tbuckley/cabot-search huggingface dataset:
Efficacy of neoadjuvant docetaxel and cisplatin followed by concurrent cisplatin-radiotherapy in locally advanced nasopharyngeal carcinoma (NPC): A randomized phase II study
Authors: E. P. Hui, B. B. Ma, S. F. Leung, A. King, F. Mo, M. K. Kam, K. H. Yu, W. H. Kwan, B. C. Zee, A. T. Chan
Journal: Journal of Clinical Oncology (2007)

6037 Background: The current standard treatment for locally advanced NPC is chemoradiation (CRT) ± adjuvant chemotherapy. However, adjuvant chemotherapy is often poorly tolerated after intensive CRT. Our previous study of neoadjuvant chemotherapy followed by CRT showed encouraging toxicity profile and disease control in advanced NPC (JCO 2004: 22: 3053–60). The current study compared the safety and efficacy of neoadjuvant chemotherapy (neoadj) followed by CRT. Methods: Newly diagnosed patients (pts) with stage III to IVB NPC were randomized (stratified by stage III vs IV) to: (1) Neoadj-CRT: docetaxel 75 mg/m 2 D1, cisplatin 75 mg/m 2 D1, q3w × 2 cycles, followed by cisplatin 40 mg/m 2 weekly × 6–8 cycles concurrent with RT (= 66 Gy in 2-Gy fractions), or (2) CRT: cisplatin-RT (same as arm 1) without neoadj. The primary endpoint was toxicity. Secondary endpoints included survival and quality of life. Planned accrual was 30 pts per arm to detect a 20% difference in toxicity on one side of a 95% confidence interval (CI). Results: From 11/2002 to 11/2004, 65 pts were recruited. Five pts were excluded after randomization but before treatment started (three pts were subsequently found ineligible, and two pts withdrew consent). There was a higher rate of G3–4 neutropenia (100% vs 16%, p&lt;0.001), but not neutropenic fever (3% vs 4%) or other non-hematologic toxicity in the neoadj-CRT vs CRT arm. The proportion of pts progressing at 2-yrs by group was compared by Fisher’s Exact Test (p=0.158). At median follow-up of 2.74 yrs, there were 10 deaths and 13 progressions. The 2-yr progression free survival for neoadj-CRT vs CRT was 80% vs 71% (hazard ratio 0.42; CI 0.14− 1.27; p=0.11). The 2-yr overall survival was 93% vs 76% (hazard ratio 0.17; CI 0.037–0.82; p=0.013). Conclusions: Neoadjuvant docetaxel and cisplatin followed by CRT was well tolerated with a manageable toxicity profile and allowed subsequent delivery of full dose CRT. Preliminary result suggested improved survival. A phase 3 study to definitively test this strategy is warranted. Acknowledgement: Sanofi-Aventis Hong Kong Ltd supported this study in part. No significant financial relationships to disclose.
Phase I/II trial of docetaxel plus oxaliplatin and 5-fluorouracil (D-FOX) in patients with untreated, advanced gastric or gastroesophageal cancer
Authors: J. A. Ajani, A. Phan, L. Ho, E. D. Tetzlaff, J. Baker, Q. Wei
Journal: Journal of Clinical Oncology (2007)

4612 Background: Docetaxel combined with cisplatin/5-fluouracil resulted in significantly longer time-to-progression and survival but also 30% rate of complicated neutropenia (JCO 2006; 24:4991). To improve the safety profile of docetaxel-based therapy, we studied docetaxel with oxaliplatin/5-fluorouracil (D-FOX) to establish the first-cycle MTD (phase II trial to follow). Methods: Patients with histologic proof of gastric or gastroesophageal adenocarcinoma with untreated stage IV cancer were eligible. ECOG PS of &lt;2, near-normal organ function, and written consent were other eligibility criteria. The initial doses of oxaliplatin (85mg/m 2 ) and 5-fluorouracil (2.2g/m 2 as 48-hour infusion), given every 2 weeks, were kept constant. Docetaxel was started at 20mg/m 2 (Level 1) every 2 weeks in a typical 3x3 phase I design. Subsequent levels (+5mg/m 2 every 4 weeks) were added. Fatigue, incompletely treated nausea, and oxaliplatin/5-flurouracil-related toxicities were excluded to determine the MTD. Results: A total of 36 patients have been treated. Currently, docetaxel dose is 47.5mg/m 2 every 2 weeks (Level 11). MTD was not reached at Level 10. Overall, grade 3 or 4 first-cycle toxicities have occurred in &lt;5% of patients and without complicated neutropenia. Fifteen of 34 patients have had a confirmed partial response, 13 had stability, and 6 patients had progression. Conclusions: The MTD of D-FOX has not yet been established but its safety profile (D-FOX with 45mg/m 2 of docetaxel every 2 weeks) is excellent and the regimen is quite active against untreated gastric or gastoresophageal cancer. Translation studies and additional clinical data will be presented. Supported in part by sanofi-aventis pharma. [Table: see text]
Glycopeptidolipids for evaluating the role of non-tuberculous mycobacteria in latent tuberculosis infection diagnosis
Authors: Mar Serra, Irene Latorre, Jordi Torrelles, Maria Tsolia, Virginia Amanatidou, Neus Altet, Jéssica Díaz, Alicia Lacoma, Maria Luiza De Souza-Galvao, Juan Ruiz-Manzano, Cristina Prat, Vicenç Ausina, Jose Domínguez
Journal: European Respiratory Journal (2013)

A disagreement between TST and IGRAs was reported in non-BCG vaccinated children population. The role of non-tuberculous mycobacteria (NTM) sensitisation in latent tuberculosis infection (LTBI) diagnosis had been studied using NTM sensitins. Although in some cases a NTM sensitin positive response was observed, due to the reported cross-reaction with some Mycobacterium tuberculosis antigens, a true LTBI can not be rejected.

The aim was to study the role of NTM in LTBI diagnosis using Mycobacterium avium complex specific glycopeptidolipids (GPLs).

38 individuals were classified in five groups: study group (6 non-BCG vaccinated children with discordant results: positive TST and negative T-SPOT.TB), negative healthy individuals (8 children with a negative TST and T-SPOT.TB), 16 paediatric LTBI patients (positive both TST and T-SPOT.TB), 6 patients with M. avium complex infection microbiologically confirmed and 2 children with active TB. PBMCs were isolated from each individual and stimulated with M. avium serovar 4 GPLs. The presence of sensitised T-cells against the antigens was analysed by means of ELISPOT in house .

From study group individuals, 100% responded to the stimulation with GPLs. Any negative healthy individual showed a positive ELISPOT result after stimulation. The response to GPLs in LTBI individuals was negative in all cases. In valid cases, a positive result in response to GPLs was obtained in patients with confirmed M. avium complex infection (5/5). One of the TB patients responded when stimulated with GPLs.

The results reinforce the hypothesis that non-BCG children who respond to TST and have a negative IGRA result, could be sensitised to NTM.
Concurrent and adjuvant docetaxel with three dimensional conformal radiation therapy (3-D CRT) for poor-risk localized prostate cancer: A phase II trial
Authors: J. FERRERO, M. Bolla, P. Maingon, J. Buffet-Miny, A. Bougnoux, J. Bauer, J. Descotes, M. Conil, M. Colonna
Journal: Journal of Clinical Oncology (2007)

5003 Background: Docetaxel increases survival in hormone refractory prostate cancer. The objective of this trial is to evaluate the feasibility of concomitant weekly docetaxel with 3-D CRT and adjuvant docetaxel in unfavorable localized or locally advanced prostate carcinoma. Methods: Sixteen patients with poor risk localized carcinoma (T1c-2b N0M0) and 34 with locally advanced tumors (T3N0- 1M0) according to the 1997 UICC classification, underwent 3-D CRT (72Gy/36 fractions); docetaxel 20mg/m 2 iv was delivered concurrently on weeks 1–2-3–5-6–7; adjuvant docetaxel 60mg/m 2 q3w started 4 weeks after the completion of radiotherapy for 3 cycles. The patients had to receive LHRH agonist, 6 months to 3 years, according to the number of poor prognostic factors. Acute toxicity was assessed with the NCI CTC v:2.0. Results: From November 2003 to November 2005, 50 patients were included (438 cycles) from six institutions. Median age was 50 years (48–76), median PSA 17.7 ng/ml (3.4–260) and median follow-up 17 months (9–38). Forty six patients completed the chemoradiation regimen (423 cycles), with full dose of docetaxel, 4 patients did not, due to: 1 grade 4 GI toxicity during the cycle 3, 1 grade 3 dysuria after cycle 6, 1 grade 4 myocardial infarction after cycle 6, 1 grade 4 anal fistula between two cycles of adjuvant docetaxel; these patients were excluded. The percentage of grade 3 acute toxicity was 10.8% (5/46): 1 grade 3 neutropenia, 1 grade 3 rectal bleeding, 2 grades 3 diarrhea, 1 grade 3 dysuria. Grade 2 toxicity (nausea, diarrhea and rectitis) were observed, in a percentage of 26%; no grade 2–3 toxicity occurred as regard hypotension, venous thrombosis, peripheral neuropathy, respiratory morbidity, oedemas. Twelve months after the end of the treatment, 44 patients were in complete remission (clinical and biological) and two patients suffer from distant metastases. Conclusion: The feasibility of this combined chemo-radiation regimen deserves to be followed by a phase III trial. No significant financial relationships to disclose.
Health economic analysis of breast cancer index in patients with ER+, LN- breast cancer.
Authors: Gary Gustavsen, Brock Schroeder, Patrick Kennedy, Kristin Ciriello Pothier, Catherine A. Schnabel, Mark G. Erlander
Journal: Journal of Clinical Oncology (2013)

e11504 Background: Numerous studies have demonstrated the cost utility of gene expression-based assessment of recurrence risk in breast cancer. Cost savings rely primarily on decreased use of adjuvant chemotherapy in patients predicted to be low-risk. Breast Cancer Index (BCI) is a gene expression-based test that significantly predicts overall risk of recurrence, late (≥5y) recurrence and likelihood of benefit from extended (≥5y) endocrine therapy in patients with ER+, LN- breast cancer. This study evaluated the potential cost utility of BCI from a US third-party payer perspective. Methods: A fact-based economic model was developed which projected the cost and effectiveness of BCI in a hypothetical population of patients with ER+, LN- breast cancer compared to standard clinicopathologic diagnostic modalities. Patients flowed through the model based on patterns of care and BCI data. Costs associated with adjuvant chemotherapy, toxicity, follow-up, endocrine therapy, and recurrence were modeled over 10 yrs. Model inputs were based primarily on published literature, and supplemented by interviews with disease experts and payers. Sensitivity analyses were performed around key inputs to estimate effects on the model. Results: Use of BCI is projected to be cost saving in this patient population, with a net cost savings of $4,005 per patient tested after accounting for BCI cost. Gross cost savings were projected to be achieved through targeted use of adjuvant chemotherapy ($5,785), reduced recurrence in patients receiving extended endocrine therapy based on BCI ($2,350), and reduced recurrence in previously non-compliant patients ($370). Sensitivity analyses demonstrated that results were most sensitive to chemotherapy utilization in low- and intermediate-risk patients, cost of adjuvant chemotherapy, cost of recurrence, and percentage of patients classified as low risk. Conclusions: BCI is projected to be cost saving in an ER+, LN-, breast cancer patient population. Cost savings are achieved through projected impact on adjuvant chemotherapy use, extended endocrine therapy use, and endocrine therapy compliance. These findings require validation in additional cohorts, including studies of real-world clinical practice.
Malignant salivary gland tumors: A large single-institutional series evaluating long-term outcome
Authors: S. Limaye, R. Dulala, R. Roy, A. Thomas, D. Janson, J. Fantasia, B. Mehrotra
Journal: Journal of Clinical Oncology (2007)

16523 Background: Malignant salivary gland tumors comprise 3 to 6% of Head and Neck cancers. Long term survival data for salivary gland tumors are lacking. We undertook an analysis of all such patients treated at our institution over a 15 yr period. Methods: IRB approval was obtained for this retrospective analysis. Tumor registry data were reviewed for all adult patients diagnosed with salivary gland malignancies for the years 1990 - 2005. Age, Gender, Stage, histology, treatment modalities and survival data were recorded. Results: 200 patients were identified. Median age was 64 yrs (59–69). M:F ratio was 1:1.1 (M: 96; F: 104). Histology and stages: ( Table 1 )Mucoepidermoid Carcinoma (n=50), Adenoid Cystic Carcinoma (n=21), Acinar Cell Carcinoma (n=19), Adenocarcinoma (n=22; Stages: I= 7, II= 4, III= 3, IV= 8), Squamous (n= 12; Stages: I= 1, II= 3, III= 3, IV=5), Poorly Differentiated Carcinoma(n=10), Epithelial Myoepithelial Carcinoma (n=7), Malignant Mixed Carcinoma (n=4), Malignant Myoepithelioma (n=2), Carcinoma in Pleomorphic Adenoma (n=2) and Others (n=15). Hodgkin's and NHL (n=36).Treatment modalities: Surgery (S): n=88 (44%), Radiotherapy (RT): n=6 (3%); Chemotherapy (CT): n=6 (3%); S+RT: n =76(38%); S+CT: n=8 (4%); RT+CT: n =2(1%); S+RT+CT: n =4 (2%). Observation only : n=10(5%). Survival data (Med. survival and 5 yr OS respectively) for all histologies excluding lymphomas are: Stage I - 84 mos,93%; II - 93 mos,85%; III - 39 mos,60 %; IV - 24 mos, 40%. Survival data (Med survival and 5 yr OS) for lymphomas: Stage I - 55 mos,85%; II - 20 mos, 0%; III - 100 mos, 100%; IV- 48 mos, 25%. Median survival of all histology types excluding lymphoma by treatment: S=55 mos, S+RT= 60 mos, S+ CT= 56 mos, RT= 53 mos, RT+CT=15 mos, CT= 24 mos. Conclusions: This large series provides long term outcome data for a relatively rare group of HNCs. Long term survival is noted in several histological sub-types even in the setting of advanced disease. These data should help further define the natural history and biological behaviors of these tumors. [Table: see text] No significant financial relationships to disclose.
In vitro evaluation of the effectiveness of a novel closed suctioning system in biofilm removal from the endotracheal tubes
Authors: Elad Lancau, Nimrod Adi, Michal Pfeffer, Roni Shapira
Journal: European Respiratory Journal (2014)

Introduction 

Biofilm formation in endotracheal tube (ETT) is the major cause of ventilator-associated pneumonia (VAP) in intensive care unit (ICU) patients. Biovo Technologies (Tel Aviv, Israel) developed a novel device (AirwayMedix Closed Suction System).

Objectives 

1. Develop a reproducible system of in vitro biofilm formation and evaluation in ETT by P. aeruginosa 2. Compare the amount of biofilm removal after cleaning with AirwayMedix versus the KIMVENT* device.

Methods 

Over night cultures of P. aeruginosa PAO1were diluted to 1x107 CfU's/mL in Luria broth medium (LB) in 8 mm diameter closed ETT and incubated horizontally at 37 for 24 h. Planktonic bacteria were removed by washing with three volumes of the ETT tubes and were divided into three groups: biofilm removal with AirwayMedix, KIMVENT* (Kimberly Clark, USA) or control. Quantification of attached bacteria was performed on 4 cm segments from the middle part of the ETT.

Results 

The conditions of in vitro biofilm formation by P. aeruginosa in ETT and its evaluation were achieved. Enumeration of the attached bacteria: control=1X107 CFU/cm2, KIMVENT=4.86x106 CFU/cm2 (p= 0.01), AirwayMedix 1.1X104 CFU/cm2 (p=0.01).

Conclusions 

The AirwayMedix system proved to be superior to the KIMVENT system in its ability to remove bacterial biofilms from ETT.
Severity of obstructive sleep apnea dependent upon aldosterone status in subjects with resistant hypertension
Authors: C. C. Gonzaga, K. K. Gaddam, E. Pimenta, D. A. Calhoun
Journal: Circulation (2008)

Background: Obstructive sleep apnea (OSA) and hyperaldosteronism are common in subjects with resistant hypertension. Prior results from our laboratory relate severity of OSA to aldosterone levels in patients with resistant hypertension suggesting that the 2 disease entities may be mechanistically linked. Objective: This study prospectively evaluated the relation between OSA severity and aldosterone status in subjects with resistant hypertension. Methods: One hundred nine consecutive subjects (age 55.9±9.3 years; 50% male) with resistant hypertension referred to a university clinic for resistant hypertension were prospectively evaluated with plasma renin activity (PRA), plasma aldosterone concentration, and 24-hr urinary aldosterone excretion. Hyperaldosteronism was defined as a PRA <1.0 ng/mL/hr and 24-h urinary aldosterone excretion ≥ 12 µg/24-hr. Remaining patients were considered as having normal-aldosterone status. All subjects were evaluated by full-night attended diagnostic polysomnography. OSA was defined as an apnea-hypopnea index (AHI) ≥ 5 events/hr. Results: Hyperaldosteronism was present in 28% of subjects. Overall, OSA was diagnosed in 77% of subjects; 81% of the high-aldosterone and 74% of the normal-aldosterone subjects. In subjects with hyperaldosteronism, plasma aldosterone and urinary aldosterone excretion correlated with AHI (r = 0.723, p <0.001 and r = 0.639, p <0.001, respectively) but not in the normal-aldosterone subjects (r = 0.008, p = 0.94 and r = 0.042, p = 0.71 respectively). Atrial natriuretic peptide (ANP) levels were significantly higher in the high-aldosterone compared to normal-aldosterone subjects (89±57 vs. 67±102 pg/ml; p = 0.03). Conclusion: OSA is extraordinarily common in patients with resistant hypertension. A significant correlation between both plasma and urinary aldosterone levels and severity of OSA is observed in high-aldosterone but not normal-aldosterone subjects. The higher level of ANP in high-compared to normal-aldosterone subjects suggests greater intravascular fluid retention in the former subjects. These results suggest worsening of OSA in patients with hyperaldosteronism secondary to chronic aldosterone-induced intravascular fluid retention.
Seriously depressed preschoolers
Authors: J H Kashani, G A Carlson
Journal: American Journal of Psychiatry (1987)

In a prospective and comprehensive evaluation (including DSM-III diagnoses) of 1,000 preschoolers in a child development unit, nine children were found to meet the criteria for major depressive disorder. The symptoms of these children are described and compared with those of a control group of children from the same sample. The diagnosis of major depressive disorder was associated with physical symptoms, including somatic complaints, and the likelihood of parental abuse or neglect.
Evaluation of quality of life (QoL) in patients (pts) with metastatic colorectal cancer (MCRC) treated with capecitabine (X)
Authors: J. Segalla, B. van Eyll, M. Federico, M. Perdicaris, S. Cabral, N. Skare, E. Saltz, G. Moura, U. Filho, F. Franke
Journal: Journal of Clinical Oncology (2005)

8090 Background: The oral fluoropyrimidine X has superior efficacy and improved safety compared with 5-FU/LV in MCRC and early-stage colon cancer. Consequently, X is replacing 5-FU/LV as the backbone of MCRC therapy and is now moving into the adjuvant setting. The QoL benefits of oral agents like X over traditional i.v. drugs are becoming increasingly important in MCRC alongside well-established measures of treatment response. Methods: Pts with MCRC who received standard oral X (1250 mg/m2 twice daily on days 1–14, every 3 weeks) completed EORTC QLQ C-30 (v3.0) and CR-38 questionnaires at baseline, before cycle 1, at weeks 7 and 13, and at the end of treatment. The proportion of pts with improvement, stabilization or worsening of QoL scores from week 7 was analyzed using linear models with repeated measures (generalized estimating questions technique) and SAS (v8.2). Results: Here we report QoL findings in 693 pts (M/F, 50%/50%); median age 59 years (20–89); median ECOG PS 1 (0–3); majority Caucasian (85%). Almost half of the pts completed the QoL questionnaires through to the end of treatment. At least 60% of pts experienced improved or maintained QoL for most domains. Overall global health status score was improved or maintained in 39% and 30% of female pts, respectively. Female pts also had significant improvements in emotional functioning (p<0.0001), pain (p=0.0024), future perspective (p<0.0001), defecation problems (p=0.0296), and weight loss (p<0.0001). In male pts, X led to significant improvements in global health status (p=0.0005), constipation (p=0.0009), future perspective (p=0.0002), sexual functioning (p=0.0269), and weight loss (p<0.0001). Conclusion: Treatment with X led to improvements or maintenance of QoL in most pts. These data support its increasing use in the first-line and adjuvant settings. The efficacy, safety and convenience benefits of X as reported previously allow pts with MCRC to maintain a normal lifestyle and have a direct impact on QoL. No significant financial relationships to disclose.
Phase II study of neoadjuvant chemotherapy with gemcitabine and vinorelbine in resectable non-small-cell lung cancer (NSCLC)
Authors: N. Ramnath, E. Sommers, L. Robinson, C. Nwogu, D. Tan, A. Sharma, A. Cantor, D. Lawrence, G. Simon, G. Bepler
Journal: Journal of Clinical Oncology (2005)

7277 Objective: We assessed the efficacy of a non-platinum doublet chemotherapy of gemcitabine and vinorelbine as induction therapy in surgically resectable pathological stage IB-IIIA and selected IIIB NSCLC. The primary endpoint was radiographic response rate (RR). The secondary endpoints were pathological RR, treatment-related toxicity, surgical resectability, overall and disease- free survival (OS, DFS). Methods: All patients were staged with computed tomography of chest and abdomen, FDG positron emission tomography and mediastinoscopy. Gemcitabine (1,000 mg/m2) and vinorelbine (25 mg/m2) were administered on days 1, 8, 22, and 29. Imaging studies were repeated between days 43–50. Disease response was assessed by RECIST criteria; patients without progressive disease were offered surgery between days 50–70. Patients were followed every 3 months for 2 years after resection. Results: There were 62 patients, median age of 67 (range 32–82 years). Forty-five were men, 17 women. Twenty-seven patients had pathologic stage IB, 15 stage II and 20 stage III. After induction chemotherapy 21/61 (34%) had objective clinical response, 1/61 (3%) had complete pathological response, 56/62 (90%) underwent thoracotomy, and 48/62 (77%) had a complete resection. There were 4 postoperative deaths. Chemotherapy toxicities were moderate with no mortality. The 1 and 2-year OS rates were 78% (95% CI, 67–89%) and 68% (95% CI, 54–82%), and the median OS was 38.2 months. Conclusions: Induction chemotherapy with gemcitabine and vinorelbine had lower radiographic and pathologic RR compared with platinum doublets. However, 1, 2-year and median survival times are comparable to those obtained with platinum doublets. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly, Glaxo