tbuckley/cabot-search huggingface dataset:
Prognostic value of different standard uptake values (SUV) of primary tumor measured with FDG-PET in resectable non-small cell lung cancer
Authors: W. K. De Jong, H. F. Van der Heijden, J. Pruim, W. J. Oyen, H. J. Groen
Journal: Journal of Clinical Oncology (2006)

7214 Background: The SUV is a measure for the preferential uptake of a radiopharmaceutical in a tumor compared with a homogenous distribution in a body. SUV can be based on the maximum value (SUVmax) or on the mean value in a region outlined by isodensity contours, e.g., 70% and 50%. The prognostic value of the different SUVs in non-small cell lung cancer (NSCLC) is not clear. We evaluated the prognostic value of SUVmax, SUV 70% and SUV 50% in patients (pts) with resectable NSCLC. Methods: All consecutive pts who underwent an attenuation corrected whole body FDG-PET scan were selected. All data were reconstructed iteratively. Only pts with stage I through IIIA NSCLC were included. By adjusting the isocontour in the region of interest, the SUVmax, SUV 70% and SUV 50% of the primary tumor were calculated. Cox regression analysis was used to calculate the relation between the different SUVs and survival. Results: Eighty-four pts (67 males, median age 64 years, range 38–86) were included. Histology was squamous cell carcinoma (n = 43), adenocarcinoma (n = 27), large cell carcinoma (n = 13), and 1 patient with bronchoalveolar carcinoma. Nineteen pts had stage IA, 28 stage IB, 4 stage IIA, 19 stage IIB, and 14 stage IIIA. Median (range) SUVmax, SUV 70%, and SUV 50% were 6.9 (1.6–32.5), 5.5 (1.0–23.2), and 4.5 (0.9–21.9), respectively. Analysis of residuals of SUVmax as a continuous variable suggests no cut-off point and no indication of time-dependency. By univariate analysis, all pts with a SUV higher than the median value had a worse survival than pts with a SUV lower than median (Hazard ratio’s for SUVmax, SUV70% and SUV 50% were 2.3 (p = 0.024), 2.5 (p = 0.015), and 2.7 (p = 0.010), respectively). Conclusions: SUVmax, SUV 70% and SUV 50% measured with FDG-PET have a similar prognostic impact. No cut-off point for SUVmax has been observed. No significant financial relationships to disclose.
Inclusion of rituximab in standard chemotherapy regimens for non-Hodgkin's lymphomas and risk of progressive multifocal leukoencephalopathy.
Authors: D. Focosi, M. Tuccori, C. Blandizzi, F. Maggi, M. Pistello, S. Montagnani, L. Antonioli, M. Fornai, P. Pepe, M. Petrini
Journal: Journal of Clinical Oncology (2010)

e18541 Background: Rituximab is an anti-CD20 monoclonal antibody which has improved treatment rates of non-Hodgkin lymphomas (NHL). Case series of progressive multifocal leukoencephalopathy (PML) in patients receiving rituximab within polychemotherapy regimens have lead to the introduction of a black box warning, but no risk estimation has been ever provided. Methods: We run a retrospective, monocentric cohort study on 976 NHL patients diagnosed in 1994-2008, including 517 patients who received at least one dose of rituximab. Results: Inclusion of rituximab into standard chemotherapy regimens for NHL caused a significant increase in the number of PML cases (rate difference: 2.2 every 1,000 patient/years; 95%CI: 0.1–4.3). Conclusions: Based on this finding clinical surveillance for PML-related symptoms is recommended in these patients. No significant financial relationships to disclose.
Observational GHEA study: Adjuvant trastuzumab treatment of HER2-positive breast carcinomas in the Italian clinical setting compared to HERA trial.
Authors: M. Campiglio, E. Tagliabue, A. Balsari, R. Bufalino, E. Ferri, S. Ménard
Journal: Journal of Clinical Oncology (2010)

672 Background: GHEA (Group Herceptin in Adiuvant Treatment), an Italian multicentric observational study, was designed with the aim to investigate on adjuvant trastuzumab therapy of HER2-positive breast carcinomas in conventional clinical setting. Methods: Eligible patients should have been treated with trastuzumab in adjuvant setting and were collected among 35 oncologic Italian centers. Results: The 516 patients registered in the GHEA database had a median age of 52 years and 50% were in post-menopause at the time of trastuzumab therapy, similarly to the patients enrolled in HERA (median age of 49 years and postmenopause status in 46%). Primary breast tumors in GHEA were mainly of ductal type (93%) of high grade (53% were GIII) and small in size (50% T1); moreover, 7% of the samples were classified as N- negative and T1micro, T1a and T1b, and around 4% were T4, four categories not included in HERA. ER-PgR-positive tumors were 42%, thus higher than in HERA (31%). Negative lymph nodes were present in 42% of cases compare to 32% in HERA. Thus, in GHEA study are included earlier breast cancers than in HERA. Moreover, some GHEA cases are not fitting selection criteria of HERA trial, therefore the follow-up of those patients will give us indication of trastuzumab efficacy that are lacking in those categories, right now. In the Italian clinical practice 96% of patients completed 1-year trastuzumab-treatment with around 2% of patients registered cardiac toxicity. GHEA DFS at 21 months of FU resulted similar to the one of HERA DFS at 23.5 months of FU. To date, half of patients progressed during trastuzumab treatment with some distant metastasis (i.e., bones, liver, lung, SNC). Conclusions: The purpose of the present study is to gather information from a large number of patients related to the effect of adjuvant trastuzumab treatment in conventional clinical setting. Furthermore, the inclusion of patients' categories not included in clinical trials can be used to design further clinical trials to better define guideline for trastuzumab adjuvant therapy and for the treatment of these patients at relapse. Supported by AIRC and Roche. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche
Experience with IntelliDose: An outpatient computer order entry system
Authors: B. Dubeshter, C. Walsh, K. Altobelli, C. Angel
Journal: Journal of Clinical Oncology (2005)

6081 Background: The elimination of errors related to chemotherapy administration remains an elusive goal. Computerized order entry has been shown to reduce errors. We studied whether errors related to calculations, decimal points, handwriting, cumulative dosing and maximum safe dose could be eliminated using computerized order entry. The time required to produce chemotherapy order sets by hand or by computer was also assessed. Methods: A retrospective study of all patients treated with chemotherapy over a six month period was performed. Chemotherapy order sets done via computerized order entry were assessed for correct drug, dose, decimal point errors, cumulative dose errors and a user set maximum safe dose. The time required to produce 10 orders by hand or with computer order entry was measured. Results: Ninety-one patients received 390 cycles of chemotherapy using 21 different treatment regimens. There were no errors in dose calculations, decimal points, or drug administration. In no instance did the calculated dose exceed the maximum safe dose or the cumulative dose limit. The average time saved per order set using computer order entry was 10 minutes. Conclusions: Using computer order entry with error checking algorithms, it may be possible to eliminate a number of types of errors associated with chemotherapy administration without sacrificing efficiency. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration IntrinsiQ Research
A Retrospective Cohort Study of Interferon-α Therapy in Myeloproliferative Neoplasms; Adverse Events, Thromboembolic Incidence and Causes of Termination of Therapy
Authors: Marie Lindgren, Jan Samuelsson, Lars Nilsson, Håvar Knutsen, Waleed Ghanima, Maria Åström, Elisabeth Ejerblad, Anna Hugosson, Peter L. Johansson, Björn Andréasson
Journal: Blood (2014)
A phase II study of imatinib mesylate (IM) in patients (pts) with unresectable hepatocellular carcinoma (HCC)
Authors: A. Y. Lin, G. Fisher, S. So, C. Tang, L. Levitt
Journal: Journal of Clinical Oncology (2005)

4223 Background: HCC is a devastating disease with limited treatment options in advanced stage. Level of platelet-derived growth factor (PDGF), a potent mitogen, correlates with the severity of liver cirrhosis. Over-expression of the PDGF receptor (PDGF-R) has been demonstrated in human HCC tumors and cell lines. IM, a tyrosine kinase inhibitor, inhibits PDGF-R. To assess the efficacy and safety of IM in HCC pts, we performed a phase II trial. Methods: HCC patients with reasonable organ function, unresectable but measurable disease, not candidates for chemoinfusion, age above 18 years, performance status of 0–2, and able to give informed consent were eligible. IM was started at 300 mg/day orally with 100 mg/week dose escalation up to a maximum dose of 800 mg/d. Results: Between February 2003 and November 2004, 13 patients (M: F = 11:2), median age 49 years (range 22 - 76 years) were enrolled. Most (8) of them had HBV as a risk factor for HCC. Others include: HCV (1), alcohol (1), and non-identifiable (3). Metastatic disease (AJCC, stage IV) were noted in 7 pts and locally advanced (stage III) in the remainder. One pt developed pulmonary embolism before starting IM. Among twelve pts treated with IM, the median dose-level of IM was 500 mg/d (range: 300–800 mg/d). Two pts had stable disease lasting 2+ -3+ months, respectively. Ten patients progressed within 2 months of IM treatment. No grade 3 or 4 hematological toxicity was observed. One patient had a grade 3 elevated AST during treatment; otherwise, there was no grade 3 or 4 non-hematological toxicity noted. The most common adverse events were: cough (N=7), fatigue (N=5), edema (N=5), abdominal pain (N=5), nausea (N=4), and myalgia (N=4). Conclusions: While the study is still on going, the preliminary results suggest that IM is well tolerated in pts with the degree of liver dysfunction allowed in this study. However, IM has limited efficacy for the treatment of HCC when administered as a single agent. No significant financial relationships to disclose.
Correlations among vitality, physical competence, lipid profile and measures of inflammation in transplant survivors with chronic graft versus host disease
Authors: L. Gerber, S. Mitchell, L. Li, G. Diao, J. Odom, N. Atlam, E. Cowen, C. Sportes, M. Bishop, S. Pavletic
Journal: Journal of Clinical Oncology (2007)

7108 Background: Chronic graft vs. host disease (cGVHD) is a multi-system disorder and a late complication of cancer therapy experienced by more than 50% of survivors after allogeneic hematopoietic stem cell transplantation. An improved understanding of the underlying biology and its relation to clinical symptoms may guide the development of better treatments for cGVHD. Methods: In a prospective, cross-sectional natural history protocol we examined the associations among organ/system dysfunction, measures of physical performance and health status with clinical measures of inflammation and fat metabolism. Variables included: 1. a composite severity score (CAS) rated by clinician-specialists (skin, eyes, mouth, gastrointestinal/liver, hematological, gynecological, pulmonary function evaluations); 2.functional measures [2 minute walk time (WT), grip strength (GS), SF-36 physical component summary score (PCS), vitality (VT) subscale, maximal activity score (MAS) of the Human Activity Profile]; 3.Laboratory tests (glucose, LDH, hemoglobin, ferritin, platelets, lymphocytes, pre-albumin, cholesterol, lipoproteins (HDL, LDL), triglycerides (TG), beta-2microglobulin (B2), and CRP. Results: 43 pts (mean age 47 yrs) with prior hematologic malignancy participated (mean 3 yrs post transplant). An average of 3.5 organ systems were affected, 77% were on systemic treatment for cGVHD, and 67% had prior acute GVHD. The mean body mass index (BMI) was 25, TG 255, cholesterol 222, LDL 132. They were moderately disabled by self-report (MAS), had slower than normal WT (540 ft/min), lower than normal GS (63 pounds), PCS (36) and VT (46) than a healthy population. Using a backward selection model with a significance of 0.1, low lung diffusing capacity (p&lt;.001) and low PCS (p=0.01) correlated with high CAS. VT correlated negatively with LDH, platelets, B2 and LDL (all p&lt;0.01). Low GS correlated with high LDH and B2 (p=0.01). Conclusions: Reported physical function and vitality in cGVHD patients are associated with abnormal lipid profiles and markers of inflammation. Establishment of such profiles is a critical step in the development of testable and validated outcome measures and for evaluation of new therapies in cGVHD. No significant financial relationships to disclose.
Maintenance gefitinib (G) after chemoradiotherapy (CRT) in patients (pts) with unresectable stage IIIA/B non-small cell lung cancer (NSCLC): A phase II trial of the Minnie Pearl Cancer Research Network
Authors: J. R. Gray, D. R. Spigel, J. D. Hainsworth, E. Vazquez, J. D. Peyton, E. L. Raefsky, R. Malik, T. Marsland, J. Waples, F. A. Greco
Journal: Journal of Clinical Oncology (2006)

7188 Background: Concurrent CRT improves outcomes for pts with unresectable stage III NSCLC compared with radiation (RT) alone. The EGFR inhibitor G benefits select pts with advanced NSCLC. This multicenter community phase II trial examined the role of CRT followed by G for pts with unresectable stage III NSCLC. Methods: Theprimary endpoint was 2-year overall survival (OS) in pts with unresectable stage IIIA/B NSCLC (effusions, N 3 mediastinal nodes &gt;4 cm excluded) treated with CRT followed by G. Induction(I) treatment (tx): docetaxel (D) 40 mg/m 2 IV and gemcitabine 800 mg/m 2 IV D1, 8 Q 21D × 3 cycles. Pts without progressive disease (PD) began: D 20 mg/m 2 IV and carboplatin (C) AUC = 1.5 IV weekly × 6 and RT 61.2 Gy, 1.8-Gy M-F weekly × 7 (starting 1 week prior to D/C). If no PD, pts received G 250 mg PO daily × 2 years or until PD. Eligibility:measurable disease, ECOG PS 0–1, informed consent. Intent to treat analysis. Results: One-hundred three pts were enrolled from 7/03 to 4/05. Baseline features: medianage 60 years (37–79); male/female 54%/46%; ECOG PS 0/1:26%/74%; adenocarcinoma (26%), squamous (32%), large cell (28%), mixed/not specified (14%); IIIA/B (46%/54%). Grade 3/4 toxicities were limited to ≤ 8% except for neutropenia (17%, during I) - with notx-related deaths. Complete/partial responses after I were seen in 1 pt/34 pts, respectively, for an overall response rate (RR) of 34% (95% CI 26%-44%). Forty-two pts (41%) had stable disease (SD) and 12% had PD (9 pts were unevaluable.) Seventy-four pts (72%) received D/C/RT which resulted in an overall RR of 44% (95% CI 35%-54%). Fifteen percent had SD. Fifty-six pts (54%) received G for a median of 28 weeks (1–107). Median PFS and OS are 9.9 and 15 months, respectively. After a median follow-up of 19 months, actuarial 1- and 2-year progression-free survival (PFS) is 41% and 12%, respectively. 1- and 2-year OS rates are 64% and 21%, respectively. Subset analyses by smoking, gender, histology, and stage are in progress. Conclusions: Maintenance G following CRT in unresectable NSCLC does not appear to improve survival. It is possible that further analysis may suggest a role for G in selected pts. [Table: see text]
Race and survival following brachytherapy-based treatment for men with localized or locally advanced adenocarcinoma of the prostate
Authors: K. M. Winkfield, M. Chen, D. E. Dosoretz, S. A. Salenius, M. J. Katin, R. Ross, A. V. D’Amico
Journal: Journal of Clinical Oncology (2009)

5068 Purpose: We investigated whether race was associated with risk of death following brachytherapy-based treatment for localized prostate cancer. Methods: The study cohort was comprised of 4,880 men with clinical stage T1–3N0M0 prostate cancer and minimum follow-up of 2 years who underwent brachytherapy-based treatment at 20 centers within the 21st Century Oncology consortium. A Cox regression multivariable analysis was used to evaluate the risk of death in African-American (AA) and Hispanic (H) men as compared to Caucasian men adjusting for age, pretreatment PSA, Gleason score, clinical T stage, year and type of treatment, and comorbidity level. Results: After a median follow-up of 5 years, there were 924 deaths. AA and H race were significantly associated with an increased risk of ACM (adjusted hazard ratio [AHR] 1.42 and 1.66, [95% confidence interval (CI): 1.01 to 1.99 and 1.14 to 2.41]; p = 0.045 and 0.008, respectively). As shown in the table , other factors significantly associated with an increased risk of death included age (p&lt;0.001), PSA (p = 0.02), Gleason score 8 to 10 (p = 0.001), year of brachytherapy (p&lt;0.001), and presence of 2 or more significant comorbidities (p = 0.003). The risk of ACM was decreased following trimodality therapy (p = 0.02). Conclusions: African-American and Hispanic race as compared to white race appear to confer a higher risk of mortality following brachytherapy-based treatment in men with localized or locally advanced prostate cancer. [Table: see text] No significant financial relationships to disclose.
Should large cell neuroendocrine carcinoma of the lung (LNEC) be classified and treated as a small cell lung cancer (SCLC) or with other large cell carcinomas (OLC)?
Authors: M. M. DeCamp, J. M. Varlotto, J. C. Flickinger, E. Schaefer, A. Recht
Journal: Journal of Clinical Oncology (2010)

7047 Background: To compare the presenting and prognostic characteristics, cause-specific survival (CSS) rates, and overall survival (OS) rates of patients with LNEC to those with SCLC or OLC, particularly those undergoing definitive resection without radiotherapy (S- NoRT). Methods: The Surveillance Epidemiology and End Results Database (SEER-17) from 2000-2006 was used. Differences between population characteristics were compared using chi-square and Kruskal-Wallis tests. The logrank test was used to compare differences in OS and CSS. Results: There were 1001 pts with LNEC (281 in the S-NoRT group), 9,417 patients with OLC (1212 S-noRT), and 35,047 SCLC patients (414 S-noRT). Patients with SCLC were more likely to be female, white non-Hispanic, and present with stage IV disease than patients with LNEC or OLC. Among S-no RT, those with SCLC were more likely to have nodal and mainstem bronchus involvement and to undergo a sublobar resection than patients with LNEC or OLC. Median follow-up in the S-noRT patients was 14 months (range, 3-83 months). OS and CSS of SCLC patients were significantly worse than that for patients with either LNEC or OLC. Multivariate analysis showed that OS was significantly affected by age, sex, stage, number of nodes resected or positive, and tumor size. When restricted to patients with stages T1A-BN0, CSS and OS remained worse in the SCLC group than the other groups. Conclusions: Presenting characteristics and survival of patients with LNEC are more similar to that of OLC than SCLC. Our results confirm patients with LNEC should be classified and treated as OLC. No significant financial relationships to disclose.
Prognostic value of VEGFC, HER2 and HER3 gene expression in recurrent squamous cell head and neck tumors
Authors: G. Fountzilas, N. Angouridakis, R. M. Wirtz, S. Claas, A. Nikolaou, K. T. Kalogeras
Journal: Journal of Clinical Oncology (2006)

5538 Background: The main prognostic variables of head and neck squamous cell carcinoma (HNSCC) are the location and size of the tumor and the presence of cervical lymph node metastases. Differential gene expression of members of the HER and VEGF families is a common feature in HNSCC. To elucidate the prognostic value and the interrelation of these factors we performed a detailed gene expression analysis within HNSCC tissue samples Methods: We analyzed fresh frozen tissue from 48 recurrent HNSCC tumors stored at -80 o C. RNA was isolated with the RNeasy kit (Qiagen, Inc.), followed by kinetic one-step RT-PCR for the expression of 8 candidate genes (EGFR, HER2, HER3, HER4, VEGFA, VEGFB, VEGFC and VEGFD). Raw data (Ct values) were normalized to RPL37A expression (housekeeper gene) and candidate gene expression between patient groups with differential clinical outcomes was analyzed by using Genedata Expressionist and GraphPad Prism 4 software packages. Median patient follow-up from initial diagnosis was 27 months. Results: Overexpression of VEGFA and EGFR was prominent in most tumors, but did not appear to have any prognostic value. However, VEGFC expression was significantly higher (p = 0.0002) in the tumors of patients with poor overall survival (&lt; 27 months). Interestingly, these tumors were further characterized by significantly lower expression levels of HER2 and HER3. Median survival of patients with tumor VEGFC expression levels of &gt;600 was calculated to be 42 months from initial diagnosis (Kaplan-Meier Survival Analysis), compared to 182 months in the rest of the patients. Conclusions: We have found that elevated VEGFC expression and low expression of HER2 and HER3 correlate with poor outcome in recurrent HNSCC patients. VEGFC preferably binds to the VEGFR3, which is predominantly expressed on lymphatic vessels. Overexpression of VEGFC may therefore result in the establishment of intratumoral lymphatic vessels, which have been shown to facilitate the dissemination of tumor cells into lymph nodes and the formation of distant metastases. We conclude that the determination of VEGFC, HER2 and HER3 expression may be of high prognostic value in HNSCC patients and that it may serve in the early identification of aggressive HNSCC subtypes. No significant financial relationships to disclose.
Signatures of Evolutionary Adaptation in Quantitative Trait Loci Influencing Trace Element Homeostasis in Liver
Authors: Johannes Engelken, Guadalupe Espadas, Francesco M. Mancuso, Nuria Bonet, Anna-Lena Scherr, Victoria Jímenez-Álvarez, Marta Codina-Solà, Daniel Medina-Stacey, Nino Spataro, Mark Stoneking, Francesc Calafell, Eduard Sabidó, Elena Bosch
Journal: Molecular Biology and Evolution (2015)

Essential trace elements possess vital functions at molecular, cellular, and physiological levels in health and disease, and they are tightly regulated in the human body. In order to assess variability and potential adaptive evolution of trace element homeostasis, we quantified 18 trace elements in 150 liver samples, together with the expression levels of 90 genes and abundances of 40 proteins involved in their homeostasis. Additionally, we genotyped 169 single nucleotide polymorphism (SNPs) in the same sample set. We detected significant associations for 8 protein quantitative trait loci (pQTL), 10 expression quantitative trait loci (eQTLs), and 15 micronutrient quantitative trait loci (nutriQTL). Six of these exceeded the false discovery rate cutoff and were related to essential trace elements: 1) one pQTL for GPX2 (rs10133290); 2) two previously described eQTLs for HFE (rs12346) and SELO (rs4838862) expression; and 3) three nutriQTLs: The pathogenic C282Y mutation at HFE affecting iron (rs1800562), and two SNPs within several clustered metallothionein genes determining selenium concentration (rs1811322 and rs904773). Within the complete set of significant QTLs (which involved 30 SNPs and 20 gene regions), we identified 12 SNPs with extreme patterns of population differentiation (FST values in the top 5% percentile in at least one HapMap population pair) and significant evidence for selective sweeps involving QTLs at GPX1, SELENBP1, GPX3, SLC30A9, and SLC39A8. Overall, this detailed study of various molecular phenotypes illustrates the role of regulatory variants in explaining differences in trace element homeostasis among populations and in the human adaptive response to environmental pressures related to micronutrients.