tbuckley/cabot-search huggingface dataset:
Mortality risk for stage I NSCLC with poor histologic grade, tumor size ≥4 cm, and non-upper lobe tumor location: An epidemiologic study of 19,702 patients in the California Cancer Registry from 1989 to 2003
Authors: S. I. Ou, J. A. Zell, A. Ziogas, H. Anton-Culver
Journal: Journal of Clinical Oncology (2007)

7558 Background: Platinum-based adjuvant chemotherapy in randomized trials has failed to provide a survival benefit in stage I non-small-cell lung cancer (NSCLC). Using data from California Cancer Registry (CCR), we explored factors that have detrimental effect on survival in stage I NSCLC to identify a subset of patients at high risk for relapse and subsequent mortality. Methods: 19,702 stage I NSCLC cases in the CCR from 1989 to 2003 were identified and subgrouped into stage IA &amp; IB disease. Patient demographic factors, tumor characteristics and treatment delivered were examined. Kaplan-Meier survival curves were calculated to estimate survival rates. Cox proportional hazards ratios were used to identify independent prognostic factors for survival. Results: Advanced age at diagnosis, male sex, low socioeconomic status (SES), non-surgical treatment &amp; poorly-differentiated histologic grade (stage IA: hazard ratio [HR] = 1.14; 95% confidence interval [CI]: 1.08–1.19 &amp; stage IB: HR = 1.11; 95% CI: 1.07–1.16) were factors identified with increased mortality risk on multivariate analysis. Non-upper lobe tumor location (RML/RLL/LLL) and tumor size ≥ 4 cm (vs &lt; 4 cm; HR = 1.22; 95% CI: 1.15–1.30) were additional factors with increased mortality risk among stage IB patients. Conversely, bronchioloalveolar carcinoma (BAC)(vs adenocarcinoma: stage IA: HR = 0.81; 95% CI: 0.72–0.91 &amp; stage IB: HR = 0.87, 95% CI: 0.77–0.98) &amp; Asian ethnicity (vs Caucasian: stage IA: HR = 0.81, 95% CI: 0.70–0.94 &amp; stage IB: HR = 0.80, 95% CI: 0.72–0.90) were associated with decreased mortality risk in stage I NSCLC. Lobectomy had the lowest HRs for death among all surgical techniques for both stage IA &amp; IB NSCLC in the Cox proportional hazards model. Conclusions: Poorly-differentiated stage IA &amp; IB NSCLC and stage IB NSCLC located in non-upper lobes or tumor size ≥ 4 cm carried an increased mortality risk on adjusted analysis. No significant financial relationships to disclose. [Table: see text]
The histological subtype and grade work as prognostic indicators for platinum-based chemotherapy (CTX) of advanced ovarian carcinoma (AOC)
Authors: Y. Shimizu, F. Murakami, N. Ogawa, M. Yamada, S. Saskurai, T. Ishiya, K. Katase, K. Hasumi, S. G. Silverberg
Journal: Journal of Clinical Oncology (2007)

16015 Background: We previously reported the new histopathologic grading system applicable for all histological types of ovarian carcinoma (Cancer 82:893–901, 1998), which thereafter was reappraised by several investigators. The aim of the present study is to investigate the relationship of the histopathologic type and grade with the effect of CTX for AOC. Methods: Between 1/89 and 12/05, 272 consecutive patients (pts) with pT3 (FIGO stage III or IV) AOC pts received 6 cycles or more of cisplatin (70 mg/m2 for 1 cycle)-based CTX combined with aggressive debulking surgery consisting of hysterectomy, bilateral adnectomy, omentectomy, pelvic to paraaortic lymphadenectomy, with or without more extensive surgery including intestinal resections. Histological types and grade were diagnosed according to the WHO classification system and our system reported method, respectively. Results: Of the eligible 261 pts, response was achieved in 67% (CR: 21.8%, PR: 45.2%) of the pts. Response (CR+PR/total) by histological type was 86% (36+91/148) for serous, 97% (16+13/30) for transitional cell, 67% (5+13/27) for endometrioid, 4% (0+1/29) for mucinous, and 0% (0+0/27) for clear cell, respectively. Response (overall/CR) for chemo-sensitive histological types (serous/transitional cell/endometrioid) by grade (G) was 86%/52% for 21 G1, 90%/31% for 64 G2, and 83%/28% for 118 G3 (CR rate: G3 vs G1 + G2: p=0.02). Response duration (CR/PR) by G was not reached/30 months (mo) for G1, 85 mo/23 mo for G2, 40 mo/16 mo for G3. Response (overall/CR) to 2 nd line CTX was 75%/38% for G1, 73%/17% for G2, and 47%/10% for G3. Conclusions: Histological type correlated with platinum-CTX sensitivity. CTX regimens should be designed based on the histological subtypes. New “non-platinum” regimens should be considered for both mucinous and clear cell carcinoma. Histological grade worked as an indicator for CR rate, response duration (thus, progression rate), and response rate to 2 nd line CTX. Thus, the grade is considered to be a significant prognostic factor for platinum-sensitive AOC. No significant financial relationships to disclose.
Synthetic tumor-specific breakpoint peptide vaccine in patients (pts) with chronic myeloid leukemia (CML) and minimal residual disease: A phase II trial
Authors: N. Jain, H. M. Kantarjian, G. Garcia-Manero, G. Borthakur, T. Ebarb, J. E. Cortes
Journal: Journal of Clinical Oncology (2008)

7056 Background: The Bcr-Abl fusion creates a unique sequence of amino acids that could constitute a target for immunomodulation. Short peptides derived from the fusion region can bind MHC and induce in vitro HLA-restricted cytotoxicity. Native peptides may have low immunogenicity because they bind with low affinity to the MHC. Synthetic peptides containing mutations in the sequences of these peptides can bind with higher affinity and may generate a cross-reactive T cell response to the native sequence (heteroclitic response). Methods: A mixture of heteroclitic and native peptides derived from both b3a2 and b2a2 sequences was used to vaccinate pts with CML in complete cytogenetic remission (CCyR) on imatinib (IM) therapy with stable bcr-abl transcript levels. Montanide ISA51 and GM-CSF were used as immunological adjuvants. Pts were required to have received IM for ≥12 months with no change in dose for at least 6 months and were not allowed any dose increases after registration. Vaccines were given every two weeks x 4, then every 3 weeks x 1, then monthly x 10 for a total of 15 vaccinations. Results: 10 pts have been enrolled. Median age is 45 years (range 28–63) and pts had received IM for a median of 62 months (range 34–70) at a median dose of 600mg (range 300–800). Median follow-up after start of vaccination is 15 mos (range 9–21). 9 pts have completed all 15 vaccinations (one patient - 13 vaccines). All pts had b2a2 transcript, including 2 pts with co-expression of b2a2 and b3a2. Three of the 10 patients have achieved one log reduction in BCR-ABL transcript levels, including the 2 pts with prior interferon therapy. Nine pts continue in CCyR and 1 lost CCyR and was switched to dasatinib. Vaccine has been well tolerated with no grade ≥3 adverse events. Most common adverse events are local site reactions. Conclusions: BCR-ABL peptide vaccine used in this study is modestly effective with minimal side effects. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis, Breakthrough Therapeutics
Influence of comorbidities in the clinical presentation of invasive pneumococcal disease (IPD) in adults in Spain, 2010-2013. The ODIN study
Authors: Catia Cilloniz, Emilio Bouza, Inmaculada Grau, Luis Molinos, Miguel Salavert, Pedro Llinares, José Luis De la Cruz, Inmaculada Alfageme, Olga Rajas, Asunción Fenoll, Josefina Liñares, Isabel Cifuentes
Journal: European Respiratory Journal (2014)

Objectives: To explore comorbidities associated with the different clinical presentations of IPD in adults in Spain.

Methods: A prospective, active, hospital-based surveillance of culture-confirmed IPD episodes in adults (≥18years) was performed in 9 Spanish hospitals (August 2010-June 2013). IPD was considered as isolation of S. pneumoniae from normally sterile fluids. Comorbidities, risk habits, clinical presentation [complicated pneumonia -CP-(presence of pleural effusion/empyema and/or multilobar infiltration), non-complicated pneumonia -N-CP-, meningitis -M-, primary bacteremia -PB-, peritonitis -P- and others -O-], and outcome were recorded. Comorbidities known to increase the risk of IPD were compared between the different clinical presentations.

Results: Among the 637 IPD cases identified, up to 90.3% of the patients had ≥1 comorbidity and/or risk habits. Table shows comorbidities with significant association with any of the IPD clinical presentations.

Severe sepsis/septic shock occurred in 22% of the patients. Overall mortality was 14.8%, being the highest in PB (21.2%) and CP (20%). Mortality in patients developing severe sepsis/septic shock was 35%.

![Figure][1] 



Conclusions: This is the first study that clearly demonstrates that some underlying conditions influence the clinical presentation of IPD and thus the mortality rate.

 [1]: pending:yes
Differential Tumorigenicity of Growth Factor-Dependent Versus-Independent CCL39 Lung Fibroblast Lines in Nude Mice&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: D E Renwick, A J Franchi, J M Pouysségur, A E Lagarde
Journal: JNCI Journal of the National Cancer Institute (1986)

Several cell lines derived from CCL39 Chinese hamster fibroblasts were characterized so that comparison could be made of their tumorigenic potential and their ability to proliferate in vitro in response to growth factor stimulation. Tumor formation was assessed by implanting single-cell suspensions into the flanks (sc), peritoneal cavity (ip), or tail vein (iv) of BALB/c athymic nude mice, whose ages ranged from 8–10 days (neonatal), to 5–7 weeks (adult), to more than 5 months (old). Serum, insulin (INS), epidermal growth factor (EGF), and α-thrombin (THR) were tested for promoting short-term cell proliferation in serum-free medium. CCL39 fibroblasts arrestable in the Go phase required INS and EGF or THR to divide optimally. They formed sc tumors after a long latent period and only in the young and adult mice. Among such tumors, those composed of growth factor-independent variants became lethal ip and iv and grew sc earlier and rapidly in all age groups. These properties were shared by polyomavirus-transformed CCL39 fibroblasts and 1 mutant that divided without growth factors. Mutants that escaped only partially the growth factor requirements had been implanted ip but not iv. They grew at the sc site in newborn and adult mice, with kinetics comparable to that of CCL39 cells. Their expansion in old animals was variable, transient or slow. Neither CCL39 nor 39T10 tumor cells were susceptible to cytotoxic reactions mediated by activated macrophages or natural killer cells. These observations indicate that distinct anatomical regions in nude mice and factors related to their age contribute to present CCL39 heterotransplants with environments that are more or less permissive to their growth. These observations also suggest that cells that achieve growth factor autonomy are more malignant than cells in which growth factor controls of division are less stringent but not abrogated.
Use of tumor budding with K-RAS gene analysis to identify potentially responsive metastatic colorectal cancer patients treated with anti-EGFR therapies.
Authors: A. Lugli, F. Molinari, P. Saletti, S. de Dosso, L. Mazzucchelli, M. Frattini, I. Zlobec
Journal: Journal of Clinical Oncology (2010)

e14042 Background: Tumor budding in colorectal cancer is recognized by the International Union against Cancer as a highly relevant, additional prognostic factor and defined as single cells or clusters of up to 5 cells at the invasive tumor front. In metastatic colorectal cancer (mCRC), K-RAS gene analysis is now routinely performed to identify patients who are more likely to respond to anti-EGFR therapies. The aim of this study was to assess the predictive value of tumor budding and to determine whether this feature can complement K-RAS gene analysis to help identify mCRC patients who may benefit from anti-EGFR therapies. Methods: 43 patients with mCRC treated with cetuximab or panitumumab were entered into this study. Objective tumor response was evaluated using the RECIST guidelines. 30 patients had progressive or stable disease and classified as non-responsive (NR), while 13 patients had complete or partial response. Mutation in K-RAS occurred in 11 (35.6) cases. Tumor budding was evaluated from whole tissue sections stained for pan-cytokeratin. Tumor buds in the densest region of tumor budding were counted using a 40x objective. Based on receiver-operating characteristics (ROC) curve analysis, the cut-off score for “low” and “high” tumor budding (LTB and HTB) was 15 buds/high power field. Results: Tumor budding and K-RAS mutation both correctly classified patients into response groups with 68% accuracy. All patients with K-RAS mutations were NR to therapy. Of the remaining 32 patients with wild-type (WT) K-RAS, 7 (21.9%) had HTB and all were NR to therapy. All patients with PR were K-RAS WT and had LTB. The combination of K-RAS and tumor budding improved the overall accuracy of K-RAS mutation alone to 80%. Conclusions: This appears to be the first evidence suggesting that a histomorphological parameter, namely tumor budding, could have potential predictive value in patients with mCRC treated with anti-EGFR agents. The analysis of tumor budding in addition to K-RAS gene status may represent an effective approach to further optimize the management of mCRC patients treated with anti-EGFR therapies. No significant financial relationships to disclose.
Predictors of BRCA-positive parents' disclosure of cancer risk and risk reduction options to offspring.
Authors: L. J. Patrick-Miller, B. Egleston, O. I. Olopade, M. B. Daly, C. Daugherty, C. B. Sands, H. Schmidheiser, C. Gulden, K. Pawlowski, A. R. Bradbury
Journal: Journal of Clinical Oncology (2010)

6074 Background: Many BRCA mutation carriers (BRCA+) report discussing their genetic test results with offspring < 25 YO. Mediators and content of disclosure have potential to inform interventions to facilitate adaptive response to genetic risk for adult onset cancers. Methods: 108 parents (215 parent-offspring pairs) completed survey of communication of genetic risk to offspring (111 female; 104 male). Parents reported disclosure (DIS/NONDIS) of their BRCA1/2 result in a nonspecific, and content specific questions. Regression analyses identified predictors of disclosed content. Results: 79/134 (59%) offspring learning of parents' BRCA+ status (DIS), offspring learned of parental cancer risk (97%), own chance of inheriting BRCA+ cancer risk (82%), parent risk reduction strategies (76%), and own risk reduction options (63%). Among 55 (41%) offspring not learning of parent BRCA+ status (NONDIS), offspring learned of parent BRCA+ cancer risk (31%), offspring BRCA+ cancer risk (9%), parent (36%), and offspring (35%), risk reduction options. Older offspring age (OOA) predicted DIS (p = 0.00). OOA (p = 0.00), female parent gender (FPG p = 0.01), parent cancer diagnosis (CADX p = 0.17) and > education (p = 0.03) predicted disclosure of parental cancer risk. OOA and CADX predicted disclosure of offspring's BRCA+ associated cancer risk. OOA (p = 0.003), female offspring gender (FOG p = 0.01) and FPG (p = 0.007) predicted communication of parent risk reduction strategies; OOA (p = 0.03), FOG (p = 0.06), and CADX (p = 0.06) predicted communication of offspring risk reduction options. Conclusions: Information that BRCA+ parents share with offspring < 25 YO varies considerably. Parents who report sharing BRCA1/2 test results frequently share parent BRCA+ status and child's related cancer risk, but less frequently, risk reduction options. Some parents who report not disclosing their BRCA1/2 results do share parent cancer risk reduction strategies and offspring risk reduction options. Further analyses of parent and offspring mediators/moderators of disclosure content and offspring outcomes will guide development of interventions to facilitate adaptive responses to communication of genetic risk to at-risk offspring. No significant financial relationships to disclose.
Abstract 20642: Why Arrhythmogenic Cardiomyopathy is Still a Major Cause of Sudden Death in Competitive Athletes Despite Preparticipation Screening?
Authors: Cristina Basso, Stefania Rizzo, Kalliopi Pilichou, Domenico Corrado, Gaetano Thiene
Journal: Circulation (2014)

Introduction: The incidence of sudden death (SD) in young competitive athletes has declined in Italy since the introduction of systematic screening including ECG. Mortality reduction was predominantly due to a lower incidence of SD from cardiomyopathies Hypothesis: Arrhythmogenic cardiomyopathy (AC) should have also declined as a cause of SD in competitive athletes. Results: During the study period 1981-2014, 75 competitive athletes died suddenly. Major causes at postmortem examination were AC, 27%; atherosclerotic coronary artery disease (CAD), 24%; congenital CAD, 16%; normal heart 10%; conduction system disease, 7%; hypertrophic cardiomyopathy, 5%; myocarditis, 4%; mitral valve prolapse, 3%. When analyzing the 26 AC cases, we subdivide those occurring before (group A, n.13 cases) and after 1998 (group B, n. 13 cases). In group A 11/13, 85% had typical AC, with inverted T wave in &gt; V1-V2 and left bundle branch block (LBBB) ventricular arrhythmias (VA), but echocardiography was performed only once; and only 2 cases had left ventricular variant, not reaching the AC diagnostic criteria. All 13 cases of group B had left ventricular or biventricular variant of AC, with inverted T wave in V5-V6 (7/13, 54%), low QRS complex in 4 (4/13, 31%), LBBB or right bundle branch block VA (7/13, 54%). Echocardiography did not show morpho-functional abnormalities, while cardiac magnetic resonance (CMR) was performed only once with left ventricular late enhancement. At postmortem, all these AC cases demonstrated a subepicardial-midmural fibrofatty replacement of the left ventricular free wall, without thinning/aneurysm or dilatation. Conclusions: AC still represents a major cause of SD in athletes in Italy since the left ventricular or biventricular variant without aneurysms escape routine echocardiographic detection. Athletes with inverted T waves in lateral leads and/or low QRS voltage as well as unexplained VA and normal echocardiography require further examination including CMR before allowing sport participation.
Immunosuppressive mechanisms in glioblastoma: Fig. 1.
Authors: Edjah K. Nduom, Michael Weller, Amy B. Heimberger
Journal: Neuro-Oncology (2015)

Despite maximal surgical and medical therapy, the treatment of glioblastoma remains a seriously vexing problem, with median survival well under 2 years and few long-term survivors. Targeted therapy has yet to produce significant advances in treatment of these lesions in spite of advanced molecular characterization of glioblastoma and glioblastoma cancer stem cells. Recently, immunotherapy has emerged as a promising mode for some of the hardest to treat tumors, including metastatic melanoma. Although immunotherapy has been evaluated in glioblastoma in the past with limited success, better understanding of the failures of these therapies could lead to more successful treatments in the future. Furthermore, there is a persistent challenge for the use of immune therapy to treat glioblastoma secondary to the existence of redundant mechanisms of tumor-mediated immune suppression. Here we will address these mechanisms of immunosuppression in glioblastoma and therapeutic approaches.
Lung Function, Allergic Sensitization and Respiratory Symptoms Among Children and Adolescents with Sickle Cell Disease
Authors: Gustavo Wandalsen, Maíra Moya, Carolina Cobra, Cíntia Jonhston, Josefina Braga, Dirceu Sole, Fernanda C. Lanza, Andrea Angel
Journal: Journal of Allergy and Clinical Immunology (2016)
Pharmacodynamics and pharmacokinetics of a 72-hour infusion of 9-aminocamptothecin in adult cancer patients.
Authors: C H Takimoto, W Dahut, M T Marino, H Nakashima, M D Liang, N Harold, R Lieberman, S G Arbuck, R A Band, A P Chen, J M Hamilton, L R Cantilena, C J Allegra, J L Grem
Journal: Journal of Clinical Oncology (1997)

PURPOSE To investigate the pharmacokinetics and pharmacodynamics of 9-aminocamptothecin (9-AC) infused over 72 hours at doses of 5 to 74 micrograms/m2/h. PATIENTS AND METHODS 9-AC lactone and total (lactone plus carboxylate) plasma concentrations were measured in 44 patients with solid tumors using a high-performance liquid chromatography (HPLC) assay. Fifteen patients underwent extended pharmacokinetic sampling to determine the distribution and elimination kinetics of 9-AC. RESULTS At steady-state, 8.7% +/- 4.7% (mean +/- SD) of the total drug circulated in plasma as the active 9-AC lactone. Clearance of 9-AC lactone was uniform (24.5 +/- 7.3 L/h/m2) over the entire dose range examined; however, total 9-AC clearance was nonlinear and increased at higher dose levels. In 15 patients treated at dose levels &gt; or = 47 micrograms/m2/h, the volume of distribution at steady-state for 9-AC lactone was 195 +/- 114 L/m2 and for total 9-AC it was 23.6 +/- 10.6 L/m2. The elimination half-life was 4.47 +/- 0.53 hours for 9-AC lactone and 8.38 +/- 2.10 hours for total 9-AC. In pharmacodynamic studies, dose-limiting neutropenia correlated with steady-state lactone concentrations (Css) R2 = .77) and drug dose (R2 = .71). CONCLUSION Plasma 9-AC concentrations rapidly declined to low levels following the end of a 72-hour infusion and the mean fraction of total 9-AC circulating in plasma as the active lactone was less than 10%. The pharmacokinetics of 9-AC may have a great impact on its clinical activity and should be considered in the design of future clinical trials of this topoisomerase I inhibitor.
Abstract 18473: Rates and Risk Factors for Faster Aortic Root Growth in Pediatric Patients with Marfan Syndrome
Authors: Nitya Viswanathan, Claudia Pedroza, Shaine A Morris
Journal: Circulation (2014)

Background: Marfan Syndrome (MS) is associated with progressive aortic dilation and aortic dissection. Aortic dissection is typically preceded by aortic dilation. The goal of this study is to identify factors associated with faster rates of aortic root dilation in children with MS. Methods: Patients undergoing serial transthoracic echocardiograms (TTE) with MS were retrospectively identified from an institutional database. Those with &gt;2 TTEs over 1 year apart and &lt;21 years of age at first TTE were included. TTEs performed after aortic surgery were excluded. Using multivariable longitudinal linear regression analysis, sex, medication, presence of ectopia lentis, need for scoliosis surgery and infantile type of MS were evaluated for associations with rate of change in aortic root dimension and aortic root z-score over time. Results: Of 240 patients with MS, 146 were included. Median age at first TTE was 8.1 yrs (range 0-20.9 years), median length of follow up 6.5 years (range 1.0-20.1 years), and median number of studies was 8 (range 2-25). Sixty-one percent were male. Of the 146 patients, 123 (84%) were documented to be on medical therapy: 14 angiotensin receptor blocker (ARB), 66 B-Blocker (BB), 10 prior history of both, 5 BB+ARB, 27 were in the Pediatric Heart Network medication trial, 1 ACE inhibitor. Sixteen patients underwent root replacement surgery at a median age of 14.6 years (range 1.8-24). No patients had aortic dissection. Three patients had infantile MS. All of these patients underwent root replacement at 1.8, 2 and 4 years of age. Two underwent subsequent aortic root replacement at 6 and 8 years old. Mean rate of aortic root growth in the cohort was 0.12cm/year, and mean change in z-score was 0.02/year (p=0.23 compared to expected rate of no change). The only variable associated with faster root growth was infantile MS (1.3cm/year, p&lt;0.001; z-score change of 6.9/year, p&lt;0.001). There was no significant difference in the rate of aortic root growth between patients who received therapy with BB vs. ARB vs. BB+ARB. Conclusions: Children with MS did not have a significant change in aortic root z-score over time, and the only factor associated with more rapid aortic root growth was infantile type MS.