tbuckley/cabot-search huggingface dataset:
Lymph node metastasis and prognostic value of NPC based on the UICC lymph node staging for cervical lymph node levels.
Authors: Jin Yi Lang, Mei Feng, Peng Xu, Weidong Wang, Guangquan Yang, Shun Lu
Journal: Journal of Clinical Oncology (2017)

e18136 Background: Nasopharyngeal carcinoma (NPC) is the most common cancer originating in the nasopharynx. The neck lymph node (LN) metastasis is very common in NPC; it plays an important role in tumor staging which is guide the choice of treatment. Methods: 324 patients were pathologically diagnosed as non-metastatic NPC from Jan. 2005 to Dec.2010 were recruited retrospectively to analysis. All of them treated with standard IMRT. The clinical data including CT/MRI images, followed up were collected, while the OS, DFS, DMFS and RRFS were calculated. Survival analysis was performed by Kaplan-Meier method, and COX regression model was used for multivariate analysis. Results: The median follow-up time was 66 months (6-134 months). The 5-year LRFS,NRFS,DMFS,DFS and OS was 93.5%, 97.4%, 73.4%, 69.1% and 79.2%,respectively. The most common metastatic LN levels were II level 83.9%, retropharyngeal LN level 69.1%, followed by III level 16.9%, Va level 8% ,IV level 5.2% and Vb level 4%. All the retropharyngeal LNs were involved in the lateral group while no medial ones was found. In cervical LN, necrosis was involved in 40.0% patients with positive nodes and extracapsular invasion was noted in 58.6%. Bilateral positive LN was involved in 66.5%, and there was 11.4% in the lower cervical region. Univariate analysis showed that LN diameter greater than 3 cm, extracapsular invasion, LN necrosis and LN laterality are independent prognostic factors for DMFS and DFS (P &lt; 0.05). T staging and N staging were independent prognostic factors for the DMFS (P = 0.024, 0.012, respectively). Lower cervical involvement had no significant effect on DMFS and DFS. Multivariate analysis showed that T staging, extracapsular invasion and laterality were independent prognostic factors (P &lt; 0.05) for DFS, and extracapsular invasion was an independent prognostic factor (P = 0.048) for DMFS. Conclusions: Our results suggested II level and retropharyngeal LN have the highest metastasis rate. All retropharyngeal LN were involved in the lateral group but not medial one. Laterality, maximum diameter and necrosis are independent prognostic factors for DFS and DMFS. The involvement of the lower cervical region had no significant effect on DFS and DMFS.
Nutritional counseling with or without systematic use of oral nutritional supplements in head and neck cancer patients undergoing radiotherapy.
Authors: Paolo Pedrazzoli, Emanuele Cereda, Silvia Cappello, Sara Colombo, Catherine Klersy, Ilaria Imarisio, Annalisa Turri, Marilisa Caraccia, Alberto Verlicchi, Marco Benazzo, Franco Corbella, Riccardo Caccialanza
Journal: Journal of Clinical Oncology (2017)

10098 Background: The benefit of systematic use of oral nutritional supplements (ONS) in addition to nutritional counseling in head and neck cancer (HNC) patients undergoing radiotherapy (RT) has not still been properly assessed. Methods: In a single-center, randomized, pragmatic, parallel-group controlled trial (ClinicalTrials.gov: NCT02055833; February 2014 - August 2016), 159 newly diagnosed HNC patients suitable for to RT regardless of previous surgery and induction chemotherapy were randomly assigned to nutritional counseling in combination with omega-3 enriched ONS (N = 78) or without ONS (N = 81) from the start of RT and continuing for up to 3 months after its end. The primary endpoint was the change in body weight at the end of RT. Secondary endpoints included changes in protein-calorie intake, muscle strength, body composition and quality of life (EORTC-QLQ-C30) over the study time points and anti-cancer treatment tolerance. Results: In patients in whom all the variables could be assessed, counseling plus ONS (N = 67) resulted in smaller loss of body weight than nutritional counseling alone (N = 69; mean difference, 1.6 kg [95%CI, 0.5 to 2.7]; P = 0.006). Imputation of missing outcomes provided consistent findings. In the ONS-supplemented group, higher protein-calorie intake and improvement in quality of life over time were also observed (P &lt; 0.001 for all). The use of ONS reduced the need for changes in scheduled anti-cancer treatments (i.e. for RT and/or systemic treatment dose reduction or complete suspension, HR = 0.40 [95%CI, 0.18 to 0.91], P = 0.029). Nine patients reported gastrointestinal intolerance to ONS. Conclusions: In HNC patients undergoing RT or RT plus systemic treatment, and receiving nutritional counseling, weight loss could not be completely prevented, but the use of ONS resulted in better weight maintenance, increased protein-calorie intake, improved quality of life and better anti-cancer treatment tolerance. Clinical trial information: NCT02055833.
Influence of chlamydia infection on DNA damage in patients with cervical cancer.
Authors: Nailya Guskova, Irina A. Goroshinskaya, Oleg Ivanovich Kit, Ekaterina Igorevna Surikova, Olga Vladimirovna Tarnopolskaya, Ekaterina Guskova, Nadezhda Golomeeva, Svetlana V. Abakumova, Irina V. Tselishcheva, Kristina Avanesova, Anastasia Nozdricheva, Viktoria Zakharchenko, Svetlana V. Belgova
Journal: Journal of Clinical Oncology (2017)

e17020 Background: The role of Chlamydia trachomatis (Ch. tr.) in development of cervical neoplasia is widely discussed. However, molecular mechanisms of Ch. tr. contribution to carcinogenesis are poorly studied. The purpose of the study was to analyze degrees of DNA damage in blood leucocytes in patients with cervical cancer with Ch. tr. infection and in non-infected patients and healthy women. Methods: DNA damage was assessed by the comet assay, the alkaline single-cell gel electrophoresis (20 min, 300 mA, 20 V, 2 V/cm, 4°C) allowing detection of DNA base modifications leading to alkali-labile sites. The preparations were stained with ethidium bromide solution and microscoped (Axio Imager M2, Zeiss) at the excitation wavelength 520 nm and emission wavelength 640 nm. 200 cells were analyzed in each preparation. Percentage of DNAs in the comet tail (T%DNA) was used as an indicator of DNA damage. DNA damage was assessed in 14 patients with cervical cancer and in 13 healthy women. The data were analyzed using Exsel and Statistika 6.0 programs and Mann-Whitney U test and Student's t-test. Results: Mean T%DNA in 8 cervical cancer patients non-infected with Ch. tr. was 4.35±0.63, being significantly (р=0.012580) higher (by 53.7%) than in women without oncopathology (2.83±0.20). The value in infected patients was 10.44±0.11 which was significantly higher than in non-infected patients (by 2.4 times, р=0.000056) and in healthy women (by 3.7 times, р=0.000000). Thus, presence of Ch. tr. was associated with more than 2 times increase in DNA damage in cervical cancer patients. The results are consistent with previously reported data of cell culture studies according to which chlamydia causes histone modification and DNA double strand breaks [Chumduri C. et al., 2013]. Conclusions: The results confirm the role of chlamydia infection in DNA damage in blood cells in cervical cancer patients which promotes malignant development in organs of the female reproductive system.
Abstract B023: Identification and biochemical validation of piperlongumine as a potent therapeutic against neuroendocrine prostate cancer
Authors: Kamlesh K. Yadav, Khader Shameer, Jennifer A. Stockert, Cordelia Elaiho, Ben Readhead, Shalini S. Yadav, Joel Dudley, Ashutosh K. Tewari
Journal: Cancer Research (2018)

Abstract Introduction and Objectives: Recent studies have highlighted the existence of a highly lethal and drug-resistant variant of prostate cancer (PCa) termed neuroendocrine prostate cancer (NEPC). We have used a genomics-based drug-repositioning approach to identify piperlongumine, a natural product constituent of the fruit of the long pepper (Piper longum), as a potential therapeutic against NEPC. The efficacy of this drug was tested in the NEPC cell line model NCI-H660 and compared to several other PCa cell lines in a modified WST-1 assay. Preclinical testing in mouse xenograft models of NEPC was also undertaken. Finally, the ability of piperlongumine to inhibit p-STAT3 signaling and promote apoptosis in cell lines and extracted tumors were measured by Western blot analyses. Methods: PCa cell lines (LNCaP, 22Rv1, Du145, PC3, H660, and RWPE) were grown in complete media (RPM1 10% FBS, Advanced DMEM 5% FBS, or Keratinocyte-SFM) and treated with piperlongumine for 3 or 7 days. IC50 values were generated from WST assay data using Prism6. Nude mice (n=5) were injected with 1.5x106 H660 cells on each flank, and intraperitoneally administered with either 2.5mg/kg piperlongumine (n=3) or DMSO (n=2) daily for 3 weeks after tumors formed 200mm3 in volume. Tumor volume was measured daily with calipers. Western blot analyses were performed on protein lysates extracted from tumors and PCa cells treated with 0-10 μM of drug. Results: Piperlongumine was highly effective in inhibiting the growth of H660 cells (IC50 = 0.4 μM) compared to LNCaP, 22Rv1, Du145, PC3, and RWPE cells. On average, the growth rate of untreated tumors was 2.7 times greater than those treated was piperlongumine. Treated H660 cells exhibited significant inhibition of p-STAT3 and increases in cPARP1 levels while other cell lines displayed little to no fluctuation. Conclusions: Using drug-repositioning approaches we have identified a lead compound that inhibits the growth of the highly drug-resistant NEPC cell line NCI-H660. Remarkably, piperlongumine happens to be a water-soluble plant product with no known side effects. Citation Format: Kamlesh K. Yadav, Khader Shameer, Jennifer A. Stockert, Cordelia Elaiho, Ben Readhead, Shalini S. Yadav, Joel Dudley, Ashutosh K. Tewari. Identification and biochemical validation of piperlongumine as a potent therapeutic against neuroendocrine prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr B023.
<i>MYC/BCL2/BCL6</i> triple hit lymphoma: A study of 33 patients who had an aggressive clinical course similar to patients with double hit lymphomas.
Authors: Shaoying Li, Wenting Huang, Yasuhiro Oki, L Jeffrey Medeiros
Journal: Journal of Clinical Oncology (2017)

7559 Background: Large B cell lymphomas with MYC, BCL2, and BCL6 rearrangements, designated as triple hit lymphoma (THL), are uncommon. Large series studies of THL are scant and studies comparing THL to different types of double hit lymphoma (DHL) are lacking. Methods: We studied the clinicopathologic features and prognosis of 33 patients with THL and compared them to 83 patients with MYC/BCL2 DHL and 13 patients with MYC/BCL6DHL. Results: There were 21 men and 12 women, with a median age of 63 years (range, 34-85). Six patients had a history of low-grade B cell lymphoma and 27 had de novo lymphoma. These tumors were classified histologically as: 21 DLBCL, 10 high grade B-cell lymphoma, one concurrent DLBCL and follicular lymphoma (FL), and one concurrent DLBCL and mantle cell lymphoma. Immunohistochemical analysis showed that these tumors were positive for CD10 (94%), BCL6 (80%), BCL2 (93%), and MYC (69%, 40% as cutoff). 62% of tumors (8/13) with available data showed coexpression of MYC and BCL2. Using the Hans algorithm, 30 of 33 (91%) tumors had a germinal center B cell like (GCB) immunophenotype. All 7 cases tested by conventional cytogenetics showed a complex karyotype. Although BCL2 was always translocated with IGH, BCL6 translocated to MYC in 2of 7 cases of THL. Twenty-nine patients had treatment information available and all received immune-chemotherapy induction, including 11 with R-CHOP, 14 with R-EPOCH, 3 with R-HyperCVAD, and one with RICE (patient had a history of FL). The clinicopathological features of THL including induction chemotherapy were very similar to both the MYC/BCL2 DHL and MYC/BCL6 DHL (all P&gt;0.05). There was no significant difference in median overall survival (OS) between patients with de novo lymphoma and those with a history of low-grade lymphoma (P=0.99). The OS in THL patients was 17.9 months, similar to the OS (17.2 months) of patients with MYC/BCL6 DHL and those with MYC/BCL2DHL (19.9 months) (P=0.60). Conclusions: MYC/BCL2/BCL6 THL is an aggressive B cell lymphoma and &gt;90% of cases have a GCB immunophenotype. THL patients usually have an aggressive clinical course and a poor prognosis, similar to patients with double hit lymphomas.
Mature progression-free survival (PFS) milestones in real world stage IV, non-squamous, non-small cell lung cancer patients (nsqNSCLC) treated with first line pemetrexed(Pem)/platinum(Plat) +/- bevacizumab(Bev) followed by pem +/-bev maintenance.
Authors: Parva Kiran Bhatt, Philip D. Bonomi, Sanjib Basu, Mary J. Fidler, Marta Batus
Journal: Journal of Clinical Oncology (2018)

e21063 Background: Pemetrexed maintenance therapy is associated with superior survival in stage IV nsqNSCLC patients. We have observed long term disease control in patients treated with Pem/Plat +/- Bev followed by Pem +/- Bev maintenance therapy. To our knowledge, there is no mature data regarding the tail of the PFS curve in these patients. The objectives of this retrospective analysis are to determine the frequency of long term disease control on Pem+/- Bev maintenance and to identify parameters associated with absence of disease progression. Methods: Our study looked at patients (pts.) with Stage IV nsqNSCLC who received first line Pem/Plat followed by Pem maintenance between May 2010 and December 2017. We identified 241 pts. from our database and analyzed their demographics, lab values, dates of therapy, and dates of progression. PFS was estimated by the Kaplan-Meier method and associations with patient characteristics were assessed by log-rank tests and Cox proportional hazards analysis. Results: Median age was 66 years, 60% female, and 72% Caucasian. Baseline ECOG performance status (PS) was 0(22%), 1(50%) and ≥ 2(22%). Disease progression was seen in 233 of 241 pts. with median PFS of 6.2 months. Absence of disease progression was observed in 34 pts. (14.2%) at 2 years, 19 pts. (7.9%) at 3 years, and 3 pts. (1.2%) at 5 years. Improved PFS was strongly associated with lower baseline neutrophil: lymphocyte ratio (NLR) when using NLR≤3.5 vs > 3.5 (median PFS 9.7 mo vs 5.2 mo, p = 0.004) as well as in a continuous scale (HR = 1.04, p < 0.001). ECOG PS of 0/1 was also associated with superior PFS (p < .001). Conclusions: The similarity in median PFS in our patients (6.2 mo) and clinical trial data suggests that our group of real world patients did not have uniquely favorable baseline characteristics. Although long term absence of progression may have been solely due to favorable natural history of disease, we believe that it was also due to Pem maintenance. As a result, continued development of Pem plus immunotherapy regimens in nsqNSCLC may result in a higher rate of long term disease control.
ICR gene signature to identify differential immune landscapes in anatomic subsites of head and neck squamous cell carcinomas and implications in personalized medicine.
Authors: Sara I. Pai, Daniel Clayburgh, Mihir Patel, Richard Bryan Bell, Bevan Yueh, Derrick Lin, Kyle Halliwell, Tolga Turan, Josue Samayoa, Belinda Cairns, Jong Chul Park, Rom S. Leidner, Lori J. Wirth, Nabil F. Saba, Dong Moon Shin, Manish Patel, Naomi Fujioka, Francesco Marincola, Daniel E. Afar, Debra Chao
Journal: Journal of Clinical Oncology (2018)

6052 Background: Head and neck squamous cell carcinoma (HNSCC) patients have a 16-25% response rate to single agent immune checkpoint inhibitors (ICI). Prognostic biomarkers to ICIs are needed to identify patients who may most benefit from immunotherapy and to deliver personalized treatment to patients. The Immunologic Constant of Rejection (ICR) 18-gene signature reflects activation of both innate and adaptive immune effector mechanisms required for successful host immune-mediated tissue-specific destruction. Methods: The ICR transcriptional signature was applied to 109 primary HNSCCs and matched tumor-involved lymph nodes (oral cavity (OC, N = 40), oropharynx (OP, N = 32), and larynx/hypopharynx (L/HP, N = 37)). Results: The ICR signature varied substantially across anatomic subsites, with OC and OP tumors having significantly higher ICR scores than L/HP tumors (p = 1.5e-06). The ICR signature between primary and matched metastatic lymph nodes were concordant in most cases, suggesting that sampling of either the primary or metastatic site yields concordant results in determining an immune-inflamed or immune-deserted landscape. Conclusions: Our data suggest that L/HP primaries are less likely to respond to ICIs based on a reduced ICR gene expression profile within the tumor microenvironment. Based on this hypothesis, we are performing a retrospective analysis of HNSCC patients treated with ICIs and will evaluate their objective clinical responses with respect to anatomical subsite. This is the first report that identifies anatomic subsites within the head and neck region to have differential immune landscapes. Correspondingly, differential responses to ICIs may be linked to the evolutionary biology of the various HNSCC primary subsites.
Gene expression profiling to identify new prognostic markers in glioma.
Authors: Elise Deluche, Barbara Bessette, Stephanie Durand, François Caire, Valerie Rigau, Sandrine Robert, Alain Chauvanel, Francois Labrousse, Marie-Odile Jauberteau, Karine Durand, Fabrice Lalloue
Journal: Journal of Clinical Oncology (2018)

e14054 Background: As glioma are heterogeneous tumors, it therefore appears increasingly necessary to associate with the histological examination molecular markers to improve diagnosis and targeted therapy glimpse of glioma. The aim of this study was to characterize a new signature in glioma. Methods: Glioma samples, histologically verified and graded according to WHO classification 2007, were obtained from 81 adult patients who underwent surgery at Limoges and Montpellier University Hospitals from 1993 to 2013. Gene expression profiling by TaqMan Low Density Array and hierarchical clustering were performed on 96 selected genes. IDH mutation and ARTX loss were achieved by immunohistochemical staining on tissue microarray. Our expression dataset was validated on independent cohort (n = 671), composed of RNA-seq expression data retrieved from glioblastoma (GBM) and lower grade glioma (The Cancer Genome Atlas (TCGA) project (http://www.xenabrowser.net/). Results: To have a homogenous cohort, we studied only 64 patients (26 women, 38 men, median age: 47 years, range: 22–81) with primary brain tumors obtained from resected surgical specimens and naive from radiotherapy and/or chemotherapy. Tumors were diagnosed as grade II oligo-astrocytoma (n = 9), grade III oligo-astrocytoma (n = 10), grade III astrocytoma (n = 8), GBM (n = 17), grade II oligodendroglioma (n = 10) and grade III oligodendroglioma (n = 10). IDH1 (R132) mutations were detected in 20 of 53 tumors. Thanks to two methods, we put in evidence a set of 28 genes, highly associated to gene expression patterns that classify tumors into two prognostic groups: a poor prognosis group with a median survival of 26.0 ± 4.5 months, and a good pronostic group with a median survival of 118.0 ± 0.8 months (p < 0.001). The hierarchical clustering analysis of TCGA cohort based on our selection of 28 genes showed similar results (p < 0.001). Furthermore, gene expression profiling was associated to IDH mutation to define good prognostic group. Conclusions: Based on 28 genes, we identified new biomarkers, which have not yet much explored, for differential diagnosis and prognosis in glioma.
Abstract 18635: Development of a Swine Model of Chronic Postcapillary Pulmonary Hypertension: Long Term Characterization by Cardiac Catheterization, Magnetic Resonance and Pathology
Authors: Daniel Pereda, Ana García-álvarez, Damián Sanchez-Quintana, Mario Nuño-Ayala, Rodrigo Fernández-Jiménez, Leticia Fernández-Friera, Jose Manuel García-Ruiz, Elena Sandoval, Manel Castella, Roger Hajjar, Valentin Fuster, Borja Ibañez
Journal: Circulation (2013)

Background: Postcapillary pulmonary hypertension (PH) has high prevalence and morbimortality. There are no large-animal models that fully reproduce postcapillary-PH. We aimed to develop and characterize a model that reproduced chronic postcapillary-PH including typical features in lungs and RV. Methods: Thirteen (10 banding, 3 sham) 4 week-old pigs underwent non-restrictive banding of the confluent of both inferior pulmonary veins. Chronic PH develops as the animal grows. Right heart catheterization and cardiac magnetic resonance (CMR) were performed immediately before and after the procedure and monthly thereafter during 4 months. Histopathology study of the heart and pulmonary vessels (Masson trichrome and picrosirius red staining) was performed at the end of the study. Results: All banded animals developed chronic PH. Compared to sham, mPAP in banded subjects was significantly higher after 1 month [median (1st-3rd quartile): 26mmHg (25-31) vs. 21mmHg (14-22), p=0.03], increased progressively and reached a plateau after month 3 [33mmHg (28-40) vs. 35mmHg (32-38) at months 3 and 4 respectively; Figure]. PVR behaved similarly and achieved significance after 2 months [5.2WU (3.8-7.1) vs. 2.3WU (2.1-3.5), p=0.03]. CMR demonstrated significant differences in indexed-RV end-systolic volume [42mL/m2 (36-53) vs. 24mL/m2 (24-33); p=0.03], indexed-RVmass [28g/m2 (27-29) vs.19g/m2 (18-23); p=0.02] and RVEF [59% (54-63) vs.66% (64-68); p=0.03] from the 2nd month and thereafter. Histopathology revealed vascular remodeling of pulmonary arteries including hypertrophy and fibrosis of the media, intimal fibrosis and RV myocardial disarray and fibrosis (Figure). Conclusions: We have successfully developed a large-animal model that produces chronic PH similar of that found in patients, associated with RV remodeling and typical pathology changes. The stability on PAP between months 3 and 4 makes this period the best to test therapies.