tbuckley/cabot-search huggingface dataset:
Predictors of readmission for hospitalized cancer patients: A cohort study.
Authors: Shiva Shrotriya, Davendra Sohal, Alberto J. Montero, Alok A. Khorana
Journal: Journal of Clinical Oncology (2016)

e18185 Background: Reducing unplanned hospital readmissions is a national policy priority aimed at improving health care quality. It is unclear if readmissions are preventable in cancer patients with ongoing complexities of care. We conducted a retrospective cohort study to identify rates and predictors of readmission among cancer inpatients. Methods: We conducted a retrospective cohort study including all consecutive admissions with between January and December 2013 at the general medical oncology floor Cleveland Clinic. We conducted logistic regression analyses to identify predictors of readmission. Results: There were 1210 admissions. Of these, 262 inpatients were readmitted within 30 days (21.6%). Of the readmitted patients, 57% were females; mean age (±SD) was: 63 ± 12.2 years; 72% were Caucasians and 23% were African Americans. Median (range) length of stay among readmitted patients was 4(0-46) days. Common cancers were renal (72%), lymphoma (22%), lung (21%) and breast (17%). On univariate analysis, those with renal (RR: 1.62; 1.33-2.05) and gastric (RR: 1.04; 0.99-1.09) cancers were at higher readmission risk. Comorbidities such as respiratory illness (RR: 3.32; 2.27-5.83), anemia (RR: 2.24; 1.62-3.32), infections (RR: 1.86; 1.44-2.39), hypertension (RR: 1.40; 1.10-1.81), venous thromboembolism; VTE (RR: 1.31; 1.16-1.50), diabetes (RR: 1.21; 1.10-1.36), hepatic diseases (RR: 1.18; 1.04-1.35), anxiety (RR: 1.14; 1.02-1.30), congestive heart failure (RR: 1.10; 1.02-1.87), pressure ulcers (RR: 1.12; 1.04-1.22) cerebrovascular diseases (RR: 1.12; 1.05-1.21) increased ALT (RR: 1.05; 0.99-1.11) and increased AST (RR: 1.05; 0.99-1.11) were also associated with increased readmission risk on univariate analysis. On multivariate analysis, only infections (OR: 2.01; 1.06-3.80) and respiratory illnesses (OR: 4.21; 1.58-11.19) remained independent predictors of readmission. Conclusions: Hospitalized cancer patients are at high risk of readmission. Comorbidities, particularly infections and respiratory illnesses, are independent predictors of readmission. Interventions aimed at reducing readmissions should target this high-risk population to reduce health care resource utilization and burden to patients.
Prognosis of melanoma progression based on its cytokine microenvironment.
Authors: Elena Yurievna Zlatnik, Oleg Ivanovich Kit, Sergey Kochuev, Aleksandra Demidova, Yury Valentinovich Przhedetskiy, Viktoria V. Pozdnyakova, Olga V. Khokhlova, Inna Arnoldovna Novikova
Journal: Journal of Clinical Oncology (2018)

e21625 Background: The purpose of the study was the development of a mathematical model of predicting the progression of cutaneous melanoma based on an assessment of its local cytokine microenvironment. Methods: Tumor and peritumoral tissues of 56 patients (21 women and 35 men aged 31-86 years, Breslow thickness T1-T4) were studied. Tissue sampled were obtained during surgery and homogenized, levels of TNF-α, IL-1ß, IL-1RA, IL-6, IL-8, IFN-α and IFN-γ were determined by ELISA as pg/mL per 1 g of protein; tumor diploidy/aneuploidy was evaluated by DNA cytometry. Patients received surgery with following chemoradiotherapy or interferon therapy. The observation period was 3-24 months long. Statistical processing of the data was performed using STATISTICA software. The cut-off point was determined with the maximal diagnostic sensitivity and specificity for every parameter. ROC curves were used to assess the quality of tests. Results: An analysis of the cytokine microenvironment in comparison with the clinical course of melanoma allowed revealing parameters that were statistically significant for the prognosis: IL-6˃4.45 pg/mL/g in tumor tissues, IL-1β˃11.03 pg/mL/g and IL-2˃1.71 pg/mL/g in peritumoral tissues were associated with the disease progression. As a result, we developed a formula involving the parameters, and a criterion for the tumor extent and ploidy allowing calculation of the C coefficient. C˃0.64 indicated the risk of the melanoma progression. Conclusions: The comparison of the studied parameters of the cytokine microenvironment with the disease course during the observation period and biological characteristics of tumors allowed the development of a mathematical model of predicting the progression of cutaneous melanoma. The local cytokine microenvironment of melanoma can be considered a prognostic factor for the disease course.
Efficacy of immunotherapy in advanced melanoma: A network meta-analysis.
Authors: Belal Firwana, Mohamad Bassam Sonbol, Shebli Atrash, M. Hassan Murad, Issam Makhoul, Laura Fulper Hutchins, Fade A. Mahmoud
Journal: Journal of Clinical Oncology (2016)

e21033 Background: Checkpoint inhibitor therapy exhibited a paradigm shift in advanced melanoma. Available clinical trials provide direct comparison of T-lymphocyte–associated protein 4 (CTLA-4) blocking antibody, ipilimumab, and programmed cell death 1 (PD1) inhibitors, pembrolizumab or nivolumab, with no head-to-head trials to compare PD1 inhibitors against each other. We conducted a network meta-analysis (NMA) to summarize the evidence on immunotherapy efficacy in patients with advanced melanoma. Methods: We included randomized controlled trials (RCTs) that evaluated the efficacy of ipilimumab versus pembrolizumab or nivolumab in patients with previously untreated metastatic stage IV or unresectable stage III melanoma. Efficacy outcome measures included complete response rate (CRR), best overall response rate (ORR) which consists of both complete and partial response rates, and progressive disease (PD) after treatment, in accordance with RECIST. Bayesian NMA method was used to conduct this NMA that pools evidence from direct and indirect comparisons to facilitate simultaneous inference regarding all treatments used. Results: Five trials enrolling 2841 patients with advanced melanoma were identified. NMA demonstrated superiority of PD1 inhibitors, nivolumab or pembrolizumab, over ipilimumab. The combination of nivolumab plus ipilimumab had the highest probability of achieving ORR of 94% (credibility intervals [CrI] 0.0-1.0) and CRR of 61% (CrI 0.0-1.0) compared to other treatments and had the least probability of PD. Either Nivolumab or pembrolizumab alone had the second probability of being best interchangeably, with similar efficacy profiles between the two drugs. Conclusions: PD1 inhibitors are associated with higher probability of achieving efficacy compared to CTLA-4 inhibitor in terms of better ORR and CRR, and lower PD. The certainty of the evidence in this NMA is limited by indirectness and severe imprecision, however our results parallel the evidence based practice. Both nivolumab and pembrolizumab have similar efficacy. NMA is not a substitute for well conducted RCTs investigating direct comparisons.
Active surveillance (AS) in the management of patients (pts) with metastatic renal cell carcinoma (mRCC).
Authors: Philipp Ivanyi, Hendik Eggers, Christoph Alexander Seidel, Christoph Reuter, Arnold Ganser, Viktor Gruenwald
Journal: Journal of Clinical Oncology (2016)

e16070 Background: AS might reflect a feasible approach in mRCC pts. Therefore, we explored pts who were assigned to AS in our clinic to identified predictive characteristics. Methods: mRCC pts with first-line (1stL) treatment (Rx) initiation and/or primary diagnosis of mRCC from 04/2000-06/2012 were retrospectively analyzed. Data were extracted from pts records. Pts receiving 1stL Rx deferred by >6 months after mRCC diagnosis were considered AS pts. Descriptive statistics, Kaplan-Meier and cox-regression were applied. Results: 222 mRCC pts at a median age of 62 (range (r):26-86) years, predominantly male (68.9%), whereof 94.3% received nephrectomy revealing in 80.2% a clear cell RCC were identified. 68 AS pts were identified (median time to1stL Rx:21.4(r:6-199) months). Overall-survival (OS) from 1stL Rx was superior in AS pts (AS:32.7(23.9-41.5), non-AS:24.6(17.3-31.9) months, log-rank: p=0.003). Time from diagnosis of mRCC to 1stL Rx, an initial N+ stage, and time from RCC to mRCC ≤1 year were identified as independent risk parameter for OS. Conclusions: AS is feasible in selected pts. Delay of therapy had no negative impact on OS and was applied in 30.6% of pts. Ultimately, AS defers toxicity and potentially improves quality of life. mRCC with aggressive behavior achieve an inferior outcome and may not be suitable for AS. Additional studies are warranted. Cox-regression of parameters influencing OS. Univariate Multivariate HR (95%-CI) p HR (95%-CI) p Age 1 (0.98-1.01) 0.915 T Stage >2 vs. ≤2 1.26 (0.89- 1.77) 0.188 N Stage N+ vs. N- 2.52 (1.59- 4.01) <0.001 2.12 (1.26- 3.57) 0.005 Grading >2 vs. ≤2 1.93 (1.33- 2.8) 0.001 N.S AS vs. non-AS 0.59 (0.41- 0.84) 0.004 N.S. Time mRCC to 1stL Rx, months 0.98 (0.97- 0.99) 0.001 0.98 (0.98- 0.97) 0.021 Time RCC to mRCC >1 vs. ≤1 year 0.57 (0.41- 0.8) 0.001 0.59 (0.37-0.95) 0.03 Number metastatic organ sites 1.13 (1-1.27) 0.031 N.S. Pulmonary metastasis 1.37 (0.99- 1.9) 0.053 N.S. Liver metastasis 1.6 (1.07- 2.41) 0.023 N.S. Lymphnodal metastasis 1.6 (1.24- 2.16) 0.008 N.S. Parameters with p≤0.1 were considered for multivariate analysis. N.S.: not significant.
Enhancing clinician confidence on the therapeutic management of non-small cell lung cancer (NSCLC) through continuing medical education (CME).
Authors: Hamsa Jaganathan, Anne Roc, Mark A. Socinski, Wendy Turell
Journal: Journal of Clinical Oncology (2017)

e18271 Background: The evolving strategies to personalize NSCLC treatment have challenged clinicians to remain abreast of and integrate targeted therapy into practice. To address this challenge, 2 CME programs on NSCLC were developed in 2 formats (1-hour cumulative program and a series of 3-1 hour specified programs). Participant responses were compared between the 2 formats to examine differences in learner confidence and competence regarding the management of NSCLC with targeted therapy. Methods: PlatformQ Health developed and executed 2 virtual CME programs in NSCLC. The first program, broadcast in August 2015 and offered for 6 months, attracted 225 learners. This 1 hour program reviewed the latest data of EGFR inhibitors (EGFRi), ALK inhibitors (ALKi), and immunotherapy. In 2016, these 3 topics were divided into a series of 3-1 hour CME programs and offered across the year, which has attracted 371 learners. Survey-based evaluations targeted self-reported clinician data on competence (via patient case studies) and confidence. Results: As of January 2017, learner surveys from EGFR- and ALK-focused education were analyzed. It was observed that learners gained more confidence in managing EGFRi-related toxicities after the 2016 serial education vs the 2015 cumulative education (62% vs 43%, respectively). Learners also felt more confident when evaluating data of available and emerging ALKi (49% vs 35%). Greater competence in management was observed with serial vs cumulative education regarding EGFRi (42% and 15%, respectively) and ALKi (30% and 4%) therapies. Both programs demonstrated a high learner commitment to change in: medical and practice knowledge (93% and 91%, respectively), care attitudes (87% and 87%), practice behavior (85% and 79%), and patient clinical outcomes (86% and 77%). Data analysis on immunotherapy education is ongoing. Conclusions: Overall, education on targeted therapy for NSCLC have demonstrated positive learner outcomes. However, designing education in a serial format that dives deeper into each therapeutic target class affords greater improvements in clinician confidence and learner competence in the therapeutic management of NSCLC.
Prognosticating Outcomes in Interstitial Lung Disease by Mediastinal Lymph Node Assessment. An Observational Cohort Study with Independent Validation
Authors: Ayodeji Adegunsoye, Justin M. Oldham, Catherine Bonham, Cara Hrusch, Paul Nolan, Wesley Klejch, Shashi Bellam, Uday Mehta, Kiran Thakrar, Janelle Vu Pugashetti, Aliya N. Husain, Steven M. Montner, Christopher M. Straus, Rekha Vij, Anne I. Sperling, Imre Noth, Mary E. Strek, Jonathan H. Chung
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Rationale: Mediastinal lymph node (MLN) enlargement on chest computed tomography (CT) is prevalent in patients with interstitial lung disease (ILD) and may reflect immunologic activation and subsequent cytokine-mediated immune cell trafficking.Objectives: We aimed to determine whether MLN enlargement on chest CT predicts clinical outcomes and circulating cytokine levels in ILD.Methods: MLN measurements were obtained from chest CT scans of patients with ILD at baseline evaluation over a 10-year period. Patients with sarcoidosis and drug toxicity–related ILD were excluded. MLN diameter and location were assessed. Plasma cytokine levels were analyzed in a subset of patients. The primary outcome was transplant-free survival (TFS). Secondary outcomes included all-cause and respiratory hospitalizations, lung function, and plasma cytokine concentrations. Cox regression was used to assess mortality risk. Outcomes were assessed in three independent ILD cohorts.Measurements and Main Results: Chest CT scans were assessed in 1,094 patients (mean age, 64 yr; 52% male). MLN enlargement (≥10 mm) was present in 66% (n = 726) and strongly predicted TFS (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.12–2.10; P = 0.008) and risk of all-cause and respiratory hospitalizations (internal rate of return [IRR], 1.52; 95% CI, 1.17–1.98; P = 0.002; and IRR, 1.71; 95% CI, 1.15–2.53; P = 0.008, respectively) when compared with subjects with MLN <10 mm. Patients with MLN enlargement had lower lung function and decreased plasma concentrations of soluble CD40L (376 pg/ml vs. 505 pg/ml, P = 0.001) compared with those without MLN enlargement. Plasma IL-10 concentration >45 pg/ml predicted mortality (HR, 4.21; 95% CI, 1.21–14.68; P = 0.024). Independent analysis of external datasets confirmed these findings.Conclusions: MLN enlargement predicts TFS and hospitalization risk in ILD and is associated with decreased levels of a key circulating cytokine, soluble CD40L. Incorporating MLN and cytokine findings into current prediction models might improve ILD prognostication.
PD.1.01 Health-Related Quality of Life with Pembrolizumab or Placebo + Pemetrexed + Platinum in Non-Squamous NSCLC: KEYNOTE-189
Authors: M. Garassino, D. Rodríguez-Abreu, S. Gadgeel, E. Esteban, E. Felip, G. Speranza, M. Domine, M. Hochmair, S. Powell, S. Cheng, H. Bischoff, N. Peled, M. Reck, R. Hui, E. Garon, M. Boyer, J. Yang, T. Burke, M.C. Pietanza, L. Gandhi
Journal: Journal of Thoracic Oncology (2018)
Potentially curative combination of TGF-b1 inhibitor losartan and FOLFIRINOX (FFX) for locally advanced pancreatic cancer (LAPC): R0 resection rates and preliminary survival data from a prospective phase II study.
Authors: Janet E. Murphy, Jennifer Yon-Li Wo, David P. Ryan, Wenqing Jiang, Beow Y Yeap, Gabriel Dan Duda, Jill N. Allen, Lawrence Scott Blaszkowsky, Cristina Ferrone, Aparna Raj Parikh, Ryan David Nipp, Andrew X. Zhu, Lipika Goyal, Keith D Lillemoe, Thomas F. DeLaney, Rakesh K. Jain, Jeffrey W. Clark, Yves Boucher, Carlos Fernandez-del Castillo, Theodore S. Hong
Journal: Journal of Clinical Oncology (2018)

4116 Background: FFX is under study in LAPC for its potential for curative resection, but the downstaging rate remains low. Preclinical data suggest that inhibition of the renin-angiotensin system with losartan reduces TGF-b1 activity, enhancing intratumoral penetration of chemotherapy by remodeling desmoplasia and improving perfusion. This study investigated the R0 resection rate of FFX/losartan in LAPC. Methods: LAPC pts (per NCCN criteria), ECOG PS 0-1 were enrolled in a single institution NCI-sponsored phase II study (NCT01821729). Pts received 8 cycles FFX/losartan. If the tumor was radiographically resectable after chemotherapy, pts received short-course chemoradiation (CRT) in 5 fractions (protons 25 GyE, capecitabine 825 mg/m2 bid). If the tumor still abutted vasculature, pts received CRT to 50.4 Gy with a vascular boost to 58.8 Gy. Primary endpoint was R0 resection rate. Secondary endpoints were mPFS, mOS and circulating biomarkers of losartan activity. Results: 50 pts enrolled from 8/2013 to 7/2017. One pt withdrew consent, and 49 pts were evaluable for this analysis. Median age was 63y (42-78), tumor size was 41mm (18-68). Tumor was in the pancreatic head in 31 (63%) of pts. 39 pts received 8 cycles of FFX/losartan, while 10 had fewer than 8 cycles due to progression (4), losartan intolerance (3), and toxicity (3). Grade 3 or greater toxicity occurred in 25 (51%) pts, including diarrhea , thrombocytopenia, nausea, and neutropenia/febrile neutropenia. No single grade 3+ toxicity occurred in more than 14% of pts. 46 pts recieved CRT: 7 pts (14%) had short-course, while 39 pts (80%) had long-course CRT. 39 pts underwent attempted surgery, with 34 pts resected. R0 resection was achieved in 30 pts (61% of evaluable pts, 88% of resected pts), with R1 resection in 4 pts. Overall mPFS was 17.5 months and mOS 31.4 months. Among resected pts, mPFS was 21.3 months and mOS was 33.0 months. Biomarker analysis showed superior OS in pts with lower plasma levels of HGF at baseline. Conclusions: FFX/losartan achieved a remarkably high (61%) R0 resection rate in LAPC pts. A multi-center randomized Phase II trial is planned. Clinical trial information: NCT01821729.
Circulating tumor cell subsets and macrophage polarization to predict efficacy of cabozantinib in advanced prostate cancer with visceral metastases.
Authors: Edwin M. Posadas, Jie-Fu Chen, Manisha Tripathi, Yi-Tsung Lu, Alexander Montes, Ann Go, Alexander Ureno, Karen Angelica Cavassani, Margarit Sievert, Andre Rogatko, Suwicha Limvorasak, Amy Oppenheim, Nancy P. Moldawer, Leland WK Chung, Neil Bhowmick, Hsian-Rong Tseng, Robert A. Figlin
Journal: Journal of Clinical Oncology (2017)

5031 Background: The presence of VM in metastatic, castration-resistant prostate cancer (mCRPC) predicts poor survival. Cabozantinib (cabo) is a multi-kinase inhibitor that has clinical activity that did not improve survival in an unselected mCRPC population. Subgroup analyses suggested that the benefit may exist for patients (pts) with mCRPC-VM. The effect of cabo includes the tumor microenvironment, monocytes in particular, which in turn can alter tumor behavior. Methods: We conducted a single-arm study of cabo in men with mCRPC-VM. Pts received cabo 60 mg daily. Radiographs were used to assess response. Correlative blood samples were collected for the enumeration and characterization of circulating tumor cells using the NanoVelcro Assay and analysis of circulating monocytes by FACS. Results: A total of 17 pts enrolled with 16 evaluable for response. At 12 weeks, 19% experienced partial responses (PR), 44% stable disease (SD), and 38% progressive disease. The clinical benefit rate (PR+SD) at 12 weeks was 63%. Safety profile was consistent with previous reports. CTCs were detected in 80% of pts. NanoVelcro CTC counts showed reduction by week 8 in both PR+SD (88%) and PD (71%) groups with re-emergence at progression. Among pts with liver metastases, very-small-nuclear CTCs ( &lt; 8.5 μm) were seen in 29% of pts with clinical benefit compared to 60% in non-benefiters. Analysis of monocyte polarization after initiation of therapy showed that reduction of M1 polarization was associated with improvement in bone pain and/or bone scan. Conclusions: In heavily-pretreated mCRPC-VM, cabo provided clinical benefit with acceptable toxicity. Circulating biomarkers related to both tumor and microenvironment may be useful in identifying patients who benefit from this type of therapeutic approach. Clinical trial information: NCT01834651.
The clinical impact of miRNA34a and P53 gene expression in colon cancer
Authors: S.F. Gohar, E.A. Badr, M. Assar, M. Badr, R. Hathout, S. El-Kousy
Journal: Annals of Oncology (2018)

Background: The potential role of miRNA34a gene expression as biomarkers of colorectal cancer is not well known , the current study aimed to evaluate its diagnostic and prognostic value and its relationship with P53 gene expression, fate, stage, metastasis and overall survival of colorectal cancer. Methods: This study was carried out on patients with colonic adenocarcinoma (group I), patients with begin colon polyp (group II) and controls (group III). All studied subjects were submitted to estimation of body mass index and laboratory investigations including determination of serum carbohydrate antigen 19-9 (CA19-9) and carcino-embryonic antigen (CEA) levels and Estimation of microRNA 34a and P53 gene expression by real time PCR. Results: The results of the present study showed statistically significant lower gene expression in colon cancer group compared to others. There was a significant negative relation between serum tumor markers (CEA and CA19-9) and micro RNA 34a gene expression in cancer patients. Also there was statistically significant positive relation between micro RNA 34a and P53 gene expression in both patients groups. The diagnostic accuracy of miRNA34a gene expression was both sensitive and specific for colon cancer compared to serum levels of both CEA and CA19.9. Micro RNA 34a and P53 gene expression had statistically significant relation with tumor stage and presence of metastases. Conclusions: It can be concluded that the level of miRNA34a can be used to differentiate between colon cancers and begin adenomas. MiRNA34a gene expression has a main role in prognosis of colon cancer. MiRNA34a can be used as a therapeutic agent in colon cancer. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
TCT-380 Impact of direct stenting on myocardial injury assessed by cardiac magnetic resonance imaging and prognosis in ST-elevation myocardial infarction
Authors: Mohammed Saad, Thomas Stiermaier, Georg Fuernau, T. Suzanne de-Waha Thiele, Steffen Desch, Holger Thiele, Ingo Eitel
Journal: Journal of the American College of Cardiology (2018)