tbuckley/cabot-search huggingface dataset:
Clinical impact of age on outcomes following anatomic lung resection for stage I non-small cell lung cancer
Authors: M. J. Schuchert, B. Pettiford, A. Kilic, J. P. Landreneau, J. R. Landreneau, N. A. Christie, A. Pennathur, K. S. Nason, D. O. Wilson, J. D. Luketich, R. J. Landreneau
Journal: Journal of Clinical Oncology (2009)

7515 Background: There is an increasing body of evidence that anatomic segmentectomy may represent an equivalent approach compared to lobectomy in the management of stage I NSCLC. Comorbidities associated with age may result in improved survival with sublobar resection for stage I cancer in the elderly. We report our single institution experience with segmentectomy vs. lobectomy for stage I non-small cell lung cancer stratified by age. Methods: A total of 232 consecutive anatomic segmentectomies were performed for stage IA (n=137) or IB (n=95) NSCLC from 2002–2007. Lobectomy was performed in 594 patients for stage IA (n=297) and IB (n=295) during the same period. Results of segmental resection were compared with lobectomy, stratified by the following age groups: &lt;60, 60–69, 70–79 and = 80. Primary outcome variables included complications, mortality, recurrence patterns, and survival. Statistical analysis included t-test and Fisher's exact test. Results: Mean age (69.9 vs. 68.2), gender distribution and tumor histology were similar between the segmentectomy and lobectomy groups. There was no significant difference in complications, mortality, recurrence, and overall survival in the younger age groups (Table). Segmentectomy was associated with reduced mortality (7.8% vs. 2.8%) and improved overall 3-year survival (p=0.02) in patients &gt;80 years old. Conclusions: Anatomic segmentectomy can be performed with similar morbidity, mortality, recurrence, and survival compared to lobectomy in stage I lung cancer. This approach may be particularly advantageous in the elderly age group, achieving comparable oncologic outcomes with less mortality and improved overall survival. [Table: see text] No significant financial relationships to disclose.
American Society of Clinical Oncology: Where Have We Been? Where Are We Going?
Authors: James O. Armitage
Journal: Journal of Clinical Oncology (1998)

Article Tools ASCO SPECIAL ARTICLE Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1998.16.1.381 Journal of Clinical Oncology - published online before print September 21, 2016 American Society of Clinical Oncology: Where Have We Been? Where Are We Going? James O. ArmitagexJames O. ArmitageSearch for articles by this author https://doi.org/10.1200/JCO.1998.16.1.381 First Page PDF © 1998 by American Society of Clinical Oncology
Phase I Study of Ceritinib (LDK378) in Japanese Patients with Advanced, Anaplastic Lymphoma Kinase-Rearranged Non–Small-Cell Lung Cancer or Other Tumors
Authors: Makoto Nishio, Haruyasu Murakami, Atsushi Horiike, Toshiaki Takahashi, Fumihiko Hirai, Naoko Suenaga, Takeshi Tajima, Kota Tokushige, Masami Ishii, Anthony Boral, Matthew Robson, Takashi Seto
Journal: Journal of Thoracic Oncology (2015)

Introduction:Anaplastic lymphoma kinase (ALK)-rearranged non–small-cell lung cancer (NSCLC) is sensitive to ALK inhibitors, but resistance develops. This study assessed the maximum-tolerated dose, safety, pharmacokinetics (PK), and antitumor activity of ceritinib, a novel ALK inhibitor (ALKi), in Japanese patients with ALK-rearranged malignancies.Methods:This phase I, multicenter, open-label study (NCT01634763) enrolled adult patients with ALK-rearranged (by fluorescence in situ hybridization and/or immunohistochemistry) locally advanced/metastatic malignancy that had progressed despite standard therapy. The study comprised two parts: dose escalation and dose expansion. Ceritinib (single-dose) was administered orally in the 3-day PK run-in period, then once daily, in 21-day cycles. Adaptive dose escalations were guided by a Bayesian model.Results:Twenty patients (80% with ALKi treatment history [ALKi-pretreated]; 19 NSCLC; one inflammatory myofibroblastic tumor) received ceritinib 300 to 750 mg (19 during dose escalation, one in dose expansion). Two dose-limiting toxicities occurred: grade 3 lipase increase (600 mg); grade 3 drug-induced liver injury (750 mg). The most common adverse events were gastrointestinal (nausea: 95%; diarrhea, vomiting: 75%). Ceritinib PK profile was dose proportional across 300 to 750 mg dosages; steady state was reached by day 15. Overall response rate was 55% (11 of 20 patients). Among patients with NSCLC, partial response was observed in two of four ALKi-naive patients, five of nine crizotinib-pretreated patients, two of four alectinib-pretreated patients, and one of two crizotinib and alectinib/ASP3026 pretreated patients. The ASP3026-pretreated inflammatory myofibroblastic tumor patient achieved partial response.Conclusions:Ceritinib maximum-tolerated dose was 750 mg once daily in Japanese patients. Antitumor activity was observed irrespective of prior ALKi treatment history. Dose expansion, examining the activity of ceritinib in alectinib-resistant patients, is ongoing.
Outcomes associated with minimally invasive esophagectomy techniques.
Authors: Andrea M. Abbott, Matthew Doepker, Ravi Shridhar, Sarah E. Hoffe, Khaldoun Almhanna, Kenneth L. Meredith
Journal: Journal of Clinical Oncology (2015)

171 Background: Surgery is pivotal in the management of patients with esophageal cancer. Recent prospective data demonstrates advantages of minimally invasive techniques. However, varying surgical techniques precludes the recommendation of a standard approach. We sought to examine our outcomes with differing approaches to minimally invasive esophagectomy. Methods: We queried a prospective esophageal database to identify patients who underwent minimally invasive esophagectomy (MIE) from 1994 and 2014. Surgical approaches included trans-hiatal (TH), Ivor Lewis (IVL), and robotic assisted Ivor Lewis (RAIL). Demographics, operative variables and post-operative complications were all compared. Results: We identified 280 patients who underwent MIE with a mean age of 65.65 ± 10.5 and a median follow-up of 48 months. Fifty-seven patients underwent IVL, 78 underwent TH, and 145 underwent RAIL. The length of operation was significantly longer in IVL and RAIL approaches compared to TH (TH=242, IVL=320, RAIL=415, p=0.001). Estimated blood loss did not differ between cohorts (TH=150, IVL=125, RAIL=158, p=0.8). Anastomotic leakage, stricture, pneumonia, and wound infections were all higher in the TH compared to the trans-thoracic approaches p=0.04, p=0.02, p=0.01, and p&lt;0.001 respectively. Operative mortality was low for each cohort and did not differ between approaches (TH=2.6%, IVL=0%, RAIL=2%, p=0.2). The median length of hospitalization also did not differ between groups (TH=10 days, IVL=8.5 days, and RAIL=9 days, p=0.15). Adequacy of oncologic resection was measured by margins and nodal harvest. There was decreased R1 resections in both the IVL and RAIL compared to TH (TH=8%, IVL=0%, and RAIL=0% p=0.04). Additionally, the mean number of lymph nodes harvested was lower in patients undergoing TH compared to IVL and RAIL groups (TH=9.2, IVL=12.8, and RAIL=20.6, p=0.05). Conclusions: In our large series comparing minimally invasive approaches to esophageal resection we have demonstrated improved operative outcomes and oncologic outcomes in trans-thoracic approaches compared to trans-hiatal approaches. We recommend that patients undergoing minimally invasive esophagectomy be strongly considered for a trans-thoracic approach.
Concurrent chemotherapy plus cetuximab or chemotherapy followed by cetuximab in advanced non-small cell lung cancer (NSCLC): A randomized phase II selectional trial SWOG 0342
Authors: K. Kelly, R. S. Herbst, J. J. Crowley, J. McCoy, J. N. Atkins, P. N. Lara, S. R. Dakhil, K. S. Albain, E. S. Kim, D. R. Gandara
Journal: Journal of Clinical Oncology (2006)

7015 Background: Randomized clinical trials have failed to show a survival benefit for small molecule EGFR tyrosine kinase inhibitors plus chemotherapy in patients with advanced NSCLC. In contrast, pilot trials of EGFR targeted antibodies plus chemotherapy have suggested enhanced anti-tumor activity. This large randomized phase II trial was designed to select a cetuximab -chemotherapy regimen for future evaluation in a phase III setting. Methods: Untreated patients (pts) with stage IIIB (by pleural effusion) or IV (without brain metastases) NSCLC, with a performance status of 0–1 and adequate organ function were randomized to received paclitaxel (P) 225 mg/m2 and carboplatin (Cb) AUC=6 every 3 weeks plus cetuximab (C) 400 mg/m2 loading dose followed by 250 mg/m2, weekly for 4 cycles followed by maintenance C or the same doses of PCb for 4 cycles followed by C. C was continued until disease progression or 1 year of therapy. The primary endpoint was overall survival; the statistical design required a median survival of ≥ 10 months for a regimen to be selected for subsequent phase III trial evaluation. The probability of correctly choosing the superior arm is 91% when the true hazard ratio is 1.3. Results: From July 2004 to June 2005, 225 eligible pts were enrolled into the study. Preliminary results are described below: Conclusions: At the time of this analysis, efficacy and toxicity were similar in the two treatment arms; both regimens were well tolerated. Assuming these results are sustained, the concurrent regimen of PCb + cetuximab has met the criteria for continued evaluation. A phase II trial of PCb + cetuximab + bevacizumab (B) is in development in anticipation of a phase III trial testing PCbB ± cetuximab. Molecular correlative studies of the EGFR signaling pathway are ongoing. [Table: see text] [Table: see text]
Quantitation of steatosis by magnetic resonance imaging (MRI) and spectroscopy (MRS) in liver disease: effect of hepatic fibrosis and iron
Authors: S. McPherson, G. Cowin, P. O'Rourke, A. Volp, L. Horsfall, L. Burke, J.R. Jonsson, A. Clouston, J. Fawcett, G. Galloway, M. Benson, E. Powell
Journal: Gut (2009)
Massachusetts Medical Society
Authors: Robert J. Haggerty
Journal: New England Journal of Medicine (1958)

Christmas Holiday Poison Hazards†Many of the agents potentially poisonous to children show a marked seasonal incidence — plants in the springand summer, pesticides in summer and mothballs in fall and spring. Probably no group occur during such a localized period, however, as those associated with the activities of the Christmas season. Christmas-tree bubbling light fluid accounts for several telephone consultations to the Boston Poison Information Center each Christmastime. All the stimuli to exploration and ingestion — bright colors, movement, light and the eternal allure of the Christmas tree — make these particularly attractive to small children, who may . . .
A phase Ib/II, dose-escalating, safety, and efficacy study of imprime PGG and cetuximab in patients with advanced colorectal cancer (CRC).
Authors: M. B. Tamayo, G. H. Cornelio, J. B. Bautista, M. L. Flores, P. S. Tioleco, M. R. Kurman, L. M. Marsh, M. A. Gargano, M. L. Patchen
Journal: Journal of Clinical Oncology (2010)

e14103 Background: Imprime PGG (Imprime PGG Injection) is a beta-glucan polymer being developed for treatment of cancer in combination with complement-activating monoclonal antibodies. A sequential 2-arm study in CRC patients (pts) evaluated the effects of Imprime PGG administered in combination with cetuximab plus irinotecan (Arm 1) and in combination with cetuximab alone (Arm 2). Results of Arm 1 were previously reported (JCO 27, 2009; abstr e15062). Results of the recently completed Arm 2 are presented here. Methods: Pts with recurrent/progressive CRC (Karnofsky ≥ 70%) previously treated with 5-FU (alone or combined with other therapies) were treated weekly with cetuximab (loading dose 400 mg/m2, then 250 mg/m2) and Imprime PGG and were evaluated in 6-wk cycles. Imprime PGG dosing started at 2 mg/kg and escalated to 4 and 6 mg/kg after safety review. Safety (primary endpoint) was assessed by adverse events (AEs) and efficacy (secondary endpoint) by RECIST. Results: Imprime PGG was dosed in 4 pts at 2 mg/kg and in 9 pts each at 4 and 6 mg/kg. Median age was 57. Of the 22 pts enrolled, 1 pt was discontinued in Week 6 due to protocol violations and 21 pts completed the study. No protocol-defined dose-limiting toxicities were observed. AEs experienced by > 25% of pts included acneiform rash (82%); AST increase (50%), ALP increase, ALT increase, bilirubin increase, and leukocytosis (each 46%); bicarbonate decrease, hypokalemia, paronychia, and pedal edema (each 41%); dry skin and GGT increase (each 36%); anemia and uric acid increase (each 32%); and amylase increase, ANC increase, and hyponatremia (each 27%). No related grade 3 or 4 SAEs were reported. In the per protocol population (n = 21), the overall objective response rate (ORR) was 24% (5 pts), the stable disease rate (SD) was 38% (9 pts) and the disease control rate (ORR + SD) was 62% (13 pts). The median time to progression was 12 wks. Conclusions: Imprime PGG combined with cetuximab in CRC pts was safe and efficacy warrants further investigation. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Biothera Biothera Biothera
The effect of sunitinib on biomarkers and tumor heterogeneity in metastatic clear cell renal cancer.
Authors: Grant Stewart, Alexander Laird, Fiach O'Mahony, Lel Eory, Alexander Lubbock, Jyoti Nanda, Marie O'Donnell, Alan Mackay, Peter Mullen, Alan McNeill, Antony Riddick, Michael Aitchison, Daniel Berney, Axel Bex, Ian Overton, David James Harrison, Tom Powles
Journal: Journal of Clinical Oncology (2014)

408 Background: The purpose of this work was to investigate the effect of sunitinib on tumour biomarkers and assess intratumoural heterogeneity in metastatic clear cell renal cancer (mRCC). Primary tumours and metastatic sites were examined. Methods: Multiple fresh frozen tissue samples (median=4) were taken from sunitinib naive (n=23) and sunitinib treated (18 weeks at sunitinib 50mg) patients (n=27) with mRCC. Tissue was taken from the primary renal tumours. Multiple analysis of DNA (aCGH), mRNA (Illumina Beadarray) and protein lysates (reverse phase protein array) were performed on each tumour sample. Analysis of metastatic tissue occurred where possible (n=4). A cohort of matched untreated and sunitinib/pazopanib treated paraffin embedded mRCC samples from 3 clinical trials was used for validation with automated quantitative analysis. Results: Treated and untreated patient had similar patient characteristics. Significant intratumoural heterogeneity in DNA, RNA and protein occurred. Sunitinib was associated with increased intratumoural heterogeneity in protein expression (p&lt;0.05), but not DNA or RNA. Despite this heterogeneity, significant changes to protein expression with sunitinib occurred. Four proteins changed significantly in terms of both expression and variance with sunitinib (BCL2, MLH1, CAIX and mTOR; p&lt;0.05 for each). Elevation of CAIX expression in sunitinib treated patients was confirmed in the validation cohort (p=0.01). Low levels of CAIX correlated with poor outcome in treated samples (HR=0.26, 95% CI: 0.11-0.61, p=0.001). A positive correlation between protein expression in the primary tumour and metastatic sites occurred. Individual metastasis within patients exhibited a variable radiological response to therapy, which was equally marked in the genetically more homogeneous primary tumours. Conclusions: Intratumoural heterogeneity occurs on many levels in mRCC. Sunitinib is associated with increase in protein heterogeneity. Despite this, upregulation of CAIX is a potential prognostic biomarker.
Acetylation phenotype, platelet monoamine oxidase inhibition, and the effectiveness of phenelzine in depression
Authors: J Davidson, M N McLeod, M R Blum
Journal: American Journal of Psychiatry (1978)

The authors treated 16 depressed patients with up to 90 mg/day of phenelzine. After acetylation phenotype was determined and platelet monoamine oxidase (MAO) activity measured, no significant relationship was observed between clinical improvement and acetylation phenotype or between MAO inhibition and acetylation. Discrepant findings regarding acetylation phenotype and the effects of phenelzine are discussed. The authors do not recommend a sulfamethazine phenotype test as a predictor of outcome for phenelzine.
Trans-arterial chemoembolization (TACE) of liver metastases (LM) from colorectal cancer (CRC) adopting irinotecan-eluting beads: Results of a phase II clinical study
Authors: G. Fiorentini, C. Aliberti, P. Giovanis, M. Tilli, S. Rossi, G. Benea
Journal: Journal of Clinical Oncology (2007)

14525 Background: Patients with LM from CRC have a poor prognosis with survival rates of 31% at 1 year and 2.6% at 3 years. Surgery is feasible in a minority of patients and most them received systemic chemotherapy. Irinotecan (IRI) is an active drug in the treatment of advanced CRC. The advantage of delivering chemotherapy by hepatic arterial infusion is the achievement of high-dose of the drug in the target . TACE is a combination of local drug infusion with selective embolization of the feeding arteries of the liver metastases. DC bead is a new embolic microsphere product that can be loaded with IRI before administration in TACE. The purpose of this study is to assess the safety and efficacy of this new embolic microspheres IRI loaded and administered as TACE in patients with LM from CRC. Methods: 35 patients with LM from CRC Stage II-III Pettavel Classification pretreated were observed from Nov 2005 to Dec 2006. 25 gave their written consent to be treated with one o more cycles of TACE. Imaging was performed before, immediately and 4 weeks after TACE to determine response and the need for further treatment. Each patient received i.v hydration, antibiotics, analgesics and medications against nausea before TACE. Survival was calculated with Kaplan-Meier method. Results: 60 cycles were administered. We observed a Response Rate of 80% by RECIST criteria. A month after TACE we had a reduction of +50% of CEA in 60% of patients. A reduction of the lesional contrast enhancement of the metastases was observed in 80% of patients. 22 patients are alive, with a median survival of 9.5 months (range 6–13). Median duration response was 16 weeks (range 12–25). 14 cases experienced WHO Grade 2 right upper quadrant pain (RUQP) and 11 cases Grade 3 lasting 12 hours (range 3–30). All patients had 2 days Grade 2 fever (range 1–7), ten had 3 days Grade 3. 20 have had Grade 2 nausea and vomiting for 6 hours (range 4–29). No alopecia or marrow toxicity was reported. Conclusions: DC bead -TACE was feasible and effective in patients with LM from CRC. RUQP seems the most significant toxic event and needs analgesic therapy. No survival data are conclusive because the follow up is short. DC bead of IRI 100 mgr-TACE myght be an appropriate palliative therapy for these patients. No significant financial relationships to disclose.
A phase II open-label study of cetuximab in unresectable hepatocellular carcinoma: Final results
Authors: V. Gruenwald, L. Wilkens, M. Gebel, T. F. Greten, S. Kubicka, A. Ganser, M. P. Manns, N. P. Malek
Journal: Journal of Clinical Oncology (2007)

4598 Background: Hepatocellular carcinoma (HCC) express the epidermal growth factor receptor (EGFR), and EGFR-targeting therapies are known to block tumor growth. We tested the activity of cetuximab (CET) in HCC and evaluated serial tumor biopsies for biomarker analyses. Methods: Patients (pts) with advanced or metastatic HCC with ECOG = 2 and adequate organ function were eligible. Prior therapy was permitted. CET was given iv weekly (400 mg/m2 loading dose, 250 mg/m2 thereafter). The primary endpoint was the rate of progression-free survival (PFS) at 24 wks. Serial tumor biopsies were performed prior to treatment, after 4 wks and at time of progression. 32 pts were enrolled. 27 pts are evaluable for tumor response. Results: Stable disease (SD) was achieved in 44.4% (12 pts) for at least 8 weeks of treatment. 55.6% failed to respond to CET (15 pts). The median time to progression (TTP) for all pts was 8.0 wks. Pts, which were stable for more than 8 wks achieved a median TTP of 22.5 wks (11–48 wks) compared to a median TTP of 6.0 wks (3–8 wks) in progressive pts. No treatment-related severe adverse events were noted throughout the study. Preliminary evaluation of surrogate markers showed no correlation with cytogenetic abnormalities based on FISH analyses for chromosome 1 and 8. Furthermore, only 5 of 21 tumor specimens were positive for EGFR expression without gene amplification, evaluated by FISH analyses. Serial tumor specimens are available in 5 responding and in 7 non-responding pts for changes of p27 and p21 expression. p27 and p21 were upregulated simultaneously in 60% (3/5 pts) of responding pts, whereas in pts with treatment failure p27 and p21 expression was detectable in 14% (1/7 pts) only. Conclusions: Cytogenetic aberrations of chromosome 1 and 8 failed to predict response to CET. In a subgroup of pts with SD &gt;8 weeks, induction of p21 and p27 were associated with prolonged TTP &gt;20 wks. Further evaluation of p21 and p27 as early molecular tumor response is warranted to identify pts, which benefit from anti-EGFR therapies. [Table: see text] No significant financial relationships to disclose.
Burden of hospitalizations associated with skeletal related events in patients with breast cancer or lung cancer and bone metastases or multiple myeloma
Authors: M. Lage, D. J. Harrison, B. Barber, S. Jun
Journal: Journal of Clinical Oncology (2007)

17083 Background: Patients with bone metastases secondary to cancer often experience skeletal related events (SREs) including pathological fracture, spinal cord compression, hypercalcemia, bone surgery or radiotherapy, or initiation of opioid analgesic use. These SREs result in major morbidity and reduced quality of life. This research examines hospitalizations associated with SREs. Methods: Data for this study were obtained from i3 LabRx Database (05/01/2000 to 03/31/2005). Individuals were included in the analyses if they had at least two diagnoses of breast cancer (based upon an ICD-9 code of 174.xx), lung cancer (162.xx), or multiple myeloma (203.0x) and had at least two diagnoses of bone metastases (198.5x) after the first diagnosis of cancer. In addition, individuals were required to have at least one SRE (based upon a previously published algorithm) on or after their initial diagnosis of bone metastases (their index date). Individuals were required to be continuously insured for at least 6 months prior to, and at least one month post their index date. Data were analyzed until 03/31/2005 or until the end of their continuous coverage, whichever occurred first. Descriptive statistics for each of these cohorts are provided. Results: A total of 1,204 individuals with breast cancer, 1,094 with lung cancer, and 258 with multiple myeloma were included in the study. The vast majority of individuals with breast cancer (96.5%), lung cancer (95.9%), or multiple myeloma (96.8%) were hospitalized. All three patient groups were likely to have SRE-related hospitalizations; multiple myeloma 43.4%, breast cancer 36.2% and lung cancer 35.6%. The average number of days per patient year that patients were hospitalized related to a diagnosis or procedure for a SRE was 6.75 days for patients with lung cancer, 6.56 days for patients with multiple myeloma, and 3.75 days for patients with breast cancer. Conclusion: Hospitalizations related to SREs are common and the number of days per year is substantial. No significant financial relationships to disclose.