bluuebunny/crossref_metadata_2025_split huggingface dataset:
The relationship between RASSF1A aberrant methylation and survival in small sized lung adenocarcinoma
Authors: Miyajima K. , Ohira T. , Usuda J. , Saji H. , Tsuboi M. , Hirano T. , Kato H. , Suzuki M. , Toyooka S. , Gazdar A. F. 
Published: March 2020

7199 Background: Aberrant methylation of CpG islands in promoter regions of tumor cells is one of the major mechanisms for silencing of tumor suppressor genes. The RAS association domain family 1A (RASSF1A) gene was isolated from the 3p21.3 region homozygously deleted in lung cancer cell lines, and it was shown to be inactivated by hypermethylation of the promoter region in lung cancers. In this study, we investigated the clinicopathological significances of RASSF1A methylation in the development and/or progression of small-sized (less than 2.0cm) lung adenocarcinoma. It is important to identify a marker for high-risk early stage patients who should benefit from new investigational adjuvant therapies. Methods: Surgically resected specimens from 77 cases of small-sized primary lung adenocarcinoma. We determined the frequency of aberrant promoter methylation of the RASSF1A genes in small-sized adenocarcinoma. Aberrant promoter methylation was examined using methylation-specific PCR (MSP). Results: Twenty-five of 77 (32.5%) tumors showed RASSF1A methylation. RASSF1A methylation was dominantly detected in smoker (P < 0.03). There was no significant correlation of RASSF1A methylation with gender, age, T stage, N stage and pathological stage. RASSF1A methylation correlated with adverse survival by univariate analysis (P < 0.005) as well as multivariate analysis (P = 0.0062; RR 4.251; 95% C.I., 1.507–11.993). Furthermore, RASSF1A promoter hypermethylation in resected stage I small-sized lung adenocarcinoma was associated with impaired patient survival (P < 0.01). Conclusions: Aberrant promoter methylation of the RASSF1A was present in 25 of 77 (32.5%) of small-sized lung adenocarcinoma by MSP assay. These results indicated that epigenetic inactivation of RASSF1A plays an important role in the progression of small-sized lung adenocarcinoma, and that RASSF1A hypermethylation appears to be a useful molecular marker for the prognosis of patients with small-sized and stage I lung adenocarcinoma. RASSF1A is a potential tumor suppressor gene that undergoes epigenetic inactivation in lung adenocarcinoma through hypermethylation of its promoter region. RASSF1A methylation was significantly related to unfavorable prognosis in small-sized lung adenocarcinoma. No significant financial relationships to disclose.
Chromosomal aneusomy in sputum predicts for lung cancer in nested case-control study
Authors: Franklin W. , Schulte A. P. , Zeng C. , Wolf H. J. , Yin X. , Hirsch F. R. , Byers T. , Miller Y. E. , Baron A. E. , Varella-Garcia M. 
Published: March 2020

7201 Background: Lung cancer usually is disseminated at diagnosis and prognosis is poor for most patients. Heavy smokers are known to be at high risk factor for lung cancer and are target population for lung cancer prevention. Sputum has long been considered a potential source of material for biomarker based early detection but no tests have been validated. Methods: Chromosome aneusomy was sought in sputum of 114 cases and 110 controls from the Colorado Sputum Screening Cohort Study, which includes heavy smokers with airflow obstruction matched on age, gender, and date of sample collection. Subject characteristics were as follows: mean age 67 (± 8 years), 75% males, 36% current smokers, mean pack-year 71.2 (± 33.5). The FISH probe LAVysion (Vysis/Abbott) was used, including the DNA targets EGFR, MYCC, 5p15 and CEP6. Results: The multi-target set showed the highest sensitivity (0.78) and specificity (0.95) rates in specimens collected within 12 months of lung cancer diagnosis. The individual probes EGFR, MYCC, 5p15 and CEP6 showed, respectively, decreasing sensitivity rates (0.78, 0.67, 0.62, and 0.29) and increasing specificity rates (0.84, 0.91. 0.86, and 0.95). Combinations of two specific probes (AND) or of any of two probes (OR) have not favorably impacted these coefficients. Proportion of abnormal sputum specimens was higher in squamous cell carcinoma than in adenocarcinoma or small cell carcinoma, both considering the set of specimens collected 12 months prior to disease diagnosis (92%, 75%, 60%) and all specimens (80%, 58%, 44%). Conclusions: Chromosomal aneusomy in sputum was demonstrated in a nested case-control cohort to be a promising marker for prediction of lung cancer risk in heavy smokers with airflow obstruction. Evaluation of four DNA targets was more effective than any single marker or combination of markers, and the test had high sensitivity in patients with squamous cell carcinoma. [Table: see text]
Five-year results of a non-randomised study evaluating spiral computed tomography (sCT) for early detection of lung cancer (LC)
Authors: Novello S. , Giajlevra M. , Lausi P. , Brizzi M. , Selvaggi G. , Sardo D. , Borasio P. , Dogliotti L. , Fava C. , Scagliotti G. V. 
Published: March 2020

7210 Background: In high-risk subjects low-dose sCT showed a 4-fold increase in the detection rate of neoplastic nodules in comparison with chest-X-ray. However, among studies there is a considerable discrepancy in the % of lung nodules, overall lung cancer and stage I detection rate as well as of the additional diagnostic work up. Subjects & Methods: From April to December 2001, 520 asymptomatic volunteers aged ≥ 55 years with a history of cigarette smoking ≥ 20 packs-year and of no previous cancer received annually chest sCT for 5 consecutive years. Results: At baseline 73% were male, median age was 59 years and 91% current smokers. At baseline sCT 127 subjects (24.5%) had nodules <5 mm while nodules ≥5 mm were detected in 114 (22%); the size of lung nodules ranged from 5 to 9.9 mm in 81.5% of the cases. The % of nodules worth of additional investigation varied over time (2 yr: 6%; 3 yr: 5%; 4 yr: 11%). Five (1%) cases of LC were detected during the 1st year (3 stage I) and in two additional resections an atypical adenomatous hyperplasia was found. Three new cases of thoracic cancers were detected in the 2nd, 3rd and 4th year of the study. Drop-out rate in the first year was 5% (2 yr 4,5%, 3 yr 2.3% and 4 yr 3%). One interval case was detected during the 3rd year. Subjects who quitted smoking in the 1st year were 13% and the % decreased over years (6% at the end of 3rd yr and 3% at 4th and 5th yr) and among quitters failure rate was 1–2%/year. In 3% of cases quitting was related to an acute cardiovascular or respiratory event. Fifty % of subjects showed some radiological signs of emphysema. Conclusions: Evidence from ongoing randomised trials is needed to support the routine use of sCT for early detection of LC. A program of smoking cessation is strongly recommended for further studies. Currently a conservative attitude should be encouraged. No significant financial relationships to disclose.
Prognostic value of different standard uptake values (SUV) of primary tumor measured with FDG-PET in resectable non-small cell lung cancer
Authors: De Jong W. K. , Van der Heijden H. F. , Pruim J. , Oyen W. J. , Groen H. J. 
Published: March 2020

7214 Background: The SUV is a measure for the preferential uptake of a radiopharmaceutical in a tumor compared with a homogenous distribution in a body. SUV can be based on the maximum value (SUVmax) or on the mean value in a region outlined by isodensity contours, e.g., 70% and 50%. The prognostic value of the different SUVs in non-small cell lung cancer (NSCLC) is not clear. We evaluated the prognostic value of SUVmax, SUV 70% and SUV 50% in patients (pts) with resectable NSCLC. Methods: All consecutive pts who underwent an attenuation corrected whole body FDG-PET scan were selected. All data were reconstructed iteratively. Only pts with stage I through IIIA NSCLC were included. By adjusting the isocontour in the region of interest, the SUVmax, SUV 70% and SUV 50% of the primary tumor were calculated. Cox regression analysis was used to calculate the relation between the different SUVs and survival. Results: Eighty-four pts (67 males, median age 64 years, range 38–86) were included. Histology was squamous cell carcinoma (n = 43), adenocarcinoma (n = 27), large cell carcinoma (n = 13), and 1 patient with bronchoalveolar carcinoma. Nineteen pts had stage IA, 28 stage IB, 4 stage IIA, 19 stage IIB, and 14 stage IIIA. Median (range) SUVmax, SUV 70%, and SUV 50% were 6.9 (1.6–32.5), 5.5 (1.0–23.2), and 4.5 (0.9–21.9), respectively. Analysis of residuals of SUVmax as a continuous variable suggests no cut-off point and no indication of time-dependency. By univariate analysis, all pts with a SUV higher than the median value had a worse survival than pts with a SUV lower than median (Hazard ratio’s for SUVmax, SUV70% and SUV 50% were 2.3 (p = 0.024), 2.5 (p = 0.015), and 2.7 (p = 0.010), respectively). Conclusions: SUVmax, SUV 70% and SUV 50% measured with FDG-PET have a similar prognostic impact. No cut-off point for SUVmax has been observed. No significant financial relationships to disclose.
Analysis of single nucleotide polymorphisms (SNPs) of cytidine deaminase (CDA) and xeroderma pigmentosum group D (XPD) genes for the prediction of clinical response to gemcitabine and cisplatin in advanced non-small cell lung cancer (NSCLC) patients
Authors: Vasile E. , Giovannetti E. , Tibaldi C. , Mey V. , Nannizzi S. , Landi L. , Stasi I. , Danesi R. , Del Tacca M. , Falcone A. 
Published: March 2020

7219 Background: Detection of genomic differences predictive of drug response may allow to customize chemotherapy to the characteristics of individual patients. Gemcitabine alone or in combination with cisplatin are two of the most common regimens used in the treatment of advanced NSCLC. We investigated the correlation between selected SNPs of genes encoding enzymes involved in the activity of gemcitabine and cisplatin, including CDA, XPD and ERCC1, and the response to chemotherapy. Methods: Forty advanced NSCLC chemo-naïve patients were enrolled into the study; 16 patients, aged > 70 years, were treated with gemcitabine; 24 patients, aged < 70 years, were treated with cisplatin plus gemcitabine. SNPs CDA A79C, XPD A751C, XPD G312A and ERCC1 C118T were analyzed with the ABI PRISM 7900HT Sequence Detection System using TaqMan probe-based assay in DNA obtained from peripheral blood samples. Statistical analysis was performed using Pearson χ2 test, Kaplan-Meier curve and log rank test. Results: Up to now 31 patients, 11 treated with gemcitabine and 20 with cisplatin plus gemcitabine, are evaluable for response with RECIST criteria; correlation between response and genotype are showed in the table. Actuarial progression free survival (PFS) was longer in patients treated with gemcitabine ± cisplatin with CDA A79A genotype than in others (respectively 11.0 vs 2.5 months, p = 0.0092), while no correlation was found between the SNPs of XPD and ERCC1 and PFS in patients receiving cisplatin and gemcitabine. Conclusions: CDA A79A genotype resulted predictive of response and longer PFS in NSCLC patients treated with gemcitabine ± cisplatin. There was also a trend toward significant correlation between XPD A751A and better response in cisplatin-treated patients, while the SNPs in XPD 312 and ERCC1 118 were not associated with response to chemotherapy. [Table: see text] No significant financial relationships to disclose.
Prospective comparison of open and thoracoscopic lobectomy techniques: Thoracoscopic lobectomy is an equivalent cancer operation for early lung cancer
Authors: Roberts J. R. 
Published: March 2020

7225 Background: Minimally invasive pulmonary lobectomy is less painful than classical techniques, and thus potentially safer. Much research has demonstrated that the surgery is at least as safe as standard techniques. However, though the techniques are decades old, they are still not widely practiced. Opponents to these techniques argue that minimally invasive pulmonary surgery has not been demonstrated to be equivalent cancer surgery. Methods: We compared our patients stage by stage undergoing open and minimally invasive resections (case-control). All patients who underwent elective anatomic lobectomy were compared with respect to demographic parameters, hospital stay, and survival, by stage. Means were compared using two-tailed student’s t test, proportions, with chi-square, and survival by nonparametric statistics. p values less than 0.05 were accepted as significant. Results: Four hundred fifty-three patients (453)underwent lobectomy over a seven year period (317 were open (OL), and 146 were thoracoscopic (TL)). No differences were seen between the ages, functional vital capacity (FVC%) and residual volume (RV%). However, TL patients had poorer FEV1% (open-69%, TL-60%, p = 0.0245) and poorer diffusing capacity (open-87%, TL-64%, p = 0.000906). Further, the open lobectomies had longer length of stays (open-9.5 dyas, TL–7.3 days, p = 0.001), longer intensive care unit stays (open-1.6 days, TL-0.129 days, p = 0.00013), and higher perioperative mortality (open open-3%, TL-0%). The survival values for stage I NSCLC patients are shown below. No differences in survival between the two techniques was seen. Conclusions: Thoracoscopic or minimally invasive lobectomy is an established technique that has been refined for more than a decade. Several studies suggest an earlier recovery from thoracoscopic lobectomy. This study demonstrates that the two approaches are equivalent cancer operations. [Table: see text] No significant financial relationships to disclose.
Effects of zoledronic acid on survival in patients with lung cancer and high baseline N-telopeptide (NTX) levels: Stratified by baseline bone alkaline phosphatase (BALP)
Authors: Matczak E. , Hirsh V. , Lipton A. , Cook R. J. , Langer C. , Hei Y. J. , Major P. 
Published: March 2020

7228 Background: Recently, it was shown that patients (pts) with bone metastases from lung cancer who had high NTX or BALP levels on study had a higher risk for skeletal-related events (SREs) and death compared with pts with low NTX or BALP. Zoledronic acid has been shown to prevent SREs; however, it is unknown whether there is a secondary survival benefit in this pt population. To assess the potential effect of zoledronic acid on survival in pts with bone metastases from lung cancer and high baseline NTX, we conducted a retrospective analysis of pts in a large, randomized, controlled trial. Methods: Patients with lung cancer and bone metastases were randomized to receive either 4 mg zoledronic acid or placebo for a total of 21 months. Survival data were evaluated in pts who had a high baseline NTX level (≥ 64 nmol/mmol) and baseline BALP level (retrospectively stratified by baseline BALP level according to these criteria: normal BALP < 146 U/L and high BALP ≥ 146 U/L). The relative risk (RR) of death was calculated for each pt group and for pts with high NTX levels overall compared with placebo. Results: The pts with high NTX levels (n = 144; men, 65% women, 35%) had a median age of 64 years. Among these pts, the RR of death was significantly reduced by 35% in pts who received zoledronic acid compared with placebo (RR = 0.650; P = .0244). The RR of death on study for pts who had both high baseline NTX and BALP levels (n = 97) was also significantly reduced by 46% in pts who received zoledronic acid compared with placebo (RR = 0.537; P = .0059). Among pts who had high baseline NTX and normal BALP levels (n = 47), the RR of death was similar between treatment groups (RR = 1.012; P = .9736). Conclusions: High levels of bone resorption may correlate with an increased risk of SREs and death. Zoledronic acid reduces bone turnover and the risk of SREs and may delay the progression of bone lesions. This retrospective analysis suggests that treatment with zoledronic acid may improve survival compared with placebo in pts with lung cancer who have high levels of bone metabolism, warranting further study in either other database analyses or prospective trials. [Table: see text]
Photodynamic therapy using Laserphyrin for centrally located early stage lung cancer
Authors: Usuda J. , Kato H. , Okunaka T. , Furukawa K. , Honda H. , Suga Y. , Hirata T. , Ohira T. , Tsuboi M. , Hirano T. 
Published: March 2020

7229 Background: In central type early stage lung cancer, the tumor must be located only as far as the segmental bronchi and be carcinoma in situ or with only limited invasion into the bronchial wall. Laserphyrin (mono-L-aspartyl chlorine e6, NPe6) is a second generation photosensitize and approved by the Japanese government and has been on sale from June 2004. Methods: Four h after the administration of Laserphyrin 40 mg/m2, we irradiated using diode laser (100 mJ/cm2). Before PDT, we evaluated the tumor lesions and tumor depth using autofluorescence bronchoscopy and endobronchial ultrasonography (EBUS), and we confirmed the area of laser irradiation. Results: From February 1980 to December 2005, a total number of 204 patients with 264 lesions of centrally located early stage lung cancer underwent photodynamic therapy (PDT) in the Department of Thoracic Surgery, Tokyo Medical University Hospital. There were 185 clinical stage 0 lesions and 79 stage I lesions. CRs and PRs were obtained in 224 lesions (84.8%) and 40 lesions (15.2%) out of 264 lesions. From July 2004 to December 2005, we performed Laserphyrin-PDT for 28 lesions of centrally located early stage lung cancer in Tokyo Medical University Hospital. The rate of CR was 92.9% (26 lesions) in 28 lesions. For Laserphyrin-PDT, Skin photosensitivity was very low and the clean-up bronchoscopies were not frequently needed, and the period of hospitalization was shorter compared to that for Photofrin-PDT. Conclusions: We conclude that PDT using Laserphyrin will be a standard option for stage 0 (TisN0M0) and stage I (T1N0M0) centrally located early stage lung cancer. No significant financial relationships to disclose.
LBH589, a novel histone deacetylase inhibitor (HDACi), treatment of patients with cutaneous T-cell lymphoma (CTCL). Changes in skin gene expression profiles related to clinical response following therapy
Authors: Prince H. M. , George D. J. , Johnstone R. , Williams-Truax R. , Atadja P. , Zhao C. , Dugan M. , Culver K. 
Published: March 2020

7501 Background: LBH589 is a novel histone deacetylase inhibitor in Phase I trials. Since other HDACi have induced disease regression in CTCL, we evaluated the activity of LBH589 and resulting changes in gene expression of LBH589 in CTCL patients (pts). Methods: Pts with advanced-stage CTCL, who had progressed following prior systemic therapy were entered into the DLT dose level 30mg M,W,F cohort (n = 1) or the subsequent MTD dose level 20mg M,W, F weekly (n = 10). LBH589 was continued until disease progression or unacceptable toxicity. The first three pts had 3mm punch biopsies from CTCL-involved skin lesions at 0, 4, 8 and 24h after administration, which were subjected to gene expression profiling using Affymetrix U133 plus 2.0 GeneChips with 47,000 probesets. Results: Eleven pts with CTCL have been entered to date. Two of the pts attained a complete response (CR), 3 attained a partial response (PR), 2 achieved stable disease (SD) with ongoing improvement, and 4 progressed on treatment (PD). Of particular interest, 2 pts who were initially SD required discontinuation because of toxicities (Grade III diarrhea at week 4, Grade II fatigue at week 12). Both had ongoing improvement in their disease achieving a CR and PR, respectively 3 months later. Of the 5 responding pts, one with a CR (discontinued after 10 doses due to Grade III diarrhea) progressed at 8m. Microarray data on the first 3 pts (2CR and 1PD) demonstrated distinct gene expression response profiles between the 3 pts. Surprisingly, the pt with PD showed the greatest transcriptional response with more than 16,000 genes activated or repressed over the 24 hr time course. Of these responsive genes, close to 60% were activated while 40% were repressed. In contrast, less than 1000 genes showed a 2-fold change in expression in the 2 pts with a CR with greater than 85% of the genes being repressed. Conclusions: LBH589 induce CR’s in CTCL pts. Regression of disease can occur some weeks after discontinuation of therapy. Preliminary microarray analysis of tumor samples indicated that LBH589 mediates changes in gene expression in vivo with an unexpected observed inverse relationship between the number of genes altered and clinical outcome. [Table: see text]
Rituximab-supplemented high-dose sequential chemotherapy (R-HDS) has better EFS and PFS than R-CHOP in poor risk follicular lymphoma (FL) at diagnosis: A multicenter randomized GITMO/IIL trial
Authors: Ladetto M. , Benedetti F. , Vitolo U. , Patti C. , Rambaldi A. , Liberati A. , Musso M. , Pulsoni A. , Gianni A. M. , Tarella C. 
Published: March 2020

7525 Background: HDS with ASCT is effective and feasible in FL at the multicenter level and suitable for Rituximab supplementation (R-HDS). This randomized trial compared R-HDS with Rituximab-supplemented CHOP (R-CHOP) in poor risk FL patients (pts) <60 yrs. Methods: Between 2000 and 2005, 136 pts have been randomized (68/arm). Eligibility required age-adjusted IPI ≥2 (125 pts) or, in the absence of this criterion, ≥3 IIL adverse factors (11 pts). Primary endpoint was EFS. Clinical features were: median age 50 yrs (22–60), stage III-IV 98%, elevated LDH 78%, bulky disease 66%, B symptoms 47%, extranodal disease (other than BM) 45%, ECOG PS >1 47%. R-HDS consisted of: i. 2 APO and 2 DHAP; ii. sequential administration of Etoposide 2g/sqm, 2 Rituximab, Cyclophosphamide 7 g/sqm with PBPC collection (in vivo-purged with 2 additional Rituximab); iii. Mitoxantrone (60 mg/sqm) + L-Pam (180 mg/sqm) followed by 5–8 × 106 CD34+ cells/kg. R-CHOP consisted of 6 CHOP courses followed by 4–6 doses of Rituximab. Cross-over was allowed. bcl-2/I gH-based minimal residual disease analysis was planned. Assessement was “intention to treat”-based. Results: Current data are updated at 31/5/05. Next closing date will be April 2006. The two arms were balanced. 68% patients concluded R-CHOP (failures were due to progression 29% and toxicity 3%) and 78% R-HDS (failures due to progression 9%, toxicity 5%, poor mobilization/refusal 8%). Toxic deaths were 4 (2 in each arm); in addition 1 gastric cancer and 1 AML occurred in the R-HDS arm. Progressions and non-responses were 31% with R-CHOP and 11% with R-HDS (p < 0.05) CRs were 58% and 87% respectively. Current median follow-up is 24 months. EFS and PFS at 24 months are 41% and 48% for R-CHOP and 66% and 75% for R-HDS (p < .001). At present OS is similar. Salvage treatment following R-CHOP is currently known in 22 pts: 16 received R-HDS, with 10 achieving CR. Molecular remission, (two PCR-neg BM samples at 6 months intervals), was observed in 54% of R-CHOP and 77% of R-HDS pts Conclusions: R-HDS induces more CRs and has better EFS and PFS than R-CHOP in this rare and aggressive population of high-risk FL patients. These results cannot be extrapolated to standard-risk pts. [Table: see text]