tbuckley/cabot-search huggingface dataset:
Phase I/II study of the A2AR antagonist NIR178 (PBF-509), an oral immunotherapy, in patients (pts) with advanced NSCLC.
Authors: Alberto Chiappori, Charles C. Williams, Ben C. Creelan, Tawee Tanvetyanon, Jhanelle Elaine Gray, Eric B. Haura, Ram Thapa, Dung-Tsa Chen, Amer A. Beg, Theresa A. Boyle, Jennifer Bendiske, Erick Morris, Aiyang Tao, Felipe K. Hurtado, Luigi Manenti, Julio Castro, Scott Joseph Antonia
Journal: Journal of Clinical Oncology (2018)

9089 Background: ATP is catabolized to adenosine in the tumor microenvironment, leading to excess adenosine and immunosuppressive effects via immune checkpoint protein adenosine 2A receptor (A2AR). NIR178 is an oral A2AR antagonist that selectively binds and inhibits A2AR, reactivating T cell-mediated antitumor immune response. This Phase I/II study evaluated NIR178 in previously treated pts with advanced NSCLC (NCT02403193). Methods: Pts (ECOG PS 0─1) had received ≥1 prior line of therapy; EGFR/ALK pts had failed prior TKI therapy. Objectives: primary – determine MTD of single-agent NIR178; secondary – efficacy endpoints, PK, and evaluation of PD-L1 expression. Results: At 13 Dec 2017 data cut-off, 24 pts had been treated: median age 68 yrs, 46% male; 79% received prior immunotherapy; 22/24 (92%) pts had discontinued (due to progression [n = 13], death [n = 2], AEs [n = 2] or other reasons [n = 5]) and 2/24 (8%) pts remained on treatment. Dose levels evaluated: 80 (n = 3), 160 (n = 3), 320 (n = 7), 480 (n = 6), 640 mg BID (n = 5). There was 1 DLT: Gr 3 nausea (640 mg). The most frequent (≥20%) any-Gr AEs regardless of causality were nausea (67%), fatigue (63%), dyspnea (46%), vomiting (33%), chest pain and other (29%), gastroesophageal reflux disease, anemia, diarrhea (all 25%), anorexia, back pain, generalized muscle weakness and cough (all 21%). Drug-related Gr 3 AEs were pneumonitis (8%) and nausea (4%); no Gr 4 AEs were reported. Potential immune-related any-Gr AEs were rash (8%), pneumonitis (8%), hypothyroidism, increased ALT/AST (all 4%). NIR178 systemic exposure (Cmax, AUC) increased more than proportionally with dose. Efficacy data for 17/24 treated pts demonstrated responses and SD across the dose range, including 1 confirmed CR (480 mg) and 1 PR (80 mg), both in immunotherapy-naïve pts. Durable SD > 44 wks with tumor shrinkage was observed in 2 ongoing immunotherapy-exposed pts. Disease control was seen in pts with both high and low baseline PD-L1 expression. Conclusions: NIR178 was well tolerated; AEs were manageable and there were no Gr 4 drug-related AEs. Immune-related AEs may indicate immune stimulation. Clinical benefit was observed in immunotherapy-exposed and -naïve pts irrespective of PD-L1 status. Clinical trial information: NCT02403193.
Outcomes after the diagnosis of brain metastases in Brazilian NSCLC patients.
Authors: Juliano Ce Coelho, Luiza Weis, Patricia Marks, Guilherme Geib, Pedro Emanuel Rubini Liedke, Rodrigo Perez Pereira, Taiane Rebelato, Maria Alice B Franzoi, Mariane Branco, Gilberto Schwartsmann, Sergio J Azevedo
Journal: Journal of Clinical Oncology (2017)

e20568 Background: Brain metastases (BM) are common and affects near half of patients with non-small-cell lung cancer (NSCLC), with poor prognosis. Few data is available about this group of patients and Brazilian are underrepresented. Methods: Patients with NSCLC that developed BM between January 05 and December 15 at Hospital de Clinicas de Porto Alegre were identified and medical records were reviewed. OS and PFS were estimated by Kaplan-Meier curves. Multivariate analysis was performed to identify factors associated with survival. Statistical analysis was performed with SPSS 22.0. Results: 113 patients were identified. Mean age was 60.1 ± 8.7 years, 50% were female, 84% were Caucasian, 87% had a positive smoking history, 71% had adenocarcinoma histology and 72% had stage IV disease at presentation. BM was present at initial diagnosis in 38% of patients. At diagnosis of BM, 39% of patients had a Karnofsky performance status &lt; 70, 20% had systemic disease under control, 31% had more than 3 brain lesions and 81% had a GPA score ≤2. 35 patients (31%) were submitted to either surgery or stereotaxic radiotherapy (SRDT), 52 (46%) to whole brain radiation (WBRT) and 26 (23%) to best supportive care (BSC). With a median follow-up of 11.2 months, 96% of patients have died. The OS was 11.2 months (95% IC, 9.4 to 13.1). The median survival time following diagnosis of BM was 4.9 months and survival according to treatment was 16.3 months for resection, 8.9 months for SRDT, 3.8 months for WBRT and 0.7 months for BSC. A Karnofsky performance status &lt; 70 at diagnosis of BM and palliative treatment to BM (WBRT or BSC) were associated with worse outcome in multivariate analysis. The GPA score wasn't statically associated with prognosis. A longer survival of patients submitted to WBRT was seen when compare to BSC, HR of 0.38. There is a trend for longer survival in patients submitted to BM resection when compared to SRDT, but without statically significance. Conclusions: To our knowledge this is the largest report of NSCLC patients with BM from Latin America. Our data is in line with previous reports. A poor Karnofsky performance status and palliative treatment to BM are associated with poor survival. WBRT is associated with longer survival when compared to BSC in all the GPA score stratus.
Global prospective cohort study of factors associated with early mortality in patients with lung cancer undergoing chemotherapy.
Authors: Nicole Maria Kuderer, Marek S. Poniewierski, Eva Culakova, Gary H. Lyman, Alok A. Khorana, Ingrid Pabinger, Giancarlo Agnelli, Howard A. Liebman, Eric Vicaut, Guy Meyer, Frances A. Shepherd
Journal: Journal of Clinical Oncology (2016)

9078 Background: There are few studies of factors associated with early mortality in patients with lung cancer in a real world setting. Preliminary studies of a risk score for venous thromboembolism may also be associated with the risk of all-cause mortality in patients with cancer. Methods: CANTARISK was a prospective, non-interventional, global cohort study including patients with lung cancer initiating a new chemotherapy regimen. Clinical data were collected at baseline and at 2, 4 and 6 months follow-up. The impact of patient-, disease- and treatment-related factors on time to death in the first 6 months was evaluated in univariable and multivariable analyses. The risk score classifies patients on the basis of cancer site, body mass index, platelet count, hemoglobin and leukocyte count. [Blood, 2008] Results: A total of 1,980 patients with lung cancer were enrolled from 2011-12 of which 82% were active or former smokers. Median age was 63 years (range, 25-91) and 63% were male. Race was white (70%), asian (22%), or black (4%) with similar numbers from North America, Europe, and other regions including Asia. ECOG PS was 0 (32%), 1 (55%), or 2 (13%) while metastatic disease was present in 70%. Comorbidities included hypertension (35%), diabetes (16%), and arterial disease (16%). Risk score was 1 (no factor other than lung cancer): 49%; 2 (1 additional factor): 34%; > 3 ( > 2 additional factors): 17%. During the first six months, 472 died including 23%, 27% and 40% with risk score 1, 2, > 3, respectively (P < 0.0001). Significant independent predictors of all-cause mortality in Cox regression included older age, current/former smoking, COPD, ECOG > 2, no prior surgery, and metastatic disease. After adjustment, the risk score remains a significant predictor of early all-cause mortality in patients with lung cancer. Conclusions: The risk score represents a significant independent predictor of early mortality in patients with lung cancer even after adjustment for other major risk factors. Intermediate or high-risk patients as defined by the risk score may benefit from additional interventions aimed at reducing early mortality.
Sensitivity to chemotherapy of low-grade endometrial stromal sarcoma (LGESS) versus high-grade endometrial stromal sarcoma (HGESS).
Authors: Roberta Sanfilippo, Vittoria Colia, Elena Fumagalli, Rossella Bertulli, Carlo Morosi, Maria Luisa Carcangiu, Domenica Lorusso, Francesco Raspagliesi, Angelo Paolo Dei Tos, Paolo Giovanni Casali
Journal: Journal of Clinical Oncology (2017)

11072 Background: LGESS and HGESS are rare uterine neoplasms of endometrial stromal origin. The activity of hormonal therapy in LGESS is reported, whilst no data are available in HGESS. The activity of chemotherapy is unknown in both. We focused on LGESS and HGESS to explore their sensibility to chemotherapy Methods: Cases diagnosed with LGHSS and HGESS from 1997 at Istituto Nazionale Tumori, Milan, or within the Italian Rare Cancer Network (RTR), were reviewed. Results: We identified 39 patients (pts), 28 with LGESS (median age:43) and 11 (median age: 54) with HGESS. Seventeen LGESS pts received systemic therapy for advanced disease (1-5 lines). Eight received an aromatase inhibitor, with 2 PR, 5 SD and 2 PD; 8 received oral progestins, with 4 PR, 5 SD and 2 PD. Nine patients (6/9 in first line, 1/9 in second line and 1/9 in third line) received antracyclines +/- ifosfamide and were evaluable for response: 2 had a CR, 4 a PR and 3 a SD. Median PFS was 7,6 months. Five patients received high-dose ifosfamide (HDIFX), obtaining 2 PR and 3 SD. Five pts received trabectedin, with 1 PR, 3 SD and 1 PD. All eleven pts with HGESS received systemic therapy for advanced disease (1-5 lines). Three patients received oral progestins, with PD. Ten pts received an antracycline-based combination chemotherapy and were evaluable for response: 5 had SD and 5 had PD. Median PFS was 3 months. Four pts received HDIFX and all progressed. Four pts received gemcitabine-based chemotherapy, obtaining 1 SD and 3 PD. Five pts received trabectedin, obtaining 1 SD and 4 PD. One pt received Pazopanib, with a PR lasting 5 months. Conclusions: In this series of endometrial stromal tumor pts treated with medical therapy, chemotherapy with antracycline-based combinations resulted in some objective responses in LGESS, while it was essentially inactive in HGESS. An observational clinical study is ongoing to expand this series.
Evaluation of a pre-transplant serum biomarker score for allogeneic hematopoietic stem cell transplant (HCT) and association with clinical factors.
Authors: Michael Leukam, Masha Kocherginsky, Lucy A. Godley, Justin Paul Kline, Richard A. Larson, Hongtao Liu, Olatoyosi Odenike, Wendy Stock, Michael Russell Bishop, Andrew S. Artz
Journal: Journal of Clinical Oncology (2016)

e18537 Background: A recent national registry study in patients with AML and MDS found pre-transplant serum c-reactive protein (CRP), ferritin and albumin were associated with overall survival (OS) after unrelated donor HCT, and derived a predictive biomarker risk score (BRS) (Artz A, Blood 2014;124). This study aims to evaluate the BRS using an independent dataset and characterize clinical factors driving abnormal biomarkers. Methods: Patients undergoing first allogeneic HCT from 2008 to 2014 for various hematologic malignancies and donor sources were reviewed, as well as available pre-conditioning serum CRP, albumin and ferritin levels (n = 278). BRS was calculated as follows: 0.44633*I(CRP > 3.54) + [0.07184+0.19646*ln(Ferritin)] + 0.44730*I(albumin < 3.4), where “I” is an indicator for the parenthetical condition. Risk groups were defined as low ( < = 1.5), intermediate ( > 1.5 and < = 2.0), and high ( > 2.0). The BRS risk categories and the individual biomarker terms were examined for association with pre-transplant clinical data: red blood cell transfusions (RBC), weight loss, bacteremia, fever, elevated creatinine, comorbidity by HCT-CI, disease risk, and age. Results: At one year, the 48% one year survival for high risk BRS differed from the 64% of low and intermediate groups (p < 0.05). 2-year OS was similar to the registry study (low risk OS of 61% [95% CI 0.52-0.73], intermediate of 52% [0.43-0.62] and high risk of 41% [0.32-0.53]), though median OS did not significantly differ (p = 0.08). Relapse rates were similar across BRS groups (p = 0.82). In multivariate analysis with pre-transplant factors, BRS was associated with RBC, weight loss and HCT-CI. CRP was associated only with bacteremia and HCT-CI, ferritin was associated only with RBC and bacteremia, and albumin was associated only with RBC and bacteremia. Conclusions: In an independent dataset, the BRS predicted worse 1-year survival in high risk patients, but OS was not significant, likely due to smaller sample size. Additional validation is needed. The modest association of various clinical factors to serum biomarkers suggest the BRS may represent a non-specific but objective measure of pre-HCT vulnerability.
The genomic and evolutionary landscape of osteosarcoma progression and lung metastasis.
Authors: Jin Wang, Hua Bao, Huaiyuan Xu, Tony WH Shek, Xue Wu, Qinglian Tang, Huizhong Zhang, Anjia Han, Junqiang Yin, Changye Zou, Yongqian Wang, Gang Huang, Sellma Batalha, Xianbiao Xie, Jinchang Lu, Guohui Song, Yao Kang, Yang Shao, YingLee Lam, Jingnan Shen
Journal: Journal of Clinical Oncology (2017)

11029 Background: Osteosarcoma (OS) is a primary malignant bone tumor that has a high potential to metastasize to lungs. Recent studies have characterized somatic mutations of primary OS tumors. Nevertheless, lung metastases of OS are poorly studied, and whether they harbor distinct genetic alterations beyond those observed in primary tumors is largely unknown. Methods: We performed whole-exome sequencing (WES) of matched primary tumors and lung metastases in a cohort of 15 OS patients. Somatic single nucleotide variations (SNV) and copy number alterations (CNA) were analyzed to characterize the genomic and evolutionary landscape of metastatic OS. Results: Compared to matched primary tumors, lung metastases exhibited higher transversion rate for base substitution, and poor overlap ( &lt; 10%) of genetic alterations was observed between primary and metastasis tumors. Multiple novel significantly mutated genes were identified, including ZNF717 in lung metastases, SPDYE1 in primary tumors, and CRIPAK in both. Copy number analysis indicated recurrent CNAs, including NEURL1B deletion and FLG amplifications in lung metastases, GSTT1 deletion in primary tumors, and CEACAM gene family deletion in both. Furthermore, phylogenetic analyses revealed that paired primary tumors and metastases underwent parallel evolution with few ubiquitous clonal mutations, suggesting that OS metastases are likely to be derived from primary tumors at a very early stage of their evolution. Conclusions: This study for the first time provides important evidence that OS metastases harbor distinct genetic alterations compared with primary tumors. Our findings strongly support a parallel evolution model of primary and metastatic tumors. Moreover, several novel CNAs and significantly mutated genes that are specifically associated with lung metastases may provide future therapeutic insight for OS.
Association of quality of life (QOL) with oncologic and functional outcomes in head and neck cancer (HNC) patients (pts).
Authors: Arun Sendilnathan, Rishi Agarwal, Ayham Deeb, Robert Bach, Changchun Xie, Farah Kaval, Courtney Robinson, Kelly Guthrie, Trisha Michel Wise-Draper, John Charles Morris, Michelle Lynn Mierzwa, Bradley Joseph Huth, Kevin P. Redmond, William Barrett, Yash Patil, Keith Wilson, David J. Adelstein, Keith Casper, Nooshin Hashemi Sadraei
Journal: Journal of Clinical Oncology (2016)

e18139 Background: Despite improved survival outcomes, HNC pts suffer significant impairment in QOL as a result of disease and treatment toxicity. We evaluated the association between QOL and oncologic & functional outcomes in HNC pts treated with standard therapy. Methods: We utilized self-reported EORTC-C30 and EORTC-HN35 questionnaires, validated for cancer and HNC pts respectively. These include HNC specific measures and general (SX), functional (FX), global health status (GHX) measures respectively. Surveys completed by HNC pts at the time of diagnosis (Dx), 3 & 6 months (mos) post treatment were analyzed. Functional and oncologic outcomes were collected through a retrospective chart review. Cox proportional hazards and logistic regression models, adjusted for age, gender and stage of disease, were used for association analyses. Results: 156 pts were evaluated; 71% males, 91% Caucasians, median age 57 y (41-86), good PS (0-1) 75%. Oral cavity (36%) was the most common site, oropharynx (26%), larynx/hypopharynx (21%). 50% Stage IV. Squamous cell (87%), p16 positive (25%), 37% received concurrent chemoradiation, 35% had radiation alone. 59 % had primary surgery,11 % salvage resection. Higher (worse) HN35 scores at Dx were associated with early recurrence, p < 0.0005 . Worse scores for HN35 categories at Dx (swallow, speech, social eating , social contact, nutrition) correlated with early recurrence and feeding tube dependence, p < 0.0001. Worse GHX, FX, SX and nutrition measures at Dx also predicted early recurrence (p < 0.01). Total HN35 score at 3 mos correlated with a shorter overall survival (OS), p < 0.003. PEG tube dependence was associated with shorter PFS (p 0.001, HR 2.86) and shorter OS (p < 0.0001, HR 8.87). Longer duration of feeding tube dependence was associated with shorter OS (p < 0.002). Conclusions: QOL scores and nutritional assessment can be easily obtained during routine HNC outpatient visits. Our study suggests poor QOL scores are associated with worse oncologic outcomes (early recurrence and death) and predict feeding tube dependence. Prospective studies can address if early interventions to improve QOL and nutritional status will translate into better oncologic outcomes.
TCT-169 Serial 3-dimensional optical coherence tomography assessment of jailed side-branch by second-generation drug-eluting absorbable metal scaffold (DREAMS 2G) in BIOSOLVE-II trial
Authors: Yuichi Ozaki, Hector Garcia-Garcia, Alexandre Hideo-Kajita, Kayode Kuku, Michael Haude, Hüseyin Ince, Alexandre Abizaid, Ralph Toelg, Pedro A. Lemos, Evald Christiansen, Javier Escaned, Ron Waksman
Journal: Journal of the American College of Cardiology (2018)
The Memorial Sloan Kettering (MSK) electronic informed consent (eIC) platform for clinical trials: An operational model and suite of tools for obtaining informed consent, and managing consent documents.
Authors: Michael T. Buckley, Joseph M. Lengfellner, Matthew J. Koch, Hector O. Pacheco, Carol Hoidra, Dorothy J. Damron, Roy Cambria, Ann Rodavitch, Paul Sabbatini
Journal: Journal of Clinical Oncology (2018)

e18577 Background: The eIC platform was developed to reduce administrative time and effort associated with paper-based consenting, improve the IC audit trail, and augment educational alternatives for research subjects. The platform includes 3 distinct tools: 1) the eIC module where the consent form is reviewed/signed; 2) an eIC management tool that sets user level access permissions, and 3) a processing utility that ensures the most recent IRB-approved consent form is discussed, displays metrics for completed consents, transmits signed forms to the electronic health record (EHR), and verifies that each sent form was received. Methods: The web-based platform is device-agnostic and browser-independent; it is now used by 13 Services in 4 institutionally-sponsored non-therapeutic clinical trials. Access to the platform is restricted to hospital WiFi (off-site via VPN). Two protocols in the platform have an educational video embedded in the eIC, and another has an embedded image flow that gives an overview of the protocol timeline for tests and visits. Results: The eIC platform was launched as a pilot program in January 2016; it went into use in our clinics in November 2016. The platform’s average monthly accrual between November 2016 and January 2017 was 28 (STDEV +/- 20). As of January 2017, 31 active consenting professionals were using the module, and 417 participants were consented. Compared with paper-based consent forms, which take ~ 72h to post to the EHR (scanning, QA/QC), the signed eIC is automatically sent and stored in the EHR and Patient Portal (for MSK study participants) in < 2 minutes. The platform decreases the administrative effort (collating, printing, and scanning) associated with paper-based consent procedures by 5-15 minutes/form. The eIC module has a robust audit trail that tracks the consent session and participant interactions via timestamps. Conclusions: The eIC platform provides an innovative operational model for electronic consenting in the academic medical setting, enhances the engagement and education of study participants, and improves quality and compliance in the consent process.
Implementation of a distress/supportive care screening tool in lung and head and neck cancer clinic.
Authors: Mary Pasquinelli, Sandra Obilade, David Rosenberg, Zane Deliu, Aakash Shah, Eileen Knightly, Lawrence Eric Feldman
Journal: Journal of Clinical Oncology (2017)

e21646 Background: Identifying and addressing depression, anxiety, and supportive care needs in cancer patients is an emerging standard of care. The Coleman Foundation “Patient Screening Questions for Supportive Care” tool was used with demographic and diagnostic data to investigate the relationships between screening scores. Methods: Lung/head/neck cancer patients at the University of Illinois Cancer Center were screened using the Coleman Foundation tool. This screening tool identified needs in several categories including Patient Health Questionnaire 4 (PHQ-4) scores; practical, family/caregiver, nutritional, treatment, physical, and spiritual/faith/religious concerns; levels of pain, fatigue, physical activity to quantitatively assess patient distress/supportive care needs. Scores were compared with age, sex, race/ethnicity, insurance, cancer type, and cancer stage. Linear regression was used for statistical analysis. Results: We performed initial screening on 164 lung/head/neck patients ages 36-88 (mean 61), with stages IA to IVC (May 2016 to Jan. 2017). Our findings are summarized in below. We found a 1 o effect that racial/ethnic minority status was significantly correlated with higher scores. We found that lung cancer was correlated with higher screening scores than head &amp; neck on initial screen. Medicare insurance was correlated with significantly lower screening scores. Conclusions: Patients with lung/head/neck cancer have significant needs and concerns that go beyond merely treating their cancer. Our findings show that certain demographic groups have especially high burdens in some specific dimensions and that these specific concerns may be predicted based on diagnostic and demographic information. Thus, these findings serve to inform providers as to where and how to focus supportive care for these patient populations. [Table: see text]