tbuckley/cabot-search huggingface dataset:
Tumor hyaluronan (HA) as a novel biomarker in non-small cell lung cancer (NSCLC).
Authors: Jun Gong, Michelle Guan, Cook-Wiens Galen, Brent K Larson, Jenny Zhou, Rishi Patel, Isaac Lapite, Richard Tuli, Ronald B. Natale, Andrew Eugene Hendifar
Journal: Journal of Clinical Oncology (2018)

e24280 Background: Accumulation of HA has been shown to promote tumorigenesis and correlate with an aggressive phenotype across several cancers. We investigated the significance of HA as a potential biomarker in a large cohort of NSCLC patients (pts). Methods: Tumor HA levels were scored based on an affinity histochemistry assay in the tumor microenvironment of archived tumor samples from NSCLC pts. Overall survival (OS) and time to progression from initiation of taxane therapy (taxane TTP) were compared using log-rank tests based on HA score and clinicopathologic factor. Mean ranks of HA scores were analyzed per pt characteristic using the Kruskal-Wallis (KW) test. Results: From 10/2006-9/2016, 174 NSCLC pts were included and 113 (65%) had adenocarcinomas, 61 (35%) had adenosquamous/squamous, 122 (70%) were recurrent/metastatic (R/M), 120 (69%) were Caucasian, and 82 (47%) were female. Of the 122 pts with R/M disease, 93 had HA scores (68 done on tumor samples at baseline) with mean HA scores that did not significantly differ based on pathologic grade (KW test, p = 0.9559), race (p = 0.7143), KRAS status (p = 0.6019), EGFR status (p = 0.3349), ECOG performance status (p = 0.4955), HA biopsy site (metastatic or primary, p = 0.514), and line of therapy at time of biopsy (p = 0.3229). Median OS for pts with R/M adenocarcinoma was 35.5 mos (95% CI 23.6-50.3) vs. 17.9 mos for squamous (95% CI 12.7-37.0, log-rank test, p = 0.0165). OS was not significantly different by HA quartiles (score ≤10, 11-20, 21-30, > 30) in the overall (n = 131, p = 0.5994) and R/M cohort (n = 90, p = 0.9422), by high (≥25) or low ( < 25) HA score and tumor histology in the R/M cohort (n = 90, p = 0.1953), and by site of HA biopsy in the overall (n = 129, p = 0.1026) and R/M cohort (n = 91, p = 0.4928). Median taxane TTP was significantly different by HA quartiles (2.8 mos, 95% CI 1.9-3.5 for HA score ≤10; 5.0 mos, 95% CI 2.2-9.6 for 11-20; 7.9 mos, 95% CI 2.5-9.7 for 21-30; 3.9 mos, 95% CI 2.4-4.7 for > 30) in the overall cohort (n = 98, p = 0.0265). Conclusions: In an initial lung cancer cohort, tumor HA level represents a potential biomarker for taxane TTP, which remains a cornerstone of cytotoxic therapy in NSCLC. Further validation is warranted to identify the HA accumulation threshold associated with clinical benefit.
Comparison of immunotherapy response rates in non-small cell lung cancer following platinum-based chemotherapy.
Authors: Taylor Mai Weis, Shannon Hough, Gregory Peter Kalemkerian
Journal: Journal of Clinical Oncology (2018)

e21175 Background: Three immunotherapy agents are currently FDA-approved for the treatment of NSCLC after platinum-based chemotherapy. These agents have demonstrated superior outcomes and tolerability compared to docetaxel in randomized controlled trials (RCTs), however response to these agents has not yet been characterized in a real-world clinical setting. This study will compare response rates between immunotherapy agents in the Michigan Medicine population and identify predictive factors of efficacy. Methods: In this single-center retrospective cohort study, we identified patients treated with nivolumab, pembrolizumab, or atezolizumab from March 1, 2015 – July 31, 2017. Patients were included with stage IV or recurrent NSCLC that progressed during or after platinum-based doublet chemotherapy. Patients were excluded for prior treatment with immune-stimulatory antitumor agents or diagnosis of other malignancies within 5 years. The primary endpoint was objective response rate (ORR), defined as complete or partial response, according to assessment by the treating oncologist. Secondary endpoints include median overall survival, progression free survival, and adverse drug events (ADEs). Results: Of 118 patients, 79 received nivolumab, 29 received atezolizumab, and 10 received pembrolizumab. Twenty-nine percent of patients had squamous and 68% had nonsquamous histology. Thirty-nine percent received steroids within 4 weeks prior to or during treatment and 28% had an ECOG performance status greater than 1. PD-L1 expression was reported in 28% of patients, however 100% of pembrolizumab patients had confirmed PD-L1 expression. ORR was 21%, 9% and 40% for the nivolumab, atezolizumab, and pembrolizumab groups, respectively. ADEs led to discontinuation in 20% of nivolumab, 14% of atezolizumab, and 10% of pembrolizumab-treated patients. The most common ADEs were fatigue (35%), rash (15%), arthralgia (12%), and diarrhea (12%). Conclusions: ORR and rates of ADEs observed in this study were numerically similar to those observed in RCTs leading to FDA-approval of these agents. The high ORR in the pembrolizumab group may be due to the high rates of PD-L1 expression and smaller sample size.
Capecitabine as upfront treatment in locally advanced nasopharyngeal cancer patients: Single institute experience.
Authors: Reyad Dada, Mohamed Ezzat El Sayed, Jamal M Zekri
Journal: Journal of Clinical Oncology (2016)

e17545 Background: Capecitabine, an oral 5-fluorouracil (5FU) derivate, has replaced 5FU in many chemotherapy regimens used in different gastrointestinal tract cancers. The experience with capecitabine in neoadjuvant chemotherapy (NAC) regimens in locally advanced nasopharyngeal cancer (LANPC) patients is limited to only preliminary results from phase III study from china (Lee et al., Cancer 2015 Apr 15;121(8):1328-38). Methods: We are retrospectively reporting on our experience with neoadjuvant capecitabine administered to 5 patients with LANPC between 3/2013 and 9/2014. Treatment consisted 2-3 cycles of chemotherapy with cisplatin 100 mg/m2 on day 1 and capecitabine 850 mg/m2 BID d 1-14 every 3 weeks. Patients who achieve excellent clinical response after second cycle underwent early radiological examination to confirm response omitting the 3rd cycle of NAC after discussion in multidisciplinary team. Thereafter, all patients received radical CCRT (cisplatin 100 mg/m2, q3 weeks during radiation). Clinical and radiological examination started 2-3 months after the end of radiotherapy, and were repeated every 3-6 months. Results: All 5 patients completed the neoadjuvant and combined modality treatment. One patient had garde 2 vomitting and two had garde 2 diarrhea during NAC. No grade 3/4 toxicities were observed. 1/5 and 4/5 patients reached complete and partial remission by the end of NAC respectively. Due to excellent responses in 2 patients the induction was stopped after 2 cycles. All of them reached clinically and radiologically complete remission by the end of the scheduled CCRT treatment. Two patients relapsed after 6 and 8 months respectively and could be successfully salvaged with palliative chemotherapy. The other 3 patients remained relapse free. Conclusions: Capecitabine (in combination with cisplatin) is a safe and effective substitute to 5FU for the neoadjuvant treatment of LANPC. It is more convenient for patients because it can be given without the need of central line in an outpatient setting. Further validation in randomized clinical studies in locally advanced NPC patients are required. For the time being, this approach can be considered in selected cases.
Biomimetic Intraneural Sensory Feedback Enhances Sensation Naturalness, Tactile Sensitivity, and Manual Dexterity in a Bidirectional Prosthesis
Authors: Giacomo Valle, Alberto Mazzoni, Francesco Iberite, Edoardo D’Anna, Ivo Strauss, Giuseppe Granata, Marco Controzzi, Francesco Clemente, Giulio Rognini, Christian Cipriani, Thomas Stieglitz, Francesco Maria Petrini, Paolo Maria Rossini, Silvestro Micera
Journal: Neuron (2018)
Exploratory analysis of percentage of genomic loss of heterozygosity (LOH) in patients with platinum-sensitive recurrent ovarian carcinoma (rOC) in ARIEL3.
Authors: Ana Oaknin, Jonathan A. Ledermann, Amit M. Oza, Domenica Lorusso, Carol Aghajanian, Andrew Peter Dean, Nicoletta Colombo, Johanne I Weberpals, Andrew R. Clamp, Giovanni Scambia, Alexandra Leary, Robert W. Holloway, David M. O'Malley, Iain A. McNeish, Elizabeth M. Swisher, Teresa Cameron, Sandra Goble, James Sun, Kevin K. Lin, Robert L. Coleman
Journal: Journal of Clinical Oncology (2018)

5545 Background: In ARIEL3, rucaparib significantly improved progression-free survival (PFS) vs placebo in all randomized patients, including patients with BRCA-mutant, BRCA wild-type/high-LOH (prespecified as ≥16% genomic LOH), or BRCA wild-type/low-LOH ( < 16% genomic LOH) rOC (Coleman et al. Lancet. 2017;390:1949-61). This exploratory analysis evaluated the optimal cutoff for percentage of (%) genomic LOH in BRCA wild-type rOC in ARIEL3. Methods: Genomic LOH of archival tumor tissue DNA was centrally assessed using Foundation Medicine's next-generation sequencing-based assay (Cambridge, MA, USA). Treatment effect for investigator-assessed PFS (invPFS) was analyzed in BRCA wild-type rOC for the prespecified cutoff (16%) and across a range of cutoffs for % genomic LOH (5%–30%). Hazard ratios (HRs) were estimated using a stratified Cox proportional hazards model. Prognostic and predictive utility of % genomic LOH was assessed by comparing invPFS between and within the treatment arms. Results: In ARIEL3, 564 patients were randomized. Of the 368 patients with BRCA wild-type associated rOC, LOH was calculable for 319. Rucaparib significantly improved invPFS vs placebo between the 5% and 23% cutoffs for % genomic LOH. Using the prespecified cutoff (16%), the HR (rucaparib vs placebo) was 0.44 (95% confidence interval [CI], 0.29‒0.66; P< 0.0001) for patients with high-LOH rOC. To further assess the % genomic LOH cutoff, we compared patients with high- vs low-LOH rOC within the rucaparib arm and found a statistically significant benefit for invPFS at the prespecified cutoff of 16% (HR, 0.70; 95% CI, 0.50‒0.97; P= 0.0338). In the placebo arm, no statistically significant benefit was observed for invPFS in patients with high- vs low-LOH rOC at any cutoff tested. Conclusions: Rucaparib improved invPFS vs placebo across the range of cutoffs tested for % genomic LOH, including the prespecified cutoff of 16% for high LOH. The observance of significant differences between patients with high- vs low-LOH rOC in the rucaparib but not placebo arm suggests that genomic LOH is a predictive but likely not prognostic biomarker. Clinical trial information: NCT01968213.
Anti-EGFR resistant clones decay exponentially after progression: Implications for anti-EGFR rechallenge.
Authors: Christine Megerdichian Parseghian, Jonathan M. Loree, Van Karlyle Morris, Allan Andresson Lima Pereira, Eduardo Vilar Sanchez, Bryan K. Kee, Kanwal Pratap Singh Raghav, A. Dasari, Ji Wu, Victoria M. Raymond, Kimberly Banks, AmirAli Talasaz, Richard B. Lanman, Michael J. Overman, Scott Kopetz
Journal: Journal of Clinical Oncology (2018)

3511 Background: Colorectal cancers (CRC) treated with EGFR inhibitor (EGFRi) evolve by a repetitive process of genetic diversification and clonal evolution. After discontinuation of EGFRi, KRAS/NRAS (RAS) and EGFR resistance mutations no longer have a growth advantage relative to other clones. Yet, the impact of time from the last cycle of EGFRi to decreases in the mutant (MT)/ wildtype (WT) allele ratio has not been well defined in mCRC. Methods: We analyzed a retrospective cohort of patients at MD Anderson Cancer Center with RAS/BRAF/EGFRWT mCRC who had been treated with EGFRi and in whom plasma samples had been collected for sequencing of ctDNA on a platform optimized for very low allele frequencies (AF) (Guardant360). Relative MT allele frequency (rMAF) was defined as ((MT AF) / MT present at the max AF in that assay) and approximates the % of tumor cells shedding the MT of interest into the circulation. rMAF results were normalized to total ctDNA concentration. Results: 135 pts were identified. There was an inverse relationship between the rMAF of RAS and EGFR and time since last treatment, but no change in truncal APC and TP53 inactivating mutations. Our analysis showed that the decline in RAS/EGFR rMAF is best described by an exponential decay model (r = 0.93 for RAS and 0.94 for EGFR). At progression on EGFRi, the median RAS rMAF and EGFR rMAF were 10.5% and 10.6%, respectively, and these clones exponentially decayed with a half-life of 3.4 mo and 6.9 mo, respectively. Our model predicts that at the time of progression only 30% of the cells in the tumor carry a mutation in RAS/EGFR/BRAF/MAP2K1. This suggests that the remaining 70% are driven by undetected autonomous mechanisms of resistance, or paracrine effects. Conclusions: We identified that RAS and EGFR MT alleles decay exponentially over time since last EGFRi. These results provide a molecular explanation for the efficacy of EGFRi rechallenge therapies after a period off EGFR inhibition. The half-life of these clones may help guide timing of rechallenge therapies, and could be monitored by ctDNA. Further, these results suggest that a subclonal tumor population may be exerting resistance through paracrine mechanisms. These data will be validated on an external dataset.
Evaluation of antibody fragment properties for near-infrared fluorescence imaging of HER3-positive cancer xenografts
Authors: Ayman El-Sayed, Wendy Bernhard, Kris Barreto, Carolina Gonzalez, Wayne Hill, Landon Pastushok, Humphrey Fonge, C. Ronald Geyer
Journal: Theranostics (2018)

In vivo imaging is influenced by the half-life, tissue penetration, biodistribution, and affinity of the imaging probe.Immunoglobulin G (IgG) is composed of discrete domains with known functions, providing a template for engineering antibody fragments with desired imaging properties.Here, we engineered antibody-based imaging probes, consisting of different combinations of antibody domains, labeled them with the near-infrared fluorescent dye IRDye800CW, and evaluated their in vivo imaging properties.Antibody-based imaging probes were based on an anti-HER3 antigen binding fragment (Fab) isolated using phage display.Methods: We constructed six anti-HER3 antibody-based imaging probes: a single chain variable fragment (scFv), Fab, diabody, scFv-CH3, scFv-Fc, and IgG.IRDye800CW-labeled, antibody-based probes were injected into nude mice bearing FaDu xenografts and their distribution to the xenograft, liver, and kidneys was evaluated.Results: These imaging probes bound to recombinant HER3 and to the HER3-positive cell line, FaDu.Small antibody fragments with molecular weight <60 kDa (scFv, diabody, and Fab) accumulated rapidly in the xenograft (maximum accumulation between 2-4 h post injection (hpi)) and cleared primarily through the kidneys.scFv-CH3 (80 kDa) had fast clearance and peaked in the xenograft between 2-3 hpi and cleared from xenograft in a rate comparable to Fab and diabody.IgG and scFv-Fc persisted in the xenografts for up to 72 hpi and distributed mainly to the xenograft and liver.The highest xenograft fluorescence signals were observed with IgG and scFv-Fc imaging probes and persisted for 2-3 days.Conclusion: These results highlight the utility of using antibody fragments to optimize clearance, tumor labeling, and biodistribution properties for developing anti-HER3 probes for image-guided surgery or PET imaging.
Abstract 15438: Incremental Prognostic Value of Plasma Volume Status and Cardiac MIBG Imaging in Patients Admitted for Acute Decompensated Heart Failure: A Prospective Study
Authors: Shunsuke Tamaki, Takahisa Yamada, Takashi Morita, Yoshio Furukawa, Yusuke Iwasaki, Masato Kawasaki, Atsushi Kikuchi, Tsutomu Kawai, Masahiro Seo, Iyo Ikeda, Eiji Fukuhara, Makoto Abe, Jun Nakamura, Kiyomi Kayama, Masatsugu Kawahira, Kazuya Tanabe, Masatake Fukunami
Journal: Circulation (2017)

Background: Increased plasma volume (PV) has been shown to be associated with poor clinical outcome in patients (pts) with chronic heart failure (CHF). In addition, cardiac MIBG imaging also provides prognostic information in CHF pts. However, there is no information available on the prognostic value of combining plasma volume status (PVS) and cardiac MIBG imaging for the prediction of re-hospitalization for worsening heart failure (WHF) in pts who are admitted for acute decompensated heart failure (ADHF). Methods: We prospectively studied 271 consecutive pts who were admitted for ADHF and survived to discharge. Body weight measurement, venous blood sampling, echocardiography, and cardiac MIBG imaging were performed just before discharge. PVS was defined as follows: actual PV = (1 - hematocrit) х [a + (b х body weight)] (a=1530 in males and a=864 in females, b=41.0 in males and b=47.9 in females); ideal PV = c х body weight (c=39 in males and c=40 in females); and PVS = [(actual PV - ideal PV)/ideal PV] х...
TCT-64 Two-Year Clinical and Imaging Outcomes of Thin Strut Sirolimus-Eluting Bioresorbable Vascular Scaffolds in De Novo Coronary Artery Lesions: The MeRes-1 Trial
Authors: Ashok Seth, Yoshinobu Onuma, Ricardo Costa, Praveen Chandra, Vinay Bahl, Cholenahally Manjunath, Ajaykumar Mahajan, Viveka Kumar, Parvin Goel, Gurpreet Wander, Samuel Mathews, Upendra Kaul, Ajit Kumar Valaparambil, Pratap Rath, Vijay Trehan, Sengottuvelu Gunasekaran, Sundeep Mishra, Alexandre Abizaid, Patrick Serruys
Journal: Journal of the American College of Cardiology (2018)
Association of FDG PET-CT (PET) avid skeletal lesions (SL) with progression-free survival (PFS) in patients (pts) with previously untreated follicular lymphoma (FL).
Authors: Joseph J. Maly, Lai Wei, Jessica Hemminger, Beth Christian, Kami J. Maddocks, Jeffrey Alan Jones, Chad Wright, Kristie A. Blum
Journal: Journal of Clinical Oncology (2017)

e19026 Background: PET scan is frequently utilized in FL. Reduced EFS has been observed in DLBCL pts with SL treated with RCHOP (Held, JCO 31:4115, 2013). Methods: We performed a retrospective single center study to assess outcomes of FL pts with PET avid SL between January 2005 and November 2015. 131 pts with newly diagnosed FL and PET performed within 1 month of diagnosis were included. Results: 32 of these pts had SL (median 4, range 1-11) on initial PET. Median age was 57 (range 43-79), 15 (47%) were female, 30 (94%) had stage IV disease, LDH was elevated in 6 (19%), 6 (19%) had bulky disease &gt; 6 cm, and FLIPI-1 score was low in 5, intermediate in 11, and high 16 pts. 27 pts had grade (gr) 1-2 FL, 2 had gr 3a, and 3 had gr 3 (not classified). All but 1 patient received rituximab (R)-containing therapy (9 received BR, 7 received RCHOP, 5 RCVP, 9 other). 8 pts received maintenance R, and none received radiation. There were no statistically significant differences in median age, tumor gr, LDH, or use of anthracycline containing therapy (28% in SL group vs 16% in non-SL group, p = 0.13) in pts with SL compared to those without SL (n = 99). Pts with SL had higher incidence of bone marrow involvement (27% vs 9%, p = 0.013). With a median follow-up of 35 months, SL pts had 44% rate of transformation to DLBCL compared 12% in non-SL pts (p = 0.004). Median PFS was 45.8 months in SL pts not-reached in non-SL pts (p = 0.003). Median OS was 105.9 months in SL pts and not reached in non-SL pts (p = 0.08). In the multi-variate analysis, SL (p = 0.037), male gender (p = 0.048), higher FLIPI-1 score (p = 0.009), and absence of anthracycline containing therapy (p = 0.005) were significantly associated with decreased PFS using backward selection. Conclusions: The presence of PET identified SL in previously untreated FL is associated with an increased risk of transformation and reduced PFS in this single center retrospective analysis. Larger studies of uniformly treated pts are needed to validate these data. The identification of high-risk PET avid SL in FL pts in future prospective therapeutic trials could be used to select pts for specific induction regimens, maintenance rituximab, or consolidative radiation.
TCT-539 Clinical outcomes in high bleeding risk patients undergoing complex PCI with the Xience everolimus eluting stent: a patient-level pooled analysis from four Xience post-approval trials
Authors: Birgit Vogel, Bimmer Claessen, Usman Baber, Sabato Sorrentino, Weiying Zhao, Mitchell Krucoff, Ken Kozuma, Junbo Ge, Ashok Seth, Raj Makkar, Sripal Bangalore, Deepak Bhatt, Dominick Angiolillo, Shigeru Saito, Franz-Josef Neumann, James Hermiller, Marco Valgimigli
Journal: Journal of the American College of Cardiology (2018)
Acute leukemia in pregnancy: A single institution experience.
Authors: Nosha Farhadfar, Sonia Cerquozzi, Hessenauer R. Michael, Louis Letendre, William J. Hogan, Mark Robert Litzow, Mrinal M. Patnaik, Ayalew Tefferi, Naseema Gangat
Journal: Journal of Clinical Oncology (2016)

7040 Background: Acute leukemia is rarely diagnosed during pregnancy. Management of acute leukemia during pregnancy presents a considerable challenge due to limited available data on optimal management including fetal and maternal outcomes. Methods: After approval by the Mayo IRB, 23 cases of acute leukemia diagnosed during pregnancy between 1962 and 2016 were identified using an institutional computerized database. Information was extracted using electronic medical records and paper chart review. Results: The majority of patients (n=18) had acute myeloid leukemia (AML) including 4 with acute promyelocytic leukemia (APL). Five patients had acute lymphoblastic leukemia (ALL). Ten patients were diagnosed in the first trimester (43.4%), 7 in the second trimester (30.4 %) and 6 in the third trimester (26.2%) of pregnancy. Eighteen patients (78%) achieved a complete remission. Approximately 50% (n=11) of pregnancies ended with elective or spontaneous abortions. Fifty percent (2 /4) of patients diagnosed in first or second trimester who delayed chemotherapy greater than 1 week died during induction therapy. Eleven patients received chemotherapy while pregnant (2 in first, 6 in second and 3 in third trimester) which lead to 4 fetal losses and 7 deliveries. The majority of neonates were of low birth weight with one having mild anemia at birth and no detected congenital malformation. At a median follow up of 55 months (range, 8-330) 7 patients (30%) are alive. Table 1 summarizes the maternal and fetal outcomes. Conclusions: Delay in therapy on the basis of fetal well-being may lead to an adverse maternal outcome. Despite higher risk of preterm low birth-weight delivery, in utero exposure to chemotherapy in the second and third trimesters did not increase the risk of fetal malformation. Overall outcomes based on trimester of pregnancy at the time of acute leukemia diagnosis. N=23 First Trimester 0-13 weeks Second Trimester 14-26 weeks Third Trimester 27-40 weeks N 10 7 6 Median time to chemotherapy (range) 11.5 (2-140) days 4 (1-6) days 1 untreated 6 (1-34) days AML 6 4 4 APL 1 2 1 ALL 3 1 1 Elective Termination 5 0 0 Fetal Outcomes N=5 N=7 N=6 Death 3 3 0 Pre-term Delivery 2 2 4 Term Delivery 0 2 2 Disease Outcomes . . . Achieved CR 8 6 4 Durable CR 3 3 2 Relapsed/Refractory 3 1 2 HSCT 3 1 2