tbuckley/cabot-search huggingface dataset:
Sentinel node mapping and molecular staging in lung cancer
Authors: D. Pulte, E. Li, B. Crawford, E. Newman, D. Mustalish, A. Alexander, D. R. Jacobson
Journal: Journal of Clinical Oncology (2004)

7191 Background: Lymph node (LN) involvement predicts relapse in patients after resection of apparently localized nonsmall cell lung cancer (NSCLC). Molecular staging (MS) techniques can be used to detect micrometastatic disease, while sentinel lymph node (SLN) mapping can indicate which LNs are most likely to contain micrometastases. Methods: We used SLN mapping and MS to more sensitively detect LN micrometastases. RT-PCR for cytokeratin7 (CK7), a gene expressed in normal and malignant lung, but not in LNs, was used to identify tumor-derived material in LNs. Results: SLN mapping was performed in 13 patients during resection, 1–3 SLNs were identified in each, and sufficient RNA for molecular studies was obtained in 12/13 patients. No major adverse reactions occurred. 11/12 of the primary tumors expressed CK7. 65 LNs were examined, including 21 SLNs from the 11 evaluable patients. Overall, 32/65 LNs were CK7+, including 13/21 SLNs. 10/11 patients with evaluable SLNs had at least one CK7+ SLN. Routine histology showed T1N0-T2N0 disease in 8 patients, T3N0 in 1 patient, and N1 in 2 patients. Of the 9 patients with N0 disease by routine histology, 8 were upstaged by RT-PCR. All LN that were positive by routine histology were RT-PCR-positive. Conclusions: SLN mapping with MS is feasible in NSCLC. SLN mapping identifies LNs likely to contain micrometastases. In this study, SLN status by RT-PCR predicted total LN status in all patients; there were no “skip metastases.” This suggests that molecular study of SLNs alone may be sufficient for MS, which would make MS feasible in the routine clinical setting. This technique may be of use in stratifying patients with N0 disease by routine histology into high (molecular N1) and low (molecular N0) risk groups. Our results suggest that LN micrometastasis is pervasive in resected NSCLC; true molecular N0 disease appears to be rare. No significant financial relationships to disclose.
BIG 1–98: Randomized double-blind phase III study to evaluate letrozole (L) vs. tamoxifen (T) as adjuvant endocrine therapy for postmenopausal women with receptor-positive breast cancer
Authors: B. J. Thurlimann, A. Keshaviah, H. Mouridsen, L. Mauriac, J. F. Forbes, R. Paridaens, M. Castiglione-Gertsch, R. D. Gelber, I. Smith, A. Goldhirsch
Journal: Journal of Clinical Oncology (2005)

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Expression of tumor endothelial markers (TEMs) in vitro in a canine hemangiosarcoma model of malignant angiogenesis.
Authors: Jackie M. Wypij, Timothy M. Fan, Holly Pondenis
Journal: Journal of Clinical Oncology (2012)

e21145 Background: Expression of tumor endothelial markers (TEMs) in tumor-associated blood vessels presents opportunities for targeted therapy. TEM7 and TEM8 are selectively expressed and are associated with a worse prognosis in cancer patients. TEM expression is conserved across species, however species differences do exist as TEM7 is undetectable in murine tumor endothelium. Thus, further investigation of the role of TEMs in malignant angiogenesis is hindered by the lack of optimal animal tumor models. Canine hemangiosarcoma is relevant spontaneous model of malignant angiogenesis based on archetypal cell markers, endothelial functionality, growth factor/receptor expression, and angiogenic gene expression. The aims of this study were to characterize the in vitro expression of TEM7 and TEM8 in canine hemangiosarcoma as a novel model of malignant angiogenesis. Methods: Two canine hemangiosarcoma cell lines were assessed (Den and Fitz). Total RNA was isolated using standard technique, reverse transcribed to cDNA, and amplified by polymerase chain reaction (PCR) reaction using degenerate primers specific for human and murine TEM7 transcripts with forward and reverse primers. Protein expression of TEM7 and TEM8 in cell lysates was evaluated via Western blotting and cell surface expression was analyzed by flow cytometry. Polyclonal anti-TEM7 and anti-TEM8 antibodies (Sigma-Aldrich) were used with positive and negative controls. Results: Basal in vitro expression of TEM7 mRNA was confirmed in canine hemangiosarcoma, as well as in vitro protein expression of TEM7 and TEM8 via Western blotting and flow cytometry. Conclusions: The validation of TEM expression in canine hemangiosarcoma establishes TEM7 and TEM8 as promising targets for further evaluation in this novel model of malignant angiogenesis, and investigation of TEM-targeting is ongoing. This may represent a novel spontaneous animal tumor model for investigation of tumor vascular targeting.
Phase I/II study of atrasentan (A) in combination with carboplatin (C) and paclitaxel (P) in chemonaive patients (pts) with advanced non-small cell lung cancer (NSCLC)
Authors: A. Chiappori, E. Haura, C. Williams, G. Simon, S. Antonia, A. Cantor, M. K. Burton, R. Lush, D. M. Sullivan, G. Bepler
Journal: Journal of Clinical Oncology (2005)

7105 Background: Endothelins (ET-1, 2, 3) and their cell membrane receptors (ETAR, ETBR) establish a proliferative autocrine and paracrine loop implicated in the pathogenesis of human cancers. ET-1, acting through ETAR, can generate EGFR dependent and independent cell proliferation and VEGF mediated angiogenesis. Inhibition of the ET-1/ETAR pathway may have a direct effect on tumor cell growth. A is an oral, highly potent and selective ETAR antagonist with competitive inhibition of ET-1. We propose to assess the safety and efficacy of P/C plus A in pts with NSCLC and to determine a possible pharmacokinetic (pk) drug interaction between P and A. Methods: Eligibility: No previous chemotherapy (CT), stages IV and IIIB (malignant pleural effusion), performance status (PS) 0–1, and adequate renal, hepatic and bone marrow function. Previously treated and controlled brain metastases were allowed. Toxicity (T) and response (RR) were determined by CTCAE v2.0 and RECIST criteria respectively. Treatment consisted of P=225 mg/m2 iv, C=AUC 6 iv, d1 q 3w for 4–6 cycles (cy) plus A=10 mg po qd (starting on d4 of cy 1) until PD or T. Due to possible CYP3A/C9 inhibition by A, P clearance was determined during first 2 cy (off A/on A) in the first 10 pts. Results: 24 pts have been enrolled. Median age=68, (range=21–78), M/F=16/8, IIIB/IV=3/21, PS 0/1=6/18. Adeno/squamous/both/NSC carcinoma=10/4/2/8. Only a 15% intersubject variation in P clearance was noted (mean ± std: 23.53 ± 3.54 L/hr off A vs. 26.05 ± 3.96 L/hr on A). All pts are evaluable for T, 17 for RR. Total CT cy=78, median=3, range=1–6. T has been tolerable. G 3–4 Neutropenia=19/78 cy (24%), 7/24 pts (29%). No other G 3–4 T ≥ 10% (by cy or pts). There were 3 PR, 5 SD and 9 PD for an ORR=17.6%. 16 pts have come off study for PD (n=13) or other reasons (T=2, withdrawal=1). 8 pts continue to receive CT (7 not-evaluable for RR). Preliminary survival data will be available at meeting presentation. Conclusion: Combination P/C plus A can be safely administered in advanced NSCLC. There is no clinically significant pk interaction between P and A. Efficacy is similar to other standard CT trials. Pts continue to accrue. No significant financial relationships to disclose.
Nonepithelial ovarian cancer: Outcomes after aggressive treatment with surgery and platinum-based chemotherapy.
Authors: K. K. Machado, D. R. Nebuloni, M. D. Estevez-Diz, G. Castro, P. M. Hoff
Journal: Journal of Clinical Oncology (2010)

e15548 Background: Nonepithelial ovarian malignancies account for approximately 10% of all ovarian cancers. Germ cell tumors (GCTs) represent 5% of all ovarian neoplasms and sex cord stromal tumors (SCSTs) are rare neoplasms that account for 3%–5% of them. The aim of this study was to review treatment outcomes in patients (pts) with malignant nonepithelial ovarian cancer in a single institution. Methods: Data from all pts with nonepithelial ovarian cancer sequentially diagnosed and treated at Instituto do Câncer do Estado de São Paulo (ICESP) from 1992 to 2006 were retrospectively reviewed. Results: 38 pts were identified. Median age was 52 y (22-82) for SCTCs and 20 y (12-49) for GCTs. Twelve pts (31.6%) had granulosa cell tumors, 8 (21.1%) immature teratomas, 7 (18.4%) dysgerminomas, 4 (10.5%) endodermal sinus tumors, 3 (7.9%) Sertoli–Leydig cell tumors and 1 (2.6%) embryonal carcinoma. Pts were staged according to FIGO system and 17 (54.8%) were classified as stage I, 3 (9.7%) stage II, 9 (29%) stage III, and 2 (6.5%) stage IV. Surgery was performed in all pts: pan-hysterectomy in 51.5% (17 pts) and unilateral salpingo-oophorectomy or oophorectomy for fertility preservation in 7 (21.2%) and 8 pts (24.2%), respectively; omentectomy in 19 pts (63.3%) and lymphadenectomy in 8 pts (27.6%). Considered as having a high recurrence risk, 37 pts (97.4%) received platinum-based chemotherapy: 17 GCT pts and 14 SCTC pts with adjuvant (n = 31, 83.8%) and 6 pts with palliative intent (n = 6, 16.2%). Twenty-eight pts (75.7%) received BEP regimen and 8 pts (21.6%) were treated with carboplatin and etoposide. At a median follow-up of 4.2 y, 7 pts (18.4%) experienced disease recurrence (3 GCTs and 4 SCTCs) and 24 pts (94.7%) remained alive. One death was observed among GCT pts. The 5-year overall survival rate was 95%. Conclusions: In this high-recurrence-risk group of nonepithelial ovarian cancers, aggressive treatment with surgery and platinum- based chemotherapy resulted in excellent survival outcomes. No significant financial relationships to disclose.
High grade unclassified sarcoma of the broad ligament: A case report and literature review
Authors: D. D. Mauricio, G. Vanderlee
Journal: Journal of Clinical Oncology (2007)

20536 Background: The incidence of primary sarcoma of the broad ligament is very rare. From the first reported finding in 1968, there are only 17 documented cases worldwide of this very progressive and highly malignant gynecologic neoplasm. We present the 18 th case of this aggressive tumor to add to the scarce knowledge about this disease and to contribute in characterizing its behavior and its reasonable management. Methods: Case report and case review/series Results: This is the 18th case of broad ligament sarcoma found on routine physical examination in a woman who had previous hysterectomy for benign leiomyoma. Treatment consisted of resection of the broad ligament mass, bilateral salpingo-oophorectomy, omental and peritoneal biopsies with pelvic cytology. She is disease-free on strict clinical surveillance. An updated extensive review of previous reports was done as well. Conclusions: The scarcity of the cases of leiosarcoma of the broad ligament prevents the understanding of its biologic nature. Thus, there were different approaches on its staging, surgical management and adjuvant therapy, and tumor surveillance producing unpredictable prognosis. It appears TAH-BSO with rigid disease follow-up and subsequent chemotherapy or radiotherapy prolongs survival. No significant financial relationships to disclose.
Efficacy of 90Y-ibritumomab tiuxetan treatment for relapsed and refractory low-grade B-cell and mantle cell lymphoma
Authors: Sayuri Motomura, Atsuhiro Suda, Misato Inoue, Yoshikawa Takashi, Yamamoto Atsushi, Hidai Hiroko, Tsutsumi Hisashi, Nagashima Junichi
Journal: Annals of Oncology (2015)
<i>MMP1 1G/2G</i> promoter polymorphism and risk of esophageal adenocarcinoma
Authors: S. Singh, K. Asomaning, M. H. Kulke, W. Zhou, R. Zhai, L. Su, R. S. Heist, T. J. Lynch, D. C. Christiani, G. Liu
Journal: Journal of Clinical Oncology (2007)

10555 Background: The 2G allele of the MMP1 -1607 1G/2G promoter polymorphism creates an Ets binding site that leads to increased transcriptional and enzyme activity, particularly in the presence of growth factors and cytokines. This polymorphism has been associated with greater risk of cancer (e.g., renal cell, lung and oral cancers, glioblastomas) and cancer invasiveness (e.g., melanoma, cervical, lung and colorectal cancer). The aim of the current study was to evaluate the role of this MMP 1G/2G polymorphism in the risk of esophageal adenocarcinoma (EA). Methods: We evaluated 323 histologically confirmed EA cases and 464 healthy controls frequency-matched for age and gender. Genotyping of the MMP1 1G/2G promoter polymorphism involved a Taqman approach. All EAs had endoscopic evidence showing that the center of the tumors were located at or above the gastroesophageal junction. Odds Ratios (OR) were calculated using multivariate logistic regression, adjusted for age, gender, smoking status, and body-mass index (BMI) at the age of 18 years (to represent a healthy adult BMI). Results: Genotype frequencies were: 33% (1G/1G), 47% (1G/2G) &amp; 20% (2G/2G) in controls; in cases, 26% (1G/1G), 50% (1G/2G) &amp; 24% (2G/2G). 88% of cases were male. The MMP1 2G/2G and 1G/2G genotypes conferred a greater risk of EA, with adjusted ORs of 1.50 (95%CI=1.0–2.3) and 1.34 (95%CI=0.9–1.9), respectively, when compared with the wildtype 1G/1G genotype. The 2G allele (2G/2G + 1G/2G) conferred an adjusted OR of 1.38 (95%CI=1.0–1.9). By stage, the adjusted ORs for the 2G allele were 1.26 (95%CI=0.8–2.1), 1.45 (95%CI=0.9–2.3), &amp; 1.54 (95%CI=0.9–2.7) for node negative, node-positive, and metastatic disease, respectively. Conclusions: The 2G allele of the MMP1 -1607 1G/2G polymorphism was associated with an increased risk of EA in this analysis. In addition, there was a non-significant trend towards conferring greater risk in the more advanced stages of EA, suggesting a possible role of this polymorphism in the invasiveness of this cancer. No significant financial relationships to disclose.
Abstract 19605: Aortic Valve Morphology Influences Outcomes of Balloon Aortic Valvuloplasty in Children with Congenital Aortic Stenosis
Authors: Christopher J Petit, Kevin Gao, Bryan H Goldstein, Sean M Lang, Sung I Kim, Ritu Sachdeva
Journal: Circulation (2014)

Background: In isolated congenital aortic valve stenosis (AS) early and late outcomes following BAV vary widely despite near uniform procedural and technical factors. Anatomic factors may account for some of this variability in outcomes. We sought to identify morphologic factors that may influence outcomes of BAV. Hypothesis: Aortic valve anatomy influences outcomes after BAV. Methods: We reviewed all pts who underwent BAV at two large pediatric institutions between 2007-2013. Pre- and post-BAV echocardiography (echo) was reviewed. Anatomic indices including valve leaflet excursion, valve annulus area (AA), valve orifice area (OA), valve morphology, and raphe (fusion) length were measured on all pre- and post-BAV echo. Primary endpoint was favorable tear (FT), defined as tear along a commissure. Unfavorable tear (UT) was defined as tear into a leaflet, and no tear (NT) defined as no visible tear. Secondary endpoint was aortic insufficiency increase ≥2 degrees (AI+). Results: A total of 88 pts had complete...
Explaining the increased arrest rate among mental patients: a cautionary note
Authors: L Sosowsky
Journal: American Journal of Psychiatry (1980)

The author compared the annual arrest rates through 1978 of 301 state mental hospital patients released in 1972--1975 with arrest rates of the local county (San Mateo County) population in 1978. The data do not easily allow acceptance of the explanation for the increasing arrest rate among ex-patients suggesting that a definable group with previous arrests accounts for the increase. In San Mateo County, ex-patients with no previous arrests were arrested roughly three times more often than the local county population and five times more often for serious violent crimes.
Patient preference between pazopanib (Paz) and sunitinib (Sun): Results of a randomized double-blind, placebo-controlled, cross-over study in patients with metastatic renal cell carcinoma (mRCC)—PISCES study, NCT 01064310.
Authors: Bernard J. Escudier, Camillo Porta, Petri Bono, Ugo De Giorgi, Omi Parikh, Robert E. Hawkins, Emmanuel Sevin, Sylvie Negrier, Sadya Khan, Lauren McCann, Faisal Mehmud, David Cella
Journal: Journal of Clinical Oncology (2012)

CRA4502 The full, final text of this abstract will be available at abstract.asco.org at 12:01 AM (EDT) on Saturday, June 2, 2012, and in the Annual Meeting Proceedings online supplement to the June 20, 2012, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Saturday edition of ASCO Daily News.
Massachusetts Medical Society
Authors: Donald Glicklich
Journal: New England Journal of Medicine (1958)

TOXIC HAZARDS*Salicylate Poisoning — II.†In the previous article on salicylate poisoning,1 the history of a patient who died from accidental salicylate ingestion was reviewed. The following case* illustrates a newer method of treatment that is often life saving:R.D., a 2-year-old boy, accidentally drank an unidentified amount of oil of wintergreen on a Sunday afternoon. That night he was admitted to a hospital near New York City, where gastric lavage was performed, and he was then taken to his home near Pittsfield, Massachusetts. On the following morning fever, hyperventilation and unconsciousness developed. On admission, the temperature was 107°F., . . .
Phase II study of NKTR-102 in women with platinum-resistant/refractory ovarian cancer.
Authors: I. B. Vergote, J. P. Micha, C. H. Pippitt, G. G. Rao, D. L. Spitz, N. Reed, G. G. Dark, A. Garcia, D. J. Maslyar, G. J. Rustin
Journal: Journal of Clinical Oncology (2010)

5013 Background: NKTR-102, a topoisomerase I inhibitor-polymer conjugate with reduced peak concentrations and a continuous concentration profile, demonstrated broad antitumor activity based on RECIST criteria in a phase I study, including ovarian cancer. The GCIG criteria integrate RECIST with CA-125. This study evaluated the GCIG, RECIST, and CA-125 responses (50% decline in CA-125) in patients (pts) with platinum-resistant or - refractory ovarian cancer following treatment with NKTR-102. Methods: This open-label, phase II randomized study enrolled pts to receive NKTR-102 IV at a target dose of 145 mg/m2 q14d or q21d; each schedule followed a two-stage Simon design. Eligible patients had resistant/refractory ovarian cancer (“refractory” defined as progression within 3 weeks of last platinum), ECOG PS 0-1, adequate renal, hepatic, and marrow function. The primary endpoint was GCIG response rate; secondary endpoints were safety, PFS, and OS. Results: 71 pts were randomized and treated (36 on the q14d and 35 on the q21d schedule). Median age was 61; ECOG PS 0/1 equaled 52%/48%; median number of prior platinum-based and total regimens was 2 and 3, respectively. Of the 71 pts, 42 were platinum-resistant and 27 were platinum- refractory (2 pts were entered with platinum-sensitive disease). In pts with resistant/refractory disease, GCIG response rates (confirmed and unconfirmed) based on composite RECIST/CA-125 data was 47% for the q14d and 41% for the q21d schedules. RECIST responses (confirmed and unconfirmed) were 27% and 22% for the q14d and q21d schedules, respectively. CA-125 responses were 61% (q14d) and 52% (q21d); median time to first 50% decline of CA-125 was 31 days. Common related grade 3/4 toxicities (q14d/q21d schedules) were diarrhea (22%/11%), dehydration (14%/6%), hypokalemia (14%/6%), fatigue (6%/11%), nausea (14%/3%), and neutropenia (8%/9%). One pt each died due to neutropenic sepsis and pre-renal azotemia. Conclusions: Single-agent NKTR-102 demonstrates significant anti-tumor activity in heavily pretreated pts with platinum- resistant/refractory disease based upon GCIG and RECIST criteria with a tolerable toxicity profile. CA-125 responses were rapid, generally occurring within one month. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Nektar Therapeutics
Effect of wnt aberrant methylation and epidermal growth factor receptor pathway mutation on responsiveness of non-small cell lung cancer to gefitinib and erlotinib.
Authors: J. Zhu, J. Wang, H. Bai, J. Zhao, Z. Wang, M. Zhuo, T. An, J. Duan, L. Yang, M. Wu, Q. Guo, X. Liu, S. Wang, Y. Wang
Journal: Journal of Clinical Oncology (2011)

e18011 Background: Wnt or Epidermal growth factor receptor (EGFR) signaling pathways play critical roles in predicting outcome of non-small-cell lung cancer treatment. Little is known about the synchronous effect on EGFR tyrosine-kinase inhibitors (EGFR-TKIs) treatment in NSCLC. Methods: Tumor samples from 138 patients with stages IIIB to IV NSCLC taking EGFR-TKIs therapy were analyzed for EGFR mutations in exons 19 and 21 by using denaturing high-performance liquid chromatography. Wnt antagonist methylation,including sFRP1, sFRP2, sFRP5, DKK-3, WIF-1, APC, were also analyzed from these samples through methylation specific PCR method. Results: We found that EGFR mutations were related to smoking status and gender, while methylation of wnt antagonists did not have these trends. The wnt antagonists tend to methylate simultaneously. Methylation of sFRP1 and sFRP5 are reversely correlated with EGFR mutation (P=0.037 and P=0.048). Patients with EGFR mutations have a significant longer progression-free survival (PFS) than those without mutations (7.8 ms vs 2.0 ms, P=0.009), while patients with methylation of sFRP5 and WIF-1 have a significant shorter PFS than those without methylation in TKI treatment (1.2 ms Vs 5.3 ms, P=0.002; 1.1 ms Vs 4.9 ms, P=0.006). Methylation of sFRP5 is an independent factor affecting PFS in multivariate analysis. Patients with sFRP1 methylation have no a significant shorter PFS than patients without its methylation in TKI therapy. Patients with WIF-1 methylation have a significant shorter overall survival (OS) than patients without its methylation (P=0.006 by log-rank test). Conclusions: Patients without sFRP5 or WIF-1 methylation are more likely to benefit from EGFR tyrosine-kinase inhibitor (TKIs) therapy. Methylation of sFRP5 and WIF-1 could be predictive markers related to poor PFS in TKIs treatment.