tbuckley/cabot-search huggingface dataset:
Propensity score regression analysis of esophageal cancer treatment with surgery alone or neoadjuvant chemotherapy.
Authors: Wyn Griffith Lewis, Arfon GMT Powell, Adam Christian
Journal: Journal of Clinical Oncology (2020)

405 Background: The aim of this study was to examine the outcomes of oesophageal adenocarcinoma (OC) treatment with either surgery alone (S), or with neoadjuvant chemotherapy (NAC) followed by surgery (NACS), by means of propensity score (PS) regression analysis, in order to examine whether the benefits reported in the MRC OE02 trial were reproducible in UK cancer network clinical practice. Methods: Consecutive patients undergoing potentially curative treatment for OC in a regional cancer network were studied. Multiple regression models, including PS were developed to account for confounding factors and the primary outcome measure was disease-free (DFS) and overall survival (OS). Results: A cohort of 440 patients was included in a regression analysis controlling for confounders (176 S, 264 NACS). NACS was associated with positive margin status (NACS vs. S, 42.4% vs. 26.7%, p&lt;0.05), poor 5-year DFS (32.1% vs. 56.9, p&lt;0.001), and poor 5-year OS (27.5% vs. 47.3%, p&lt;0.001). On regression adjustment based on propensity scores, NACS was not associated with DFS (p=0.220) or OS (p=0.431). Mandard tumour regression grade (TRG) was significantly associated with DFS (hazard ratio (HR) 0.21,95% CI 0.07-0.70) and OS (HR 0.27 (95% CI 0.13-0.59). Five-year DFS and OS related to TRG was 63.6 and 61.5% vs. 8.0 and 8.6% (p&lt;0.001) for good and poor responders respectively. Conclusions: Prescribing NAC to all OC patients risks delay in effective treatment of patients who are relatively chemo-resistant, given the variabilityin pathological response. Identifying OC patients who derive the most NAC benefit should be the focus.
Modified Controlling Nutritional Status score: A refined prognostic indicator depending on the stage of gastric cancer.
Authors: Chul Hyo Jeon, Han Hong Lee
Journal: Journal of Clinical Oncology (2020)

294 Background: The role of controlling nutritional status (CONUT) score in predicting cancer survival remains uncertain. This study aimed to investigate the predictive value of the CONUT score and to develop a more appropriate scoring system beyond CONUT for gastric cancer (GC). Methods: We retrospectively reviewed 1307 patients who underwent curative gastrectomy between 2009 and 2015. The CONUT and three modified scores with modified lipid components (L-CONUT: albumin/total lymphocyte count [TLC]/low density lipoprotein, H-CONUT: albumin/TLC/high density lipoprotein, and T-CONUT: albumin/TLC/triglyceride) were calculated. The predictive value of each scoring system on long-term survival was assessed. Results: The values of the four nutritional scores were categorized into three groups (low, medium, and high). The CONUT (P &lt; 0.001), L-CONUT (P &lt; 0.001), H-CONUT (P &lt; 0.001), and T-CONUT (P &lt; 0.001) scores showed significant differences in overall survival in the three groups. Survival analysis according to the pathological stage showed that advanced age, Eastern Cooperative Oncology Group performance status, male sex, and high H-CONUT score (HR, 3.93; 95% CI, 1.81–8.55; P = 0.001) were independent worse prognostic factors for overall survival in the stage I group. In the stage II group, CONUT score (HR, 5.077; 95% CI, 1.65–15.65; P = 0.005) was significantly associated with poor prognosis. In the stage III group, no scoring system showed significant results. Conclusions: In advanced GC (beyond stage II), the prognostic impact of the nutritional scoring system was uncertain. However, the H-CONUT score is a promising indicator of prognosis in stage I GC, and the CONUT score is useful for predicting long-term survival in stage II GC.
Soluble ST2 (sST2) as potential marker for hepatic cystic echinococcosis activity
Authors: Mengting An, Yuejie Zhu, Cheng Xu, Yujiao Li, Nannan Pang, Xiao Zhao, Zhiwei Li, Hongying Wang, Fengbo Zhang, Jianbing Ding
Journal: Journal of Infection (2020)
Organ preservation with chemoradiotherapy plus local excision for rectal cancer: 5-year results of the GRECCAR 2 randomised trial
Authors: Eric Rullier, Véronique Vendrely, Julien Asselineau, Philippe Rouanet, Jean-Jacques Tuech, Alain Valverde, Cecile de Chaisemartin, Michel Rivoire, Bertrand Trilling, Mehrdad Jafari, Guillaume Portier, Bernard Meunier, Igor Sieleznieff, Martin Bertrand, Frédéric Marchal, Anne Dubois, Marc Pocard, Anne Rullier, Denis Smith, Nora Frulio, Eric Frison, Quentin Denost
Journal: The Lancet. Gastroenterology & hepatology (2020)
Aggressive Posterior Retinopathy of Prematurity
Authors: Kellyn N. Bellsmith, James Brown, Sang Jin Kim, Isaac H. Goldstein, Aaron Coyner, Susan Ostmo, Kishan Gupta, R. V. Paul Chan, Jayashree Kalpathy-Cramer, Michael F. Chiang, J. Peter Campbell
Journal: Ophthalmology (2020)
Effect of plinabulin, a novel late-clinical stage immunotherapeutic agent on the adaptive and innate immune system.
Authors: Ramon W. Mohanlal, Lan Huang
Journal: Journal of Clinical Oncology (2020)

8 Background: Plinabulin (Plin) is a small molecule Dendritic Cell modulator, which in the presence of antigen, increases T-cell proliferation in an antigen-dependent manner marrow. The addition of Plin to Docetaxel (Doc) improved mOS with 4.6 months vs Docetaxel monotherapy, and prolonged DoR with more than 1 year (p &lt; 0.05), which is indicative of an immune-mediated mechanism of action (Mohanlal, ASCO-SITC 2017). Neutrophils are our first line of innate immune defense against foreign invaders. We previously reported that Plinabulin prevents chemotherapy (Chemo) Induced Neutropenia (CIN) in patients receiving Doc or TAC throughout the cycle (Doc, Doxorubicin, Cyclophosphamide) (Blayney ASH 2018, St Gallen 2019). Here we analyzed the onset time of neutrophil increase following Plin administration. In addition, we analyzed the impact of Plin on plasma haptoglobin, which is an acute phase protein with anti-inflammatory effects together with immune-enhancing effects and is an integral part of innate immunity (Kristiansen Nature 2001). Methods: Absolute neutrophil count (ANC) and haptoglobin data were analyzed from Phase 2 study BPI-2358-106 (NCT03294577) with 10 (n = 15), 20 (n = 15) and 30 mg/m2 (n = 12) Plin in Breast Cancer patients receiving TAC. Plin was administered on Day 1. ANC and Haptoglobin were analyzed by a Central Laboratory (Covance), from blood draws at predose, and post-dose Plin at Day 2,3,6,7,8,9,10,11,12,13 and 15, and changes relative to predose value were evaluated. Results: Plin dose-dependently increased ANC within 1 day (P &lt; 0.001) and Haptoglobin within 3 days (P &lt; 0.03) of dosing. Mean haptoglobin (P &lt; 0.0005) and ANC (P &lt; 0.001) levels increased with ~two-fold vs baseline levels. ANC levels remained increased for approximately 1 week and haptoglobin levels for &gt; 3 weeks. Conclusions: Based on Plinabulin’s ability to stimulate the innate system, together with its previously reported evidence as a potent activator of the adaptive immune system (Mohanlal, ASCO-SITC 2017), it is concluded that Plinabulin is a potent stimulator of the adaptive and innate immune system. Clinical trial information: NCT03294577.
A phase I study evaluating COM701 monotherapy and in combination with nivolumab in patients with advanced solid malignancies.
Authors: Ryan J. Sullivan, Emerson A. Lim, Manish Sharma, Dale Randall Shepard, Amita Patnaik, Erika Paige Hamilton, Gini F. Fleming, Kyriakos P. Papadopoulos, Adam ElNaggar, Adeboye H. Adewoye, John Hunter, Ecaterina Elena Ileana Dumbrava, Bartosz Chmielowski, Drew W. Rasco, Daniel A. Vaena
Journal: Journal of Clinical Oncology (2020)

TPS23 Background: COM701 is a novel 1st-in-class monoclonal antibody that binds with high affinity to poliovirus receptor related immunoglobulin domain containing (PVRIG) blocking its interaction with its ligand, PVRL2. In preclinical experiments inhibition of PVRIG alone and in combination with a PD-1 inhibitor leads to activation of T cells in the tumor microenvironment generating an anti-tumor immune response leading to tumor growth inhibition. Novel checkpoint therapies are needed for the treatment of patients with advanced malignancies. We hypothesized that COM701 monotherapy and in combination with nivolumab will be safe and tolerable and demonstrate preliminary antitumor activity in pts with advanced solid malignancies. Methods: This ongoing phase 1 study (NCT03667716) is evaluating the safety and tolerability of escalating doses of COM701 monotherapy IV Q3 or Q4 weekly and in combination with nivolumab 360 mg IV Q3 weekly or 480 mg IV Q4 weekly. Key Inclusion Criteria: Age ≥18 yrs, histologically or cytologically confirmed advanced solid malignancy and has exhausted all available standard therapy, ECOG performance status 0-1, prior ICI permissible. Key Exclusion Criteria: Symptomatic interstitial lung disease or inflammatory pneumonitis, untreated or symptomatic central nervous system metastases. Primary outcome measures are the incidence of adverse events and dose-limiting toxicities (21-day or 28-day DLT window), pharmacokinetics of COM701 and to identify the maximum tolerated dose and/or the recommended dose for expansion. Key secondary outcome measures are to characterize the immunogenicity and preliminary antitumor activity of COM701 as monotherapy and in combination with nivolumab. Study Design: Hybrid accelerated titration and 3+3 study design. Statistical Considerations: Adverse events graded as per CTCAE v4.03, responses as per RECIST v1.1. Analyses of all study objectives are descriptive and hypothesis generating. As of the date of this submission dose level 8 of COM701 monotherapy and dose level 3 of the combination arm are open to enrollment. Updated data will be presented at the conference. Clinical trial information: NCT03667716.
Hemodynamic Response to Exercise in Patients Supported by Continuous Flow Left Ventricular Assist Devices
Authors: Noah Moss, Val Rakita, Anuradha Lala, Aditya Parikh, Julie Roldan, Sumeet S. Mitter, Anelechi Anyanwu, Michelle Campoli, Dan Burkhoff, Donna M. Mancini
Journal: JACC Heart Failure (2020)
Recruitment of endogenous progenitor cells by erythropoietin loaded particles for in situ cartilage regeneration
Authors: Amirhossein Hakamivala, None Shuxin li, Kayti Robinson, YiHui Huang, Shuai Yu, Baohong Yuan, Joseph Borrelli, Liping Tang
Journal: Bioactive Materials (2020)

Cartilage injury affects millions of people throughout the world, and at this time there is no cure. While transplantation of stem cells has shown some success in the treatment of injured cartilage, such treatment is limited by limited cell sources and safety concerns. To overcome these drawbacks, a microscaffolds system was developed capable of targeting, reducing the inflammatory response and recruiting endogenous progenitor cells to cartilage-defect. Erythropoietin (EPO)-loaded-hyaluronic acid (HA) microscaffolds (HA + EPO) were fabricated and characterized. HA-microscaffolds showed good cell-compatibility and could target chondrocytes via CD44 receptors. HA + EPO was designed to slowly release EPO while recruiting progenitor cells. Finally, the ability of HA + EPO to repair cartilage-defects was assessed using a rabbit model of full-thickness cartilage-defect. Our results showed that the intra-articular administration of EPO, HA, and EPO + HA reduced the number of inflammatory cells inside the synovial-fluid, while EPO + HA had the greatest anti-inflammatory effects. Furthermore, among all groups, EPO + HA achieved the greatest progenitor cell recruitment and subsequent chondrogenesis. The results of this work support that, by targeting and localizing the release of growth-factors, HA + EPO can reduce inflammatory responses and promote progenitor cells responses. This new platform represents an alternative treatment to stem-cell transplantation for the treatment of cartilage injury.
Durvalumab (D) and PET-directed chemoradiation (CRT) after induction FOLFOX for esophageal adenocarcinoma.
Authors: Geoffrey Yuyat Ku, Abraham Jing-Ching Wu, Smita Sihag, Bernard J. Park, David Randolph Jones, Ping Gu, Steven Brad Maron, Ryan Sugarman, Sree Bhavani Chalasani, Marina Shcherba, Lara Feder, Kendall Cowie, Jaclyn Norris, Valerie Johnson, Laura H. Tang, David H. Ilson, Yelena Y. Janjigian, Daniela Molena
Journal: Journal of Clinical Oncology (2021)

226 Background: Based on the positive results of the CALGB 80803 study (J Clin Oncol 2017;35:1 [abstr]), we have added D to induction FOLFOX and pre-op CRT. Methods: Patients (Pts) had T any N+ or T3-4N any M0 esophageal and Siewert Type I-III GEJ adenocarcinoma staged by EUS, PET/CT and CT. Pts received mFOLFOX6 ×2 prior to repeat PET/CT. PET responders (PETr) received 5-FU or capecitabine and oxaliplatin with RT to 50.4Gy, while induction PET non-responders (PETnr) received carboplatin/paclitaxel with RT. All Pts received D 1,500 mg q4W ×2 starting 2 wks prior to and during CRT. Esophagectomy was planned 6-8 weeks after CRT. Pts who had R0 resections received adjuvant D 1,500mg q4W ×6. Results: 36 Pts have been enrolled: 25 GEJ, 11 esophageal; 23 N+ and 32 T3/4. 26 of 36 Pts (72%) are PETr. 2 Pts developed metastatic disease after CRT and 9 Pts remain on preop treatment. 25 Pts have had surgery (Table). Pathologic complete response (pCR) was seen in 6 (24%); 5 Pts (20%) had ypT1N0 tumors with 99% response and 2 Pts (8%) had ypT0N1 with 99% response. 20 Pts (80%) had &gt;90% response. 3 Pts had MSI tumors (2 PETr; 1 pCR, 1 T1aN0 99% response, 1 ypT2N0 90% response). Notable grade (gd) 3/4 adverse events (AEs) observed were neutropenia in 8 Pts (22%), diarrhea and vomiting in 2 Pts each (6%). Notable gd 1/2 AEs in ≥20%: anemia (31 Pts), thrombocytopenia (29 Pts), nausea (21 Pts), fatigue (25 Pts), increased AST (20 Pts), constipation and diarrhea (9 Pts), diarrhea (8 Pts). Immune-related AEs noted were gd 2 dermatitis (2 Pts), gd 3 hepatitis and gd 1 hypothyroidism in 1 Pt each. Median length of post-op stay was 8 days, with 12% anastomotic complication rate, including 1 Pt who died of hematemesis 16 days after discharge from 55-day hospitalization. Conclusions: The addition of D to induction FOLFOX and PET-directed CRT is safe and feasible. pCR and near-pCR in ½ of operated Pts is encouraging and compares favorably to the pCR rate of 31% in CALGB 80803 Pts who received induction FOLFOX. The final pCR rate and correlatives for the fully accrued study will be presented. Clinical trial information: NCT02962063. [Table: see text]
Tumor mutational burden (TMB) as a predictive biomarker of immune checkpoint blockade (ICB) in metastatic solid tumors.
Authors: Chester Kao, Eric Powers, Michael B. Datto, Michelle Green, Michael Roger Harrison, Andrew J. Armstrong, Daniel J. George, Jeffrey Melson Clarke, John H. Strickler, Tian Zhang
Journal: Journal of Clinical Oncology (2020)

80 Background: TMB is a promising predictive biomarker for ICB, but recent studies have shown that TMB varies substantially between tumor types. We examined the association between TMB and clinical response to ICB in metastatic urothelial carcinoma (mUC), renal cell carcinoma (mRCC), and non-small cell lung cancer (mNSCLC). Methods: We conducted a single center retrospective study inclusive of 1444 consecutive patients (pts) initiating ICB prior to 1/2019, cross-referenced with pts with Foundation One testing with TMB (mut/Mb), resulting in 17 mUC, 10 mRCC, and 60 mNSCLC. PD-L1 status was determined by the Dako 22C3 antibody. Pts were divided into clinical responders (R) and non-responders (NR) based on clinical assessment per their oncologist. The primary outcome of the study was to describe the relationship between TMB and clinical benefit, including duration of clinical response and overall survival (OS). A t-test was performed between R groups. Kaplan Meier (KM) curves and Cox-Mantel log rank tests were performed for PFS/OS comparing high TMB (≥ median) to low TMB pts. Results: For mUC, 8/17 (47%) were R with median TMB 7.74 (Interquartile range or IQR 6.04-9.78) compared to 9 NR, median TMB 7.57 (IQR 3.78-11.41) [p = 0.36]. For mRCC, 4/10 (40%) were R with median TMB 1.75 (IQR 1.75-1.97), versus 6 NR with median TMB 5.79 (IQR 3.07-7.48) [p = 0.02]. For mNSCLC, 30/60 (50%) were R with median TMB 11.38 (IQR 9.65-16.24), significantly higher than 30 NR with median TMB 9.46 (IQR 7.65-13.87) [p = 0.05]. For mNSCLC, no difference in PD-L1 positivity was found between R (17/30, 56%) and NR (16/30, 53%), and concurrent chemotherapy with ICB was the same in both R (10/30 (33%)) and NR (10/30 (33%)). KM analysis showed equivocal results for duration of clinical response and OS between high TMB vs low TMB in the three solid tumors, except OS in mUC which favored high TMB (p = 0.03) [cutoff TMB: mUC 7.57, mRCC 2.63, mNSCLC 11.35]. Conclusions: Higher TMB was associated with a greater likelihood of clinical benefit to ICB in our cohort of NSCLC patients and mUC. This correlation was not detected among mRCC patients, although these data are limited by relatively small number of cases.
Cisplatin plus irinotecan versus cisplatin plus gemcitabine in the treatment of advanced or metastatic gallbladder or biliary tract cancer: Results of a randomized phase II trial (NCT01859728)– the Gambit trial.
Authors: Lucas Vieira dos Santos, Gustavo Sanches Faria Pinto, Mauricio Wagner Souto Ferraz, Arinilda Bragagnoli, Florinda Santos, Sarah Haddad, Ana Barros, Isadora Clarissa Cordeiro Dias, Joao Paulo SN Lima, Kathia C Abdalla
Journal: Journal of Clinical Oncology (2020)

529 Background: The combination of gemcitabine-cisplatin (GC) is the current standard of care chemotherapy for metastatic/unresectable biliary tract cancer (BTC). However, the prognosis remains poor. This randomized trial aimed to evaluate the efficacy and safety of irinotecan plus cisplatin (IP) versus GC in advanced or metastatic BTC. Methods: Patients with biopsy-proven, chemo-naïve, unresectable or metastatic BTC, ECOG 0-2, measurable disease per RECIST 1.1, adequate organ function and written informed consent were stratified by ECOG (0 or 1 vs 2) and distant metastases and randomized to receive irinotecan 65 mg/m² IV D1 and D8 plus cisplatin 60 mg/m² D1 repeated every 3 weeks (IP) or gemcitabine 1000 mg/m² IV D1 and D8 plus cisplatin 25 mg/m² IV D1 and D8 repeated every 3 weeks, until disease progression or unacceptable toxicity. The primary endpoint was overall response rate (ORR). Results: Between January 2013 and April 2018, 47 pts were randomized (1:1) to receive IP (N = 24) or GC (N = 23). Overall, groups were well balanced according to prognostic factors. The ORR was 35% (complete response 5%, partial response 30%) and 31.8% in IP and GC arms, respectively. Median progression-free survival were 5.3 vs 7.8 months (HR = 1.165, 95%CI 0.628-2.161, p = 0.628) and median overall survival were 11.9 and 9.8 months (HR = 0.859, 95%CI 0.431 – 1.710, p = 0.665) for IP and GC, respectively. Adverse events were not statistically different between arms, and results were consistent with previous experiences with these regimens. No therapy-related death were reported. Conclusions: Irinotecan-cisplatin combination is active in BTC, with similar ORR, PFS and OS when compared to gemcitabine-cisplatin. Irinotecan-cisplatin were well tolerated, and adverse events were manageable. Irinotecan-cisplatin could be considered as an alternative to gemcitabine-cisplatin. Clinical trial information: NCT01859728.
Use of gastrin vaccine to increase gamma-delta and NKT cells and alter pancreas tumor microenvironment to improve survival.
Authors: Jill P Smith, Nicholas Osborne, Rebecca Sundseth, Hong Cao, Martha D Gay, Robin D. Tucker, Alexander H Kroemer, Lynda Youngpeter Sutton, Allen Cato
Journal: Journal of Clinical Oncology (2020)

696 Background: Pancreatic cancer (PC) has been called a “cold” tumor as it responds poorly to immune-based therapies. Strategies to render PC susceptible to immunotherapy are under investigation by methods that alter immune cell signatures such as increasing the population of double negative CD4-CD8-T-cells, or changing the polarization of tumor-associated macrophages (TAMs). Our current aim was to determine if a gastrin vaccine, Polyclonal Antibody Stimulator (PAS) influences double negative T-cell phenotype and polarization of TAMs to improve survival of PC. Methods: Two cohorts of C57BL/6 mice were injected either sc or orthotopically with syngeneic mT3 murine pancreatic cancer cells. After 1 week, groups were treated with PBS; PAS (100μg); PD-1 antibody (150μg); or the combination of PAS and PD-1 Ab. PAS was given ip at weeks 0, 1 and 3. Anti-PD-1 was given on days 0, 4, 8, 15 and 21. Spleens were collected from the sc experiment for T-cell surface analysis by flow cytometry. Orthotopic tumors were measured for growth rate, metastases, and stained for M1 (inos) and M2 (arginase) polarized TAMs, and mouse survival was analyzed. Results: PAS therapy increased expression of double negative T-cells. The percentage of gamma-delta T-cells in the (CD3 + /CD4 − /CD8 − /CD44 − /CD62L − ) TEMRA subpopulation of mice treated with PAS or combinations of PAS with PD-1 Ab were increased approximately 40% compared to PBS-treated controls or PD-1 Ab-treated mice. NKT cells from PAS-vaccinated mice were 2.5-fold higher than controls. M2+ TAMS were significantly decreased in tumors of PAS treated mice compared to PBS treated mice (p = 0.017). PAS monotherapy resulted in a nearly 10-fold increase in M1 TAMs relative to controls (p = 0.002). PAS monotherapy decreased tumor metastases by 69% and prolonged survival. Primary tumor growth decreased with PAS in combination with PD-1 Ab (p=0.0025). Conclusions: PAS decreases PC tumor growth and metastases by increasing CD4-CD8-, gamma-delta, and NKT T-cell populations. Furthermore, PAS monotherapy significantly increases M1 and decreases M2 TAMs. These immune cell changes with PAS vaccination may render tumors more susceptible to other cancer therapies and improve survival.