tbuckley/cabot-search huggingface dataset:
Salvage surgery following chemoradiotherapy in management of esophageal cancer: Is it a viable therapeutic option? Results of a multicenter European study.
Authors: Sheraz Markar, Caroline Gronnier, Alain Duhamel, Jean-Yves Mabrut, Jean-Pierre Bail, Nicolas Carrere, Jeremie H. Lefevre, Bernard Meunier, Denis Collet, Christophe Mariette
Journal: Journal of Clinical Oncology (2015)

109 Background: Salvage esophagectomy (SE) has traditionally conferred a high rate of mortality and morbidity in small, monocenter, and old publications. The aim of this large multicenter study was to assess the impact of SE following definitive chemoradiotherapy (SALV) on clinical outcomes. Methods: Data from consecutive adult patients undergoing resection for esophageal cancer in 30 European centers from 2000–2010 were collected. Among this population, the first step was to compare SALV (n=308) and neoadjuvant chemoradiotherapy followed by planned esophagectomy (NCRS group, n=540) groups. The second step was to focus on the SALV group and to compare patients that benefited from SE for persistent (PERS group, n=234) versus recurrent (REC group, n=74) disease. Propensity score matching and multivariable analyses were used to compensate for differences in some baseline characteristics. Results: Comparison of SALV and NCRS groups: In-hospital mortality was similar in both groups (8.4% vs. 9.3%). The only significant differences in complications were seen for anastomotic leak (17.2% vs. 10.7%; P=0.007) and surgical site infection, which were both increased in the SALV group. At 3 years, the groups had similar overall (43.3% vs. 40.1%; P=0.542) and disease-free (39.2% vs. 32.8%; P=0.232) survivals, along-with similar overall (46.8% vs. 47.9%; P=0.829), locoregional (18.8% vs. 15.9%; P=0.544), distant (24.3% vs. 28.1%; P=0.949) and mixed (13.0% vs. 13.5%; P=0.888) tumor recurrence. Comparison of PERS and REC groups: There were no significant differences between the groups in the incidence of in-hospital mortality or major complications, apart from reoperation, which was increased in the PERS group (17.9% vs. 8.1%; P=0.042). Overall (23.4% vs 39.2%, p=0.054) and disease free survivals (21.1% vs37.8%, p=0.070) were lower in the PERS group. Conclusions: The results of this large multi-center study suggest that SE can offer acceptable short and long-term outcomes in experienced centers. Randomized controlled trials are required to validate the SE strategy as a viable option in complete esophageal cancer responders.
The quantitatively analysis of epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) and its correlation with response rate of EGFR tyrosine kinase inhibitors (TKI)
Authors: Jun Li, Zhao Chen, Daqiang Sun, Meilin Xu, Xun Zhang, Junpu Xu
Journal: Clinical Cancer Research (2010)

Abstract Background and Purpose: Lung cancer is the most frequent malignant tumor in China. Epidermal growth factor receptor (EGFR) had been validated as one of the most important therapeutic targets of non-small cell lung cancer (NSCLC), and tyrosine kinase inhibitors (TKI) have improved the overall outlook and quality of life for most of EGFR mutation positive NSCLC patients; however, the fact that 30% of EGFR mutation positive patients still do not response to TKIs. The current diagnostic test qualitatively measures the overall EGFR mutation status of the cancer tissue, ignored the impacts of nonmutated, TKI-unresponsive cancer cells. 274 NSCLC patients were recruited for the study to carry out the mutation analysis and its correlation with the response rate to EGFR TKIs with a novel quantitative methodology. Experimental Procedures: 1) Selection of paraffin sections of each recruited patients by pathologist to ensure the tumor cells exceeds 70% of total tissue; 2) Extraction of genomic DNA from paraffin sections; 3) Construction of plasmids of both mutated transcripts and wild-type transcripts for each mutation to be analyzed; 4) Real-time PCR amplification of extracted genomic DNA samples with both mutated probes and wild-type probes, and measurement of mutated copy numbers and wild-type copy numbers of each sample with standard curves made by mutated plasmids and wild-type plasmids respectively; 5) Confirmation of the mutation status of each sample with sequencing; 6) Calculation of the percentage of mutated EGFR copy numbers among the total EGFR copy numbers to derive quantitatively mutation data of each patient sample; 7) Observation of EGFR mutations and its demographic features with quantitative data; 8) Evaluation of the outcomes of the therapy with EGFR TKIs (including gefitinib and erlotinib) and analysis of the correlation of increased EGFR mutated transcripts with response rate to EGFR TKIs Summary of New Data: 1) 94 recruited samples was detected with EGFR mutation among total samples, the mutation ratio various from 5% to 90%; 2) The most frequently detected EGFR mutations among the 94 samples are deletions of Exon 19 (56 cases) and L858R (23 cases); 3) The mutation positive NSCLC patients are divided into 4 groups: a) low mutation rate + gefitinib; b) high mutation rate + gefitinib; c) low mutation ratio + erlotinib; d) high mutation rate + erlotinib. There are significant differences between group a and group b, group c and group d. 4) There is no significant difference between various EGFR mutation types against response rate to TKIs. Conclusions: 1) The EGFR mutation ratios in NSCLC patients are various; 2) The EGFR mutation ratio is significant correlated with the response rate to TKIs. This talk is also presented as Poster B36.
Minocycline hepatotoxicity: Clinical characterization and identification of HLA-B∗35:02 as a risk factor
Authors: Thomas Jacob Urban, Paola Nicoletti, Naga Chalasani, José Serrano, Andrew Stolz, Ann K. Daly, Guruprasad P. Aithal, John Dillon, Victor Navarro, Joseph Odin, Huiman Barnhart, David Ostrov, Nanye Long, Elizabeth Trilby Cirulli, Paul Brent Watkins, Robert John Fontana
Journal: Journal of Hepatology (2017)
Immunohistologic Evaluation of the Lymphoreticular Infiltrate of Human Central Nervous System Tumors2
Authors: Gary W. Wood, Robert A. Morantz
Journal: JNCI Journal of the National Cancer Institute (1979)

Journal Article Immunohistologic Evaluation of the Lymphoreticular Infiltrate of Human Central Nervous System Tumors Get access Gary W. Wood, Gary W. Wood 3Department of Pathology and Oncology, University of Kansas Medical Center, College of Health Sciences and Hospital, 39th and Rainbow Blvd., Kansas City, Kans. 66103. Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert A. Morantz Robert A. Morantz 4Department of Surgery, University of Kansas Medical Center. 5We thank Ms. Katherine Gollahon for performing the analysis; Ms. Veronica Routt, Ms. Marsha Plank, and Ms. Martina Clark for the preparation of the samples; Dr. Charles Brackett and Dr. Seui Rengachary for supplying clinical material; and Ms. Sally McNevin and Ms. Diane Marlatt for secretarial assistance. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 62, Issue 3, March 1979, Pages 485–491, https://doi.org/10.1093/jnci/62.3.485 Published: 01 March 1979 Article history Received: 16 May 1978 Accepted: 03 September 1978 Published: 01 March 1979
Induction of Lung Cancer in Germfree, Specific-Pathogen-Free, and Infected Rats by &lt;italic&gt;N&lt;/italic&gt;-Nitrosoheptamethyleneimine: Enhancement by Respiratory Infection&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Hans Schreiber, P. Nettesheim, W. Lijinsky, C. B. Richter, H. E. Walburg, Jr.
Journal: JNCI Journal of the National Cancer Institute (1972)

The effect of chronic respiratory infection on the development of lung cancer induced by N-nitrosoheptamethyleneimine was tested in rats. The nitrosamine was administered in drinking water for 22 weeks to germfree and specific-pathogen-free (SPF) rats and to rats with chronic murine pneumonia. All animals were killed 2 weeks after the last treatment. The incidence of lung neoplasms was 17% in germfree males, 37% in SPF males, and 83% in infected males. An incidence of 90–100% was found among females in all 3 experimental groups. The results in males demonstrate that chronic respiratory infection can enhance the neoplastic response of the lungs to a systemic carcinogen. The normal microbial flora does not seem to be essential for tumor induction by this nitrosamine. There was no significant difference in incidence of esophageal tumors among the 3 groups.—J Natl Cancer Inst 49: 1107–1114, 1972.
Effect of antacid co-medication on imatinib disposition: A healthy volunteer study
Authors: B. A. Sparano, M. J. Egorin, R. A. Parise, J. Walters, K. A. Komazec, R. L. Redner, J. H. Beumer
Journal: Journal of Clinical Oncology (2008)

2547 Background: Imatinib mesylate, a potent inhibitor of Bcr-Abl and c-kit tyrosine kinases, is widely used to treat gastrointestinal stromal tumors and Philadelphia chromosome-positive leukemias. Imatinib often causes gastric upset and is therefore frequently administered with an antacid (AA). Yet, the resulting elevated gastric pH, delayed gastric emptying, or introduction of Mg2+ and Al3+ could change imatinib absorption, thereby affecting the therapeutic effectiveness of imatinib. To test this hypothesis, we sought to define the effect of AA on the plasma pharmacokinetics of imatinib. Methods: 12 healthy subjects (6 M, 6 F; 20–51 years) were enrolled in a 2- period, open-label, randomized cross-over, fixed-sequence study. In one period, they received 400 mg imatinib p.o., in the other 20 mL Maximum Strength Maalox Max Antacid/Anti-gas (1.6 g Al(OH)3 + 1.6 g Mg(OH)2) 15 min prior to 400 mg imatinib p.o. The periods were separated by a wash-out period of ≥ 14 days. Plasma samples from 0–72 h after dosing were obtained. Plasma concentrations of imatinib and its active metabolite CGP74588 were determined with an LC-MS assay and data were analyzed non-compartmentally. The study was powered to detect a 30% difference in imatinib AUC with 80% power and a 5% type I error. Results: See table. Conclusions: This study demonstrates that the use of Mg2+-Al3+ based AA to treat imatinib-induced gastric upset does not significantly affect imatinib plasma AUC. The small difference in imatinib half-life, detected by an unplanned statistical test, should not affect the average steady-state concentration achieved after multiple doses, and therefore is not likely to be clinically significant. Support: Novartis; NIH/NCRR/CTSA Grant UL1 RR024153 Analyte Arm AUC0-inf Cmax tmax t1/2 V/F Cl/F (ug/mL*h) (ug/mL) (h) (h) (L) (L/h) Imatinib Alone 32.6 (8.0) 2.12 (0.43) 2.8 (0.9) 14.3 (1.5) 267 (75) 13.1 (3.7) Imatinib +AA 33.1 (6.0) 2.10 (0.45) 3.4 (0.7) 15.1 (1.8) 273 (72) 12.6 (3.1) p-value 0.73 0.85 0.08 0.03 0.68 0.40 CGP74588 Alone 6.04 (1.43) 0.27 (0.06) 2.5 (0.9) 30.5 (5.3) 3077 (945) 69.9 (17.1) CGP74588 +AA 6.45 (1.67) 0.26 (0.09) 3.1 (0.5) 33.3 (9.4) 3012 (1295) 61.2 (25.1) p-value 0.078 0.85 0.11 0.35 0.84 0.10 Mean (SD) Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis Novartis Novartis
Neoplastic Transformation in Tissues of Rats Exposed to Monocrotaline or Dehydroretronecine23
Authors: R. C. Shumaker, K. A. Robertson, I. C. Hsu, J. R. Allen
Journal: JNCI Journal of the National Cancer Institute (1976)

Journal Article Neoplastic Transformation in Tissues of Rats Exposed to Monocrotaline or Dehydroretronecine Get access R. C. Shumaker, R. C. Shumaker Search for other works by this author on: Oxford Academic PubMed Google Scholar K. A. Robertson, K. A. Robertson Search for other works by this author on: Oxford Academic PubMed Google Scholar I. C. Hsu, I. C. Hsu Search for other works by this author on: Oxford Academic PubMed Google Scholar J. R. Allen J. R. Allen Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 56, Issue 4, April 1976, Pages 787–790, https://doi.org/10.1093/jnci/56.4.787 Published: 01 April 1976 Article history Received: 04 August 1975 Accepted: 24 October 1975 Published: 01 April 1976
Leptomeningeal carcinomatosis of gastric cancer: Multicenter retrospective analysis of 54 cases
Authors: S. Oh, S. Kim, H. Kwon, H. Kim, I. Hwang, J. Kang, S. Lee, J. Lee, W. Kang
Journal: Journal of Clinical Oncology (2009)

e15658 Background: Leptomeningeal carcinomatosis occurs in approximately 5% of patients with cancer. The most common cancers involving the leptomeninges are breast and lung cancer. However, gastric adenocarcinoma has been rarely reported with leptomeningeal carcinomatosis (LMC). Methods: We analyzed 54 cases of cytological confirmed gastric LMC at 4 institutions from 1994 to 2007. Results: Male to female ratio was 1.5:1. Median age of these patients was 49 years. The majority of patients had advanced disease at the initial diagnosis of gastric cancer. The clinical or pathologic TNM stages of the primary gastric cancer were IV in 38 patients (70%). The median interval from the diagnosis of the primary malignancy to the diagnosis of LMC was 6.3 months (range, 0 - 73.1 months). Of the initial endoscopic finding available 45 patients, Bormann type III and IV were 23 (51%) and 15 (33%) patients, respectively. Headache (85%) and nausea/vomiting (58%) were most common presenting symptoms of LMC. The intrathecal (IT) chemotherapy was administered to 36 patients - mainly with methotraxate alone (59%) or combination with ara- C/hydrocortisone (41%). Median IT treatment number was 7 (range, 1–18). Concomitant radiotherapy or chemotherapy was done in 25 patients and 10 patients, respectively. 17 patients (46%) were achieved cytological negative conversion. Median OS duration from diagnosis of LMC was 6.7 weeks (95% CI; 4.3–9.1 weeks). Clinically, initial advanced stage was predictive value of poor prognosis (P=0.009). But, Cytology negative conversion was predictive value of relatively longer survival duration (P=0.005). And, not only IT chemotherapy but also intravenous chemotherapy had been shown improvement of survival duration (P=0.010, P=0.005, respectively). Conclusions: Although gastric LMC has dismal prognosis, IT and IV chemotherapy could be help to extend survival duration of gastric LMC. No significant financial relationships to disclose.
The balance of available evidence supports its use
Authors: S. P Harding
Journal: BMJ (1995)

Relation between various factors and response to mammographic screening 1991-2 Did not respond Responded Characteristic (n=34) (n=217) Age range (average) (years) 52-65 (57) 50-65 (57) Non-response for cervical screening 20** 16** Not known personally to general practitioner 22* 77* Marital status: Married 24 176 Widowed 5 29 Divorced 4 5 Single 1 7 *P=0*01, **P=0 001.ascertained whether the following factors were associated with non-attendance: non-response for cervical screening, marital status, and whether the patient had personal knowledge of the general practitioner.The only factors that reached signifi- cance (table) were non-attendance for cervical screening (P< 0 001) and no personal knowledge of the general practitioner (P < 001)).
WHO sets out $56m Zika virus response plan
Authors: Michael McCarthy
Journal: BMJ (2016)

The World Health Organisation (WHO) released a report on 16 February outlining its $56m (£39m; $50m) strategic plan to respond to the ongoing outbreaks of Zika virus disease in the Americas. The plan provides a framework for WHO and its partner organizations’ Zika response through to June.1

The mosquito-borne virus, first detected in the western hemisphere in 2014, is now reported to be circulating in 26 countries and territories in Latin America and the Caribbean. Of particular concern are reports linking Zika virus infection to fetal and newborn microcephaly and serious neurologic complications such as Guillain-Barre syndrome. WHO declared the outbreak in the Americas to be a public health emergency of international concern on 1 February.

In the new …
Pharmacokinetics (PK) of ibrutinib in patients with chronic lymphocytic leukemia (CLL).
Authors: Juthamas Sukbuntherng, Purvi Jejurkar, Stephen Chan, Anh L. Tran, Davina Moussa, Danelle Frances James, David Loury
Journal: Journal of Clinical Oncology (2013)

7056 Background: Ibrutinib is a first-in-class selective small molecular inhibitor of Bruton’s tyrosine kinase (BTK) under development for the treatment of B-cell malignancies. Because of covalent binding to cys-481 of BTK, ibrutinib has a sustained pharmacodynamic (PD) effect. The aim of this study was to determine the PK of ibrutinib in patients (pts) with CLL. Methods: A Phase 1b/2 study (PCYC-1102-CA) of an oral dosing of single agent ibrutinib was conducted in pts with treatment-naïve (TN) or relapsed/refractory (R/R) CLL. Pts were enrolled into one of the following groups: R/R pts at 420 mg/day (n=27), TN pts at 420 mg/day (n=26), R/R pts at 840 mg/day (n=34), R/R high-risk pts at 420 mg/day (n=24), TN pts at 840 mg/day (n=5), and R/R pts at 420 mg/day for food-effect evaluation (n=16). One cycle was 28 days. Blood samples for PK assessment were obtained during the first cycle. PK parameters were calculated using non-compartmental analyses. Results: A total of 132 pts (98 males and 34 females) with CLL were treated across the 6 groups. Median ages for Groups 1 through 6 were 64, 71, 64, 68, 71, and 62 years, respectively. Ibrutinib exhibited rapid absorption (median Tmax of 2 h) and a mean elimination plasma half-life of approximately 6-9 hours. The AUCtau increased approximately proportional to doses from 420 to 840 mg/day. No accumulation of ibrutinib was apparent on Day 8. Ibrutinib exposure in males and females was similar. At 420 mg/day, pts ≥ 65 years old had AUC values that were ~30% higher than those of pts &lt; 65 years. In R/R pts, there were no substantive differences in systemic exposure to ibrutinib between the del 17p positive and del 17p negative pts. An increase in ibrutinib exposure (&lt;2-fold) was observed when administration with high-fat breakfast was compared to administration following an overnight fast. In all cases, %CV of AUC ranged from 50 to 100%. Conclusions: Ibrutinib demonstrated rapid absorption and elimination and was well tolerated at doses of 420 and 840 mg/day. Lack of significant exposure differences with respect to age, gender, or 17p del status indicates that dose adjustment in these populations is not required. Because of a sustained PD effect ibrutinib can be dosed once daily despite a relatively rapid clearance. Clinical trial information: NCT01105247.
Hospitalization rates among survivors of childhood and adolescent cancer: A report from the Childhood Cancer Survivor Study (CCSS)
Authors: B. A. Kurt, V. G. Nolan, K. K. Ness, J. P. Neglia, J. M. Tersak, M. M. Hudson, G. T. Armstrong, W. M. Leisenring, L. L. Robison, M. Arora
Journal: Journal of Clinical Oncology (2009)

9556 Background: Survivors of childhood cancer have a high burden of chronic health conditions following cancer therapy, but the risk for subsequent hospitalization has not been reported. Methods: Hospitalizations during 1996–2000 among a cohort of 10,367 5-yr survivors of childhood cancer (diagnosed 1970–1986) and 2,540 siblings were ascertained. Age-and gender-stratified standardized incidence ratios (SIRs) for hospitalization were calculated using the sibling cohort and U.S. population from the National Hospital Discharge Survey (NHDS). Associations between demographic, cancer/treatment-related risk factors and non-obstetrical hospitalization among survivors were evaluated in multiple variable logistic regression models. Results: At follow-up, survivors were a mean of 20.9 yrs. from diagnosis (SD: 4.6, range: 13.3–32.2) and mean age of 28.6 yrs. (SD: 7.7, range: 13–51). Overall hospitalization rates among survivors were 1.5 times (95% CI 1.44–1.52) that of siblings and 1.2 times (95% CI 1.16–1.22) that of the U.S. general population. Increased risk of hospitalization was noted irrespective of gender, age at follow-up, or cancer diagnosis, with highest SIRs noted for male (SIR=12.7, 95% CI 9.5–15.8) and female (SIR=72.1, 95% CI 58.8–85.5) survivors aged 45–54. Females (OR=1.2, 95% CI 1.04–1.3) and survivors with a chronic health condition (OR=1.6, 95% CI 1.5–1.8) were more likely to have been hospitalized for non-obstetrical causes after adjusting for age at diagnosis, age at follow-up, cancer diagnosis, household income, insurance, and history of relapse/second malignancy. Among survivors, those with Hodgkin's lymphoma had the highest hospitalization rates for neoplastic, infectious, endocrine, pulmonary and cardiovascular causes. CNS malignancy survivors had the highest hospitalization rates for neurologic, psychological and external (e.g. traumatic) causes. Conclusions: Therapy for childhood and adolescent cancer is associated with a significant increase in subsequent hospitalization rates. Regular medical follow-up and early intervention for chronic health conditions may help to limit severe toxicity that would require hospitalization. No significant financial relationships to disclose.
Preliminary results of a phase II study of gemcitabine and epirubicin in platinum-resistant or refractory advanced ovarian cancer
Authors: C. Arcuri, R. Sorio, O. Caffo, S. Scalone, C. Griso, A. Lucenti, F. Valduga, M. Frisinghelli, E. Arisi, E. Galligioni
Journal: Journal of Clinical Oncology (2005)

5071 Background: . Gemcitabine (G) and Antracyclines are active as single agent in resistant or refractory ovarian cancer (OC). The aim of this study was to assess the efficacy and toxicity of G and Epirubicin (E) combination in patients (pts) with recurrent OC. Methods: Pts with recurrent epithelial OC or peritoneal carcinoma or carcinoma of the tuba, failing platinum- regimens (free-interval ≤ 12 months), measurable tumor, WHO PS ≤ 2, age ≥18 and ≤ 75, no previous antracycline were included. Treatment consisted of G 1000 mg/m2(day 1, 8) and E 60 mg/m2 (day 1) every 3 weeks for 3 to 6 cycles (in pts with objective response or stable disease after 3 cycles). Between june 02 and october 04, 26 pts were included. Median age: 59 yrs (43–74). Median PS: 1 (0–2). Figo: Stage III 12 and stage IV 14. Serous: 18/26; endometrioid 1/26; unclassified adenocarcinoma: 5/26; tuba 1 and peritoneal carcinoma 1. Median platinum free interval was 6 months (range 0–12). Median of previous regimens was 1 (range 1–4). Results: 132 cycles were administered (median 6 for patient). Two pts are not evaluable for response (one too early, the other for early PS worsening and PD). 24 pts are evaluable for response, according to Recist criteria. Overall response rate (ORR) was 45,8% (1 CR+ 10 PR). 8 pts (33,3%) had SD and 5 (20,8%)PD. Median time to response was 10 wks (range 8–20) and median duration of response was 8 mos (range 5–12). Kaplan-Meier estimate of 8 mos OS was 81% and the PFS 42,8%. Toxicity (NCI criteria) in the 26 pts evaluable was: Grade 3–4: leucopenia 30%, neutropenia 57%, thrombocytopenia 4%, anemia 11,5%, liver 15%, mucositis 7,6%; 8 pts 30% required G-CSF and 3 pts 11,5% blood transfusion. The median interval between cycles was 21 days, only 13 treatment delays for toxicity. No life threatening events occurred. Conclusions: In our study the combination of G and E has shown in these platinum resistant/refractory recurrent OC pts encouraging activity with a 45% ORR and 33% SD, and manageable toxicity. No significant financial relationships to disclose.