tbuckley/cabot-search huggingface dataset:
Association between level of tumor markers and development of venous thromboembolism in patients with pancreatic, colorectal and ovarian cancer: A retrospective case-control study.
Authors: Srijana Rai, Nelly Awkar, Ram Katpally, Hamid Salim Shaaban, Megan McGarry, Resty Tibayan, Gunwant K. Guron, Michael Maroules
Journal: Journal of Clinical Oncology (2015)

e14565 Background: Whether higher tumor marker levels in Pancreatic, Colorectal or Ovarian cancers are associated with increased risk of Venous Thromboembolism (VTE) is not known. Methods: We performed a retrospective case control study of patients admitted to two community hospitals with a diagnosis of Pancreatic, Colorectal or Ovarian cancer between January 2001 to December 2011. Tumor marker levels (CA 19-9, CEA and CA 125 respectively) were obtained from the patients and they were divided into those with a positive scan for either Deep Vein Thrombosis (DVT) via Ultrasonography or Pulmonary Embolism (PE) via CT angiography (VTE + group) and those with negative scans (VTE - group). The primary aim of the study was to determine whether higher tumor marker levels of CA 19-9, CEA and CA 125 were associated with a diagnosis of VTE in Pancreatic, Colorectal and Ovarian cancer patients respectively. Results: A total of 173 patients were included in the study with 72 patients in the VTE + group and 101 patients in the VTE - group. In our study, 66.7% (48/72) patients with high tumor markers were positive for VTE while 65.3% (66/101) with low (normal) tumor markers were negative for VTE, thus showing an association of high tumor marker levels with the diagnosis of VTE. This was statistically significant with an odds ratio of 3.77 and p-value of < 0.0001 (95% CI of 1.99-7.14). When the VTE group was further divided into DVT and PE groups, 70.2 % (40/57) patients in the the DVT positive group had high tumor markers with a p value of < 0.0001 and an odds ratio of 3.99 (95% CI of 2.02 to 7.89). The pulmonary embolism group had a 57.9% (11/19) patients with high tumor markers with a positive pulmonary embolism; this was, however, not statistically significant (p-value of 0.35 and a CI of 0.59 to 4.10). Conclusions: In this retrospective study of 173 individuals with a diagnosis of either Pancreatic, Colorectal or Ovarian Cancer, higher tumor marker levels (CA 19-9, CEA and CA 125 respectively) were associated with an increased risk of VTE, either DVT or PE. However, when further divided into either DVT or PE groups, the association remained statistically significant for DVT but not for PE.
Interim analysis of ibrutinib plus paclitaxel for patients with advanced urothelial carcinoma previously treated with platinum-based chemotherapy.
Authors: Daniel E. Castellano, Rafael Morales-Barrera, Ignacio Duran, Bhumsuk Keam, Ik Joo Chung, Hendrik-Tobias Arkenau, Ulka N. Vaishampayan, Mark Tuthill, Pablo Gajate, Sang Joon Shin, S. Paul Dang, Chia-Hsin Ju, Jennifer Lin, George W. Cole, Danelle Frances James, Oscar Reig
Journal: Journal of Clinical Oncology (2019)

4522 Background: Patients (pts) with advanced urothelial carcinoma (aUC) who progressed after platinum-based chemotherapy (PBCT) have a median overall survival (OS) of ~6 mo on CT and 8-10 mo on novel immune checkpoint inhibitors (ICIs). Treatment (tx) with ibrutinib (ibr), a first-in-class, once-daily inhibitor of Bruton’s tyrosine kinase (BTK) with immunomodulatory properties, plus paclitaxel (pac) may improve outcomes for pts with aUC. Methods: Pts with aUC who had 1-2 prior tx (≥1 PBCT and/or ICIs) formed one cohort of this phase 1b/2 study. Recommended phase 2 dose per phase 1b was ibr 840 mg/d + weekly pac 80 mg/m 2 in 21-d cycles; starting ibr dose of 560 mg/d. nanoString gene expression assay (NanoString Technologies) was used for preliminary assessment of ibr-targeted kinases in baseline tumor biopsies. Results: This interim analysis included the first 29 pts treated (ibr 840/560 mg/d, n = 25/4; median age 67 y). 52% had 2 prior regimens (prior PD-L1 inhibitors, 100%). Median time on study/tx was 7.2/2.3 mo (max tx: 11.5 mo). Unconfirmed overall response rate (ORR) was 41% (complete/partial response: 10%/31%). Disease control rate was 62%. ORR was 71% for 7 pts with only lymph node metastases; ORR was 36% for 14 pts with 1 prior tx and 47% for 15 pts with 2 prior tx. Median duration of response was 4.2 mo (90% CI: 1.9-7.1). Median progression-free survival was 3.6 mo (90% CI: 1.6-5.4). Median OS was 14.7 mo (90% CI: 7.7-15.9). Follow-up is ongoing for durability/survival with 6 pts alive without progression, including 4 still on ibr. 76% of pts had grade ≥3 adverse events (AEs); 4 discontinued ibr + pac due to AEs and 1 had major hemorrhage. Pac exposure was not impacted by ibr; pac geometric mean C max (2066 ng/mL) and AUC 0 -∞ (3813 ng·h/mL) were consistent with historical data. Preliminary tumor biopsy data showed a nonsignificant trend of higher BTK/ITK/BMX expression in tx responders; analyses are ongoing. Conclusions: Ibr + pac shows promising results for ORR/OS in pts with aUC previously treated with PBCT and ICIs. No unexpected safety signals were seen; ibr + pac seemed tolerable. Follow-up of these and additional pts will support the activity and safety of ibr + pac in this study. Clinical trial information: NCT02599324.
Presurgical anemia as a predictor of relapse and survival in bladder carcinoma treated with cystectomy.
Authors: Alvaro Pinto, Luis Eduardo García, Esther García, Noelia Herradon, Enrique Espinosa
Journal: Journal of Clinical Oncology (2019)

382 Background: Bladder carcinoma is the fifth most common neoplasm in developed countries. When muscle-invasive disease is diagnosed in a localized stage, radical cystectomy is the standard treatment, with or without perioperative chemotherapy. In this retrospective study we aim to identify presurgical factors that correlate with relapse risk and survival in patients being treated with radical cystectomy without neoadjuvant chemotherapy. Methods: Patients with a history of radical cystectomy for non-metastatic muscle-invasive bladder carcinoma from 1995 to 2010 were included. They had to have an appropriate follow-up, and tissue available for further correlative studies. Demographic baseline features and therapy outcomes were collected in a retrospective fashion. Results: A total of 158 patients were included, with a median overall survival (OS) for the entire cohort of 51 months (95% IC: 17.1–84.9 months). Median relapse free survival (RFS) is 39 months (95% IC: 3.8–74.1 months). In univariate analysis, the following features were prognostic factors for RFS: ECOG performance status (0 vs ³1; 72 vs 20 months, p=0.014), hemoglobin levels (normal vs low; 144 vs 21 months, p=0.001), free surgical margins (yes vs no; 39 vs 11 months, p=0.004), lymph node status (pN0 vs pN+; 119 vs 18 months, p&lt;0.001) and pT stage (pT2 vs pT3-4; 167 vs 20 months, p&lt; 0.001). Other previously described factors, such as neutrophil-lymphocite ratio, thrombocytosis, creatinine clearance or the presence of hydronephrosis, were not significant in our group of patients. In the multivariate analysis, only ECOG (HR 2.32), lymph node status (HR 2.0) and hemoglobin levels (HR 1.71) were independent predictors for RFS. Conclusions: In our group of patients, apart from ECOG performance status and lymph node status, the presence of presurgical anemia could be an indicator of poorer outcomes after cystectomy. These patients should be monitored closely and maybe considered for further therapeutic procedures, such as adjuvant systemic therapy.
Pre-operative ctDNA predicts survival in high-risk stage III cutaneous melanoma patients
Authors: J.H. Lee, R.P. Saw, J.F. Thompson, S. Lo, A.J. Spillane, K.F. Shannon, J.R. Stretch, J. Howle, A.M. Menzies, M.S. Carlino, R.F. Kefford, G.V. Long, R.A. Scolyer, H. Rizos
Journal: Annals of Oncology (2019)

BackgroundThe outcomes of patients with stage III cutaneous melanoma who undergo complete surgical resection can be highly variable, and estimation of individual risk of disease recurrence and mortality remains imprecise. With recent demonstrations of effective adjuvant targeted and immune checkpoint inhibitor therapy, more precise stratification of patients for costly and potentially toxic adjuvant therapy is needed. We report the utility of pre-operative circulating tumour DNA (ctDNA) in patients with high-risk stage III melanoma.Patients and methodsctDNA was analysed in blood specimens that were collected pre-operatively from 174 patients with stage III melanoma undergoing complete lymph node (LN) dissection. Cox regression analyses were used to evaluate the prognostic significance of ctDNA for distant metastasis recurrence-free survival and melanoma-specific survival (MSS).ResultsThe detection of ctDNA in the discovery and validation cohort was 34% and 33%, respectively, and was associated with larger nodal melanoma deposit, higher number of melanoma involved LNs, more advanced stage and high lactate dehydrogenase (LDH) levels. Detectable ctDNA was significantly associated with worse MSS in the discovery [hazard ratio (HR) 2.11 P < 0.01] and validation cohort (HR 2.29, P = 0.04) and remained significant in a multivariable analysis (HR 1.85, P = 0.04). ctDNA further sub-stratified patients with AJCC stage III substage, with increasing significance observed in more advanced stage melanoma.ConclusionPre-operative ctDNA predicts MSS in high-risk stage III melanoma patients undergoing complete LN dissection, independent of stage III substage. This biomarker may have an important role in determining prognosis and stratifying patients for adjuvant treatment.
External validation of prostatectomy incontinence nomogram (PIN).
Authors: Rubin Pinkhasov, Alexandr M. Pinkhasov, Kristopher Attwood, Michall Abaev, Willie Underwood
Journal: Journal of Clinical Oncology (2019)

106 Background: Using previously developed prostatectomy incontinence nomogram (PIN) we sought to externally validate the nomogram that predicts probability of incontinence at 6-, 12-, and 24-months after robot assisted radical prostatectomy (RARP). Methods: Prospective data from 663 men with prostate cancer that underwent RARP from 2010 to 2014 at two comprehensive cancer centers and three large group practices was queried. The performance of the previously developed model was evaluated using calibration plots (predicted continence rates versus observed continence rates with 95% CI obtained using Jeffrey’s prior method) and receiver operating curves (ROC). Using Expanded Prostate Cancer Index Composite (EPIC-50) Urinary Function questionnaire, perfect continence was defined as 0 pads, social continence was defined as 1 or 2 pads, and incontinence was defined as ≥ 3 pads used after RARP. Results: The 6-, 12-, and 24- month social continence rates were 77%, 88%, and 93%, respectively. Similar to the 6- and 12-month model development cohort, the external validation cohort has modest predictability with a 6- and 12- month AUC of 0.61, and 0.62, respectively. The 24-month AUC of 0.62 in the external validation cohort is worse than what was reported in the development cohort (AUC 0.80). Conclusions: The externally validated prostatectomy incontinence nomogram is generalizable but has modest 6-, 12-, and 12-month predictability in risk of incontinence after RARP.
Abstract P130: Disparities in Out-of-hospital Cardiac Arrest Rates Among Adults, Aged ≥18 Years Old, With 9-1-1 Emergency Medical Service Activation’s in the United States, 2016
Authors: Isaac Nwaise, Erika C Odom
Journal: Circulation (2019)

Introduction: Out-of-hospital cardiac arrest (OHCA) is a significant public health issue. Hypothesis: This study aims to assess whether patients’ age, sex, race/ethnicity, and urban/non-urban status are associated with the rate of OHCA events among adults who accessed 9-1-1 emergency medical services (EMS) in 2016. Methods: We conducted a cross-sectional analysis using the 2016 National Emergency Medical Services Information System (NEMSIS), a national EMS database. OHCA events among adults aged ≥18 years were extracted by sex, age group, race/ethnicity, urban and non-Urban categories. Those with unknown race/ethnicity (45.8%) or of other race (1.3%) were excluded. Rates of OHCA events were calculated and Chi-square tests were used to assess associations. Results: We identified 205,461 OHCA events with EMS activations among non-Hispanic (NH) whites (68.1%), NH blacks (23.2%), and Hispanics (8.7%) in the 2016 NEMSIS dataset. Of the OHCA events, 59.5% were among males, 81.1% among urban residents, and 15.4% among non-urban residents. The overall OHCA rate was 19.6 per 1,000 EMS activations. OHCA rates per 1,000 EMS activations increased with age for adults until age 74, ranging from 11.2 (18-34 years) to 25.1 (65-74 years), then decreased with age for older adults ≥75 ranging from 22.3 (75-84 years) to 20.8 (≥85 years) ( p &lt;.0001). OHCA rates were higher among males 25.3, Hispanics 20.9, and urban residents 21.7 than females 15.6, other race ethnicities (NH whites 19.8 and NH blacks 18.7), and non-urban residents 17.6 ( p &lt;.0001) respectively. Conlusions: OHCA incidence rates among EMS activations increased with age until age 74. Adult males, Hispanics, and urban patients had statistically significant higher EMS activations for OHCA rates. Findings can be incorporated in community planning for improving EMS services.
Blood myeloid derived suppressor cells (MDSC) in metastatic urothelial carcinoma (mUC) are correlated with neutrophil-to-lymphocyte ratio (NLR) and overall survival (OS).
Authors: Iris Yeong- Fung Sheng, C. Marcela Diaz-Montero, Patricia A. Rayman, Wei (Auston) Wei, Jaleh Fallah, James Finke, Jin Sub Kim, Paul G. Pavicic, Marcelo Lamenza, Donna Company, Andrew J. Stephenson, Steven Campbell, Georges-Pascal Haber, Byron H Lee, Omar Y. Mian, Timothy D. Gilligan, Brian I. Rini, Jorge A. Garcia, Petros Grivas, Moshe Chaim Ornstein
Journal: Journal of Clinical Oncology (2019)

436 Background: MDSC have been linked to the chronic inflammatory microenvironment of tumor cells and pathologic outcomes in UC patients (pts) undergoing cystectomy. NLR is an established inflammatory biomarker with prognostic properties in mUC. We hypothesized that MDSCs correlate with NLR and OS in mUC. Methods: MDSCs were measured in blood samples from mUC patients by fresh unfractionated whole blood (WB) and peripheral blood mononuclear cells (PBMC). MDSCs were identified by flow cytometry in WB and defined as LinloCD33+/HLADR- (Total MDSC). MDSC subsets were defined as polymorphonuclear (PMN-MDSC: CD15+/CD14-), monocytic (M-MDSC: CD15-/CD14+), and uncommitted (UC-MDSC: CD15-/CD14-). MDSC populations were presented as % of live nucleated blood cells from PB and absolute numbers from WB. Spearman’s correlation assessed correlations between MDSC &amp; NLR. Kaplan Meier curves and log rank test estimated OS from the time of MDSC collection to last follow up or date of death. Results: Of 79 pts, 77% were men and 42% were never smokers with a median age of 69 (31-83). Overall, 71% had pure UC and 81% had lower tract UC. Prior therapies include intravesical therapy (22%), neoadjuvant chemotherapy (31%), and cystectomy/nephroureterectomy (61%). Median follow up was 12 months (range: 0.6-36.5). PMN-MDSC was the predominant subset in WB and PBMC. There was significant correlation between individual MDSC subsets in WB and PBMC (p≤0.001). Negative correlation was noted between NLR and WB UC-MDSC:PMN-MDSC ratios (rho = -0.27, p = 0.03), as well as NLR and PB UC-MDSC:PMN-MDSC (rho = -0.28, p = 0.02). Median survival was 17.7 months (95% CI: 11.0-NA months). Overall 1-yr and 3-yr survival were 0.60 (95% CI: 0.49-0.73) and 0.15 (95% CI: 0.03-0.67), respectively. Higher WB UC-MDSC levels were associated with shorter OS (HR 2.85, 95% CI: 1.43-5.65, p = 0.003). Conclusions: Specific MDSC subsets correlate with NLR. Higher WB UC-MDSC levels have negative prognostic roles for OS. Given the feasibility of serial blood draws, dynamic assessment of MDSC over time and further validation with longer follow up are needed.
The biology of mental disorders: What are we talking about?
Authors: Alfonso Troisi
Journal: Behavioral and Brain Sciences (2019)

Abstract After the Darwinian revolution, biology is not only the study of the operation of structural elements (functional biology), but also the study of adaption and phylogenetic history (evolutionary biology). From an evolutionary perspective, the biology of mental disorders is not just “neurobiology and genetic constitution” but also adaptive reactions to adverse situations. Evolutionary explanations of mental disorders are biological and non-reductionist.
Survival rates after retroperitoneal lymph node dissection (RPLND) for testicular seminoma.
Authors: Alexandra Tabakin, Sinae Kim, Charles Polotti, Brian Shinder, Zorimar Rivera-Nunez, Joshua Sterling, Nicholas Farber, Kushan Dilip Radadia, Isaac Yi Kim, Eric A. Singer, Thomas Jang
Journal: Journal of Clinical Oncology (2019)

534 Background: RPLND as first-line treatment for testicular seminoma is less well defined than for testicular nonseminomas. Furthermore, RPLND performed in the post-chemotherapy (PC) setting for seminoma patients with a PET avid residual mass &gt; 3 cm can be technically challenging. We describe utilization of RPLND in the primary and PC settings and report on overall survival rates following surgery for these men. Methods: Using 2004-2014 data from the National Cancer Database, we identified 62,727 men with 1° testicular cancer, of which 31,068 men were diagnosed as having seminoma. After excluding men with benign, non-germ cell, and nonseminoma histologies, those who did not undergo RPLND, and those whose clinical stage (CS) or survival data were unavailable, 412 men comprised our final cohort. Men were further stratified according to whether they had 1° RPLND vs PC-RPLND, with 1° RPLND defined as RPLND performed for CS IA-IIB without prior chemotherapy, and PC-RPLND classified as RPLND performed for CS IIA-IIIC after chemotherapy. Descriptive statistics were used to summarize clinical and demographic factors. The Kaplan-Meier method was used to determine overall survival. Results: From 2004-2014, 412 men with testicular seminoma underwent RPLND, of which 89% and 11% were in the 1° and PC settings, respectively. There were no significant differences in clinical or demographic characteristics when comparing men in these 2 groups. The majority of men with testicular seminoma undergoing PC-RPLND were treated at an academic center (63.8%) or comprehensive community cancer program (21.3%). The median follow-up was 4.1 years. Of 372 patients with available survival data, five-year overall survival was 94.2% and 89.0% in the 1° RPLND and PC- RPLND groups, respectively. Conclusions: Though RPLND is rarely used as 1° therapy in testicular seminoma, overall survival rates appear to be excellent, as they do for men with testicular seminoma after PC-RPLND. Ongoing trials evaluating the use of RPLND for early metastatic, low-volume disease will clarify its role in the management of testicular seminoma.
Prognostic factors in patients with second and third line treatment for testicular germ-cell tumors (TGCT): analysis of patients treated at the National Institute of Cancer (INCan), Mexico.
Authors: Miguel A. Alvarez, Nora Sobrevilla-Moreno, Jose Luis Aguilar, Rodrigo Espinosa-Fernandez, Jorge Martinez-Cedillo, Yolanda Miranda-Ponce, Alejandro Escalona-Ledesma, Miguel Jimenez, Angel Herrera Gomez
Journal: Journal of Clinical Oncology (2015)

e15548 Background: TGCT is the most common malignant solid neoplasm in young men. Those with advanced disease have survival rates between 40 to 80%, 30% will relapse. Treatment and prognostic facto...
Role of endothelial-specific growth-factors in efficacy of cetuximab in pts with head and neck squamous cell carcinoma (HNSCC).
Authors: Liubov Yu Vladimirova, Elena Mikhaylovna Frantsiyants, Marina Engibaryan, Aza Agieva, Yulia A. Pogorelova, Natalya A Abramova, Irina Viktorovna Pustovaya
Journal: Journal of Clinical Oncology (2015)

e17013 Background: The EGFR transduction pathway is known to regulate tumor angiogenesis. Impairments in this growth factor system could be a reason for inappropriate tumor response. The aim of the study was to investigate endothelial specific growth factors in the tumor tissue and around (perifocal zone and intact tissue-tumor resection line) depending on Cetuximab (C) efficacy in the treatment of patients with HNSCC. Methods: 27 pts (77,7% (21) male and 22,3% (6) female, mean age 57,5+1,7 years,T3-4N0-1M0) were recruited. C was administered 400 mg/m2 D1 and 250 mg/m2 q1w with Carboplatin AUC5 in D1 and Fluorouracil 1000 mg/m2 D 1-4 of 21 day cycle.VEGF/EGF, VEGFA/VEGFB, VEGFA/TGF rations were studied in the tumor tissue, its perifocal zone and intact tissue by ELISA. The tissue samples of the pts treated without C were used as the control. Results: In patients with tumor response the tumor tissue 3,5-fold decrease in VEGFA/EGF ratio, 4,8-fold decrease in VEGFA/VEGFD, 3,2-fold decrease in VEGFA/TGF ratio were found in compared to the control. In the perifocal tissue 3,2-fold decrease in VEGFA/EGF, 5,7-fold decrease in VEGFA/VEGFD, 2,3-fold decrease in VEGFA/TGF were found compared to the control. In the intact tissue 1,7-fold decrease in VEGFA/EGF, 2,5-fold decrease in VEGFA/VEGFD, 1,7-fold decrease in in the tumor tissue VEGFA/TGF were found (p < 0,05). In pts with tumor progression 2,3-fold decrease in VEGFA/EGF, 1,6-fold decrease in VEGFA/TGF were found, meanwhile 2,4-fold increase in VEGFA/VEGFD was found. In the perifocal zone 3,2-fold decrease in VEGFA/EGF, 1,6-fold increase in VEGF/VEGFD were found, and VEGFA/TGF ratio had not changed (p < 0,05). In the intact tissue 1,4-fold increase in VEGFA/EGF, 2,6-fold increase in VEGFA/VEGFD were found (p < 0,05). Conclusions: The data reported give a great evidence on neoangiogenesis suppression, caused by C in cases with tumor response. Growth factors activity in the tumor as well as in tissues around plays a great role in tumor response to C.