tbuckley/cabot-search huggingface dataset:
Generation of anti-human TIM-3 monoclonal antibody for cancer immunotherapy.
Authors: Yu-Chen Yang
Journal: Journal of Clinical Oncology (2018)

e15135 Background: Many clinical trials show that immunotherapy become one of effective strategy in cancer treatment. The benefits of PD-1 and CTLA-4 have revealed the huge success in different type cancer. However, how to significantly improve the overall response rate and find a suitable ethnic group has become an urgent problem in this field. Many checkpoint receptors on T cell surface are showed the potential as the drug target. T-cell immunoglobulin and mucin-domain containing-3(TIM-3) is one of the most important targets, and highly correlated in different types of cancer. Therefore, Development Center of Biotechnology (DCB) has developed the humanized antibody, DCB-8, against human TIM-3 to evaluate the potential of this antibody for cancer immunotherapy. Methods: The recombinant protein of human TIM-3 extract cellular domain as antigen to immunize mice, and generated the hybridoma clone. All antibodies were analyzed via in vitro and ex vivo assays. These potential clones had cloned the CDR sequence and generated humanized antibodies. After functional assay and disease animal model to evaluate the potency of anti-tumor, the DCB-8 is produced via mammalian cell system for further pre-clinical development. Results: In the ELISA and BIAcore experimental results, DCB-8 has showed excellent affinity and specificity. Analysis of cytokines secretion via human T cells treatment shows that DCB-8 significantly enhances cytokine secretion. DCB-8 shows high purity in mammalian cell production systems, and significantly inhibits tumor growth in the disease model. Conclusions: Taken together, these data demonstrate that DCB-8 is a potent TIM-3 antibody with TGI property that supports its further investigation in pre-clinical phase.
TCT-427 Role of Residual Stent Under-expansion ersus In-stent Minimum Lumen Area in Percutaneous Coronary Intervention Outcome: a CLI-OPCI Project Substudy
Authors: Enrico Romagnoli, Laura Gatto, Alessio La Manna, Francesco Burzotta, Nevio Taglieri, Francesco Saia, Francesco Amico, Valeria Marco, Vito Ramazzotti, Alessandro Di Giorgio, Giovanni Ruscica, Luca Di Vito, Alberto Boi, Marco Contarini, Gary Mintz, Francesco Prati
Journal: Journal of the American College of Cardiology (2018)
Clinical interpretation of lung cancer molecular profiles using rule-based artificial intelligence
Authors: D. Tihanyi, C. Hegedüs, E. Várkondi, R. Schwab, I. Vályi-Nagy, I. Peták, L. Urbán
Journal: Annals of Oncology (2018)

Background: In the era of precision oncology, tumor genomic information is incorporated in clinical decision making to personalize treatment strategies; however, drawing clinically relevant conclusions from tumor molecular profiles are not straightforward if more druggable drivers or targets are identified, more drugs are linked to the same genetic alteration or evidence are conflicting. Here, we present the analysis of 704 lung cancer profiles using our proprietary algorithm and the personalized treatment protocols established by the rule-based artificial intelligence software, the RealTime Oncology Treatment Calculator. Methods: Lung cancer samples (469 adenocarcinomas, 115 squamous cell carcinomas, 57 small cell carcinomas, 63 other histology) were profiled using next generation sequencing of 50-58-600 cancer genes, fluorescent in situ hybridization, and immunohistochemistry. Variants were classified by the Molecular Treatment Calculator algorithm, which dynamically aggregates and ranks all relevant scientific and clinical evidence to find the most efficient drug for the best target of the strongest driver in the given tumor. Results: 1008 different genetic variants were identified. 417 (41%) variants were classified as drivers and 49 (5%) as non-drivers. No direct evidence was available for 541 (54%) of the alterations, 460 (85%) of which were classified as drivers by the algorithm based on the aggregated evidence related to the cancer gene itself or other mutations in the same gene. 354 (50.3%) patients had more than one driver mutations, where the algorithmic ranking of drivers and related compounds was particularly warranted. The algorithm linked molecular targets to 799 (90%) of the driver variants. Conclusions: Molecular treatment calculator algorithm is an efficient tool to classify tumor genetic variants and link them to molecular targets and drugs based on the curated, continuously expanding evidence database and the more than 20 000 rules of the RealTime Oncology Treatment Calculator. Calculator results represent optimal input for Molecular Tumor Boards to design personalized treatment strategies. Legal entity responsible for the study: Oncompass Medicine Hungary Ltd. Funding: National oncogenomic and precision oncotherapy program funded by the Hungarian Innovation Agency. Disclosure: All authors have declared no conflicts of interest.
Real world data in colorectal cancer: A retrospective analysis of overall survival in metastatic colorectal cancer patients between 2011-2015 treated in Spain—Preliminary results (RWD-ACROSS study).
Authors: Carles Pericay, Javier Gallego Plazas, Ana Fernandez Fernandez Montes, Helena Oliveres, Helena Asensio-Martínez, Jesus García-Gómez, Julen Fernández Plana, Maria Marin Alcala, María Ballester Espinosa, Mercedes Salgado Fernández, Ismael Macias Declara, Lucía Gómez González, Leticia Iglesias Rey, Luis Cirera
Journal: Journal of Clinical Oncology (2018)

e18731 Background: Colorectal cancer is a global problem due the incidence and prevalence. Clinical trials do not represent treatment of real life population effectiveness , so real world data trials are needed. Aim: We present preliminary results based on a registry for Spanish metastatic colorectal cancer (mCRC) patients. Methods: Cohort study including 4 hospitals in Spain. Inclusion criteria: Aged≥18 years(y), histological confirmation mCRC, at least 1 cycle of chemotherapy(CT) administered, mCRC diagnosed between 01/2011-12/2015. Overall survival(OS) was calculated from time of mCRC diagnosis to death or date of last contact. Kaplan-Meier curves were used to estimate median survival and survival rates. The study was approved by Ethics Committees. Results: 804pts were analyzed. Median age: 65.7y. Ratio male/female: 64.9%/35.1%. Synchronous or methacronous tumors: 5.7%. RAS-mutations were seen in 50.1%, BRAF-mutations in 1.6% and RAS/BRAF-wild type in 48.3% of pts. MSI(Microsatellite Instability) was in 3.4%. Ratio left/right: 73.4%/26.1%. Metastatic site location at diagnosis: liver 36.6%, lung 8.6%, peritoneal 8.7%, liver+lung 10.1% and liver+peritoneal 6.1%. 63.8%pt received 2 lines, 28.5% 3 lines and 9.1% 4 or more lines. In the cohort analysed, 74.8%pt had died. Relation of lines of therapy and drugs used are shown in Table1. mOS: 23.4 months(m). mPFS(Progresion free survival): 1stline: 9.6m, 2ndline: 7.6m and 3rdLine: 6.7m. OS left/right: 25.2m vs 18.0m (HR:0.634, P < .001). The probability of surviving beyond 12m was 73.3%, beyond 24m was 48.2%, beyond 36m was 30.7% and beyond 48m was 21.1%. Conclusions: The RWD-ACROSS study is the first data-base for mCRC patients in Spain including information on CT, biologics, OS, PFS, and prognostic and predictive factors. Funded by Merck, S.L.(Merck KGaA, Darmstadt, Germany). Table 1: Relation of lines of therapy and drugs used Line CT Oxaliplatin Irinotecan FU CT alone CT+Ab EGFR.Ab VEGF.Ab 1st(100%) 55.3% 27.4% 12.4% 51.6% 48.4% 46.0% 53.2% 2nd(63.8%) 26.3% 57.5% 9.0% 51.5% 48.5% 38.8% 60.7% 3rd(28.5%) 23.6% 32.5% 20.2% 59.2% 40.8% 36.3% 49.5%
Peroral antegrade pancreatoscopy for pancreaticolithiasis after endoscopic ultrasound-guided recanalization of a complete pancreaticojejunal stenosis
Authors: Eduardo Bonin, Raquel Canzi Almada de Souza, Eloy Taglieri, Nelson Silveira Cathcart, Elisandre dos Santos, Ricardo Schmitt de Bem, José Ardengh
Journal: Endoscopy (2018)

Pancreaticoduodenectomy may result in symptomatic pancreaticojejunal stenosis in 2 % – 10 % of cases [1]. As an alternative to surgery, endoscopic pancreatic duct decompression may be performed by retrograde (enteroscopy) or antegrade (endoscopic ultrasound [EUS]-guided transgastric access) approach [2]. The latter is more likely to be technically successful (up to 70 % of cases) [3], and also enables anastomotic recanalization [4]. For pancreaticolithiasis treatment, an antegrade pancreatoscopy procedure has been recently described as feasible and useful [5].
Randomized phase II trial evaluating treatment with EGFR-TKI versus EGFR-TKI associated with anti-estrogen in women with non-squamous advanced stage NSCLC: IFCT-1003 LADIE trial.
Authors: Julien Mazieres, Fabrice Barlesi, Isabelle Rouquette, Benjamin Besse, Isabelle Monnet, Clarisse Audigier-Valette, Anne Claire Toffart, Patrick-Aldo Renault, Severine Moreau Fraboulet, Sandrine Hiret, Bertrand Mennecier, Didier Debieuvre, Virginie Westeel, Philippe Masson, Anne Madroszyk, Elodie Amour, Franck Morin, Gerard Zalcman, Denis Moro-Sibilot, Pierre Jean Souquet
Journal: Journal of Clinical Oncology (2018)

9097 Background: The incidence of lung cancer is increasing dramatically in women with recent findings as the preferential involvement of the EGFR pathway and the potential impact of hormonal factors in women. Preclinical data have shown that the combination of an EGFR-TKI with an anti-estrogen could overcome resistance to EGFR-TKI. Methods: IFCT-1003 LADIE Trial was a 2x2 arms parallel open-label randomized phase II trial. PS 0-2 post-menopausal women with advanced stage lung adenocarcinoma were treated with gefitinib (G 250 mg/day) vs. G + fulvestrant 500 mg / month with a supplementary dose at day 15 (G+F) in the EGFR mutated group (EGFR+) in 1st or 2nd line setting or with erlotinib (E 150 mg/day) vs. E + fulvestrant (E+F) in the EGFR wild-type group (EGFR WT) in 2nd or 3rd line setting until progression or unacceptable toxicity. Primary objective was progression-free survival (PFS) at 3 and 9 months for EGFR WT and EGFR+ patients, respectively. Results: From 02/2012 to 03/2017, 204 pts (G 104, G+F 100) and 175 (E 87, E+F 88) were enrolled in the EGFR+ and EGFR WT cohorts respectively. The median number of fulvestrant injections was 10 in the G+F group and 3 in the E+F group. The tolerance was correct (grade 3/4: 24.2% in the G+F group vs 21.3% in the G group, 16.0% in the E+F group vs 13.8% in the E group) and no treatment-related death. In the EGFR+ cohort, the primary endpoint was reached as 54 pts in the G+F group were non-progressive at 9 months. Nevertheless, addition of F to G was not associated with significant better PFS (9.9 vs 10.1 months) or OS (22.1 vs 29.9 months). In the EGFR WT cohort, the primary endpoint was not reached as 29 patients were non-progressive at 3 months. Here also, addition of F to E was not associated with better outcome (PFS 1.8 vs 2.0 and OS 10.0 vs 7.3 months). No PFS difference was observed in the subgroup of patients with positive staining for REα. Conclusions: Addition of fulvestrant to EGFR-TKI is feasible and is associated with good PFS in the EGFR mutated group. Nevertheless, the lack of benefit associated with the combination of fulvestrant to EGFR-TKI does not support its future development in a phase 3 trial in women with NSCLC. Clinical trial information: NCT01556191.
Comparison of noninvasive hypoxia imaging with 18F-fluoroerythronitroimidazole and 18F-fluoromisonidazole PET/CT in lung cancer: A pilot clinical study.
Authors: Yuchun Wei, Wei Zhao, Yong Huang, Ning Liu, Song Gao, Jinming Yu, Shuanghu Yuan
Journal: Journal of Clinical Oncology (2016)

e20006 Background: Intratumoral hypoxia increases tumor aggressiveness, chemo- and radio-resistance. This is a clinical study to compare noninvasive hypoxia imaging using 18F-fluoroerythronitroimidazole (18F-FETNIM) and 18F-fluoromisonidazole (18F-FMISO) positron emission tomography/computed tomography (PET/CT) in patients with inoperable stages III–IV lung cancer. Methods: A total of forty-two patients with inoperable stages III–IV lung cancer underwent 18F-FETNIM PET/CT (n = 18) and 18F-FMISO PET/CT (n = 24) before chemo/radiation therapy. The maximum standard uptake value (SUVmax) of malignant and mean standard uptake value (SUVmean) of normal tissues depict 18F-FETNIM PET/CT and 18F-FMISOPET/CT uptake. Tumor-to-blood ratios (T/B) were used to quantify hypoxia. Results: All patients with lung cancer underwent 18F-FETNIM PET/CT and 18F-FMISO PET/CT successfully. Compared to 18F-FMISO, 18F-FETNIM showed similar uptake in muscle, thyroid, spleen, pancreas, heart, lung and different uptake in blood, liver, and kidney. A significantly higher SUVmax and T/B ratio with 18F-FMISO (2.56±0.77, 1.98±0.54), as compared to 18F-FETNIM (2.12±0.56, 1.42±0.33) was seen in tumor, P =0.022, < 0.001. For the patients with different pathological subtypes, no significant difference of SUVmax (or T/B ratio) was observed between 18F-FMISO and 18F-FETNIM in tumor except that a slightly higher T/B ratio with 18F-FMISO as compared to 18F-FETNIM was observed in squamous carcinoma, P =0.026. 18F-FMISO showed a significantly higher T/B ratio or SUVmax than 18F-FETNIM, when the longest tumor diameter is more than 2 cm. 18F-FMISO showed a significantly higher T/B ratio than 18F-FETNIM both in stage III and IV and a significantly higher SUVmax (or T/B ratio) with stage IV as compared to stage III was seen with the two tracers. Conclusions: 18F-FMISO showed significantly higher uptake than 18F-FETNIM in tumors and might be the better hypoxia biomarker in lung cancer.
A retrospective study of curcumin in combination with intravenous vitamin C (IVC) on triple negative breast cancer(TNBC).
Authors: Junwen Ou, Xinyu Zhu, Xinting Zhang, Hongyu Zhang, Xiaopu Wang, Tao Zhang
Journal: Journal of Clinical Oncology (2018)

e13118 Background: TNBC is associated with increased mortality compared to other breast cancer sub-types. There is an urgent need to develop novel, low toxicity and effective therapies for TNBC. Methods: Records of 70 advanced triple negative breast cancer patients treated from July 2012 to July 2017 in our hospital were retrospectively analyzed.35 patients received Gemcitabine{day 1 and day 8, 100mg/m2} + Cisplatin{day2,75mg/m2} (control group) and 35 patients received the above chemotherapy regimen in combination with oral curcumin(500mg/d) and IVC{1g/kg.d, starts from the 3rd day when chemotherapy finished,two times a week, totally 15 treatments}(combination group).The effects of the above treatment methods on tumor size, functional status score, progression free survival and overall survival time were analyzed systematically. Results: By using RECIST 1.1 criteria, 2/35 cases had complete remission (CR), 15/35 cases had partial remission (PR) and 13/35 cases had stable disease (SD) in the treatment group. The response rate(RR) was 49%. In the control group, there were no CR cases, 14 cases had PR, 14 cases had SD, the RR was 40%. There was no significant difference in RR between the two groups(P > 0.05). The median progression free survival time(PFS) and median overall survival time(OS) was 7 months (95% CI:1.5 to 28.5 months) and 27 months (95% CI:4 to 40 months) in the combination group compared with 4.5 months (95% CI:1.5 to 8 months) and 18 months (95% CI:3 to 26 months) in the control group. Kaplan-Meier survival analysis revealed that both PFS and OS in the combination group were significantly longer than that in the control group. (P < 0.05). All patients experienced adverse reaction in GI tract and myelosuppression. The incidence of adverse reactions in the treatment group was significantly lower than that of the control group. (P < 0.05). Conclusions: Although there was no significant difference in short-term efficacy between the two groups,this study suggested that curcumin supplementation in combination with IVC can be used during chemotherapy to reduce adverse reactions. Moreover, it helps to prolong PFS and OS of patients with late stage triple-negative breast cancer.
Outcomes of chemoradiation (CRT) for locoregionally advanced (LRA)squamous cell carcinoma of the head and neck (SCCHN): Outcomes with weekly cisplatin (WC) in an academic community based hospital.
Authors: Bruce Brockstein, Marit Uglane, Shalin Shah, Mihir Bhayani, Vathsala T. Raghavan, Ranjeev Nanda, Arif Shaikh, Nicholas Paul Campbell
Journal: Journal of Clinical Oncology (2018)

e18081 Background: CRT is a component of treatment (tx) for LRA SCCHN. High dose cisplatin (HDC) on weeks 1, 4, 7 is a standard but toxic regimen. Additionally, many cases of SCCHN are now attributable to HPV with better prognosis. A less toxic WC regimen has been used as an alternative for HDC. We sought to review our experiences with this regimen. Methods: We reviewed our outcomes of 298 consecutive LRA SCCHN patients (pts) treated with IMRT based therapy from 7/2003 through 7/2015 via data warehouse extraction and chart review. Tx setting was noted as definitive or post-op. Chemotherapy was categorized as induction yes/no, and CRT in 4 groups (none (n = 60 )/WC (n = 121 )/ FHX (5FU, hydroxyurea, taxol( n = 35 )/
Carboplatin (CBDCA), S-1 and concurrent thoracic radiotherapy (TRT) for elderly patients with locally advanced non-small cell lung cancer (NSCLC): A phase I study.
Authors: Seiji Niho, Kiyotaka Yoh, Keisuke Kirita, Shigeki Umemura, Shingo Matsumoto, Hironobu Ohmatsu, Koichi Goto, Yukio Hosomi, Hiroshi Tanaka, Hiroaki Okamoto, Keiji Nihei, Tetsuo Akimoto, Yuichiro Ohe
Journal: Journal of Clinical Oncology (2016)

e20050 Background: S-1 is an oral anticancer agent containing a mixture of tegafur, 5-chloro-2, 4-dihydroxypyridine, and potassium oxonate, which has been shown to have a radiosensitizing effect in preclinical models. Recent phase II studies have shown that chemoradiotherapy using cisplatin and S-1 yields promising progression-free survival (PFS) durations of 15 to 20 months in non-elderly (less than 75 years old) patients (pts) with locally advanced NSCLC. We conducted a phase I study of CBDCA, S-1 and TRT for elderly pts with locally advanced NSCLC. Methods: The eligibility criteria included pts with unresectable stage III NSCLC, a chemotherapy-naïve status, PS 0 to 1, and age ≥ 71 years. Pts received CBDCA (AUC 3-5) on day 1 and S-1 (30-40mg/m2 twice daily) on days 1 to 14, q4w, up to 4 cycles, plus concurrent TRT at a total dose of 60Gy. The initial dose of CBDCA was AUC 3 and that of S-1 was 60mg/m2/day. Three to 6 pts were entered at each dose level. Results: In all, 18 pts were enrolled between August 2011 and May 2015 from 4 hospitals in Japan. The patient characteristics were as follows: median age, 77 years (71-83 years); male/female ratio, 16/2; PS 0, 11 pts; tumor histopathological type: adenocarcinoma in 7 pts, squamous cell carcinoma in 7 pts, and NSCLC- NOS in 4 pts. All 4 cycles of CBDCA plus S-1 could be completed in 9 pts (50%), and the median number of cycles was 3.5 (range, 1 to 4). TRT at 60 Gy was completed in all 18 pts (100%). At dose level 4 (CBDCA 4 and S-1 40mg/m2 twice daily), 2/3 pts showed dose-limiting toxicities (DLTs), including G4 thrombocytopenia, G3 esophagitis and febrile neutropenia, and at dose level 3 (CBDCA 3 and S-1 40mg/m2 twice daily), 2/6 pts showed DLTs, including G3 pneumonitis and fatigue. PR was achieved in 12 pts, and the overall response rate was 67%. The median PFS was 15.3 months (95% confidence interval, 13.1 to 17.6 months), with a median follow-up period of 12.3 months in censored cases. Conclusions: The recommended doses of CBDCA and S-1 for a phase II study were determined to be AUC 3 and 40mg/m2 twice daily, respectively. A phase II study of this treatment is underway. Clinical trial information: UMIN000005794.
Prognostic significance of weight loss and nutritional markers during induction chemotherapy of newly diagnosed acute myeloid leukemia (AML) patients.
Authors: Zachary Smith, Gabriel Vidal, Michael Machiorlatti, Summer Frank, Sara Vesely, Minh Duc Phan, Mohamad Osama Khawandanah, Mohamad Ali Cherry
Journal: Journal of Clinical Oncology (2016)

e21591 Background: A wide landscape of factors exists to stratify the prognosis of patients (pts) with newly diagnosed AML including age, race, cytogenetics, and functional status. However, weight loss and nutritional assessment have yet to be fully evaluated as possible prognostic indicators.This study aims to investigate weight loss and nutritional markers during induction chemotherapy and their prognostic significance on treatment. Methods: We retrospectively analyzed all pts diagnosed with AML and treated at the University of Oklahoma over 18 years of age from January 2000 to June 2012 .215 AML pts were identified. Demographics, laboratory and pathologic findings including cytogenetic risks were recorded. BMI and albumin levels over time were examined using mean plot over 3 treatments (beginning of induction and first 2 consolidations). Pts treated before 2005 were excluded due to poor documentation of height/weight. Subsequently,total of 121 pts were identified with BMI measurements for the first 2 time periods, while 89 had BMI measured at all 3 time periods.Plots of the average BMI and albumin level at each time point were created. Differences of BMI over treatment periods were calculated for each individual and 2 new covariates were created: 1) BMI increase and 2) BMI decrease.Cox proportional hazards model was used to assess univariate association of each covariate with survival. Results: In the intermediate cytogenetic risk group, BMI was found to be significantly associated with OS; those with increased BMI have 2.38 times the hazard of death relative to those with BMI decrease over time, adjusting for age group. BMI group is not significantly associated with OS in any other model. BMI was marginally significant at p < 0.10 level for those with a BMI increase over time having 0.42 times the odds of complete remission relative to those with a BMI decrease. Conclusions: Age was found to be a more significant prognostic indicator than BMI, and BMI increase over time was found to have an increased hazard of death in the intermediate risk group. Further studies are needed to examine the prognostic significance of weight loss/gain during induction chemotherapy.