methods: I2E of Linguamatics (IQVIA, Inc), a natural language processing software, was used to identify participant race in oncology trials. Data extracted included trial identifier, year of completion, sponsor, cancer type, and race. Studies were limited to academic, cooperative group and government studies headquartered in the US. Clinical trial results were compared to the racial distribution of SEER 2010 data using z-test. Results: Data from 35,686 patients (14,220 enrolled to 236 phase 2 and 21,471 enrolled to 47 phase 3 trials) were available for analysis. A summary by race is provided in the Table, excluding unknown, which represented 8.5% of phase 2 and 3.5% of phase 3 trials. The proportions of white/black patients enrolled to phase 2 and phase 3 trials beginning in 2010-12 were 84.4%/11% and 83.1%/9.9%, respectively (total enrollment 84.9%/9.6%). For trials beginning in 2015-17, white/black enrollment represented 88.5%/8.1% of patients enrolled to phase 2 and 86.4%/10.1% of patients in phase 3 trials. Black patients represented 9.6% of all trial participants, in contrast with the SEER data where 12% of all patients were black (p < 0.001). For lung cancer trials, black participants represented only 7.9% of all trial participants whereas in breast cancer trials, 10.2% of participants were black, versus the SEER data specific to these tumor types (black patients represent 10.9%/11.5% of lung/breast cancer diagnoses between 2013 to 2017, both p < 0.01). Conclusions: This study suggests that over the past decade most races (other than white) have been significantly underrepresented in US oncology clinical trials, and is even more pronounced for black patients with lung cancer. Based on this analysis, there is no evidence that trial enrollment distribution, particularly of white versus black participants, has changed since 2010. Data are limited to the relative lack of studies reporting results that began enrollment after 2017. These findings suggest that the development of new strategies to improve the recruitment of racial minorities to oncology clinical trials are warranted.[Table: see text]
Relationship between insurance status and diagnosis of cutaneous immune-related adverse events.
Authors: Chang Michael , Krasnow Nira A. , Blum Amy E. , Pahalyants Vartan , Murphy William S. , Yoon Jaewon , Reynolds Kerry Lynn , Thompson Leah L. , Chen Steven T.
Published: June 2021

e18535

Background: Cutaneous immune-related adverse events (cirAEs) are among the most common side effects of immune checkpoint inhibitor (ICI) therapy. While insurance status has been shown to influence outcomes in patients treated with ICIs, its impact on cirAE management remains underexplored. We therefore evaluated insurance status in patients with cirAEs, examining its effect on rate of and time to cirAE diagnosis. Methods: Using billing data, we retrospectively identified patients who initiated anti-PD-1/PDL-1 and/or anti-CTLA-4 therapy at Massachusetts General Hospital between January 1, 2016 and March 8, 2019 (n = 2,459) for possible cirAE. Eligible cirAEs included reactions attributed to ICI by the clinician, consistent with established morphologic categories. For each patient with confirmed cirAE (n = 358), we abstracted oncologic history, cirAE features, and insurance status. Associations between insurance and cirAE diagnosis outcomes were assessed via logistic and linear regression, and adjusted for age, sex, race, ICI type, cancer diagnosis, cirAE type, and significant covariates ( P< 0.05). Results: Of the 2,459 patients who received ICIs, 2,419 (98.4%) had documented insurance status. Most ICI recipients had Medicare (n = 1,119; 46.3%) or private insurance (n = 1,156; 47.8%) relative to Medicaid (n = 104; 4.3%) or other government insurance (e.g. Tricare) (n = 40; 1.7%). We found that 358 (median age 64 years, 40.5% female) developed a cirAE. Among cirAE patients, 175 had Medicare (48.9%), 174 had private insurance (48.6%), 6 had Medicaid (1.7%), and 3 had other government insurance (0.8%). The most common cirAEs across insurance types were maculopapular rash, pruritus, and eczematous and lichenoid eruptions. In the multivariable analysis, ICI patients with Medicare insurance had a higher rate of cirAE diagnosis (adjusted odds ratio: 2.41, 95% CI: 1.00, 5.90, P= 0.05) relative to Medicaid patients. In addition, in terms of time to cirAE diagnosis at dermatology visit, Medicare insurance was associated with longer delays, with a linear regression coefficient of 132.2 (95% CI: 4.78, 259.6; P= 0.04). No significant associations were found between other insurance types and cirAE diagnosis outcomes. Conclusions: Our study shows that patients with Medicaid are less likely to be diagnosed with cirAE relative to those with Medicare, despite delays in diagnosis, when controlling for all other demographic/oncologic factors. Ultimately, these findings are reassuring that despite insurance differences, patients with cirAEs are receiving suitable care and appropriately seen by dermatologists. As insurance coverage for specialists can vary widely, these initial findings are a promising indicator that patients with cirAEs are well-connected within healthcare systems.
Kaposi sarcoma among adults enrolling for HIV care in a large HIV clinic in Nigeria: 2006-2017.
Authors: Akanbi Maxwell Oluwole , Bilaver Lucy , Achenbach Chad , Hirschhorn Lisa , Agbaji Oche , Murphy Robert , Adekolujo Samuel O
Published: June 2021

e18539

Background: Expanded access to antiretroviral therapy (ART) has led to a dramatic decline in Kaposi sarcoma (KS) among people initiating HIV care globally. In Nigeria, the country with the second-largest global HIV population, ART coverage increased from 11% in 2006 to 57% by 2017. The impact of Nigeria’s ART expansion of KS risk is unclear. We examined trends in KS risk among patients enrolled for HIV care in a large clinic in Nigeria from 2006-2017. Methods: We analyzed data of 16,431 adults (age ≥18 years) enrolled for HIV care from January 1, 2006, to December 31, 2017, in a large clinic in Jos, Nigeria. KS at enrollment was defined as KS recorded in the electronic health record within 30 days of clinic enrollment. Time trends were compared among three periods: 2006-2009, 2010-2013, and 2014-2017 (Mean national ART coverage 16%, 33%, and 50% respectively), using the Chi-test trend test and logistic regression models to identify factors independently associated with KS. The study was approved by the local institutional Institutional Review Board (IRB) and ruled exempt by the IRBs of Northwestern University and Harvard School of Public Health. Results: The study population had a mean age 35.1 (standard deviation, SD 9.5) years, and were 65.7% female (n= 10,788). The median first CD4 cell count was 192 (IQR 84-320), 215 (IQR 98-344), and 222 (IQR 94-353) in 2006-2009, 2010-2013, and 2014-2017, respectively. The overall KS prevalence at entry was 0.59 % (95% CI 0.48-0.72). KS prevalence was lowest for patient entering care during 2006-2009 (0.39%, 95% CI 0.29-0.53), increased to 1.12% (95% CI 0.82-1.52) in 2010-2013 and declined to 0.72% (95% CI 0.42-1.20) from 2014-2017 (Chi2 for trend, 12.14, p<0.01). Adjusting for age, sex, and CD4 T-cell count KS prevalence was significantly higher in 2010-2013 compared to 2006-2009 (Table). Conclusions: Despite ART expansion, KS at enrollment showed no significant decline. The low CD4+ cell count, across all periods, indicates delay in enrollment for HIV care, which increases KS risk. Interventions aimed at early HIV diagnosis and linkage to ART are critical to KS risk reduction in this population.

Factors associated with Kaposi sarcoma at HIV care enrollment in Jos, Nigeria (2006-2017).[Table: see text]