bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical significance of pleural lavage cytology in non-small cell lung cancer: A meta-analysis
Authors: Jiao X. , Langenberg P. , Zhan M. , Perencevich E. , Ioffe O. , Yuan Y. , Maruyama R. , Krasna M. J. 
Published: March 2020

18031 Background: The clinical significance of pleural lavage cytology (PLC) in non-small-cell lung cancer (NSCLC) remains controversial. This study was performed to estimate the associations of positive PLC with the main clinicopathological characteristics, and its prognostic value. Methods: PLC studies were identified on Medline, supplemented by manual search of bibliographies and proceedings. Authors were contacted for updated information. The quality of the studies was evaluated, and the data were extracted. Pooled odds ratios (ORs) and pooled hazard ratios (HRs) with confidence intervals [95% CIs] were calculated to evaluate the association of positive PLC with clinico-pathological characteristics and survival respectively. Results: Nineteen articles assessing PLC in NSCLC were selected for this study after exclusion of repeated publications or reports with little clinical detail. Positive PLC was diagnosed in 10.2% (516) of a total of 5073 patients. Positive PLC was strongly associated with lymphatic permeation (OR 4.96 [3.29, 7.54]), pleural invasion (OR 4.38 [2.16, 8.89], and vascular involvement (OR 2.94 [1.99, 4.35]). It was also found to be associated with advanced T stage, N stage, and TNM stage. Positive PLC was more frequent in adenocarcinoma than in squamous cell carcinoma (OR 2.32, [1.51, 3.52]). It was relatively more common in moderately- and poorly-differentiated tumors than in well-differentiated tumors (OR 1.89 [0.86, 4.16]). No association was found between positive PLC and fine needle aspiration cytology (OR 1.04 [0.58, 1.81]). Positive PLC was associated with high overall recurrence (OR 2.51 [1.79, 3.53]), as well as high local recurrence (OR 3.85 [1.57, 9.44]) and distant recurrence (2.58 [1.76, 3.76]). In analysis of survival, the overall HR for mortality was 2.43 [1.87, 3.16], suggesting significantly poorer survival for patients with positive PLC. Conclusions: Positive PLC in NSCLC is strongly associated with several existing poor prognosticators including pleural invasion, lymphatic spread, and vascular involvement. It may indicate locally advanced disease with high risk of recurrence and poor survival. We recommend that the PLC test be included in future clinical trials of adjuvant therapy for patients with NSCLC. No significant financial relationships to disclose.
Safety study of induction chemotherapy and synchronous radiotherapy (RT) and cetuximab in stage III non-small cell lung cancer (NSCLC): SCRATCH (Cohort I)
Authors: Hughes S. R. , Liong J. L. , Miah A. , Ahmad S. , Leslie M. , Ross P. , Harper P. , Prendiville J. , Rankin S. , Landau D. 
Published: March 2020

18032 Background: The addition of cetuximab can increase the efficacy of chemotherapy for advanced NSCLC. Concomitant cetuximab and RT is superior to RT alone for locally advanced squamous cell head & neck carcinoma. The SCRATCH study (cohort I) is a phase I study to assess the safety of synchronous cetuximab and radical RT in patients with Stage III NSCLC. Methods: Cohort I will contain 12 patients with inoperable stage III NSCLC. Inclusion criteria are performance status 0–1, adequate organ function, and disease encompassable within a radical RT volume. Exclusion criteria are previous malignancy, thoracic RT or treatment with EGFR targeted therapy. Patients receive platinum-based induction chemotherapy, followed by weekly intravenous cetuximab (initial dose 400mg/m2; maintenance dose 250mg/m2) and concomitant RT (64Gy/32fractions/45days). The primary end-point is toxicity. NCI Common Toxicity Criteria (CTC) V3.0 assessments are performed weekly during radiotherapy, and at regular follow-up visits. Results: Data from the first 9 patients is available. 2 patients stopped receiving cetuximab early due to toxicity. 1 experienced grade 3 fatigue following the initial dose, and the other declined further treatment after developing grade 2 skin toxicity. 2 patients have died, 1 from disease progression and 1 from thromboembolic disease. Both deaths occurred between months 2 and 4 post RT and were not attributed to the cetuximab therapy. Of the 7 living patients, 2 have survived 1 year (measured from the first day of induction chemotherapy). The maximum NCI CTC V3.0 scores are summarised in the table below. Conclusions: The results suggest that the early and late toxicities of synchronous cetuximab and radical RT are acceptable. Data on all 12 patients will be available by June 2007. SCRATCH Study cohorts II-IV follow on and will recruit sequentially. They will assess the safety of adding concomitant cisplatin (±vinorelbine) to cetuximab and radical RT. [Table: see text] No significant financial relationships to disclose.
A phase II study of vorinostat (NSC 701852 ) in patients (pts) with relapsed non-small cell lung cancer (NSCLC)
Authors: Traynor A. M. , Dubey S. , Eickhoff J. , Kolesar J. M. , Marcotte S. M. , Hammes L. C. , Hallahan C. M. , Moore C. E. , Zwiebel J. , Schiller J. H. 
Published: March 2020

18044 Background: Vorinostat is a small molecule inhibitor of histone deacetylase (HDAC). HDAC inhibitors have shown preclinical activity in lung cancer and are postulated to have an antitumor effect by alteration in acetylation status of histone and non-histone proteins. Methods: Pts with relapsed NSCLC who failed no more than 1 prior cytotoxic therapy were eligible. Treatment: vorinostat, 400 mg po daily in a 21 day cycle. Primary objective: response rate (RR), with goal of at least one responder in first 14 evaluable pts. Secondary objectives: time to progression (TTP), overall survival (OS), safety, and correlative assays. Results: 14 pts enrolled from 12/05- 12/06. Median age 59.5 yrs (range 47–79). 11 females. PS 0:1, 10 pts:4 pts. Thirteen of 14 pts had only 1 prior cytotoxic regimen; 1 pt had only prior erlotinib. Best response to prior treatment: stable disease (SD; 11 pts), progressive disease (PD; 3 pts). Median time since last prior therapy: 2.1 mo (range 0.2–78.5). Vorinostat treatment compliance: 95.8 %. Two pts were not evaluable for response due to not completing Cycle 1 of treatment due to PD. No objective antitumor responses have been seen in the first 12 evaluable pts. Seven pts experienced SD (median 4.2 mo, range 2–10.7). Median TTP: 2.8 mo (range 1–10.7+); median OS 6.5 mo (range 1.4–10.7+); estimated 6 mo OS rate 50% (SE 16%). Grade (Gr) 5 toxicity: CVA (1 pt). Gr 3/4 toxicities: neutropenia (Gr 4–1 pt), lymphopenia (Gr 3–2 pts), fatigue (Gr 3–1 pt), elevated alk phos (Gr 3–1 pt), memory impairment (Gr 3–1 pt), PE/DVT (Gr 3–1 pt; Gr 4–2 pts), dehydration (Gr 3–1 pt). Data from the following correlative studies will be updated: p53 status, gene expression, H3 acetylation, transcription of p21, Nur77, Hsp70, erbB1 and 2, and Akt, cell cycle arrest, and assay of isoprostanes generated by treatment with vorinostat. Conclusions: Vorinostat 400 mg daily is tolerable with more than 80% of patients completing Cycle 1. Vorinostat yields TTP in relapsed NSCLC similar to that of other targeted agents. Although 4 of 14 pts experienced vascular events on treatment, these occurrences are common in this disease setting. At least two additional pts are still to be accrued. Further studies in NSCLC should focus on combining vorinostat with other antitumor agents. No significant financial relationships to disclose.
Carboplatin (Cb) clearance (Cl) in elderly and young patients with advanced non-small cell lung cancer (ANSCLC): An exploratory analysis of the Calvert’s formula
Authors: Merino M. , Maestu I. , Tallón M. , Almenar D. , Casabó V. G. , Muñoz J. , Jiménez N. V. 
Published: March 2020

18047 Background: It seems that elderly lung cancer patients (p) respond better to combination chemotherapy than to single-agent therapy. Application of pharmacokinetic (pk) modelling to the routine therapeutic drug monitoring in elderly p help to individualize the dosage of anticancer drugs. The aim of this study was to explore the Calvert′s formula usefulness for calculating the Cb dose in elderly p by means of the predicted AUC/actual AUC ratio. Creatinine (Cr) Cl was calculated by Cockdroft-Gault equation. Methods: Between December 2005 and September 2006, 20 chemonaive ANSCLC p were included in two groups: 10 adults p ≤ 65 years and 10 aged p ≥ 75 years. Treatment consisted in Cb day 1 and gemcitabine 1250 mg/m2 days 1 and 8 every 21 days. Cb dose was calculated for a foreseen AUC = 5 in young adults and AUC = 4 in aged p. Three blood samples were collected at 1–2 hours(h), 3–5 h, 12–24 h postinfusion. Total and ultrafiltrated Cb was determined using a flameless atomic absortion spectrometer. For pk analysis non lineal effects models implemented in NONMEM program were used. Individual pk parameters were calculated and predictors in the structural model were analized. Results: Table 1 shows mean and variation coefficient of some biometric characteristics. Pk parameters analysis: ClAUC5 p = 137 mL/min; Clfactor (parameter for measuring Cl changes according to age) = 0.44; Cl AUC4 p = 59.7 mL/min. Cb Cl in elderly p was 43.55% with respect to younger p. In younger p estimated Cb Cl was 5.69% higher than Cb Cl calculated using the Calvert equation. In elderly p, the opposite effect was achieved, estimated Cb Cl was 26.85% lower than Cb Cl calculated Conclusions: The Cb Cl calculation by means of Calvert formula showed underestimation of the dose in younger p and upperestimation of the dose in elderly p. It is necessary to investigate the covariates which contribute to take away the strength of the Calvert equation, which could to affect the efficacy and toxicity of Cb. [Table: see text] No significant financial relationships to disclose.
Mutational analysis of EGFR and KIT in thymic epithelial tumor
Authors: Yoh K. , Nishiwaki Y. , Ishii G. , Goto K. , Kubota K. , Ohmatsu H. , Niho S. , Nagai K. , Ochiai A. , Saijo N. 
Published: March 2020

18049 Background: Thymic epithelial tumor has been reported to express the epidermal growth factor receptor (EGFR), and thymic carcinoma has recently been described to have overexpression of KIT. We investigated the prevalence of EGFR and KIT mutations in patients with thymoma and thymic carcinoma to explore the potential for a targeted therapy with tyrosine kinase inhibitors. Methods: Genomic DNA was isolated from 41 paraffin-embedded tumor samples including 24 thymoma and 17 thymic carcinoma. EGFR mutations in exons 18, 19 and 21, and KIT mutations in exons 9, 11, 13 and 17, were analyzed by PCR and direct sequencing. Protein expressions of EGFR and KIT were also evaluated by immunohistochemistry. Results: We detected the EGFR mutation in 2 of 20 thymoma, but none of thymic carcinoma had mutation. All of the detected EGFR mutations were missense mutations in exon 21 (L858R and G863D, respectively). Expression of EGFR was seen in 71% of thymoma and 53% of thymic carcinoma. On mutational analysis of KIT, only one thymic carcinoma displayed a missense mutation in exon 11 (L576P). Expression of KIT was observed in 88% of thymic carcinoma and 0% of thymoma. Conclusions: Our findings indicate that a small number of patients with thymic epithelial tumor exhibit somatic mutations of EGFR or KIT although expressions of EGFR or KIT are present frequently in thymic epithelial tumor. Further investigations are warranted to determine their susceptibility to tyrosine kinase inhibitors in the treatment of thymoma and thymic carcinoma with EGFR or KIT mutations. No significant financial relationships to disclose.
A systems pathology model for predicting overall survival in patients with refractory, advanced non-small cell lung cancer (NSCLC) treated with gefitinib
Authors: Donovan M. J. , Kotsianti A. , Bayer-Zubek V. , Verbel D. , Clayton M. , Hamann S. , Capodieci P. , Pang H. , Cordon- Cardo C. , Parums D. , Holloway B. 
Published: March 2020

18065 Background: The abundant expression of the epidermal growth factor receptor (EGFR) in a variety of solid tumors including non-small cell lung cancer (NSCLC), head and neck, breast, colon and brain has made it an attractive target for various selective molecular therapeutics, including the tyrosine kinase inhibitor gefitinib. The recent evidence of activating mutations in EGFR combined with clinical - demographic features has suggested that subgroups of patients with NSCLC are most likely to respond to selective therapies. We sought to determine whether the integration of clinical variables, tumor morphometry and quantitative protein profiles using support vector machines could identify a set of features which predicts overall survival in patients with NSCLC treated with gefitinib. Methods: We analyzed tumor samples from 109 patients with advanced refractory NSCLC treated with gefitinib. Formalin fixed, paraffin embedded tissue samples were evaluated with the following assays: Hematoxylin and Eosin image morphometry, EGFR DNA mutation analysis, EGFR protein immunohistochemistry and quantitative immunofluorescence with the following antibodies: CK18, Ki67, Caspase 3 activated, cd34, EGFR, phosphorylated-EGFR, phosphorylated-ERK, phosphorylated-AKT, PTEN, Cyclin D1, phosphorylated-m-TOR, PI3-K, VEGF, KDR (VEGFR2) and phosphorylated KDR. A predictive model was developed using support vector regression for censored data. Results: 4 of 87 patients had tyrosine kinase domain mutations in exons 19, 20 or 21. Utilizing 51 patients with complete data profiles (i.e. clinical, image morphometry and immunofluorescence), a model predicting overall survival was developed with a concordance index of 0.74. Poor performance status, poorly differentiated histology by morphometry and increased levels of activated caspase 3, phosphorylated KDR (VEGFR2) and cyclin D1 were associated with reduced survival. Conclusion: The integration of clinical, imaging and biomarker data identified a set of features which were associated with a more aggressive disease phenotype and resulted in overall poor survival. [Table: see text]
Phase II study of oral fluoropyrimidine (UFT) plus vinorelbine in the elderly (age > 70) with advanced non-small cell lung cancer
Authors: Suyama H. , Shigeoka Y. , Igishi T. , Matsumoto S. , Yasuda K. , Sugitani A. , Katayama S. , Yamamoto M. , Hitsuda Y. , Shimizu E. 
Published: March 2020

18075 Background: Many pts with non-small cell lung cancer (NSCLC) are in elderly population. There are few pts who can receive standard treatment with platinum-based chemotherapy because of their poor organ functions. Thus, the development of a low-toxic and highly- effective regimen is needed for these populations. We have reported schedule-dependent synergism of vinorelbine and 5-FU against NSCLC cell lines. Furthermore, we have already conducted phase I study using vinorelbine and UFT, and have decided the recommended dose of this regimen. Methods: The objective of this prospective phase II study was to assess the efficacy and toxicity of this regimen in the elderly. Chemonaive NSCLC stage IIIB or IV pts, aged 70 or more, with performance status 0/1 were enrolled in this study. The pts received a treatment consisting of 20mg/m2 of vinorelbine on days 1 and 8, followed by 600mg of UFT orally on days 2–6 and 9–13 every 3 weeks for more than 4 cycles. Results: Until April 24, 2006, of 30 pts enrolled in this study, 29 pts were evaluable. Median age was 78 (range 71–86) and median cycles of chemotherapy were 4 (1–32). Objective response rate was 27% (95% CI; 10–44%), median time to progression was 150 days (15–470) and median over all survival time was 270 days (77–892). Treatment-related toxicity were neutropenia G3 33%, G4 7%; febrile neutropenia G3 4%; pneumonia G3 10%. Conclusions: This data points out vinorelbine and UFT as an active and tolerable regimen in the elderly with advanced NSCLC. No significant financial relationships to disclose.
Dendritic cells loaded with XAGE-1b protein induce specific antitumor response against lung cancer
Authors: Zhou Q. , Wu Y. L. , Guo A. L. , Wang K. , Xu C. R. , Wang Z. , An S. J. , Yang S. Q. 
Published: March 2020

18080 Background: Dendritic cells (DCs) are the most potent antigen-presenting cells for initiating cellular immune response. Cancer-testis antigens (CTA) are the biggest tumor antigens family expressing only in some tumors and genital system but not in normal cells. XAGE-1b gene is one of CTA which highly expresses in lung cancer and has strong immunogenicity. Our study was to examine whether DCs loaded with XAGE-1b protein could induce specific antitumor response against lung cancer cells in vitro. Methods: Tumor tissues and normal lung tissues were obtained by operation from 30 non-small cell lung cancer patients. Cancer cells and normal lung epithelium cells were cultured and saved as target cells. Total RNA were isolated and RT-PCR was done to determine XAGE-1b gene expression. XAGE-1b gene was cloned by constructing expression vector and recombinant protein was expressed and purified by using BL21 (DE3) E. coli and AKTA-FPLC. Peripheral blood monocytes were isolated from 20ml blood and cultured to be DCs in serum-free DCs Medium. DCs were loaded with XAGE-1b protein through coculture and induced T lymphocytes into XAGE-1b-specific cytotoxic T lymphocytes (CTLs). The cytotoxicity of CTLs was then measured by cytotoxic assay. Results: 12/30(40%) lung cancer tissues expressed XAGE-1b gene, most of which were adenocarcinoma (11/12, 91.7%). None of normal tissues expressed it. Gene sequencing and western blot confirmed the expression vector construction and recombinant protein expression. Immunofluorescence identification showed the accumulation of XAGE-1b protein in immature DCs. T lymphocytes were stimulated twice with XAGE-1b protein-loaded DCs. Cytotoxic assay showed that the CTL cytotoxicity was much stronger for XAGE-1b positive tumor cells than for XAGE-1b negative tumor cells and it was almost none for normal lung epithelium cells. Conclusions: Our study indicates that DCs loaded with XAGE-1b protein could induce specific antitumor effect against lung cancer cells in vitro and this model offers a new approach to the immunotherapy for lung cancer. No significant financial relationships to disclose.
RNAi-based adjuvant therapy in a NSCLC mouse model prevents the development of distant metastasis
Authors: Müller-Tidow C. , Bulk E. , Hascher A. , Sargin B. , Vormoor J. , Hotfilder M. , Berdel W. E. , Serve H. 
Published: March 2020

18089 Background: Surgery cures about 50% of the patients with early stage NSCLC. Although adjuvant chemotherapy improves outcome, a considerably fraction of patients still dies due to development of distant metastasis. Microarray analyses revealed that S100P expression is a strong adverse prognostic factor in early stage NSCLC. Methods: In a mouse NOD/SCID metastasis model based on subcutaneous xenotransplants of NSCLC cell lines we analyzed the effects of S100P expression on metastasis development after curative resection of the primary tumor. Tumors were resected 3–4 weeks after inoculation into the left flank after tumors reached a specified size. Adjuvant RNAi (shRNA based) therapy against S100P was i.v.-administered on the 5 days surrounding tumor resection. Results: S100P overexpression in HTB56 lung cancer cells led to more rapid tumor growth as xenografts. After tumor resection, metastasis developed in 14% (2/12) of the control mice but in 67% (8/12) of the S100P expressing tumors p<0.05. shRNA plasmids were developed and confirmed to be active in downregulating S100P. When these plasmids were i.v.-injected before resection, a significant decrease in S100P protein expression occurred. Control plasmid did not have any effect. The size of S100P-shRNA treated tumors decreased after 2 i.v.-applications. Metastasis developed in 69% (11/16) of the mice treated with the control plasmid. In S100P-shRNA treated mice only 28% (5/18) developed metastasis (p<0.05). After i.v.-injection of NSCLC cells with endogenous S100P expression, all mice (100% - 10/10) developed metastasis when adjuvant treatment was administered with control shRNA. However, when the mice were treated with S100P-shRNA in the first week after i.v.-injection of the tumor cells 33% of the mice (3/9) did not develop lung metastasis. Conclusion: Expression of S100P is a negative adverse prognostic marker in early stage NSCLC. S100P enhances metastasis formation in a mouse metastasis model. Adjuvant therapy with shRNA against S100P is feasible and effective in at least two murine NSCLC metastasis models. These findings suggest that S100P is a potentially important target to inhibit NSCLC metastasis and RNAi based therapy approaches might offer novel ways for targeted therapy in adjuvant situations. No significant financial relationships to disclose.
A phase II study of XL999 in patients (pts) with NSCLC
Authors: March R. J. , Mirtsching B. , Modi S. , Wertheim M. 
Published: March 2020

18112 Background: XL999 is a potent spectrum-selective inhibitor of receptor tyrosine kinases including VEGFR2/KDR, FGFR1/3, PDGFR-β, FLT3, RET, KIT, & SRC. A Ph 1 clinical study in pts w/advanced malignancies evaluating weight-based (0.2 - 6.4 mg/kg) & fixed dose (200 mg & 160 mg) XL999 administered by 4hr IV infusion on a wkly or every other wk schedule has shown preliminary evidence of anti- tumor activity (3 PRs & 10 pts w/SD lasting 3–26+ months). The safety profile was characterized by hypertension & cardiovascular changes including EKG, LVEF decrease &/or cardiac enzyme elevation following 1st dose administration. DLTs were cardiac failure & transaminase elevation. A dose of 2.4 mg/kg/wk was selected for phase II evaluation. Methods: The 1 objectives of this phase II study are to determine the RR & to further evaluate the safety & tolerability of XL999. Adult pts w/NSCLC (stage IIIB with malignant effusion, stage IV, or recurrent) & previously treated with no more than 2 prior systemic cytotoxic chemotherapy regimens, including a platinum-or taxane-containing regimen, & no more than one prior target agent targeting VEGF or EGFR, are eligible. Additional inclusion criteria include ECOG PS 0–1 & absence of known brain metastases. Pts with LVEF<50% or below lower limits of normal or with significant cardiovascular abnormalities are excluded. Tumor response is assessed every 8 wks by RECIST criteria. XL999 is administered wkly at 2.4 mg/kg as a 4hr IV infusion. Results: Nine pts received XL999. Three pts remain on study drug. One pt has a confirmed PR with complete resolution of a 2cm lung nodule. Another has a total reduction of 23% in multiple hepatic lesions (by RECIST). A third pt continues with SD for 3.5 months. Six pts with PD are discontinued. AEs reported in at least 2 pts were grade 1 diarrhea, fatigue, anorexia, & dizziness. Grade 3 AEs included 1 report each of N/V. No Grade 4 or 5 AEs or serious cardiac AEs have been reported. Conclusions: Wkly IV dose at 2.4 mg/kg appears generally well-tolerated & shows preliminary evidence of anti-tumor activity in advanced NSCLC pts refractory to multiple prior anti-cancer therapies. No significant financial relationships to disclose.