tbuckley/cabot-search huggingface dataset:
Factors associated with regression of cervical dysplasia in adolescents: A retrospective study
Authors: C. Chen, F. Campbell, J. Patruno, S. Kimmel, R. Boulay, C. Meyers, M. Martino
Journal: Journal of Clinical Oncology (2009)

5582 Background: Sexually active adolescents have high rates of infection with human papilloma virus (HPV) and abnormal pap smears. They are considered a special population as they are likely to regress to normal cytology. The aim of our study was to identify factors associated with regression of cervical dysplasia in adolescents. Methods: We identified adolescent patients (aged 12–21 years) who had abnormal pap smears at the Center for Women's Medicine at Lehigh Valley Hospital in Allentown, PA, by CPT code from a database between Jan 2004 and Dec 2006. A chart review was performed to capture demographic data, cytology, smoking history, number of sexual partners, parity, race, contraceptive choice, use of barrier contraception. Chi-square analysis with logistic regression and multivariate analysis were used to identify factors associated with regression of cervical dysplasia. Results: Two-hundred two patients were identified. Mean age was 18.84 years (14–22 years). One hundred twenty-two (57.8%) were Hispanic, 71 (33.6%) Caucasian, and 16 (7.6%) Black. Fifty-two (24.6%) were pregnant at the time of diagnosis. Seventy-six (36%) were smokers. There were 125 (61.9%) cases of ASCUS, 33.7% (68 cases) LGSIL and 4.5% (9 cases) HGSIL on initial pap smear. One hundred eighteen (55.9%) patients had colposcopy, and of these, 32 (15.2%) had surgical intervention. Follow-up demonstrated that 72 (57.6%) patients had disease regression, 24 (19.2%) persistence and 29 (23.2%) progression. On multivariate analysis, patients who did not smoke were significantly more likely to show regression of cervical dysplasia on pap smear than women who smoked (OR 2.17, 95% CI 1.03–4.55, p = 0.039). Other factors were not statistically significant in predicting regression of cervical dysplasia. Conclusions: Adolescents who smoke were more likely to have persistent cervical dysplasia than non-smoking adolescents, putting smokers at an increased risk of advanced disease. We suggest that this subset have follow-up at shorter intervals and be enrolled in a smoking cessation program. No significant financial relationships to disclose.
A pilot safety and feasibility trial of a reduced carbohydrate diet in patients with advanced cancer.
Authors: E. J. Fine, C. J. Segal-Isaacson, R. D. Feinman, S. Herszkopf, M. Romano, N. Tomuta, A. Bontempo, J. A. Sparano
Journal: Journal of Clinical Oncology (2011)

e13573 Background: Most aggressive cancers share a glycolytic phenotype associated with increased uptake of 18F-2-fluoro, 2-deoxyglucose (FDG) that may be detected by positron emission tomography (PET). We hypothesized that a carbohydrate restricted (CR) diet, by inhibiting insulin secretion, enlists plausible mechanisms to limit cancer growth. Methods: Patients with advanced incurable cancer were eligible if they had a positive FDG-PET scan, an ECOG performance status of 0-2 associated with normal organ function, no diabetes or recent weight loss, and a BMI >20 kg/m2. A supervised CR diet (5% of total kCal) was monitored weekly for macronutrient intake, body weight, serum electrolytes, betahydroxybutyrate concentrations [BHB], insulin, and insulin like growth factor-1 and 2 (IGF-1and IGF 2]. A FDG-PET scan was obtained before and after the CR diet. Results: Ten subjects completed 26-28 days of the CR diet without associated adverse effects. Mean caloric intake decreased by (35 + 6)% compared to baseline predictions of caloric requirements, and weight decreased by a median of 4% (range 0.0-6.1%.). One patient had advanced but indolent disease. Patients with non-progression (n=5), representing stable disease (SD) or partial remission (PR) on the post-CR diet FDG-PET scan exhibited three-fold higher dietary ketosis (p<0.02) when compared with patients with progressive disease (PD; n=4); but non-progression was not correlated with reduced calorie intake (p=0.65) or weight loss (p=0.35). Ketosis correlated inversely with serum insulin levels (r=0.62, p<0.001). Conclusions: A carbohydrate restricted diet is feasible in selected patients with advanced cancer, resulting in reduced serum insulin concentration and ketosis. Disease stabilization is correlated with the highest degrees of ketosis, supporting further evaluation of CR as a means of insulin secretory inhibition, and as a complementary approach in conjunction with standard and endocrine therapies. Energy deficit Pt. no. PET scan Ketosis on CR diet compared with baseline levels 0.35 3* SD 2.7 ± 1.2 0.42 2 PR 23.3 ± 14.2 0.29 5 SD 13.1 ± 18.5 0.53 7 SD 14.6 ± 11.8 0.07 8 SD 8.2 ± 2.8 0.45 10 SD 23.6 ± 8.2 0.33 1 PD 2.1 ± 1.9 0.28 4 PD 2.8 ± 1.2 0.31 6 PD 4.2 ± 2.8 0.60 9 PD 11.4 ± 4.5
Long-term experience with primary non-Hodgkin’s bone lymphoma
Authors: G. Delepine, F. Delepine, H. Cornille, B. Markowska, N. Delépine
Journal: Journal of Clinical Oncology (2005)

6735 Background: Primary bone lymphomas are rare diseases accounting for 3% of primary tumors of bone and about 5% of all extranodal non-hodgkin ’s lymphomas. Inspite of a better prognosis than other lymphomas, there is no consensus about optimal treatment. We report on our experience. Methods: 17 patients (p.) were identified, among more than 650 treated for bone malignant tumors by the team from 1985. We retrospectively reviewed all cases and medical record was examinated. Age at diagnosis, sex, NHL clinical staging, clinical symptoms, treatment and response were retrieved. Results: 17 p. with newly diagnosed PLB were treated from dec. 1985 to Jan 2003. Eight patients were male and 9 female, median age was 37 years, range 19–75. 14 p. had a solitary lesion (stage 1) and 3 had tumor spread to locoregional lymphatic area (stage 2). Locations were femur (9), iliac bone (4), clavicule (2) sacral bone (2). All had B-cell grade histology. Local tumor was treated by: radiotherapy (11) en-bloc resection (4), both (2). With a median follow-up of 14 years, 14 p. are in EFS. Three p. died, one following a toxicity related to: high dose chemotherapy (1) secondary osteosarcoma related to radiotherapy -8 y post treatment -(1) vascular cerebral event (1). No progressive disease was seen. Complications from radiotherapy were important and frequent (3/13:24%): post radiotherapy osteosarcoma, epiphysis femur fracture, diaphysis femur fracture. The actuarial 10 y overall survival is 84% and actuarial event free survival years is 90% for the entire group. Conclusions: PLB is a curable malignancy as confirmed by many authors, (ASCO 2004, n° 6587 in a large cohort). This evidence leads to avoid agressive methods to cure it, as high dose chemotherapy and may be, radiotherapy. Doctors must initially prove that the lymphoma of bone is truly a primary tumor and not a classic hematologic malignancy, and in this case, give a treatment combinating conventional chemotherapy and adapted surgery. The place of radiotherapy as local treatment should be reevaluated. No significant financial relationships to disclose.
Identification of tumor biomarkers in oral squamous cell carcinoma by differential display RT-PCR.
Authors: K. S. Gopinath, None Srinivas, Nagashri M.N. Shivananda Swamy, Sanjukta Chakraborthy, Azem Mohiyuddin, Arun Kumar
Journal: Journal of Clinical Oncology (2010)

e16027 Background: Oral squamous cell carinoma (OSCC) is one of the most common cancers in the world. Despite progress in therapeutic and surgical treatments, its survival period at 5 years is the lowest among major cancers, and remains unchanged in the last two decades. The growing epidemiological relevance of oral cancer emphasizes the need for a better understanding of the molecular mechanisms underlying this disease and identify predictive tumor biomarkers. Methods: To this end, we have used the differential display RT- PCR (DDRT-PCR) technique to profile the oral tumor transcriptome and identify differentially regulated genes that may function as potential biomarkers and therapeutic targets. Results: Using this technique, we have identified 51 differentially expressed genes of which 25 were revalidated by reverse Northern analysis. Northern blot analysis further corroborated these findings for a few genes. In order to ascertain the utility of some of the identified genes as molecular markers, semi-quantitative RT-PCR analysis was carried out in a panel of matched oral normal and tumor samples. GLTP, PCNA, RBM28, C17orf75 andDIAPH1 genes were significantly upregulated in tumor samples. On the other hand, TNKS2, PAM and TUBB2C genes showed significant downregulation in tumor samples. Conclusions: Taken together, our analysis has showed several genes, belonging to diverse cellular pathways, which have been associated with OSCC for the first time. We suggest that these genes could be investigated as biomarkers and therapeutic targets for OSCC. No significant financial relationships to disclose.
EGFR mutations in lung cancers and sensitivity to gefitinib in Chinese
Authors: Y. Wu, J. Lin, K. Wang, C. Xu, Q. Zhou, G. Chen, X. Yang, J. Yang, Y. Huang, R. Liao, S. Huang
Journal: Journal of Clinical Oncology (2005)

7089 Background: Radiographic regressions of tumors treated with gefitinib were observed in 28% of patients in Japan and 10% of those studied in Europe and the U.S. The characteristics of patient response to gefitinib were female, nonsmoker adenocarcinoma and East Asian origin. Recently, two groups have shown that EGFRmutations are associated with sensitivity of NSCLC to gefitinib. There are no any data about EGFR mutation in Chinese. Methods: Frozen tumor specimens from untreated patients with Stage I-IV NSCLC (n = 120) were obtained from Cancer Tissue Bank developed by our hospital. Paraffin-embedded materials were collected retrospectively for patients with NSCLC on gefitinib (n = 15). All 28 exons of EGFR were amplified in 5 specimens and exons 18, 19 and 21 were sought in other specimens. Results: Total 135 cases were enrolled onto the study. The patient characteristic was male: female = 94:31; Adenocarcinoma: other = 82:63; Smoker: nonsmoker =80:55. The mutations of EGFR were detected in 26 patients (25 cases with adeno, 1 with squamous). The EGFR mutation rate was 19.3%(26/135). Heterozygous substitution mutations were detected in exons 21 (11.9% of 16/135) and exons 18 (0.7%, 1/127). In-frame deletions detected in exons 19(8.9%, 12/128). Both substitution mutation and deletion mutation were detected in 3 patients not previously described. For adenocarcinoma subgroup the EGFR mutation rate was 30.5%(25/82). Male adenocarcinoma subgroup the EGFR mutation rate was 30.6%(15/49). Female adenocarcinoma subgroup the EGFR mutation rate was 30.3%(10/33). Smoking male adenocarcinoma the mutation was 53.3%(8/15). Nonsmoking male adenocarcinoma the mutation was 46.7%(7/15). 83.3% of 5/6 patients with positive mutation had clinically significant responses to the Gefitinib. Best response was seen in patients with exons 21 mutation (66.7% of 4/6). Conclusions: The in-frame deletions only occurred in exons 19 and most substitution mutation in exon 21. There was no significant difference of EGFR mutations between male and female, smoker and nonsmoker in Chinese. Lung adenocarcinoma with mutations EGFR are sensitive to Gefitinib. No significant financial relationships to disclose.
Palonosetron (PALO) for prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving high-dose melphalan prior to stem cell transplant (SCT)
Authors: S. Giralt, K. Mangan, R. Maziarz, J. S. Bubalo, R. Beveridge, D. D. Hurd, F. Mendoza, E. B. Rubenstein, T. J. DeGroot, M. W. Schuster
Journal: Journal of Clinical Oncology (2008)

9617 Background: PALO, a novel 5HT3 receptor antagonist with unique pharmacologic features, is approved as a 0.25-mg IV dose and has been shown to be superior to ondansetron in preventing emesis associated with single-day emetogenic chemotherapy. This phase II, double-blind study assessed the efficacy and safety of PALO in patients receiving multiple-day high-dose chemotherapy before SCT. Historically, SCT regimens have been associated with significant CINV despite multiagent antiemetic prophylaxis. Methods: Adults with multiple myeloma receiving 2-day melphalan (100 mg/m2/d) were randomized to receive one of 3 schedules of PALO 0.25 mg IV (prior to chemotherapy, or SCT on day 0): A) day -2; B) days -2 and -1; C) days -2, -1, and 0. All patients received dexamethasone 20 mg daily on days -2 and -1. Rescue antiemetics were allowed at investigator discretion. The primary efficacy endpoint was complete protection, defined as no emesis throughout the 7-day study period. Emetic episodes and additional efficacy endpoints were collected daily using standardized patient self-report diaries; adverse events were assessed throughout the study. Results: 73 patients were randomized with no significant between-group differences in median age (59–61 yrs), gender (54–71% male), previous chemotherapy (24–33% naive), or no history of alcohol use (42–63%). The table presents primary efficacy results, and additional endpoints will be presented. PALO was well tolerated; reported adverse reactions included: diarrhea (16%), constipation (12%), headache (11%), and insomnia (8.2%); none were serious, and most were mild. Conclusions: PALO was well tolerated and remarkably effective at preventing emesis in patients receiving high-dose melphalan prior to SCT, with a trend toward better efficacy in patients receiving multiple day dosing of PALO. Complete Protection (No Emesis), Intent-to-Treat Population, % of patients Time period A) PALO Day -2 (N = 24) B) PALO Days -2, -1 (N = 24) C) PALO Days -2, -1, 0 (N = 25) p-valuea 7-day Complete Protection (Days -2 through 4) 41.7 41.7 44.0 0.434 Day -2 (-48 to -24 hrs) 95.8 95.8 96.0 0.488 Day -1 (>-24 to 0 hrs) 87.5 91.7 96.0 0.141 Day 0 (>0 to 24 hrs) 66.7 79.2 92.0 0.015 Day 1 (>24 to 48 hrs) 66.7 75.0 76.0 0.235 Day 2 (>48 to 72 hrs) 54.2 70.8 68.0 0.161 Day 3 (>72 to 96 hrs) 75.0 70.8 76.0 0.465 Day 4 (>96 to 120 hrs) 75.0 83.3 80.0 0.337 a p-value based on the exact one-sided Jonckheere-Terpstra Trend Test Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration MGI Pharma MGI Pharma MGI Pharma MGI Pharma
Molecular signature of esophageal adenocarcinoma derived from microarray analysis of paraffin-embedded specimens predicts systemic recurrence following resection
Authors: D. S. Oh, J. Cooc, S. R. DeMeester, R. Mori, H. Kuramochi, C. Rizzetto, K. Danenberg, P. Danenberg, J. A. Hagen, D. H. Harpole, T. R. DeMeester
Journal: Journal of Clinical Oncology (2007)

4563 Introduction: Surveillance endoscopy in patients with Barrett’s esophagus has resulted in the diagnosis of an increasing number of early-stage adenocarcinomas. Surgical resection alone is curative in the majority of these patients, yet some will succumb to systemic disease. We hypothesize that among patients with early esophageal adenocarcinoma, there are distinct molecular signatures of tumors that are associated with systemic recurrence and those that are cured with resection alone. Methods: From a total of 36 patients with early-stage adenocarcinoma (T1–3, less than or equal to 4 involved nodes), 20 who were alive and without recurrence at a median follow-up of 61 months after resection alone were compared by microarray analysis with similar stage tumors from 16 patients that developed systemic disease and died at a median of 13 months after esophagectomy. Following microdissection of paraffin-embedded specimens, RNA was isolated, amplified, labeled, and hybridized to Affymetrix U133 Plus 2.0 GeneChips. Results: A T-test with unequal variance assumption identified 328 differentially expressed probe sets (false discovery rate &lt;0.05; p67 mos. vs. 13 mos., respectively; p&lt;0.001). Significant canonical pathway deregulation between long and short survivors included GABA receptor, PDGF, PPAR, IL-6 signaling, oxidative phosphorylation and the pentose phosphate pathway. Conclusion: The molecular signature of early-stage esophageal adenocarcinomas may be able to distinguish patients at increased risk for the development of systemic disease and thereby guide use of adjuvant therapy and the intensity of follow-up. Confirmation of these findings in additional patients should prompt a prospective clinical trial. [Table: see text]
A safety, tolerability, and pharmacokinetic (PK) study of GW572016 in patients with solid tumors
Authors: L. Pandite, H. A. Burris, S. Jones, G. Wilding, C. Taylor, M. J. Versola, D. A. Smith, A. Stead, K. M. Koch, N. L. Spector
Journal: Journal of Clinical Oncology (2004)

3179 Background: GW572106 is a reversible inhibitor of ErbB1/ErbB2 tyrosine kinases. This phase I monotherapy study evaluated safety, tolerability, and PK in patients with advanced solid tumors at once (QD) and twice daily (BID) dosing schedules. Methods: Patients (pts) were administered GW572106 on a QD or BID continuous schedule. QD doses ranged from 175 to 1800 mg and BID doses were 500, 750, and 900 mg per dose. In addition to standard evaluations, serial MUGAs were obtained. PK on days 1 and 14 and disease assessments every 8 weeks (RECIST criteria) were obtained. Results: 81 pts with various carcinomas were enrolled; 64 pts (39 QD, 25 BID) included in safety and disease assessment; 57 included in PK. Median age was 62 yrs; 39 males/25 females. The majority of drug-related AEs were grade I (75% of pts QD, 71% pts BID). Diarrhea was the most frequent AE (17% QD, 29% BID of pts). Two pts had grade 3 diarrhea at 900 mg BID. Other AEs were fatigue (16%), nausea (16%) and rash (9%) on QD and nausea (11%) and rash (11%) on BID dosing. While serial MUGAs revealed no significant median change in LVEF, only 1 of the 81 pts experienced cardiac toxicity; a grade 2, asymptomatic decline in LVEF was observed. There were no clinically significant changes in the other safety evaluations. The severity of diarrhea and rash were not correlated with dose; severity of rash but not diarrhea appeared to correlate with serum concentration. Conclusion: Administration of GW572106 on a QD schedule was well-tolerated at all doses while 500 and 750 mg BID were better tolerated than 900 mg BID. The majority of AEs were grade 1 or 2 skin and/or GI toxicities, manageable with symptomatic treatment. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline; Pharmacia GlaxoSmithKline Bristol-Myers Squibb; GlaxoSmithKline GlaxoSmithKline
Clopidogrel Hyporesponsiveness, Interacting with Diabetes Mellitus, Predicts 2-Year Cardiovascular Outcome Among Taiwanese Population Underging Percutaneous Coronary Intervention
Authors: Ping-Yen Liu, Ling-Jay Hsu, Po-Tseng Lee, Cheng-Hann Lee, Ju-Yi Chen, Yi-Heng Li, Liang-Miin Tsai, Jyh-Hong Chen
Journal: Journal of the American College of Cardiology (2011)
N-cadherin, a potential novel therapeutic target in small cell lung cancer
Authors: M. Batus, K. A. Kaiser, J. S. Coon, S. Ahmed, A. Patel, E. F. Avery, M. A. Kemper, M. Kassar, P. D. Bonomi
Journal: Journal of Clinical Oncology (2007)

18134 Background: New treatment ideas are needed in small cell lung cancer (SCLC). N-cadherin which is associated with increased tumor invasiveness is a potential novel therapeutic target. It seems reasonable to test recently developed cyclic peptide N-cadherin antagonists in tumors with high N-cadherin expression, and it seemed likely that high N-cadherin expression would occur more frequently in aggressive tumors like SCLC. Our objective was to determine the frequency and biological significance of N-cadherin expression in SCLC. Methods: We retrospectively analyzed 86 patients with small cell lung cancer, most of whom received treatment: chemotherapy with or without radiation. We reviewed their clinical charts and obtained: date of diagnosis, age, gender, performance status, treatment dates and treatment response (CR/PR, stable disease, progression), and death or last encounter date. We also analyzed their pathology specimens for frequency of expression of N-cadherin and grouped them into three categories: no expression, some expression of N-cadherin &gt;1% but &lt;35%, and strong expression 36–100%. Subsequently, we determined the correlation between the N-cadherin frequency groups and the overall survival for all 86 patients. We also determined the time to progression in a subset of 56 patients (with available treatment response data). Results: Out of the 86 patients, 18 (21%) did not express N-cadherin, 10 (11.6%) patients showed &gt;1% but &lt;35% expression of N- cadherin, and 58 (67.4%) had a strong expression &gt;36%-100%. There was no association found between N-cadherin expression and overall survival using either the Log-Rank Test or the Wilcoxon Test. In the subset of 56 patients with available treatment response data there was no association between N-cadherin expression and progression free survival. Conclusions: N-cadherin was expressed relatively frequently in this group of SCLC patients, and these results suggest that phase II trials of the novel cyclic peptide N-cadherin antagonists are warranted in SCLC. N-cadherin did not appear to have prognostic value in our study. No significant financial relationships to disclose.
Efficacy and safety of gefitinib as an option in the first- or second-line treatment of Indian patients with advanced NSCLC with poor performance status.
Authors: S. M. Nag, C. Koppiker, N. Abhyankar, M. Pungliya
Journal: Journal of Clinical Oncology (2010)

e18079 Background: Gefitinib shows high rates of clinical benefit in Asian patients with advanced NSCLC due to their increased incidence of EGFR mutations. Patients with poor performance status do not have a good outcome with conventional chemotherapy and gefitinib may be a better and safer option for this subgroup. Methods: The study includes 37 patients with advanced NSCLC treated either first-line or after progression on standard chemotherapy. Only patients with adenocarcinoma histology and PS > or equal to 2 were allowed on this study. The number of patients achieving CR,PR or SD were noted as well as the median duration of response to Gefitinib therapy (months). EGFR mutations were evaluated in 12/37 patients retrospectively. Results: From Jan 2007 till date 42 patients with advanced NSCLC were treated with first-line or second-line gefitinib. Of these 37 patients were evaluable for response. 21 patients recieved first-line therapy and 16 patients recieved second line Gefitinib. 35 patients had PS > or equal to 2. 2 patients had a LVEF < or equal to 35 and were not considered fit for chemotherapy. In addition 1 patient also had decompensated liver cirrhosis at presentation. The median age was 60. There were 22 males and 15 females. 18 patients were smokers or ever smokers, 19 were nonsmokers. 20 patients used tobacco in some form. In the group with first-line Gefitinib there was 1 complete response. 9 partial responses, 8 with stable disease and 3 with progressive disease. The median duration of response was 7.5 months (4-15 months). In the group of patients recieving Gefitinib second-line there were 9 partial responses, 4 with stable disease and 3 patients had progressive disease. The median duration of response was 8 months (2-15 months). Acneform rashes were seen in 29 patients and diarrhoea in 7. There were no grade IV toxicities and no patients discontinued treatment due to side-effects. EGFR mutations were studied in 12 patients whose paraffin blocks were retrievable. This data will be presented. Conclusions: Gefitinib as first or second line treatment for Indian patients with advanced NSCLC and a poor performance status is an effective and safe treatment with durable responses. No significant financial relationships to disclose.