tbuckley/cabot-search huggingface dataset:
Expression of soluble DC-HIL/gpnmb receptor in the blood of metastatic non-small cell lung carcinoma treated with anti-PD1/PDL1 monoclonal antibodies.
Authors: Jin-Sung Chung, Vijay Ramani, Masato Kobayashi, Vinita Popat, Ponciano D Cruz, David E. Gerber, Kiyoshi Ariizumi
Journal: Journal of Clinical Oncology (2019)

e14038 Background: Anti-PD1/PDL1 therapy benefits only a minority (10-20%) of treated NSCLC. Identifying markers distinguishing responders vs. non-responders will improve management of NSCLC. DC-HIL receptor is a new checkpoint whose inhibitory mechanisms are divergent from the PD1 pathway. Tumor cells express DC-HIL receptor and its soluble form (sDC-HIL). We tested whether sDC-HIL expression regulates NSCLC response to anti-PD1/PDL1 Ab using animal models and human clinical samples. Methods: Tet-Off controlled sDC-HIL-transfected LL2 lung cancer cells were i.v. injected into mice (lung mets) and treated with doxycycline (Dox). Day 6, mice were sorted into 2 groups with/without Dox and treated with i.p. 200 μg Ab, every 2 d /6 shots. Day 18, # of lung-LL2 cells were counted by FACS and IFN-γ + T cells in tumors analyzed. Advanced NSCLC patients (n = 51) treated with immune checkpoint inhibitors were every 6 weeks evaluated for partial response (PR), stable (SD) and progressive disease (PD) by RECIST. Serum were collected on weeks 0, 2, and 6 and assayed for sDC-HIL amounts by ELISA. Results: In mice treated with Dox (halt sDC-HIL expression), anti-PDL1 Ab treatment markedly reduced lung mets and increased IFN-γ + T cells (p &lt; 0.001), whereas this excellent outcome was not noted in Dox-untreated mice (induce sDC-HIL). For NSCLC, PD1/PDL1 therapy produced PR (n = 3), SD (n = 25) and PD (n = 23) at week 6. sDC-HIL blood levels at week 0 did not correlate with tumor size, but the levels at week 6 of PD patients were significantly higher than PR/SD patients (8.4 ± 5.6 vs. 4.0 ± 1.6 ng/ml, p = 0.001, Mann-Whitney test) and healthy donors (2.6 ± 0.9 ng/ml). Most patients (26 out of 30 cases) showed fluctuation in sDC-HIL levels during treatment. PD-patients (14/15 cases) showed increasing or persistently elevated levels ( &gt; 4 ng/ml), with one case at low levels ( &lt; 4 ng/ml). SD/PR-patients (13/15) had decreasing or persistently low levels, with 2 exceptions with high levels in all time points. Conclusions: sDC-HIL blood level may serve as a biomarker to indicate tumor-resistance of advanced NSCLC patients to PD1/PDL1 therapy. The degree and direction of sDC-HIL fluctuation may be useful to predict prognosis for NSCLC.
Patient experience of an intervention combining nurse navigators and e-Health technologies for use of oral anticancer agents.
Authors: Marie Ferrua, FATIMA YATIM, Aude Fourcade, Marilène Guillet Lacaze, Etienne Minvielle, Olivier Mir
Journal: Journal of Clinical Oncology (2019)

e23149 Background: An intervention (named CAPRI) combining Nurse Navigators (NN) and a mobile application dedicated to patients treated with oral anticancer agents was implemented in 2016 at Gustave Roussy (Villejuif, France). NN provide regular telephone follow-ups to manage patients' symptoms and assess toxicities, adherence to treatment and supportive care needs. Patients can have access to a mobile application to record tracking data, contact NN via secure messaging, view therapy and side effect information or store documents. Methods: A questionnaire was addressed to patients after using for 5 months the CAPRI intervention in order to assess their experience with the device. In parallel, interviews were conducted with patients. To determine patient utilization of the mobile application, data were extracted over a 24-month period. Results: 148 patients completed the evaluation (response rate = 81%). 15 interviews were conducted. Patients' experience with CAPRI intervention is very positive: The open-ended comments on the questionnaires and interviews with patients highlighted the importance of listening, having a contact person who is easily reachable, available and empathetic. 83% of patients preferred contacting NN by phone rather than through the mobile application. Only 50% (n = 74) of patients reported having tried to connect to the mobile application and 38% reported monitoring data at least once. Conclusions: Patients' experience is highly positive about the intervention. However, the application is poorly used, patients seems to prefer human contact. In perspective, results from the randomized trial currently conducted will evaluate the impact of the intervention on clinical criteria.[Table: see text]
The effect of ticagrelor on growth of small abdominal aortic aneurysms—a randomized controlled trial
Authors: Anders Wanhainen, Kevin Mani, Joel Kullberg, Sverker Svensjö, Adam Bersztel, Lars Karlsson, Jan Holst, Anders Gottsäter, Anneli Linné, Peter Gillgren, Marcus Langenskiöld, Rebecka Hultgren, Joy Roy, Nils-Peter Gilgen, Håkan Ahlström, Frank A Lederle, Martin Björck
Journal: Cardiovascular Research (2019)

To evaluate if ticagrelor, an effective platelet inhibitor without known non-responders, could inhibit growth of small abdominal aortic aneurysms (AAAs).In this multi-centre randomized controlled trial, double-blinded for ticagrelor and placebo, acetylic salicylic acid naïve patients with AAA and with a maximum aortic diameter 35-49 mm were included. The primary outcome was mean reduction in log-transformed AAA volume growth rate (%) measured with magnetic resonance imaging (MRI) at 12 months compared with baseline. Secondary outcomes include AAA-diameter growth rate and intraluminal thrombus (ILT) volume enlargement rate. A total of 144 patients from eight Swedish centres were randomized (72 in each group). MRI AAA volume increase was 9.1% for the ticagrelor group and 7.5% for the placebo group (P = 0.205) based on intention-to-treat analysis, and 8.5% vs. 7.4% in a per-protocol analysis (P = 0.372). MRI diameter change was 2.5 mm vs. 1.8 mm (P = 0.113), US diameter change 2.3 mm vs. 2.2 mm (P = 0.778), and ILT volume change 12.9% vs. 10.4% (P = 0.590).In this RCT, platelet inhibition with ticagrelor did not reduce growth of small AAAs. Whether the ILT has an important pathophysiological role for AAA growth cannot be determined based on this study due to the observed lack of thrombus modulating effect of ticagrelor.The TicAAA trial is registered at the US National Institutes of Health (ClinicalTrials.gov) #NCT02070653.
Do the ASCO Value Framework and the ESMO Magnitude of Clinical Benefit Scale measure <i>Absolute</i> or <i>Relative</i> clinical benefit?
Authors: Ronak Saluja, Louis Everest, Sierra Cheng, Matthew C. Cheung, Kelvin K. Chan
Journal: Journal of Clinical Oncology (2019)

e18378 Background: It is unclear whether the clinical benefit scores from the ASCO or ESMO valuation frameworks were intended to measure absolute or relative survival benefit. To empirically examine the measurement characteristics of these frameworks, we compared their survival efficacy components (ASCO-CBS and ESMO-PMCBGs) with established measures of absolute (median survival difference and restricted mean survival time (RMST) difference) and relative (HRs) survival benefit. Methods: FDA’s Hematology/Oncology Approvals and Safety Notifications pages were reviewed to identify phase III RCTs cited in oncology drug approvals between January 2006 and December 2017. In our primary analysis, ASCO-CBS and ESMO-PMCBGs were calculated for the included trials using the framework defined endpoint (Fr). Sensitivity analyses were conducted by calculating the scores using 1) Fr + tail-of-curve bonus points (ASCO) or long-term plateau adjustments (ESMO) (defined as Fr + TOC), 2) overall survival (OS) data only, and 3) progression-free survival (PFS) data only. For both primary and sensitivity analyses, Spearman correlation coefficients were calculated to examine the relationships between 1) ASCO-CBS/ESMO-PMCBGs and RMST difference, 2) ASCO-CBS/ESMO-PMCBGs and median survival difference, and 3) ASCO-CBS/ESMO-PMCBGs and HRs. Results: 107 RCTs were included. Compared to measures of absolute survival, ESMO-PMCBG showed low-moderate correlations with RMST difference and moderate-high correlations with median survival difference (Rho = 0.44 and 0.64, respectively). ASCO-CBS showed low-moderate correlations with both measures of absolute benefit (Rho = 0.43 and 0.44 for RMST difference and median survival, respectively). Compared to a relative measure of survival (HRs), ESMO-PMCBG revealed a moderate correlation (Rho = 0.47) while ASCO-CBS showed a higher correlation (Rho = 0.76). Conclusions: Both frameworks do not perform solely as absolute measures of survival benefit. We recommend that the frameworks consider incorporating a direct measure of absolute clinical benefit, such as RMST difference, into the survival efficacy components of their algorithms.
Liver cancer systemic treatment patterns in the largely rural state of New Mexico.
Authors: Natalia Cadavid, Lisa M. Anselmo, Erika Maestas, Heloisa P. Soares
Journal: Journal of Clinical Oncology (2019)

e18166 Background: New Mexico (NM) has one of the highest rates for hepatocellular carcinoma (HCC) in the US. Systemic therapy (ST) for HCC is typically reserved for patients with unresectable or metastatic disease. Sorafenib has been commonly used as the first-line (1L) systemic agent for HCC after its FDA-approval in 2007. Since 2017, several other agents have been FDA-approved for HCC including lenvatinib as 1L therapy and regorafenib, cabozantinib, ramucirumab and checkpoint inhibitors (nivolumab and pembrolizumab) as second-line (2L) treatment options. This retrospective study describes the HCC treatment patterns of patients seen at the University of New Mexico Comprehensive Cancer Center (UNMCCC). Methods: Following approval by the institutional review board, a retrospective chart review of all consecutive HCC patients at the UNMCCC between January 1, 2012 and August 30, 2018 was performed. Patients were identified accessing the UNMCCC tumor registry database. Data on patients’ characteristics, treatments and outcomes were collected. Descriptive statistics were conducted for this initial analysis. Results: A total of 99 of the 380 patients seen at the UNMCCC within the study period were considered for systemic therapy. Most patients were males (82.8%) and of Hispanic/Latino (57.6%) ethnicity. The majority of patients had one or more risk factors for HCC including a history of hepatitis (70.7%), cirrhosis (70.7%), and history of alcohol use (72.7%). Child Pugh class A and B were seen in 30.3% and 44.4% of patients, respectively. Ninety-six patients were prescribed sorafenib initially; however, only 67 patients (70%) successfully initiated treatment. The median time between sorafenib prescription and treatment initiation was 15 days. Only fifty percent of patients started sorafenib with the FDA-recommended dose of 400mg PO BID. Commonly reported adverse events were fatigue, diarrhea, hand and foot syndrome and LFT elevation. After 2017, when 2L options became available, 11 of 27 patients that started on sorafenib continued on to 2L (9 patients received nivolumab and 2 patients received regorafenib). Outcome data are currently being analyzed and will be reported. Conclusions: Although systemic options are available for the treatment of HCC, a significant number of patients are still not accessing and receiving treatment. A detailed analysis of factors affecting treatment patterns in New Mexico is warranted.
Bevacizumab-associated intracerebral hemorrhage in patients with CNS malignancy: A single-center retrospective cohort study.
Authors: Nathan Clarke, Michael Ruff
Journal: Journal of Clinical Oncology (2019)

e13509 Background: Gliomas are a known risk factor for the development of spontaneous intracranial hemorrhage (ICH) independent of therapies directed against them, with studies reporting an incidence of 1.9-3.8%. Bevacizumab (BEV) is a humanized monoclonal antibody targeting vascular endothelial growth factor (VEGF) FDA approved for recurrent glioblastoma. ICH is commonly considered to be a potential adverse effect of BEV use in patients with glioma, with previous retrospective studies describing incidence of intracerebral hemorrhage ranging from 1.9-3.3%. Methods: We performed a single center (Mayo Clinic, Rochester, MN) retrospective chart review of all patients who received BEV therapy at our institution for a diagnosis of primary CNS malignancy. We used ICD-9 and ICD-10 codes to identify adult patients with primary CNS neoplasms that subsequently developed ICH. Results: We screened 10,507 adult patients with a diagnosis of primary CNS neoplasm treated at our center from 01/31/2008 to 12/31/2018 and found 644 patients treated with bevacizumab. Of these, 23 (3.6%) suffered an ICH within 12 weeks of a BEV infusion (median 9 days post infusion, 1-24 IQR). The dose of BEV in all hemorrhages was either 10 mg/kg every two weeks (n = 21) or 15 mg/kg every three weeks (n = 2). No patients treated with infusions at 7.5 mg/kg every three weeks (n = 79) or 5 mg/kg every two weeks (n = 17) suffered ICH events, however this did not meet significance (P = 0.06) when compared to patients on 10 mg/kg or above. The median ICH score was 1 (0-2 IQR). There was an increase in ECOG scores documented at clinical follow up following the hemorrhage compared to the pre-hemorrhage functional status (ECOG 3.28 versus 1.2, p = &lt; 0.0001), with 13 patients (56%) having developed severe debility or death (ECOG 4 n = 3, ECOG 5 n = 10). Conclusions: In our single-center cohort of patients with a primary diagnosis of CNS neoplasms treated with BEV, ICH occurred in 3.6% of patients. Those who experienced an ICH in proximity to BEV infusion had significant morbidity and mortality with a clear decline in functional status. There was a signal of dose response as far as ICH incidence in our cohort with dosages 10 mg/kg per infusion or above.
CheckMate 214 post-hoc analyses of nivolumab plus ipilimumab or sunitinib in IMDC intermediate/poor-risk patients with previously untreated advanced renal cell carcinoma with sarcomatoid features.
Authors: David F. McDermott, Toni K. Choueiri, Robert J. Motzer, Osvaldo Rudy Aren, Saby George, Thomas Powles, Frede Donskov, Michael Roger Harrison, Jeronimo Rafael Rafael Rodriguez Cid, Yuko Ishii, M. Brent McHenry, Sabeen Fatima Mekan, Brian I. Rini, Nizar M. Tannir
Journal: Journal of Clinical Oncology (2019)

4513 Background: Patients (pts) with advanced renal cell carcinoma with sarcomatoid features (sRCC) have poor prognosis and suboptimal outcomes with anti-VEGF targeted therapy. Nivolumab plus ipilimumab (N+I) demonstrated superior objective response rate (ORR) and overall survival (OS) vs sunitinib (S) in previously untreated pts with International Metastatic RCC Database Consortium (IMDC) intermediate/poor (I/P)-risk, clear-cell, advanced RCC in the phase 3 CheckMate 214 trial. Methods: We performed a post-hoc exploratory analysis of N+I vs S in CheckMate 214 sRCC pts. The presence of sarcomatoid features was assessed by keyword search for “sarcomatoid” in pts with available local pathology reports accompanying pretreatment tumor samples. Results: 842 (77%) of 1096 intention-to-treat pts had local pathology reports available, including 112 randomized pts with I/P-risk sRCC (N+I, n = 60; S, n = 52). Baseline characteristics of sRCC pts were balanced between arms. Notably, 47% vs 53% of I/P-risk sRCC pts in the N+I and S arms had tumor PD-L1 expression ≥1% at baseline, which was higher than in all I/P-risk pts (N+I, 26% vs S, 29%). In descriptive analyses performed at a minimum follow-up of 30 months, confirmed ORR and complete response rate per investigator (RECIST v1.1), OS, and progression-free survival (PFS) per investigator were improved with N+I vs S in I/P-risk pts with sRCC (Table). No new safety signals were seen in sRCC pts. Conclusions: In this post-hoc descriptive subgroup analysis of CheckMate 214, N+I demonstrated promising efficacy and prolonged survival vs S, with consistent safety, in previously untreated, I/P-risk, advanced clear-cell RCC with sarcomatoid features. Prospective studies of N+I that include pts with sRCC are ongoing. Clinical trial information: NCT02231749. [Table: see text]
Molecular characterization of the tumour microenvironment in neuroendocrine malignancy.
Authors: David James Pinato, Anu Vallipuram, Joanne Evans, Clement Wong, Hua Zhang, Matthew Brown, Roberto Dina, Pritesh Trivedi, Ayse Akarca, Teresa Marafioti, Francesco A Mauri, Rohini Sharma
Journal: Journal of Clinical Oncology (2019)

4107 Background: A comprehensive characterization of the tumour microenvironment is lacking in neuroendocrine tumors (NETs), where immunotherapy is undergoing efficacy testing. We investigated drivers of cancer-related immunosuppression across NETs of various sites and grade using multi-parameter immunohistochemistry and targeted transcriptomics. Methods: Tissue microarrays (n = 102) were stained for PD-L1 &amp; 2, Indoleamine-deoxygenase-1 (IDO-1) and evaluated in relationship to functional characteristics of tumor-infiltrating T-lymphocytes (TILs) and biomarkers of hypoxia/angiogenesis including VEGF-A, Hif-1α and Carbonic Anhydrase-IX. PD-L1 expression was tested in circulating tumour cell (CTCs, n = 12) to evaluate its relationship with metastatic dissemination. Results: PD-L1 expression was highest in lung NETs (n = 30, p = 0.007), whereas PD-L2 was highest in pNETs (n = 53, p &lt; 0.001) with no correlation with grade, stage or biomarkers of hypoxia. Incubation of QGP-1 and BON-1 NET cells in 1% O2 did not induce PD-L1 expression confirming transcriptional independence from hypoxia. PD-L1 + NETs (n = 26, 25%) had frequent IDO-1 co-expression (p = 0.03), greater CD4 + /FOXP3 + and CD8 + /PD1 + TILs (p &lt; 0.001) and necrosis (p = 0.02). CD4 + /FOXP3 + infiltrate was highest PD-L1/IDO-1 co-expressing tumours (p = 0.006). Survival was predicted by tumour grade (p &lt; 0.001) and necrosis (p &lt; 0.001) but not PD-L1, PD-L2 nor IDO-1. High-grade NETs had lower CD4 + /FOXP3 + and CD8 + /PD1 + TILs density (p &lt; 0.001) and Nanostring immune-profiling revealed enrichment of macrophage-related transcripts in cases with poorer prognosis. We identified PD-L1(+) CTC subpopulations in 75% of evaluated patients (n = 12). Conclusions: PD-L1 expression correlates with T-cell exhaustion independent of tumour hypoxia and is enhanced in a subpopulation of CTCs, suggesting its relevance to the progression of NETs. These findings support a potential therapeutic role for PD-L1/IDO-1 inhibitors in a subset of NETs.
Which role plays specialized palliative care in patients with relapsed and/or metastatic head and neck cancer? A retrospective analysis in Southern Switzerland.
Authors: Vittoria G. Espeli, Claudia Gamondi, Tanja Fusi-Schmidhauser
Journal: Journal of Clinical Oncology (2019)

e17503 Background: early palliative care (PC) for patients with advanced cancer improves quality of life, promotes home deaths and can improve survival. Limited data are available regarding PC in advanced head and neck cancer (HNC) patients. To investigate the effect of introducing specialized PC in patients with relapsed and/or metastatic head and neck cancer. Methods: between October 2010 and December 2018, the medical charts of all patients treated in the Oncology Institute of Southern Switzerland with relapsed and/or metastatic HNC were reviewed. Site, status of disease (metastatic at diagnosis, locally or metastatic relapsed), type and lines of treatment, treatment response and referral to specialist palliative care (yes or no) were documented. Comparisons were made between patients referred and non-referred to PC. Results: sixty-two patients with relapsed/metastatic HNC were identified, 32 (51.6%) of which were referred to specialized PC. Patients were mainly men (47, 75.8%), with a median age of 66 years (range 43 – 86). Forty-two patients (67.7%) had a metastatic disease and the most common site of tumor was the oropharynx (35.5%), followed by oral cavity (32.3%), larynx (16.1%), hypopharynx (12.9%), and unknown primary (3.2%). Forty-eight patients (77.4%) were treated with systemic treatment (75% in the PC group and 80% in the non-PC group, p = 0.638). The median overall survival was 8.1 months for all patients, 8 months for the PC group and 8.7 months for the non-PC group, without significant difference (p = 0.440). Of the deceased patients, 70% of the PC group and 73.3% of the non-PC group received chemotherapy in the last three months of life. A greater percentage of patients in the PC group died at home, but without significant difference (39.2% vs. 19%, p = 0.134). Conclusions: only half of the patient had access to specialized PC. Whereas it did not seem to affect overall survival nor influence chemotherapy prescription, it seemed to favor home deaths. Further studies investigating the impact of early PC in recurrent and/or metastatic HNC are needed to improve access to PC and maximize benefits.
Histophatological classification of idiopathic pulmonary fibrosis: the influence of cronic gastroesophageal aspiration
Authors: Ronaldo Adib Kairalla, M. E. P Carvalho, Daniel Deheinzelin, Paulo Hilário Nascimento Saldiva, Vera Luiza Capelozzi, Carlos Roberto Ribeiro de Carvalho
Journal: American Journal of Respiratory and Critical Care Medicine (2000)
Oncolytic polio/rhinovirus recombinant (PVSRIPO) against WHO grade IV malignant glioma (MG): Experience with retreatment of survivors from the phase I trial.
Authors: Annick Desjardins, Matthias Gromeier, James Emmett Herndon, Dina Randazzo, Stevie Threatt, Eric S. Lipp, Elizabeth S. Miller, Jennifer Jackman, Dani P. Bolognesi, Allan H. Friedman, Henry S. Friedman, Frances McSherry, Katherine B. Peters, Margaret O Johnson, John H. Sampson, David M. Ashley, Darell D. Bigner
Journal: Journal of Clinical Oncology (2019)

2060 Background: We completed a study evaluating a single intratumoral delivery of PVSRIPO in recurrent WHO grade IV MG patients (N Engl J Med. 2018 Jul 12;379(2):150-161). Some patients who originally benefitted from the infusion of PVSRIPO demonstrated tumor recurrence, and we hypothesized that retreatment could trigger an immune recall effect, further extending their survival. We now report the impact of second and third intratumoral reinfusion of PVSRIPO in patients treated in the original dose finding study. Methods: Eligible patients were adults with recurrent supratentorial WHO grade IV MG who were experiencing disease recurrence after having benefitted from the first infusion of PVSRIPO. Additional eligibility criteria included: solitary tumor 1-5.5cm in diameter; ≥4 weeks after chemotherapy, bevacizumab or study drug; adequate organ function; KPS≥70%; and positive anti-polio titer. One patient each was retreated at 1 x 10 7 TCID50 and 1 x 10 10 TCID50, and three patients were retreated on the identified phase 2 dose of 5 x 10 7 TCID50. Results: As of 2/09/2019, five patients have received a second intratumoral dose of PVSRIPO on study, one of which received a total of 3 doses. The patients who received two infusions of PVSRIPO were retreated 72 months, 43 months, 34 months, and 6 months after the first infusion. One additional patient received a second infusion of PVSRIPO 60 months after the first infusion and a third infusion of PVSRIPO 78 months after the first infusion. All patients demonstrated soap bubble degeneration on imaging, and two patients demonstrated tumor contraction. No grade 3 or higher adverse events related to PVSRIPO were observed after retreatment. Three of these patients remain alive more than 81, 80 and 52 months following the first PVSRIPO infusion and more than 9, 20 and 18 months after the second infusion, respectively. Two patients died 63 months and 20 months after the first infusion of PVSRIPO and 19.6 and 14 months after the second, respectively. The patient treated 3 times received the third infusion more than 2 months ago. Conclusions: Intratumoral reinfusion of PVSRIPO via CED is safe, and encouraging efficacy results have been observed. Clinical trial information: NCT01491893.