tbuckley/cabot-search huggingface dataset:
Platelet-to-hemoglobin ratio to predict progression-free survival for patients with locally advanced hepatocellular carcinoma.
Authors: Xing Li, Yan-Fang Xing, Zhi-Huan Lin, Ying-fen Hong, Dong-hao Wu, Tian-tian Wang, Xiao-kun Ma, Mingsheng Huang, Min Dong, Qu Lin, Xiang-yuan Wu
Journal: Journal of Clinical Oncology (2017)

463 Background: The prognosis of locally advanced hepatocellular carcinoma (HCC) patients is far from being identified which makes the treatment decision controversial. The present study aimed to assess role of blood cell counts, routine liver function tests in predicting the progression-free survival (PFS) of these patients. Methods: A total of 243 HCC patients staged Barcelona Clinic Liver Cancer (BCLC) B or C were analyzed retrospectively. The current staging systems of HCC were investigated about their performance on predicting PFS. And then, the novel prognostic factors were evaluated by integrating in to the best staging systems which was used to determine their independent prognostic value. Results: Cancer of the liver Italian program (CLIP) score system and advanced liver cancer prognostic system (ALCPS) stages were indentified to be testing systems with best akaike information criterion (AIC) index and linear trend χ 2 among all the current 12 staging systems for this patient subgroup. Then, the prognostic value of novel parameters was assessed by integration into CLIP and ALCPS score systems. Platelet-to-Hemoglobin Ratio (PHR) were confirmed to an independent predictor for PFS of locally advanced HCC patients when integrated into CLIP and ALCPS score systems ( p= 0.026 and 0.009, respectively) with the other parameters, including platelet and hemoglobin, failed to reach statistical significance. Moreover, PHR improved the performance of CLIP and ALCPS score systems by adjusted into it, which improved their discriminatory ability. Furthermore, PHR were designated ≤ 1.26 as low level and &gt; 1.26 as high level, according to which HCC patients were dichotomized into two groups. Locally advanced HCC patients with low PHR presented better 1 year disease progress rate (24.0% vs 41%) and overall survival (62.5% vs 38.8%) compared with patients with high PHR level. Besides, PHR level was associated with prognostic factors such as international normalized ratio, presence of ascites, serum albumin, serum α-fetoprotein, total bilirubin and portal vein thrombosis. Conclusions: The present study firstly indentified PHR as an independent prognostic factor in locally advanced HCC patients.
A prospective comparison study on EGFR mutations by direct sequencing and ARMS in completely resected Chinese non-small cell lung cancer with adenocarcinoma histology (ICAN).
Authors: Xuchao Zhang, Yi Long Wu, Jun Wang, Xiang-Yang Chu, Zhi-Dong Liu, Yi Shen, Haitao Ma, Xiang-Ning Fu, Jian HU, Nai-Kang Zhou, Yongyu Liu, Xinming Zhou, Jian-Jun Wang, Kang Yang, Lin Xu, Jian Li, Si-Yu Wang, Qun Wang, Lun-Xu Liu, Shun Xu
Journal: Journal of Clinical Oncology (2013)

1547 Background: ICAN study investigated EGFR mutation (M) status, clinical outcomes and recurrent risk factors in Chinese lung adenocarcinoma (ADC) patients (pts) after complete resection. Here we report analysis results for the overall EGFR M rate and the consistency between two EGFR M detecting methods, ARMS and PCR+direct sequencing (Seq). Methods: Pts were aged ≥18 years, with histological diagnosed lung ADC, and received surgical complete resection. Tumor sample EGFR M status (primary endpoint; positive [M+]) was determined according to clinical routine practice by whatever methods, including ARMS, Seq, liquid chip and mutant-enriched PCR. For the pts whose tissue was adequate after EGFR M testing by single method of either ARMS or Seq, the other method was applied. Results: Of 571 pts from 26 sites, 315 (55.2%) pts were EGFR M+. 420 pts’ tissues were tested by both ARMS and Seq. EGFR M+ rates were 58.1% and 54.5% respectively without statistical significance (p=0.0548). The total consistent rate (both M status and M types) between two methods was 76.7%. The following Table showed individual EGFR M types by two methods. Conclusions: The overall EGFR M+ rate in operable Chinese ADC was 55.2%. For resection samples, two common methods, ARMS and Seq, didn’t show statistical significance on EGFR M+ rate. Regarding EGFR M types, Seq found some rare mutations which ARMS kit could not detect, while ARMS seemed more sensitive for exon 20 and 21 mutations, especially for S768I and L861Q. Clinical trial information: NCT01106781. [Table: see text]
Evaluation of the accuracy of FDG-/FLT-PET for early prediction of non-progression in patients with advanced non-small cell lung cancer (NSCLC) treated with erlotinib
Authors: T. Zander, M. Scheffler, L. Nogova, M. Hellmich, E. Stoelben, W. Engel-Riedel, B. Krug, M. Dietlein, B. Neumaier, J. Wolf
Journal: Journal of Clinical Oncology (2009)

e19054 Background: EGFR mutations predict response to erlotinib treatment in advanced NSCLC. However, also a subgroup of patients with wildtype EGFR benefits from erlotinib treatment. This subgroup could not yet be defined by molecular means. In this trial we set out to prospectively evaluate the accuracy of [18F]FDG-/[18F]FLT-PET analyses for early prediction of non-progression in chemo-naive patients with advanced NSCLC treated with erlotinib. Methods: Patients with NSCLC stage IIIB/IV without prior systemic treatment for NSCLC were eligible and treated for 6 weeks with erlotinib in this single centre diagnostic pilot trial. Primary endpoint was the accuracy of [18F]FDG/18F[FLT] PET after 1 week of treatment to predict non-progression as defined by RECIST criteria in CT scans after 6 weeks of treatment. Here we present the evaluation of 20 patients of this ongoing trial in accordance with the data monitoring board (EudraCT number 2005–005393–73; NCT00568841 ). Results: Twenty patients were recruited from 9/07 to 9/08. Seventeen patients were eligible for final analysis. The AUC for [18F]FDG PET at week 1 to predict non-progression was 0.857 ±0.105 (p=0.013) and 0.643±0.137 (p=0.32) for [18F]FLT PET. Using [18F]FDG PET specificity was 1 and sensitivity 0.71 for prediction of non- progression after six weeks (p=0.006 Fishers exact). In addition, [18F]FDG PET after 1 week of treatment clearly predicted tumor non- progression after 18 weeks of treatment with a predefined cut-off of -20% change in sSUVmax. (p=0.0004, Fisher´s exact). Finally, using this cut-off value [18F]FDG-PET after one week of treatment, predicted progression free survival (p=0.001, log rank test), with differences in median PFS of 45 days vs 320 days. Using univariable Cox regression, both [18F]FDG and [18F]FLT PET predicted PFS [hazard ratio 2.1 (p=0.006, Wald test) and 2.3 (p=0.011), respectively, per standard deviation]. Conclusions: Our observations indicate that early [18F]FDG but not [18F]FLT PET analysis predicts non-progression after 6 weeks of first-line erlotinib treatment in patients with advanced NSCLC. In addition, early [18F]FDG PET predicts non-progression after 18 weeks of treatment and progression free survival. [Table: see text]
Molecular biomarkers as predictors of patient survival in pancreatic adenocarcinoma (PDA): An analysis of the Know Your Tumor initiative (KYT).
Authors: R Joseph Bender, David Halverson, Kimberly Mason, Linlin Luo, Jonathan Robert Brody, Lola Rahib, Lynn McCormick Matrisian, Andrew Eugene Hendifar, William Arthur Hoos, Sameh Mikhail, Vincent M. Chung, Vincent J. Picozzi, Corinne Ramos, Craig Heartwell, Katelyn Varieur, Metasebia Aberra, Emanuel Petricoin, Subha Madhavan, Michael J. Pishvaian
Journal: Journal of Clinical Oncology (2017)

278 Background: Recent studies have expanded our knowledge of the genomic landscape of PDA. While critical and in some cases, potentially actionable alterations are being identified, limited outcomes data have thus far made it difficult to validate the relevance of these observations. Methods: The Pancreatic Cancer Action Network (PanCAN) and Perthera have facilitated commercial tumor molecular profiling for over 400 PDA pts since 2014 through KYT, and have developed a database of molecular and clinical information useful for data mining of biomarker-survival correlations. The survival significance of biomarkers was assessed using standard statistical methodology including Kaplan-Meier analysis and Cox proportional hazard models. Results: Linked molecular and outcomes data were available for 360 pts, of which 173 had treatment (tx) information available. Pathogenic mutations from targeted NGS, protein expression from IHC, and protein phosphorylation from RPPA were screened for correlations with overall survival (OS) and progression-free survival (PFS) independent of tx received. As shown in the table, mutations in 3 genes were associated with a better OS; while mutations in 8 genes were associated with poorer OS. Only two mutations were correlated with PFS in 1 st or 2 nd -line tx ( BRCA2 and KDM6A, worse PFS). Positive expression of 7 proteins, including TS, TOP1, and RRM1, were associated with reduced OS but were not correlated with PFS. High levels of phospho-ribosomal protein S6 were associated with both poor OS (HR=10.3, p=0.001) and poor PFS (HR=9.6, p=0.006). Conclusions: Multiple biomarkers had significant correlations with OS in PDA, while fewer were correlated with PFS. Growth of this registry database will further validate tx-specific predictive biomarkers for use in pts with multi-omic profiling data. [Table: see text]
A randomized, open-label, phase II study assessing the efficacy and the safety of bevacizumab in neoadjuvant therapy in patients with FIGO stage IIIc/IV ovarian, tubal, or peritoneal adenocarcinoma, initially unresectable.
Authors: Roman Rouzier, Philippe Morice, Anne Floquet, Frédéric Selle, Eric Lambaudie, Virginie Fourchotte, Christophe Pomel, Raffaele Fauvet, Pierre Emmanuel Colombo, Elsa Kalbacher, Philippe Follana, Sandrine Martin, Anne Lesoin, Fabrice Lecuru, Patricia Pautier, Frederic Guyon, Paul H. Cottu, Florence Joly, Youssef Ghazi, Elisabeth Chereau
Journal: Journal of Clinical Oncology (2014)

TPS5614 Background: We hypothesize that improving the response rate of stage IIIC or IV and non-optimally resectable ovarian cancer patients to neoadjuvant chemotherapy would improve the optimal debulking rate at interval debulking surgery (IDS) and ultimately the survival. In the ICON7 and OCEANS trials, addition of bevacizumab to chemotherapy has been shown to improve the response rates. We assume that its administration in the neoadjuvant setting would improve the response rate and consequently will help to achieve optimal debulking rate at IDS. Methods: This study, named ANTHALYA, is a multicenter, open-label, randomised phase II study, conducted in 15 sites in France. 90 patients with FIGO stage IIIC/IV ovarian, tubal or peritoneal adenocarcinoma, initially unresectable are to be enrolled. At inclusion, patients are randomised (2:1) to receive 4 cycles of neoadjuvant carboplatin and paclitaxel chemotherapy either combined to 3 cycles of bevacizumab in the treatment arm (not given the cycle before surgery) or alone in the control arm. The control arm will be used to assess the complete resection rate in the arm treated without bevacizumab in the neoadjuvant setting. The primary objective for this study is to evaluate the efficacy of neoadjuvant bevacizumab and chemotherapy measured by the complete resection rate after IDS. Complete resection is defined as the removal of all macroscopic residual tumour at IDS (CC score = 0). The secondary objectives for this study are as follows: (1) to evaluate the safety profile of bevacizumab when added to carboplatin and paclitaxel in the neoadjuvant setting; (2) to assess the efficacy of bevacizumab measured by Objective Response Rate (ORR) for neoadjuvant period and after all courses of treatment, assessed according to RECIST criteria and CA-125 levels; and (3) to evaluate progression-free survival (PFS). Exploratory analysis are conducted to evaluate the biomarkers profile and to explore prognosis and predictive markers. Clinical trial information: NCT01739218.
Antigen spread (AgS) after sipuleucel-T (sip-T): A cross-trial comparison of 4 sip-T clinical trials of patients (pts) with prostate cancer (PC).
Authors: Lawrence Fong, Eric Jay Small, Daniel Peter Petrylak, David I. Quinn, Emmanuel S. Antonarakis, Adam S. Kibel, Nancy N. Chang, Harini Kandadi, Nadeem Anwar Sheikh, Charles G. Drake
Journal: Journal of Clinical Oncology (2017)

143 Background: Sip-T, an FDA-approved autologous immunotherapy for pts with asymptomatic or minimally symptomatic metastatic castration-resistant PC (mCRPC), is manufactured from peripheral blood mononuclear cells cultured with PA2024, a fusion antigen of prostatic acid phosphatase (PAP) conjugated to granulocyte macrophage colony-stimulating factor. In sip-T–treated pts, antibody responses to PA2024/PAP (target antigens) and AgS (antibody responses to secondary [2°] antigens) correlate with improved OS (Sheikh 2013; GuhaThakurta 2015). We assessed if a greater magnitude of AgS would be observed in an earlier PC disease stage when the immune system is more intact. Methods: Pt serum was from 1 non-metastatic, androgen-dependent PC (ADPC) sip-T trial (STAND, sip-T + androgen deprivation, NCT01431391) and 3 mCRPC sip-T trials (IMPACT, sip-T vs control, NCT00065442; STAMP, sip-T + abiraterone acetate, NCT01487863; STRIDE, sip-T + enzalutamide, NCT01981122). Using a Luminex assay, mean fold-change in IgG responses to target and 2° cancer-related antigens (PSA, LGALS3, LGALS8, ERAS, KRAS, KLK2) was evaluated from baseline to wk 6. Results: AgS was evaluated in 308 pts. The mean fold-change in IgG responses to target antigens was greater for ADPC vs mCRPC pts (p &lt; 0.01). Moreover, the magnitude of IgG responses was greater for most 2° antigens in ADPC vs mCRPC pts (p &lt; 0.05; Table), except for PSA and KLK2 in ADPC vs STRIDE pts. Conclusions: The magnitude ofantibody responses to target and 2° antigens was greater earlier in the PC disease course, consistent with increased antigen-presenting cell activation in ADPC vs mCRPC pts. Increased AgS likely reflects stronger sip-T–induced immune responses, previously associated with extended OS in mCRPC (Sheikh 2013; GuhaThakurta 2015). Future research is warranted on the clinical benefit of sip-T earlier in the PC disease course and the potential impact of androgen suppression on the magnitude of AgS and outcomes. Clinical trial information: NCT01431391; NCT00065442; NCT01487863; NCT01981122. [Table: see text]
Comparison of performance of the 2016 ACR-EULAR classification criteria for primary Sjögren's syndrome with other sets of criteria in Japanese patients
Authors: Hiroto Tsuboi, Shinya Hagiwara, Hiromitsu Asashima, Hiroyuki Takahashi, Tomoya Hirota, Hisashi Noma, Hisanori Umehara, Atsushi Kawakami, Hideki Nakamura, Hajime Sano, Kazuo Tsubota, Yoko Ogawa, Etsuko Takamura, Ichiro Saito, Hiroko Inoue, Seiji Nakamura, Masafumi Moriyama, Tsutomu Takeuchi, Yoshiya Tanaka, Shintaro Hirata, Tsuneyo Mimori, Isao Matsumoto, Takayuki Sumida
Journal: Annals of the Rheumatic Diseases (2017)

Objectives To compare the performance of the new 2016 American College of Rheumatology (ACR)-European League Against Rheumatism (EULAR) classification criteria for primary Sjögren's syndrome (SS) with 1999 revised Japanese Ministry of Health criteria for diagnosis of SS (JPN), 2002 American-European Consensus Group classification criteria for SS (AECG) and 2012 ACR classification criteria for SS (ACR) in Japanese patients. Methods The study subjects were 499 patients with primary SS (pSS) or suspected pSS who were followed up in June 2012 at 10 hospitals in Japan. All patients had been assessed for all four criteria of JPN (pathology, oral, ocular, anti-SS-A/SS-B antibodies). The clinical diagnosis by the physician in charge was set as the ‘gold standard’. Results pSS was diagnosed in 302 patients and ruled out in 197 patients by the physician in charge. The sensitivity of the ACR-EULAR criteria in the diagnosis of pSS (95.4%) was higher than those of the JPN, AECG and ACR (82.1%, 89.4% and 79.1%, respectively), while the specificity of the ACR-EULAR (72.1%) was lower than those of the three sets (90.9%, 84.3% and 84.8%, respectively). The differences of sensitivities and specificities between the ACR-EULAR and other three sets of criteria were statistically significant (p&lt;0.001). Eight out of 302 patients with pSS and 11 cases out of 197 non-pSS cases satisfied only the ACR-EULAR criteria, compared with none of the other three sets. Conclusions The ACR-EULAR criteria had significantly higher sensitivity and lower specificity in diagnosis of pSS, compared with the currently available three sets of criteria.
Comprehensive genomic profiling of relapsed and refractory small cell neuroendocrine carcinoma of the urinary bladder.
Authors: Sumanta K. Pal, Jean H. Hoffman-Censits, Julia Andrea Elvin, Jo-Anne Vergilio, James Suh, Shakti Ramkissoon, Siraj Mahamed Ali, Alexa Betzig Schrock, Hugh A.G. Fisher, Badar Mian, Tipu Nazeer, David Fabrizio, Garrett Michael Frampton, Phil Stephens, Vincent A. Miller, Laurie M. Gay, Jeffrey S. Ross
Journal: Journal of Clinical Oncology (2017)

350 Background: Small cell neuroendocrine carcinoma of the bladder (SCCB) is rare but aggressive form of genitourinary cancer that can arise de novo or in conjunction with urothelial carcinoma (UCB). Methods: DNA was extracted from 40 microns of FFPE specimen from 29 cases of relapsed, refractory and metastatic SCCB and 1,113 UCB. Comprehensive genomic profiling (CGP) was performed using a hybrid-capture, adaptor ligation based next generation sequencing assay to a mean coverage depth of &gt; 503X. Tumor mutational burden (TMB) was calculated from a minimum of 1.11 Mb of sequenced DNA as previously described and reported as mutations/Mb. The results were analyzed for all classes of genomic alterations (GA), including base substitutions, insertions and deletions (short variants; SV), fusions, and copy number changes including amplifications (amp) and homozygous deletions. Results: 29 SCCB cases were confirmed on routine histology and featured positive IHC staining for chromogranin, synaptophysin or both. Patients had a mean age of 68.1 years (range 49-90 years) and 25 (86%) were male. At the time of CGP, 3 (10%) SCCB were Stage III and 26 (90%) were stage IV. The primary SCCB was used for sequencing in 14 (48%) of cases and a metastasis sample in 15 (52%). The 29 SCCB featured 2.86 GA/case.The genomics of SCCB differed significantly from UCB (Table). The most frequent clinically relevant GA in SCCB were RICTOR amp (21%) and PIK3CA (10%), BRCA1, HGF, FBXW7 and CCND2 SV (7% each). The relatively high TMB in SCCB (7% TMB &gt; 20 mut/Mb and 28% TMB &gt; 10 mut/Mb) is similar to that seen in UCB. No SCCB cases were MSI-high. ERBB2 and FGFR1 GA frequencies (both 3%) in SCCB were lower than in similarly studied UCB. Conclusions: SCCB differs in genomic landscape from UCB in having higher frequencies of TP53 and RB1 GA and lower frequencies of FGFR3 and ERBB2 GA. However, like UCB, SCCB shares the presence of multiple GA associated with potential responses to targeted therapies and high TMB associated with response to immune checkpoint inhibitor therapy. [Table: see text]
Mutational Analysis of MDS and AML Occurring after Treatment for Acute Promyelocytic Leukemia (APL). a Report of 9 Cases
Authors: Philippe Attias, Aline Renneville, Xavier Thomas, Cecile Bally, Sandrine Hayette, Hassan Farhat, Virginie Eclache, Alice Marceau, Bruno Cassinat, Jean Feuillard, Christine Terré, Eric Delabesse, Sophie Park, Julie Lejeune, Sylvie Chevret, Lionel Ades, Claude Preudhomme, Pierre Fenaux
Journal: Blood (2016)
Breast Cancer—Major changes in the American Joint Committee on Cancer eighth edition cancer staging manual
Authors: Armando E. Giuliano, James L. Connolly, Stephen B. Edge, Elizabeth A. Mittendorf, Hope S. Rugo, Lawrence J. Solin, Donald L. Weaver, David J. Winchester, Gabriel N. Hortobagyi
Journal: CA A Cancer Journal for Clinicians (2017)

Answer questions and earn CME/CNE The revision of the eighth edition of the primary tumor, lymph node, and metastasis (TNM) classification of the American Joint Commission of Cancer (AJCC) for breast cancer was determined by a multidisciplinary team of breast cancer experts. The panel recognized the need to incorporate biologic factors, such as tumor grade, proliferation rate, estrogen and progesterone receptor expression, human epidermal growth factor 2 (HER2) expression, and gene expression prognostic panels into the staging system. AJCC levels of evidence and guidelines for all tumor types were followed as much as possible. The panel felt that, to maintain worldwide value, the tumor staging system should remain based on TNM anatomic factors. However, the recognition of the prognostic influence of grade, hormone receptor expression, and HER2 amplification mandated their inclusion into the staging system. The value of commercially available, gene-based assays was acknowledged and prognostic input added. Tumor biomarkers and low Oncotype DX recurrence scores can alter prognosis and stage. These updates are expected to provide additional precision and flexibility to the staging system and were based on the extent of published information and analysis of large, as yet unpublished databases. The eighth edition of the AJCC TNM staging system, thus, provides a flexible platform for prognostic classification based on traditional anatomic factors, which can be modified and enhanced using patient biomarkers and multifactorial prognostic panel data. The eighth edition remains the worldwide basis for breast cancer staging and will incorporate future online updates to remain timely and relevant. CA Cancer J Clin 2017;67:290-303. © 2017 American Cancer Society.