bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular and clinicopathological classification of high risk endometrial cancer (EC) treated with concurrent chemoradiation therapy (CCT).
Authors: Gil-Martin Marta , Vidal-Bel August , Valle Laura , Velasco Ana , Pardo Beatriz , Recalde Sabela , Ventura Zaa Luz , Navarro-Perez Valentín , Sanz-Pamplona Rebeca , Marin i Borras Susanna , Ponce Jordi , Marti Lola , Barahona Marc , Rovira Jordi , Piulats Josep M. , Matias-Guiu Xavier 
Published: September 2018

e17110 Background: Recently, TCGA proposed a molecular classification in EC that might hold prognostic significance. This project aim is to evaluate the outcome of high risk EC treated with CCT and its correlation with a surrogate molecular classification. Methods: A total of 49 patients (pts) treated from 2011 to 2016 were included in a prospective database. Pts were treated with 2 cycles (C) of cisplatin on days 1 and 28 concurrent with external beam radiotherapy (RT) of the pelvis, plus brachytherapy (BCT); followed by 4 C of paclitaxel and carboplatin every 3 weeks. The molecular classification into the 4 groups of TCGA (POLE mut, MSI, CN-low, CN-high/serous-like) has been performed in 38 pts using a surrogate classification that consists in POLE mutations detection by Sanger, and immunohistochemistry for p53 and MMR, as surrogate markers for TP53 mutations and MSI. Results: Pts median age was 67yo; Endometrioid pathology in 59%, serous 20% and others 20%; up to 73% were grade 3; and FIGO Stage III in 82%. All pts received full dose of RT, 80% BCT, and 75% completed 6C of CT. With a median follow-up of 39 months [17-65], 6% of pts experienced local recurrence, and 30% metastatic relapse. 3-year overall survival (OS) and cancer–specific survival (CSS) was 80%, and 3-year progression free survival was 74%. Median OS is not reached at this point. Pts were molecularly classified as: 0% POLE mut, 13% CN-low, 37% MSI and 50% CN-high. Survival data show that CN-low present an 3-y OS and CSS of 100%, MSI of 82% and CN-high of 67%. No statistically significant differences have been found, probably due to the low number of events and pts. It is remarkable the survival difference between endometrioid and serous tumors in the CN-high group (86% vs 50%, respectively). This tendency can be observed in TCGA pts as well. Conclusions: CCT followed by CT is an effective adjuvant therapy in high risk EC pts with an acceptable toxicity. Correlation with molecular prognostic classification has shown a big proportion of patients in the MSI and CN-high groups, known to have worse prognosis. Morphologic differentiation between endometrioid and serous carcinomas in CN-high group might still hold prognostic implications.
Norethindrone substituted for megestrol in the treatment of metastatic endometrial carcinoma: Three cases.
Authors: Trivedi Sumita , Williams Felicia , Read William L. 
Published: September 2018

e17111 Background: Megestrol (M) is an effective palliative treatment for endometrial carcinoma but causes weight gain via activity at the corticosteroid receptor. Norethindrone (N) is a progestin without corticosteroid activity. We report 3 women with metastatic endometrial cancer responsive to M for whom a switch to N decreased side effects with continued cancer control. Methods: Case-series Results: 1. 62 year old with endometrial adenocarcinoma underwent surgery and chemoradiation. Lung metastases were discovered 31 months later and she began M with complete response at 13 months. She suffered weight gain and lymphedema. M was switched to N and continued for 4 years to date with weight loss and without progression. 2. 54 year old with endometrial adenocarcinoma underwent surgery and radiation. Lung metastases developed 30 months later. Chemotherapy produced response but was complicated by cerebrovascular accident. lung lesions developed 3 years later and slowly grew over the ensuing year. M was started and continued for 8 months. Her lung lesions responded but weight gain impacted her already reduced mobility. She was switched to N which has continued 11 months to date, with stable disease, without further weight gain. 3. 64 year old with a history of metastatic squamous cell carcinoma of the lung developed what was thought to be a second primary endometrial adenocarcinoma. She received surgery and radiation with pelvic recurrence 34 months later. M was started and continued for 17 months with response in pelvic and lung lesions, which proved to be metastatic endometrial carcinoma presenting before her primary. Weight gain resulted in wheelchair dependence. She was switched to N with continuing response over the ensuing 2 years. 28 months after starting N, imaging showed progression and she was switched back to M, her poor performance status precluding other treatments. She died 5 months later. Conclusions: In patients with metastatic endometrial cancer responding to megestrol, switching to norethindrone improved palliative benefit. Prospective clinical trials of norethindrone or similar progestins without corticosteroid activity should be considered for this population.
miRNA profiling in a case: Control study of African American women with uterine serous carcinoma (USC).
Authors: Lee Larissa Janeen , Howitt Brooke E. , Fendler Wojciech , Stawiski Konrad , Bu Paula , Cho Linda , Chowdhury Dipanjan , Matulonis Ursula A. , Konstantinopoulos Panagiotis A. 
Published: September 2018

e17116 Background: USC is an aggressive subtype of endometrial cancer associated with worse outcomes in African American patients. We evaluated differences in tumor miRNA expression by race, clinical and tumor characteristics, and survival outcomes. Methods: FFPE tumor tissue from hysterectomy specimens was identified for 29 African American cases. Case matching was performed by computer-based random assignment in a 1:1 ratio with Caucasian controls based on age ( < 70 vs. ≥70 years), stage (FIGO I/II vs. III/IV) and histologic subtype (pure vs. mixed). RNA was extracted from 77 specimens with sufficient tumor cellularity (54 tumors and 23 matched normal endometrium). miRNA array profiling was performed by microRNA Hi-Power Labeling (Hy3/Hy5) and hybridization to miRCURY LNA microRNA Array 7th Gen (Exiqon, Denmark). Analysis was performed with R/Bioconductor using a moderated t-statistic with multiple testing correction. Validation was done using the TCGA dataset. Results: Clinical and treatment characteristics were similar for cases and controls, although use of adjuvant radiation was less common in African Americans (p = 0.03). With a median follow-up of 43 months, 17 patients had recurrent or progressive disease. DFS and OS rates were similar by race (both logrank p > 0.5). Of 968 miRNAs analyzed, 649 were differentially expressed in normal endometrium vs. tumor. When compared by race, histologic subtype, stage or presence of LVI, no differentially expressed miRNAs were identified. In patients with disease recurrence at 3 years, miR-223 was significantly upregulated (fold change 1.5; p = 0.002). In validation using a TCGA dataset of 131 patients with mixed (n = 22) or pure serous (n = 109) histology, increased miR-223 expression ( > median) was associated with worse overall survival (HR 2.47; 95%CI 0.9-6.6). After adjustment for patient age and BMI, upregulation of miR-223 was a significant risk factor for death (adjusted HR 2.94; 95%CI 1.01-8.52). Conclusions: Upregulation of miR-223 was associated with disease recurrence in a cohort of women with uterine serous carcinoma and validated by TCGA data. miRNA profiling did not identify biological differences between African American and Caucasian patients.
Multi gene panel testing in unselected patients (pts) with endometrial cancer (EC).
Authors: Cadoo Karen Anne , DeLair Deborah , Mandelker Diana , Barakat Richard R. , Brown Carol L. , Chi Dennis , Gardner Ginger J. , Jewell Elizabeth Lin , Leitao Mario M. , Long Kara , Mueller Jennifer Jean , Sonoda Yukio , Zivanovic Oliver , Berger Michael F. , Zhang Liying , Robson Mark E. , Offit Kenneth , Aghajanian Carol , Abu-Rustum Nadeem , Stadler Zsofia Kinga 
Published: September 2018

e17119 Background: Inherited mutations (muts) in Lynch Syndrome genes (LS) & PTEN are associated with EC. The prevalence of other cancer predisposition genes is unclear. The majority of studies have selected pts by age, family history or specific tumor features. We sought the prevalence of cancer predisposition genes in unselected pts attending for surgical consultation. Methods: 03/2016-10/2016, pts with new EC diagnosis were offered to consent to an IRB approved protocol. Tumor-normal sequencing, was performed via a custom next-generation sequencing panel (MSK-IMPACT) with return of results for 76 cancer predisposition genes. Per institutional standard, all ECs undergo reflex screening for LS with IHC for mismatch repair proteins (MMR P). Results:77 pts consented, median age 60 (27-84), median BMI 27 (16-66), 27% Ashkenazi Jewish (AJ) descent. Tumors: 56 (73%) stage 1, remainder stage 3 or 4, majority (52, 68%) endometrioid histology, of which 31 (60%) grade 1. 15 pathogenic germline variants were identified in 14 pts (18%) including 3 (4%) in LS genes (2 MSH6, 1 MLH1) with corresponding abnormal MMR P. One pt with a known BRCA1 mutation, without prior cancer, with prior risk reducing salpingo-oophorectomy had stage III grade 3 endometrioid EC at 47 yo, tumor LOH at BRCA1 was identified. Of the 4 pts with high-penetrance muts, 3 met criteria for genetic testing for the implicated gene due to personal/family cancer history, 1 pt with MSH6 mutation was identified via absent MMR P only. The remaining 11 pathogenic variants were incremental findings in moderate penetrance ( CHEK2 I157T, MRE11, ATM, APC I1307K, MUTYH) or autosomal recessive genes ( MUTYH, RECQL4, ATM). 5 pt had moderate penetrance variants in known AJ founder muts. Conclusions: In this cohort of unselected EC pts the prevalence of LS was as expected & reflex IHC screening captured all pts appropriately. While all high-penetrance muts were captured by clinical criteria, the incremental identification of moderate penetrance muts in these largely early stage/ low risk EC pts may alter personal & at-risk family member breast & colon cancer screening recommendations. Continuing accrual will reveal the extent to which additional high penetrance genes are seen in unselected EC pts.
Impact of metformin on survival and mTOR pathway in head and neck cancer patients: An updated analysis.
Authors: Gulati Shuchi , Takiar Vinita , Mark Jonathan , Butler Randall , NeCamp Joshua , Wise-Draper Trisha Michel 
Published: September 2018

e17500 Background: Metformin is hypothesized to suppress tumor cell growth by mTOR pathway inhibition, which mediates the phosphoinositide 3-kinase/Akt signaling pathway (frequently deregulated in human cancers). This effect is mediated by activation of the AMP protein kinase (AMPK). Despite knowledge of the mechanism, various retrospective studies show conflicting results about effect of metformin on survival in head and neck squamous cell carcinoma (HNSCC) patients (pts). Methods: We analyzed a retrospective cohort of 1500 consecutive pts (between 2009-2015) with HNSCC. We added about 1000 pts to previously presented data (e17514-ASCO 2016). These pts included those with diabetes (DM) on metformin (MET) or other anti-diabetic agents. Descriptive statistics were used for demographic and pt data. Kaplan-Meier method was used to calculate median overall survival (OS) and progression free survival (PFS), 95% CI. Cox model was used to test association between MET (or DM) and OS (or PFS) (using SPSS-24 (IBM)). Results: Of the 1500 pts with HNSCC, 329 had advanced cancer (stage III/ IV), and received definitive chemo-radiation (CRT). Of these, majority were Caucasian (90%), males (90%) and smokers (70%). Mean age at diagnosis was 57 years (SD 10). 53 pts had DM, of which 37 were on MET. Statistical results are shown in Table 1. Conclusions: This retrospective study showed no statistically significant difference between various subgroups described in the table. Given the low number of diabetics, and pts on MET, data is limiting. However, further subset analyses are ongoing to determine whether a difference in treatment (RT vs. cetuximab vs. cisplatin) had an impact on outcomes. Future experiments will utilize tissue microarrays to evaluate for association with mTOR pathway aberrations. [Table: see text][Table: see text]
Unmet needs in head and neck cancer patients: Unmet needs, emotional disorders, and pain.
Authors: Airoldi Mario , Ostellino Oliviero , Raimondo Luca , Pecorari Giancarlo , Franco Pierfrancesco , Rampino Monica , Succo Giovanni , Denegri Martina , Tosi Chiara , Botto Rossana , Torta Riccardo , Ieraci Valentina 
Published: September 2018

e17501 Background: knowledge is still lacking about head and neck patients’ unmet needs and their association with the other debilitating symptomatologies that worsen Quality of Life (QoL), compliance to treatments and prognosis. The aim of this research, so, it was to investigate the unmet needs of this type of patients in accordance with sympomts. Beside this study tried to evaluate if patients’ needs were correctly understood by their caregivers, nurses and oncologist. Methods: we surveyed 100 patients (80 men and 20 women) with head and neck cancer, during the active phase of chemotherapy treatmet,58 caregivers’ patients, nurses and the oncologist. The axious symptomatology and the depressive symptomatology were assessed by the Hospital Anxiety and Depression Scale (HADS). Distress was assessed by the Distress Thermometer (DT). Unmet needs were assessed from patients and their caregivers by Supportive Care Needs Survey-short Form (SCNS-SF34); nurses and the oncologist had to answer only to the 5 questionnaire’s macro-areas. Pain was assessed using the answer given to the SCNS-SF34’s first item. Results: having unmet needs in the psychological area is associated with the presence of symptoms in the preceding 24 hours (c2 = 10.213 , p = .001). Unmet needs in the communicative and informative area are associated with pain (c2 = 5.260 , p = .022). Unmet needs in physical conditions and daily living area are associated with pain (c2 = 9.962 , p = .002) and the presence of symptoms in the preceding 24 hours (c2 = 6.760 , p = .009). Unmet needs in patient support and health care area is associated with: distress (c2 = 4.459 , p = .035), anxious symptomatology (c2 = 4.071 , p = .044) and pain (c2 = 14.733 , p = .000). Unmet needs in sexuality area are associated with anxious symptomatology (c2 = 7.328 , p = .007) and pain (c2 = 4.833 , p = .028). Feelings about death and dying are associated with anxious symptomatology (c2 = 6.451 , p = .011) and depressive symptomatology (c2 = 5.317 , p = .021). Caregivers and patients both detect the presence of unmet needs in many areas. Conclusions: there tare several associations found between unmet needs and main symptomatologies that negatively impact with patient’s QoL and prognosis.
Could neutrophil to lymphocyte ratio (NLR), derived neutrophil to lymphocyte ratio (dNLR), platelet to lymphocyte ratio (PLT), and lymphocyte to monocyte ratio be common independent prognostic factors in head and neck squamous cell carcinoma?
Authors: Manikhas Georgy M. , Kutukova Svetlana I. , Beliak Natalia P. , Popova Natalia V. , Zhukova Natalia V. , Ivaskova Julia V. , Erdniev Sanal 
Published: September 2018

e17519 Background: The purpose of our study was to investigate prognostic role of neutrophil to lymphocyte ratio (NLR), derived neutrophil to lymphocyte ratio (dNLR), platelet to lymphocyte ratio (PLR), and lymphocyte to monocyte ratio in PFS and OS, and immunological tumor’s microenvironment in patient with HNSCC. Methods: We analysed medical records an tumor samples of 60 patients with HNSCC with stage I - IVB (37 men, 23 women; median age 59). All patients were under standard clinical complex protocol. All patients were under our supervision from 2010 to 2015. We examined demographic data, clinical stage, tumor morphological characteristics and specific level of expression of CD8(+) T-cells, in the tumor and microenvironment, and baseline level of WBC, neutrophil, lymphocyte, monocyte and PLT . Also we analysed calculated value of NLR, dNLR, PLR, and LMR. Results: The median value of NLR was 2.03 (95% CI: 1.66-2.59), dNLR - 1.44 (95% CI: 1.23-1.70), PLR - 144.58 (95% CI: 107.59-179.32) and LMR - 6.79 (95% CI: 5.34-8.17). Median of 1-year OS and PFS was non significantly lower in pts with NLR < 2.03 (16.0 vs 18.0 month, p = 0.6020 and 5.00 vs 7.00 month, p = 0.5383). But NLR correlate with expression of CD8(+) T-cell in tumor (p = 0.05). Median of 1-year OS was the same in both group (16.0 vs 17.0 month, p = 0.5453), PFS was non significantly lower in pts with dNLR < 1.44 (16.0 vs 18.0 month, p = 0.6020 and (5.00 vs 7.00 month, p = 0.7435). NLR correlate with expression of CD8(+) T-cell in tumor (p = 0.0337). Analyse of LMR showed trend of best 1-year OS in pts with LMR < 6.79 (18.0 vs 15.0 month, p = 0.4674) and equal PFS (6.00 vs 7.00 month, p = 0.4914). PFS and 1-year OS were better (nonsignificant) in pts with PLT > 144.58 (9.0 vs 5.0 month, p = 0.5854) and (18.0 vs 16.0 month, p = 0.5836). Conclusions: Important role of indicators of systemic inflammation is obvious for patient with HNSCC, but our study showed that only baseline characteristics couldn’t be strong prognostic factors by different degree of intratumor inflammation.
Human papillomavirus (HPV)-related oropharyngeal cancer cofactors: Viral co-infections, second cancers, and survival trends—A single Veterans Administration (VA) institution.
Authors: Dawson George Anthony , Zhang Yue Hua , Laurio Angela , Smith Patricia , Dellatto Michael , Innis-Gordon Fiona T. , Reino Anthony 
Published: September 2018

e17531 Background: Oropharyngeal cancers related to HPV are increasing in number. Common factors associated with HPV related head and neck cancers include ethnicity, young age, and low usage of alcohol and tobacco. All are typical of HPV+ related Oropharyngeal cancer in non-VA populations. Methods: This IRB approved chart review of 73 documented patients with Oropharyngeal cancers from co-HPV infections from 01/01/2011 - 12/31/2016. In this version of report we discuss second cancers, trends and other co-factors. Results: Overall trend was notable for a reversal (more HPV+ / less HPV- ) cases. All cancers were squamous cell variety. 2011 /2012 /2013/ 2014/2015/2016 HPV +: 4 / 4 / 0 / 6 / 11 / 7. HPV -: 6 / 8 / 4 / 8 / 6 / 5. Clinical stage: Evident adenopathy - (N2 to N3) was noted in 51/73(70%) cases: HPV+ 30/36 (83%) / HPV- 21/37(57%). As noted, there are ~40 co-factor events in each group with no clear association with HPV + or – status numbers of cases were too small for meaningful analysis. Second Cancers HPV+: PROSTATE 7 / BLADDER 2 / TESTICULAR 1 / RENAL 1 / LUNG 1 / SKIN 4. HPV- : FOM 2 / LARYNX 2 / TONSILLAR 1 / PAROTID 1 / BLADDER 1 / SKIN 5 / PROSTATE 1 / LUNG 1. Survival data results: There was evidence in our data that survival was prolonged in patients who are HPV negative, but this sample was too small to show statistical significance. Further, it appears white race improves the odds of survival p-value 0.073, however, not statistically significant, due to the small sample. Conclusions: As in the non-VA community, our data noted an increase in HPV+ oropharyngeal cancers treated at the Bronx VA during review period. Further, our HPV+ group had predominant advanced adenopathy, and whites had longer survival regardless of HPV status. Second cancers in HPV- group followed field cancerization effects in regards number new or old head / neck cancer events. Interestingly, with almost equal tobacco / alcohol use in both groups, no 2nd head and neck cancers in the HPV+ group were discovered. Potential immuno-protection for HPV+ 2nd h and N cancers.[Table: see text]
Mutational profile of HPV-driven head and neck cancers according to tobacco consumption.
Authors: Mirghani Haitham , Lacroix Ludovic , Casiraghi Odile , Auperin Anne , Rossoni Caroline , Villepelet Aude , Lacave Roger , Marty Virginie , Even Caroline 
Published: September 2018

e17535 Background: HPV-driven oropharyngeal cancer (OPC) patients are characterized by a better prognosis than their HPV-negative counterparts. However, this significant survival advantage is not homogeneous and studies have highlighted that among HPV-positive patients those with a smoking history have a significantly increased risk of disease progression and death compared to those who have never smoked. The reason why tobacco consumption impacts negatively the prognosis is still elusive. Tobacco might induce additional genetic alterations leading to a more aggressive phenotype. The purpose of this study is to characterize the mutational profile of HPV-positive OPC by smoking status. We hypothesize a higher frequency of mutations affecting among smokers. Methods: Targeted next-generation sequencing of 38 oncogenes/tumor suppressor genes that are commonly mutated in cancers caused by tobacco/alcohol consumption was performed in 62 HPV-driven OPC cases stratified by smoking status. Results: The study population included 37 (60%) non-smokers and 25 (40%) smokers distributed as follows: 1 (4%) patient smoked <10 pack-year (PY), 8 (32%) patients between 10-20 PY and 16 (64%) >20 PY. Twenty (31%) patients had no mutation, 14 (23%) had 1 mutation and 28 (46%) had 2 or more mutations. The most commonly mutated genes regardless of tobacco consumption were PIK3CA (20%), MLL2 (20%), TP53 (8%), FAT 1 (15%), FBXW7 (16%), NOTCH 1 (9%) and FGFR3 (9%). Mutation rate was not significantly different in smokers compared to non-smokers even when analyses focused on heavy smokers (>20 pack-years compared to <20 pack-years). Similarly there was no significant difference in mutations patterns according to tobacco consumption. The 3 years overall survival, disease-specific-survival and loco-regional-control rates for the whole cohort are respectively 88% (95% CI: 76.4-94.1), 88% (95% CI: 76.4-94.1) and 80.6% (95% CI: 67.5-88.8). Despite a median follow-up was 4.5 years (6 months to 11.7 years), the few number of events (13 relapses, 13 deaths including 10 due to OPC) precludes detailed prognosis analyses. Conclusions: HPV-driven OPC patients with a smoking history have a comparable mutational rate than non-smokers. Smoking impact on the prognosis isn’t attributable to the mutational burden. Further studies are warranted.