bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictive model for mediastinal lymph node status at the time of mediastinoscopy
Authors: Gainor L. , Parsons A. M. , Parker L. A. , Detterbeck F. C. , Stinchcombe T. , Hayes D. N. 
Published: March 2020

18004 Background: Mediastinal lymph node (N2) positivity in non-small cell lung cancer (NSCLC) patients is suspected based on imaging such as CT or PET scan, with confirmation by mediastinoscopy. However, the most accurate clinical information in predicting N2 status is controversial. Methods: We reviewed 147 candidates for NSCLC resection (2000–2005) who had clinical database information available and had undergone mediastinoscopy. Using suspected clinical predictors of mediastinal metastasis available prior to mediastinoscopy, we constructed a predictive model of N2 status. Results: The largest N2 node short-axis diameter on CT was by far the most influential factor in the model. Three other predictors for N2 node positivity were significant (p<0.05) in univariate analysis: indistinct tumor borders and mediastinal invasion on CT, and mediastinal PET scan positivity. However, all were less influential than N2 size on CT. Using logistic regression, these factors can be used to predict probability of positive N2 biopsy in an individual patient. The resulting diagnostic test had a ROC (receiver operator characteristic) area of 0.80 and optimal sensitivity-specificity pairing of 75% and 73%. 35% (51/147) of patients analyzed had at least one N2 node positive at mediastinoscopy. 39% (57/147) of patients had PET scan data available, and 82% (120/147) had CT data available. Conclusions: Of available data in early-stage NSCLC patients, mediastinal lymph node size on CT scan was more important than PET scan or other CT scan findings in predicting probability of positive mediastinoscopy. A predictive model is useful in more accurately determining need for invasive staging by mediastinoscopy. No significant financial relationships to disclose.
Clinical implications of tumor cavitation following therapy with angiogenesis inhibitors in non-small cell lung cancer (NSCLC) patients
Authors: Onn A. , Martinez C. H. , Herbst R. S. , Riddle J. R. , Blumenschein G. R. , Stewart D. J. , Marom E. M. 
Published: March 2020

18034 Background: Angiogenesis inhibitors are being tested in patients with advanced cancer. We sought to determine the formation of tumor cavitation in NSCLC patients treated with antiangiogenic agents at MD Anderson Cancer Center. Methods: Retrospective analysis of all NSCLC cases treated with antiangiogenic agents in our institution between 6/1998 and 6/2005. Clinical data were retrieved from medical records, and chest-imaging findings were documented. Results: One hundred and twenty four patients were treated in 10 different trials. Twelve patients (9.7%, 6 men, 6 women, median age 56 years; cell type adenocarcinoma in 9 and squamous cell cancer in 3) developed tumor cavitation during the trial (median time to event 2 months). All patients had advanced lung cancer and failed previous chemotherapy. Tumor cavitation was found in 4 of 10 trials: 7/39 patients treated with bevacizumab (5 were treated in combination with erlotinib), 3/17 with ZD6474, and 2/23 with BAY43–9006. Median progression-free survival was similar between patients with (6 months) or without (4 months) cavitation. Stable disease was noted in 50% of patients who did and in 52% of patients who did not develop cavitation. Cavitation occurred in the primary tumor or metastases. Imaging characteristics did not significantly differ between tumors with or without cavitation: being proximal to subsegmental artery (66% vs 52%), having well-demarcated margins (66% vs 56%), and soft-tissue density (90% vs 85%). The frequency of adverse events (mild rash, neuropathy) of any grade was similar in patients with (42%) or without (51%) cavitation. One patient with cavitation developed hemoptysis and died. Conclusions: Development of tumor cavitation is not rare in lung cancer patients treated with antiangiogenic agents, but the clinical implications are minimal in most cases. No significant financial relationships to disclose.
A randomized phase 2 trial of amrubicin compared to topotecan as second-line treatments in extensive disease small cell lung cancer (SCLC) sensitive to platinum-based first-line chemotherapy
Authors: Jotte R. M. , Reynolds C. H. , Conkling P. , Oliver J. W. , Allen A. 
Published: March 2020

18064 Background: SCLC accounts for about 13% of lung cancers and presents as extensive disease (ED-SCLC) in 60%-70% of patients (pts). Treatment options have been limited for ED-SCLC and survival enhanced by a median of only 2–3 months over the past 20 years. Our trial assessed response rates with amrubicin, a fully synthetic anthracycline and inhibitor of DNA topoisomerase II, versus standard therapy topotecan, for second-line treatment of sensitive SCLC. Methods: This phase 2, open-label, multicenter trial compares second-line therapy with amrubicin versus topotecan in ED-SCLC pts (=18 years, ECOG performance status =2), sensitive to first-line platinum-based therapy but with recurrence or progression =90 days later. Pts are randomized to amrubicin (40 mg/m2 via 5-minute bolus infusion daily x 3 days) or topotecan (1.5 mg/m2 via 30-minute infusion daily x 5 days), both starting on Day 1 of a 21 day cycle. Treatment is continued until disease progression, unacceptable toxicity, or withdrawal. Response is assessed using RECIST criteria. In all, 75 evaluable pts (50 randomized to amrubicin and 25 to topotecan; 2:1 per the standard topotecan therapy reference group) are planned to be enrolled. Results: To date, 22 pts are enrolled with 15 evaluable for response: 10 on amrubicin; 5 on topotecan. After 1–6 cycles, 5/10 amrubicin pts have responded (1 CR, 4 PRs). One topotecan patient responded (PR) but had progressive disease at the next visit. Seventeen pts are evaluable for safety. Hematological adverse events (AEs, = Grade 3) were the most commonly reported and were similarly observed across treatments (Table). Tachycardia (< Grade 3) was recorded for 1 amrubicin and 2 topotecan pts. No other cardiac AEs were observed. Conclusions: Amrubicin compares favorably with standard therapy topotecan as second-line treatment in sensitive ED-SCLC patients. No anthracycline- induced cardiomyopathy has been observed to date. [Table: see text] No significant financial relationships to disclose.
Quality-of-life (QoL) outcome of standard chemotherapy for advanced non-small cell lung cancer (NSCLC): A comparison between cisplatin- and non-cisplatin-based regimens
Authors: Tanvetyanon T. , Soares H. , Djulbegovic B. , Jacobsen P. , Bepler G. 
Published: March 2020

18067 Background: Among standard chemotherapy regimens for NSCLC, cisplatin-based regimen is known to be associated with significant nausea and vomiting. QoL during treatment with cisplatin-based chemotherapy, when compared with others is unclear. Methods: We performed a MEDLINE search for all phase III randomized controlled trials of NSCLC that reported QoL outcomes and used standard chemotherapy regimens containing cisplatin in one arm and non-cisplatin in the other. Two reviewers independently extracted data and assess quality. QoL reporting criteria were priori hypothesis stated, rationale for instrument reported, psychometric properties reported, cultural validity verified, adequacy of domains covered, instrument administration reported, baseline compliance reported, timing of assessment documented, missing data documented, clinical significance addressed, and presentation of results (Efficace et al, JCO 2003). Results: Out of 893 potential titles, 9 studies were identified. Two did not meet the minimum QoL reporting criteria and were excluded. Of the 7 included studies (N=3439), only one measured QoL as a primary endpoint; only two satisfied all 11 quality criteria for QoL reporting. Due to the heterogeneity of the reporting formats, we were unable to pool data on QoL. Two of seven studies indicated that a cisplatin-containing regimen was associated with a significantly worse QoL when compared with a non-cisplatin regimen (Table). Among these selected studies, treatment-related death was higher with cisplatin-based regimens [reported from 8 studies, N=3290, RR=0.66;95%CI (0.46–0.95), p=0.03]. Grade 3 and 4 neutropenia and neutropenic fever were also more common in the cisplatin-based arms. Conclusion: We found a suboptimal quality of QoL reporting and a lack of standardization of QoL analysis method in these trials. This limits a comparison between studies and the usefulness of QoL endpoint for clinical decision-making. [Table: see text] No significant financial relationships to disclose.
Distribution of promoter hypermethylation in epithelial cells collected by endobronchial brushes of patients (pts) with non- small cell lung cancer (NSCLC) and controls
Authors: De Jong W. K. , Louwagie J. , Meunier A. , Verpooten G. F. , Groen H. J. 
Published: March 2020

18078 Background: Epigenetic gene silencing by promoter hypermethylation is an early event in NSCLC development. Exposure to tobacco smoke may explain random occurrence of hypermethylation events throughout the bronchial epithelium of pts with NSCLC. We assessed the methylation status of 11 genes in brushes sampled in 3 well-defined endobronchial locations in pts with NSCLC and in brushes of controls. Methods: In pts with NSCLC we collected bronchial brushes of 1) tumor, 2) normal appearing bronchus 2–3 cm proximally of tumor, and 3) main bronchus of contralateral lung. Also, we collected a brush of the normal appearing main bronchus of controls. Methylation status of RASSF1A, GATA4, GATA5, SFRP1, RARβ2, DAPK, MGMT, p16(INK4A), p14, CHFR, and APC was determined in all samples using quantitative methylation specific PCR. Genes were considered hypermethylated if the gene/actin ratio was higher than gene-specific cut-off values previously defined in NSCLC tissue (A). Alternatively, cut-off values were defined by ratios for which no hypermethylation was observed in controls (B). Results: Ten pts with NSCLC (5 adeno, 4 large cell, 1 neuro-endocrine carcinoma) and 24 controls (20 asthma, 4 COPD) were included. Median packyears of pts 32 (range 20–60), of controls 6 (0–70). Six pts had one or more hypermethylated genes in their tumor brush using cut-off A and eight pts using B. Hypermethylation of genes in proximal or contralateral locations was only observed if the same gene was also hypermethylated in tumor brush. No hypermethylation was observed controls. Total sensitivity was 60% (A) and increased to 80% in B, while specificity remained 100%. RASSF1A showed the highest single gene sensitivity (40%). Presence of hypermethylation in pts was not associated with number of packyears (p=0.61/0.53) or histological subtype (p=0.39/0.28) for cut-off A or B, respectively. Conclusions: Hypermethylation events were observed in up to 80% of bronchial tumor brushes of NSCLC pts. Hypermethylation comes from tumor cells and not from normal bronchial epithelium near or distant to the primary tumor. No significant financial relationships to disclose.
Development of prognostic models in non-small cell lung cancer based on 60 serum markers and clinical variables
Authors: Holdenrieder S. , Nagel D. , Heinemann V. , von Pawel J. , Raith H. , Feldmann K. , Stenman U. 
Published: March 2020

18079 Background: Currently available data concerning the prognostic relevance of biochemical markers in NSCLC are conflicting. Methods: In a prospective study, 60 pretherapeutic parameters including 23 clinical factors, 22 “classical” laboratory markers, and 15 oncological biomarkers were investigated in 300 patients with newly diagnosed advanced NSCLC undergoing first-line chemotherapy. After selection of prognostically independent, clinical parameters by Cox regression analysis, biochemical markers were separately tested together with these clinical factors, and if independently prognostically relevant, simultaneously analyzed by Cox regression using both forward and backward selection. Dependent on clinical preconditions, multivariate analyses were performed on A) clinical, laboratory and oncological lung parameters and B) clinical, laboratory and all oncological parameters. Results: Concerning clinical factors, performance score (PS), weight loss, metastases other than lung (MOL), and chemotherapy showed independent prognostic relevance. Testing biochemical variables with these clinical factors revealed a plentitude of them remaining prognostically significant. When analyzing all prognostically relevant clinical and biochemical variables simultaneously, multivariate models of independently prognostic parameters included for panel A) PS, MOL, CRP, CYFRA 21–1 and chemotherapy. In panel B) CYFRA 21–1 was replaced by the combination of HCG-beta, CA72–4, CA19–9 and S100. Both models improved the prognostic information within the various PS categories significantly. Conclusion: Depending on the availability of pretherapeutic clinical and laboratory variables, various prognostic models for NSCLC patients undergoing first-line chemotherapy can be established. The resulting multivariate models improve the prognostic power over the currently used performance score and provide a more precise pretherapeutic, prognostic stratification of these patients. No significant financial relationships to disclose.
Altered expression of prostaglandin synthases in NSCLC: Therapeutic strategies and targets for intervention
Authors: Cathcart M. , Gatley K. , Kay E. , Pidgeon G. P. , O’ Byrne K. J. 
Published: March 2020

18083 Background: Prostacyclin Synthase (PGIS) and Thromboxane synthase (TXS) metabolize PGH(2) into prostacyclin and thromboxane respectively. PGIS over-expression inhibits cancer growth in a mouse model, while over-expression of TXS caused opposite effects. TXS is expressed in a variety of tumours, associated with poor prognosis and increased metastasis. The aim of this study was to examine the expression of PGIS and TXS in NSCLC, the effect of targeted TXS inhibition, and the mechanisms regulating these effects. Methods: A panel of resected human lung tumours were stained for PGIS and TXS expression by IHC and by western analysis. A 170- core tissue microarray was stained for TXS and intensity correlated with tumour grade. Cell survival was examined by BrdU assay in A-549 (adenocarcinoma) and SKMES-1 (squamous cell carcinoma) cells following 24h selective TXS inhibition with Ozagrel (500nM) alone, or in combination with chemotherapy. Multi-parameter apoptosis signalling was examined after TXS inhibition using In Cell Analyser and confirmed by DNA laddering and cell death ELISA. PCR arrays were used to examine genes involved in tumourigenesis following TXS inhibition. Results: PGIS was absent in lung cancer sections. TXS was over-expressed in lung cancer relative to matched normal, with significantly increased expression in lower grade tumours. PGIS was down-regulated or absent, while TXS expression was up-regulated in tumours v’s normal tissue. Ozagrel significantly reduced cell survival and induced apoptosis, determined by both DNA laddering and Cell Death ELISA. Multi-parameter apoptosis analysis revealed enlarged nuclei, decreased f-actin staining and decreased mitochondrial mass potential, while PCR arrays confirmed upregulation of the pro-apoptotic gene BAX following TXS inhibition. Ozagrel in combination with Doxorubicin (10nM) showed greatest efficacy compared to a number of other chemotherapy drugs. Conclusions: Expression of PGIS and TXS are altered in NSCLC. Overexpression of TXS may regulate tumour survival as its inhibition induces apoptosis, potentially through upregulation of pro- apoptotic proteins. Targeting TXS, alone or in combination with chemotherapy is a potential therapeutic strategy for the treatment of NSCLC. No significant financial relationships to disclose.
Phase II trial of huN901-DM1 in patients with relapsed small cell lung cancer (SCLC) and CD56-positive small cell carcinoma
Authors: McCann J. , Fossella F. V. , Villalona-Calero M. A. , Tolcher A. W. , Fidias P. , Raju R. , Zildjian S. , Guild R. , Fram R. 
Published: March 2020

18084 Background: HuN901-DM1, a humanized antibody-maytansinoid immunoconjugagte, binds to CD56 which is expressed in almost all cases of SCLC as well as in other small cell carcinomas (SCC), neuroendocrine carcinomas, and multiple myeloma. The immunoconjugate binds to its target antigen, is internalized, then releases DM1. Methods: Patients with relapsed SCLC and CD56- positive SCC of other sites are treated with huN901-DM1 given as an intravenous infusion at 60 mg/m2/week for four consecutive weeks every six weeks. The study consists of two stages. Fourteen patients were initially enrolled. The occurrence of an objective response among the initial 14 patients prompted expansion to a total of 35 evaluable patients. Clinical response is evaluated by RECIST criteria. Results: To date, thirty patients have been treated in the study. Four patients experienced drug related serious adverse events (SAEs). Three patients had severe headache after the initial infusion of study drug. Symptoms markedly improved after 24 hours and then completely resolved. Severe headaches did not occur in subsequent patients who were pre-medicated with steroids prior to all infusions. A patient with a history of diabetic neuropathy and prior cisplatin treatment had grade 4 hyperesthesia. There was no evidence of clinically significant myelosuppression. HuN901-DM1 generally was well tolerated and no serious infusion reactions occurred. Preliminary pharmacokinetic (PK) data reveal no prolongation of terminal half-life of the immunoconjugate when PK parameters are compared from the first and fourth dose of cycle 1. Further, there was no evidence of antibody formation to the antibody component (HAHA) or drug component (HADA) of huN901-DM1. One patient (pt) with relapsed, SCLC had an objective partial response lasting 18 weeks and a pt with cervical SCC had an unconfirmed partial response. Stable disease was observed in five patients and lasted about 6 (3 pts), 12 (1 pt), and 18 weeks (1 pt). Conclusions: The study provides evidence of clinical activity and safety of huN901-DM1. Pre-medication with steroids appears effective in preventing severe headaches. Enrollment of additional patients to the study is planned. No significant financial relationships to disclose.
Image-guided lung radiotherapy: Bringing technology into routine clinical practice
Authors: Franks K. N. , Bezjak A. , Higgins J. , Li W. , Purdie T. G. , Brade A. , Cho J. , Payne D. , Jaffray D. A. , Bissonnette J. 
Published: March 2020

18093 Background: Cone-beam CT (CBCT), an imaging system integrated into the RT treatment unit, produces 3D images far superior to the conventional 2D portal images used for verification of patient (pt) set-up. This allows direct matching to the RT treatment planning CT images, potentially increasing the precision of RT delivery. We report on the broad implementation of this new RT image-guided paradigm in lung cancer patients at our center. Methods: All lung cancer pts undergoing radical RT were planned using 4DCT and imaged daily for repositioning with CBCT since 04/06. Initially, CBCT datasets were compared with the planning CT to assess the setup error (bone surrogate), using two immobilisation methods: evacuated bags (EB) and chest-board (ChB). Discrepancies >3 mm between the two datasets, in any direction, were corrected before the start of each RT fraction. Data were retrospectively analyzed to assess the initial and residual discrepancies (43 pts; 1,128 CBCTs).Alternative matching strategies were also tested (carina & tumor) using both manual and automatic methods (30 pts). Protocols had REB approval. Results: In total, 657 (58%) RT treatments required adjustment after initial positioning on the treatment couch. The two immobilization methods were equivalent (p=0.18); the mean pt shift required for ChB pts was 55±18mm and for EB pts was 69±32mm. Given that residual uncertainties were <3 mm, margin calculations reveal that large reductions (54–79%) may be possible for tumors not influenced by respiratory motion. The performance of automatic matching was reasonable for carina (correlation [r] 0.8–0.84) and bone (r 0.58–0.81) but discrepancies were seen for tumor (r 0.63–0.69). Conclusions: Daily CBCT provides greatly increased accuracy of set-up, to within 3 mm of the planned bony anatomy, which may improve tumor control by confirming geographic accuracy. The role of image-guided RT in reducing the volume of irradiated normal tissue may play an important role in addressing toxicity concerns associated with combined modality treatment and facilitate safe RT dose escalation. In addition to increasing RT precision, daily CBCT allows routine visualisation of the tumor as well as to bony anatomy, presenting an exciting opportunity to adapt the treatment plan based on an individual response. [Table: see text]
Phase I trial of escalating doses of ABI-007 (nanoparticle albumin-bound paclitaxel) and gemcitabine in patients (pts) with thoracic malignancies
Authors: Lee C. B. , Stinchcombe T. E. , Socinski M. A. , Hayes D. N. , Goldberg R. M. , Hawkins M. J. , Obasaju C. K. , Dees E. C. 
Published: March 2020

18094 Background: ABI-007, nanoparticle albumin-bound paclitaxel, has a different toxicity profile than solvent-based paclitaxel including a lower rate of severe neutropenia. This trial was designed to determine the maximum tolerated dose (MTD) of ABI-007 in combination with gemcitabine (G) in patients with thoracic malignancies. Methods: Patients were required to have a performance status of 0–1, =3 cytotoxic chemotherapy regimens, and preserved renal, hepatic, and bone marrow function. Patients received G 1,000 mg/m2 on days 1, 8 in all cohorts and ABI-007 on day 1 at doses of 260, 300, 340 mg/m2 depending on the treatment cohort every 21 days (1 cycle = 21 days). Day 8 G dose modifications were: G held for ANC < 500 x 109/L or platelets (plts) < 50,000 x 109/L, and 75% of the G dose was given if the ANC 500–999 x 109/L or plts 50,000–99,000 x 109/L. Dose limiting toxicities (DLT) were assessed after the first cycle and were defined as: grade 3 non-hematologic toxicity, febrile neutropenia, grade 4 anemia or thrombocytopenia, ANC = 500 for = 7 days, 2-week delay in initiating the second cycle, or omission of the day 8 G. Doses were escalated in cohorts of 3–6 pts. Results: Thirteen patients were consented and 12 pts were treated (median age 62.5 years (range 35–75); median number of prior treatments 2.5 (range 1–4); tumor types: 6 non-small cell lung cancer (NSCLC), 5 small cell lung cancer (SCLC), and 1 esophageal. At an ABI-007 dose of 300 mg/m2, 1 of 6 pts experienced a DLT (omission of day 8 G due to ANC < 500), and at an ABI-007 dose of 340 mg/m2 2 of 3 patients experienced a DLT (1 pt grade 3 rash and pruritus; 1 pt grade 3 fatigue and anorexia). Additional grade 3 or 4 toxicities observed over all cycles were: neutropenia (n=2), sensory neuropathy (n=1), febrile neutropenia (n=1). G was given at full dose in 38 of the 39 cycles. Eight pts were evaluable for response by RECIST: 4 partial responses (SCLC, n=2; NSCLC, n=2), 4 stable disease (NSCLC, n=3; esophageal, n=1). Conclusions: The MTD of ABI-007 is 300 mg/m2 day 1 in combination with G 1,000 mg/m2 on days 1, 8 every 21 days. This combination was well tolerated and demonstrated activity in previously treated NSCLC and SCLC patients. No significant financial relationships to disclose.