bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of obesity on treatment and outcomes in ovarian cancer by race/ethnicity.
Authors: Martin Alexandra , Mallen Adrianne Rose , Sinha Sweta , Wells Ali , Cline Kathryn , Lam Clarissa , Peres Lauren , Chern Jing-Yi 
Published: May 2020

e18067 Background: Concern for toxicities in obese ovarian cancer patients may limit weight-based chemotherapy dosing, which has been associated with poor survival. We sought to evaluate the impact of obesity on treatment and outcomes by race/ethnicity at a National Cancer Institute (NCI)-designated Comprehensive Cancer Center (CCC). Methods: 66 minority (non-Hispanic black, Hispanic) epithelial ovarian cancer patients diagnosed 2006 and treated with frontline chemotherapy were frequency matched to two non-Hispanic white (NHW) patients by 5-year age group and stage (n = 198). For frontline carboplatin, relative dose intensity (RDI) was calculated by dividing the dose received by the expected dose, with an RDI < 0.85 indicating carboplatin dose reduction. Patient characteristics and RDI were compared by obesity and race/ethnicity. Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between obesity, race/ethnicity and RDI with mortality, adjusting for confounders. Results: Minorities were more likely to be obese, underinsured, and to experience delays in chemotherapy compared to NHW. Compared to normal/overweight patients, obese patients were more likely to experience carboplatin under dosing in the neoadjuvant (p = 0.004) and adjuvant (p < 0.0001) setting, but there were no differences in RDI by race/ethnicity or toxicities. No association with survival was observed for dose reduction and BMI. Compared to NHW, minorities had similar survival in the first 4 years after diagnosis (HR = 0.99, 95% CI = 0.60-1.63), but an increased risk of mortality > 4 years after diagnosis (HR = 4.07, 95% CI = 1.92, 8.60). Conclusions: Even though minorities were more likely to be obese, there were no differences in dosing by race/ethnicity at an NCI CCC. Minorities had similar survival to NHW in the first 4 years after diagnosis, likely due to similar access to quality care at an NCI CCC. However, > 4 years after diagnosis, the racial/ethnic survival disparity persisted after adjustment for clinical and pathologic characteristics. Expansion of this work to other patient populations may help determine if findings are similar outside of a tertiary care center.
The role of imaging in early detection of patients at risk for neuropathy during primary chemotherapy for ovarian carcinoma.
Authors: Bell Sarah , Dalton Liam , Derstine Brian , Ross Brian , Sullivan June , Wang Stewart , Uppal Shitanshu , Siedel Jean 
Published: May 2020

e18071 Background: Neuropathy is a common adverse event requiring dose reduction or regimen change in patients receiving platinum-taxane chemotherapy for ovarian cancer. Our aim was to determine whether specific biomarkers, such as skeletal muscle, visceral and subcutaneous fat cross-sectional areas, measured using computerized tomography (CT), were associated with the development of neuropathy. Analytic Morphomics, a semi-automated image analysis method, has been used to predict oncologic outcomes with immunotherapy and to identify patients at higher risk for postoperative complications from major cancer surgeries. We hypothesized that patients who required dose reductions or regimen changes would have CT imaging findings that distinguished them from their counterparts who did not require dose reduction or regimen change. Methods: All patients at our institution diagnosed with high-grade ovarian carcinoma between January 1, 2014 and December 31, 2018 were identified retrospectively. Analytic Morphomics was used to extract measures of body composition from CT images at the level of the third lumbar vertebra. Demographic and clinical characteristics were abstracted from the electronic medical record. We analyzed several binary outcomes (neuropathy, delay in chemotherapy, or dose reduction by cycle 1, 3 or 6) and used unpaired, two-tailed t-tests to compare means between each outcome group at each timepoint. Results: Of 156 patients screened for the study, 138 patients were included and had pre-treatment CT scans available and completed six cycles of platinum-taxane chemotherapy. Patients who developed neuropathy in any of the six cycles, or had a change in their chemotherapy regimen by cycle six, had higher mean visceral fat area than those who did not develop neuropathy. This finding was statistically significant throughout three cycles (p = 0.023) and six cycles (p = 0.030). Conclusions: Increased visceral fat on CT imaging was significantly associated with a higher incidence of neuropathy and change in chemotherapy regimen in patients undergoing primary platinum-taxane chemotherapy for ovarian carcinoma. Weight and BMI did not have a significant association with development of neuropathy, dose reduction, or treatment delay. Further study is needed to determine if dose reductions or regimen changes due to neuropathy can be better predicted using morphomics.
Defining the tumor cell: CA-MSC interactions which mediate ovarian cancer metastasis.
Authors: Goldfeld Ester , Atiya Huda , Frisbie Leonard , Coffman Lan Gardner 
Published: May 2020

e18072 Background: Carcinoma-associated mesenchymal stem cells (CA-MSCs) are mesenchymal stem cells (MSCs) within the tumor microenvironment (TME). We demonstrated that CA-MSCs promote ovarian cancer chemotherapy resistance through paracrine signaling with ovarian cancer cells, interact with ovarian cancer cells to form mixed-cellularity complexes which enhance metastasis, and arise from cancer cell and TME reprogramming of normal tissue MSCs. To identify mediators of the CA-MSC:tumor cell interaction, we investigated the role of tetraspanins, which are membrane-spanning proteins that have been implicated in cancer development and metastasis by influencing cell adhesion and cell-cell interactions. The tetraspanins CD9, CD81, CD151, and CD63 were identified as potential mediators of cell surface interactions between ovarian cancer cells and CA-MSCs through homo- and heterodimerization. Methods: Td-labeled OVCAR3 cancer cells were co-cultured with 3 patient-derived MSC (derived from normal tissue) and 3 patient-derived CA-MSC (derived from malignant tissue) cell lines. Flow cytometry was performed to measure surface protein expression of the tetraspanins CD9, CD81, CD151, and CD63, and was compared to control cells (not co-cultured) and their median fluorescence intensity (MFI). We next separated OVCAR3 cells co-cultured with MSCs or CA-MSCs using fluorescent activated cell sorting (FACS) based on Td expression. Following FACS, tetraspanin expression in OVCAR3 cells, MSCs, and CA-MSCs was assessed via qRT-PCR and western blotting, and compared to cell lines that were not co-cultured. Results: Flow cytometric analysis revealed an increase in MFI of CD9 and CD151 in co-cultured OVCAR3 cells, as well as CD81 and CD63 in co-cultured CA-MSCs and MSCs when compared to non-co-cultured matched cells. Increased RNA expression of CD9, CD151, and CD63 was seen in OVCAR3 cells that were co-cultured with CA-MSCs or MSCs when compared to non-co-cultured OVCAR3 cells. Increased RNA expression of CD81 and CD63 was noted in both co-cultured CA-MSCs and MSCs compared to non-co-cultured cells. Lastly, western blotting demonstrated increased protein expression of CD9 and CD151 in co-cultured OVCAR3 cells, as well as CD81 and CD63 in co-cultured CA-MSCs and MSCs compared to non-co-cultured matched cells. Conclusions: These results indicate that direct interactions between OVCAR3 cells and CA-MSCs or MSCs lead to overexpression of specific tetraspanins at the RNA and protein levels, implying that they may be facilitating tumor cell:CA-MSC and tumor cell:MSC binding.
Biomarker lead time for predicting progression in women with ovarian cancer compared to imaging.
Authors: Samborski Alexandra , Blackman Alexandra Michelle , Miller Michael Craig , Eklund Elizabeth , Messerlian Geralyn , Moore Richard G. 
Published: May 2020

e18074 Background: Both CA125 and HE4 are biomarkers used to monitor women diagnosed with epithelial ovarian cancer (EOC). When these biomarkers increase and suggest progression of disease, imaging is frequently obtained for further assessment and confirmation. This study aims to assess how far in advance these biomarkers begin to trend upwards in comparison to the radiographic evidence of disease progression. Methods: This was an IRB approved retrospective trial. Residual longitudinal serum samples drawn for serum CA125 levels during treatment and monitoring from women with EOC were obtained. The samples were drawn every 3-5-weeks for patients on chemotherapy and every 3 months while monitoring. Serum CA125 and HE4 levels in the residual sera were analyzed at each time point. Imaging data was collected for each patient. Patients were included if either HE4 or CA125 was a marker for their disease. For each patient, the date of time point when the biomarker started to trend upward was identified and the date of radiographic evidence of progression was determined. The lead time (in days) for elevation of both CA125 and HE4 prior to evidence of radiographic progression was determined for each patient. Results: A total of 48 patients undergoing 58 treatment and monitoring events were identified. Each had evidence of disease progression by CA125 levels, HE4 levels, and computed tomography (CT). CA125 was the first biomarker to trend upward for 9 events (15.5%), HE4 was the first biomarker for 10 events (17.2%), and both increased simultaneously for 39 events (67.2%). Mean lead time for CA125 elevation prior to progression on imaging was 60 days (95% CI: 43 - 78, median = 44, range = 0 - 386). For HE4, mean lead time was 66 days (95% CI: 48 – 83, median = 46, range = 0 - 386). There was no significant difference in the average lead times between the two biomarkers (p < 0.01). Conclusions: When used for EOC monitoring both CA125 and HE4 have similar average lead times (~2 months) prior to the detection of progressive or recurrent disease by CT imaging.
Malignant MIXED mullerian tumors and serous endometrial cancer: Molecular targets the need of the hour.
Authors: Shah Manan , Jain Sanjay R , Oprea Gabriela , Shafi Saba 
Published: May 2020

e18106 Background: Malignant Mixed Mullerian Tumors (carcinosarcomas) and serous variants are rare but aggressive endometrial cancers which constitute less than 5 percent of uterine tumors. Our aim was to understand the clinical and molecular features of these variants which could aid us in further management. Methods: We retrospectively reviewed cases of carcinosarcomas and serous endometrial cancers at our institution over a period of 5 years. A total number of 28 cases were identified. Baseline clinical characteristics, treatment parameters including adjuvant chemo-radiotherapy and disease status at one year follow up were noted. Molecular markers included hormone receptor status (ER/PR), p16, p53, Her-2/neu, and the MMR gene panel (MLH1, PMS2, MSH2, MSH6). Results: The mean age for carcinosarcomas was 66 ± 12 years and for serous tumors 71± 8 years. The mean BMI of patients with carcinosarcoma was 32±7 kg/m2and serous tumors was 32±4 kg/m2. African American and Hispanic females were the predominant race. FIGO stage 1 at presentation constituted 75% in patients with carcinosarcomas while FIGO stage 3 and 4 constituted 62 % in serous variants. All our patients underwent surgery (TAH/BSO or debulking) followed by adjuvant chemotherapy/radiation or both. At 1 year follow up post treatment only 33% patients with carcinosarcomas and 12% with serous tumors had stable disease. Remaining patients showed progression or new metastasis to lung, peritoneum, retroperitoneum and vaginal vault. Molecular studies revealed ER+ in 41% and PR + in 33% with carcinosarcomas and 43% and 31% with serous tumors respectively. All patients with carcinosarcomas were Her-2/neu negative while 25 % were positive in serous tumors. 88% cases were strongly positive for both p53 and p16 in the serous variant. All patients showed an intact MMR gene panel. An interesting observation was that all patients with stable disease at 1 year follow up were ER/PR+ and Her-2/neu negative. Conclusions: Overall survival of these variants remains poor. Biomarkers such as p16, p53, Her-2, MMR panel and hormone receptors have become indices for individualization of treatment and further studies using targeted agents are warranted.
Clinicopathologic and protein markers distinguishing POLE and copy-number low group in endometrial cancer.
Authors: Kim Kidong , Hwangbo Suhyun , Park Taesung , Kim Hyojin , Kim Yong Beom , No Jae Hong , Suh Dong-Hoon , Kim Ju-Hyun 
Published: May 2020

e18110 Background: Requirement of DNA sequencing to diagnose POLE group is a barrier for adoption of molecular subtyping in endometrial cancer. We aimed to identify clinicopathologic and protein markers distinguishing POLE and copy-number (CN) low group in endometrial cancer. Methods: Ninety-one samples (POLE: 15, CN low 76) classified as POLE or CN low groups by integrative clustering were selected from The Cancer Genome Atlas endometrial cancer dataset. Clinicopathologic variables and normalized reverse phase protein array expression data were extracted. We first selected clinicopathologic variables associated with group (POLE vs CN low) via univariate analysis. Then, we identified protein makers using the logistic regression model with significant clinicopathologic variables as adjusting covariates. The differentially expressed proteins were selected based on q-value of the false discovery rate for multiple comparison. With various q-value cut-off ( < 5%, 10%, 20%), several logistic models including differentially expressed markers were constructed by stepwise selection method using the area under curve (AUC) from 5-fold cross-validation (CV). Results: Among clinicopathologic variables, body mass index (BMI) and tumor grade were associated with group (p = 0.02 and p < 0.01, respectively). Being adjusted for BMI and tumor grade, 5 proteins were associated with group in q-value cut-off of < 5%. The model including clinicopathologic variables and 5 proteins identified BMI, Cyclin B1, Caspase 8, and XBP1 as markers distinguishing POLE and CN low groups. The mean of CV AUC, sensitivity and specificity of the selected model were 0.97, 0.97, and 0.60, respectively. Conclusions: BMI and expression levels of Cyclin B1, Caspase 8, XBP1 are candidate markers distinguishing POLE and CN low group. A further validation study using immunohistochemical staining is necessary to facilitate the adoption of molecular subtyping as daily practice.
A combined genomic and immune profile in patients with head and neck squamous cell carcinoma treated with immunotherapy: A pilot study.
Authors: Botticelli Andrea , Mezi Silvia , Pomati Giulia , Zizzari Ilaria , Cerbelli Bruna , Mammone Giulia , Corsi Alessandro , di Gioia Cira , D'Amati Giulia , della Rocca Carlo , Catalano Carlo , De Vincentiis Marco , Polimeni Antonella , Valentini Valentino , Tombolini Vincenzo , Nuti Marianna , Marchetti Paolo 
Published: May 2020

e18506 Background: In head and neck squamous cell carcinoma (HNSCC) only a small subset of patients (pts) really benefits from immunotherapy, suggesting the need of validated molecular and immunological predictive biomarkers. The aim of the study was to evaluate both the genomic and immune profile of HNSCC correlating it to early progression to immunotherapy. Methods: This is a pilot study evaluating immune and molecular profile in platinum-refractory HNSCC pts treated with Nivolumab. Blood samples were collected at baseline (T0) and at second cycle of therapy (T1). The immune profile was studied by multiplex assay, evaluating circulating: CD137, CTLA4, PD1, PDL1, PDL2, CD27, TIM3, LAG3, GITR, HVEM, BTLA, CD80, CD28 and IDO. The comprehensive genomic profile was evaluated at baseline on formalin-fixed paraffin-embedded samples of the tumor through Foundation One Cdx test. The results obtained were correlated with early progression (within 3 months from the start of therapy). Results: Ten pts were enrolled in the study. Early progression occurred in 6 pts (60%). Median progression free survival and overall survival were 3 months (1-11) and 6.5 months (1-12), respectively. In all patients ≥ 5 genetic mutations were detected; median number of mutation was 6 (5-14); 8/10 pts had a tumor mutational burden less than 10 Muts/mb. The more frequent genetic alterations involved the cycline-dependent-kynase pathway (9/10), the transcription factor associated gene TP53 (8/10) and the PI3K-Akt-PTEN signaling pathways (5/10). Less frequent alterations involved FGFR family (4/10), NOTCH signaling pathway (3/10) and TERT (4/10). Early progression was slightly associated with the number of mutations detected (p = 0.06). The rising or falling trend of circulating levels of biomarkers were detected in 9/10 pts and included modification in IDO (1/10), LAG3 (3/10), GITR (3/10), BTLA (3/10), CD137 (4/10), CTLA4 (4/10), PD1 (2/10), Tim3 (3/10), CD28 (3/10), HVEM (3/10), CD80 (2/10). No modifications were recorded in PDL1, PDL2 and CD27. Conclusions: Our results, although in a small cohort, highlighted the complexity and heterogeneity of landscape in HNSCC pts. A novel evaluation that combines molecular and immune profile is needed. In the context of a poor prognosis disease the combination of personalized molecular and immune approaches could represent a promising strategy to improve survival.
Long-term outcomes of locally advanced and borderline resectable esthesioneuroblastoma and sinonasal tumor with neuroendocrine differentiation treated with neoadjuvant chemotherapy.
Authors: Kumar Amit , Noronha Vanita , Patil Vijay Maruti , Joshi Amit , Menon Nandini Sharrel , Prabhash Kumar 
Published: May 2020

e18507 Background: Sinonasal tumors are a rare subgroup of head and neck cancers. Locally advanced esthesioneuroblastoma and sinonasal neuroendocrine tumors (SNEC) are treated with a multidisciplinary approach with combination of surgery followed by adjuvant radiation or chemo radiation; but have unsatisfactory outcomes. Hence we devised the approach of administering neoadjuvant chemotherapy (platinum and etoposide) followed by surgery and adjuvant chemoradiation. This approach had the advantage of improved response rates, orbital preservation and improvement in short term outcomes. The present analysis was done to estimate the 5 year outcomes and late adverse events of locally advanced sinonasal tumors treated with induction chemotherapy followed by local therapy. Methods: Twenty five patients with locally advanced esthesioneuroblastoma or SNEC treated between August 2010 to August 2014 with induction chemotherapy followed by local therapy were selected. The 5 year outcomes and late adverse events (CTCAE version 4.02) were noted. Progression free survival (PFS) and overall survival (OS) were estimated using the Kaplan Meier method. COX regression analysis was used to identify factors impacting PFS and OS. Results: The median follow up was 5.15 years. The 5 year PFS in esthesioneuroblastoma cohort and in SNEC cohort was 63.5% (95%CI 28.9-84.7) and 34.6% (95%CI 10.1-61.1) respectively (p = 0.1). The only factor impacting PFS on multivariate analysis was response to neoadjuvant chemotherapy (p = 0.033). The 5 year OS in esthesioneuroblastoma cohort and in SNEC cohort were 91.7% (95%CI 53.9-98.9) and 46.2% (95%CI 19.2-69.6) respectively (p = 0.024). Any grade late adverse event was seen in 20 patients (80%). Metabolic late adverse events were seen in 19 patients (76%). Conclusions: Neoadjuvant chemotherapy in advanced sinonasal cancers is associated with improvement in 5 year outcomes. However late side effects especially metabolic are seen in these patients and should be evaluated during follow up. Keywords: Sinonasal; Adverse event; Esthesioneuroblastoma; SNEC; Induction; Neoadjuvant [Table: see text]
Initial safety and tumor control results from a phase I prospective trial evaluating a novel alpha-emitting radionuclide for the treatment of locally advanced recurrent squamous cell carcinomas of the skin and head and neck.
Authors: Popovtzer Aron ,   Alpha Tau
Published: May 2020

e18509 Background: The purpose of this study is to report on the feasibility and safety of Diffusing Alpha-emitters Radiation Therapy (DaRT), including interstitial implantation of a novel alpha-emitting brachytherapy source, to treat locally advanced and recurrent squamous cell carcinomas (SCC) of the skin and head and neck. Methods: This prospective, first-in-human Phase I multicenter study included 28 eligible patients with 31 lesions. The primary endpoint was the feasibility and safety of the DaRT treatment approach. The secondary endpoint was initial tumor response and local progression-free survival (PFS) outcomes. Eligibility criteria included biopsy-proven SCC of the skin and head neck with either recurrent or previously-treated disease with either surgery or prior external beam radiotherapy. Toxicity was evaluated according to the Common Terminology Criteria for Adverse Events (Version 4.03). Tumor response was assessed at follow-up (30-45 days following treatment) using the Response Evaluation Criteria in Solid Tumors (Version 1.1). Results: Acute toxicity events included mostly erythema and swelling at the implantation site followed by pain and mild skin ulceration. Pain and Grade 2 skin ulcerations resolved in most patients within 3-5 weeks. Complete response (CR) to the Ra-224 DaRT treatment was observed in 22 lesions (22/28; 78.6%); seven lesions (6/28; 21.4%) manifested a partial response ( > 30% tumor reduction). Among the 22 lesions with a CR, 5 (22%) developed a subsequent local relapse at the site of DaRT implantation at a median of 4.9 months (range: 2.43-5.52 months). The one-year local PFS probability at the implanted site was 60% (95% Confidence Interval, CI: -28.61-81.35%) for complete responders. Overall survival (OS) at 12 months post-DaRT implantation was 75% (95% CI: 46.14-89.99%); among complete responders, OS was 93% (95% CI: 59.08-98.96%). Conclusions: Alpha-emitter brachytherapy using DaRT achieved significant tumor responses without Grade 3 or higher toxicities. Longer follow-up observations and larger studies are underway to validate these findings. Clinical trial information: NCT03015883 NCT03353077.