bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lack of consensus on post-operative radiotherapy (PORT) fields used in non-small cell lung cancer (NSCLC)
Authors: Senan S. , Le Péchoux C. , Spoelstra F. O. , Ishikura S. , Casas F. , Ball D. , Price A. , DeRuysscher D. , van Sörnsen de Koste J. R. 
Published: March 2020

7658 Background: Survival in patients with a completely resected stage III-N2 NSCLC may be improved by PORT. LungART is a phase III trial for patients with resected N2 disease who will be randomized to between PORT and no PORT, irrespective of the use of chemotherapy. LungArt target volumes are based upon the post-surgical findings in each patient, and on the surgical literature. A ‘dummy run’ was performed to study PORT volumes used internationally and to evaluate the LungART protocol. Methods: A CD-rom based contouring program containing the planning CT scans of 2 patients (post-lobectomy and pneumonectomy, respectively) were mailed to 17 thoracic radiation oncologists from 4 continents. Relevant clinical, radiological and pathological reports were provided in order to allow clinicans to contour their ‘routine’ clinical target volumes (CTV). Contours were saved onto a CD-rom and mailed to the study center. The LungART protocol was then provided and ‘protocol’ CTVs were generated. Contours of each case were transferred to a template CT dataset of that patient, and nodal CTVs were jointly generated by two clinicians using published definitions. An optimised treatment plan was generated for all CTV's. Results: For each case, a total of 10 routine CTVs were received. Both routine and protocol CTVs were provided for each case by 6 clinicians. The routine CTVs varied up to 3-fold between clinicians and this was significantly decreased by use of the protocol (F test, p=0.00003 and p=0.00002 for cases 1 and 2, respectively). Coverage of nodal stations 2R and 4R improved when CTVs were defined using the protocol. Risks of lung toxicity, as defined by the lung volumes treated to 20 Gy and 5 Gy, varied between the smallest and second largest routine CTVs. For the post-lobectomy case, the V20 (range) was 11.8–19.3% and a V5 of 33.8–57.9%. The corresponding V20 and V5 values were 1.5–2.1% and 31.6–39.7% for the post-pneumonectomy case. Both cardiac volumes receiving 45 Gy and spinal doses were similar for both CTVs. Conclusions: The variations in PORT volumes generated by experts led to important differences in the risk of radiation-induced lung toxicity. Standardized target definitions are needed in order to optimize the survival benefits from PORT, and the LungArt protocol may serve this purpose. No significant financial relationships to disclose.
Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) as a biomarker for the effect of PTK787/ZK 222584 (PTK/ZK) as second-line mono-therapy in patients with stage IIIB or stage IV non-small cell lung cancer (NSCLC)
Authors: Morgan B. , Horsfield M. A. , Stattaus J. , Khalil A. , Gauler T. C. , Gounant V. , Fischer B. , Laurent D. , Krissel H. , Eberhardt W. E. 
Published: March 2020

7676 Background: Overexpression of vascular endothelial growth factor receptor (VEGF-R) in NSCLC-tumors is linked to poor prognosis and shorter overall survival. PTK/ZK (PTK/ZK) is a novel, oral, anti-angiogenic compound blocking all currently known VEGF receptors (VEGF-R1–3). DCE-MRI measures early changes in tumour-associated vasculature in response to treatment and has been successfully used as a biomarker for biological activity of PTK/ZK in liver metastases from colorectal cancer. Methods: This is a prospective, multi- centre, phase-II study of PTK/ZK in pretreated patients with advanced stage NSCLC. 54 patients (pts) received 1,250 mg PTK/ZK once daily (qd), followed by 58 patients receiving 1,250 mg (500 am + 750 mg pm) PTK/ZK twice daily (bid). Response evaluation was based on RECIST. Disease stabilization of at least 12 weeks based on CT/MRI-imaging was defined as clinically relevant drug activity. DCE-MRI was performed 2- 4 hours after PTK/ZK administration, on day 2 and at day 28. Contrast enhancement for the whole tumour was assessed by calculating the transfer constant (Ktrans) using a two-compartment model. Results: DCE-MRI was performed successfully in 35 pts in the qd cohort on day 2 and 29 pts in the qd cohort at day 28. There was a statistically significant mean reduction in Ktrans at day 2 of 35.2 % (p<0.0001, N=35, paired ‘t’ test) and at Day 28 of 38.1% (p<0.0001, N=29). 32 pts with day 2 DCE- MRI were evaluable for response assessment with 10 (31%) achieving SD at 12 weeks and 22 (69%) with progressive disease (PD). Both the SD group and the PD group had significant mean reductions in Ktrans at day 2 (39.4% and 37.1%, respectively). However, the difference between SD and PD was not statistically significant. Data for the bid cohort will be presented at the meeting. Conclusions: PTK/ZK causes statistically significant reduction in tumour vascular parameters of lung tumours. Ktrans has previously been shown to correlate with clinical outcome. However, for the qd cohort, no correlation could be demonstrated. This may be due to the limitation of the sample size as well as the heterogeneity of the targeted lesions selected for this study. [Table: see text]
Liposomal cisplatin and paclitaxel versus cisplatin and paclitaxel in advanced NSCLC
Authors: Stathopoulos G. P. , Michalopoulou P. , Antoniou D. , Dimitroulis J. , Giamboudakis P. , Marosis K. , Stathopoulos J. , Tsoukalas G. , Grigoratou T. 
Published: March 2020

7684 Background: A new liposomal formulation of Cisplatin has been tested in a phase I and phase II trial in advanced solid tumors as a single agent or in combination with Gemcitabine or paclitaxel. It is a non-myelotoxic and non-nephrotoxic agent. Effectiveness has been shown, in particular when it is combined with a second agent. Objectives, comparison of toxicity, efficacy of liposomal cisplatin (lipoplatin) versus cisplatin both combined with paclitaxel for non-small cell lung cancer patients. It is a preliminary report of the study which is on-going. Methods: From April 2006 till December 2006, 61 patients were recruited. 54 are evaluable for response and toxicity. Were all untreated. Median age 65 (42–80). They were randomized in two arms A and B. Arm A patients -27- were treated with lipoplatin-paclitaxel and Arm B patients -27- with cisplatin-paclitaxel. Arm A: 24 male, 3 female, histology: 10 squamous, 10 adenocarcinomas, 7 undifferentiated. Stage: IIIa 4 patients, IIIb 11 pat., IV 12 pat. Arm B: 25 males, 2 female, histology: 11 squamous, 11 adenocarcinomas, 5 undifferentiated, stage IIIa 2 pat., IIIb 14 pat., IV 11 pat. Arm A Chemotherapy: Lipoplatin 200 mg/m2 Paclitaxel 135 mg/m2 administered on day 1 repeated every 2 weeks. Lipoplatin infused for 8 hours in 5% dextrose 1 lt. Arm B: cisplatin 75 mg/m2 (hydration of 2 lt) and paclitaxel 135 mg/m2, every two weeks. Each day treatment was 1 cycle and the plan was to give 9 cycles per patient unless disease progression was detected before 9th cycle. Results: Response: Arm A: PR: 48.15% SD: 37.03% PD: 3.7% and clinical benefit 11.11%. Arm B: PR 44.44% SD 44.44% PD: 3.7% and clinical benefit 7.41%. Toxicity: Arm A: Renal toxicity in 1 pat. (3.70%) neurotoxicity grade I-II in 7 pat. (25.92%) Nausea-vomit in 5 patients (18.52%) Myelotoxicity Grade I-II in 10 pat. (37.04%). Arm B: Renal toxicity in 7 pat. (25.92%), Neurotoxicity Grade I-III in 12 pat. (44.44%) Nausea-vomit in 7 pat. (25.92%) Myelotoxicity Grade I-III in 17 pat. (62.96%). Conclusions: Preliminary results showed liposomal cisplatin compared with cisplatin each one combined with paclitaxel, the response rate was similar but toxicity and in particular nephrotoxicity, neurotoxicity, and myelotoxicity was significantly lower in liposomal cisplatin arm. No significant financial relationships to disclose.
Role of ERCC1, XRCC3, Aurora A and TGFBR1 single-nucleotide polymorphisms (SNP) and CHFR and 14–3-3σ methylation in a customized cisplatin (cis) trial based on ERCC1 mRNA levels in stage IV non-small cell lung cancer (NSCLC) patients (pts)
Authors: Taron M. , Cobo M. , Isla D. , Massuti B. , Montes A. , Sanchez J. , Botia M. , Domine M. , Sanchez-Ronco M. , Rosell R. 
Published: March 2020

7687 Background: The primary aim of this trial was response. In both the control arm and in the genotypic arm with low tumor ERCC1 mRNA levels, pts received docetaxel (doc)/cis; in the genotypic arm with high tumor ERCC1 mRNA levels, pts received doc/gemcitabine. Response was significantly higher in the genotypic arms. We examined 324 pts for genetic markers that could influence response, including ERCC1 118 C/T, ERCC1 C8092A, XRCC3 241 (Thr to Met), Aurora A 91 T>A, Aurora A 169G>A, a SNP within intron 7 of the TGFBR1 gene (Int7G24A), and an in-frame germline deletion (TGFBR1*6A). Methylation of 14–3-3s and CHFR were also analyzed. Methods: DNA from peripheral lymphocytes was used for genotyping (Taqman assay) and methylation-specific PCR was used for 14–3- 3s and CHFR in pretreatment serum DNA. Results: There were no differences in clinical characteristics among the different SNP types, except that pts with Aurora A 91 AA had higher tumor ERCC1 mRNA levels (P=0.005). No relationship was found between ERCC1 SNPs and tumor ERCC1 mRNA levels. A strong correlation was found between the Int7G24A and XRCC3 241 SNPs (P=0.03). The Int7G24A GA type had a higher odds ratio (OR) of response (OR 2.32) than the AA type (OR 3.15) (P=0.02). XRCC3 241 MetMet had a lower probability of response (OR 0.23) (P=0.04). No other differences in response were observed according to any of the other SNPs or methylation. In the multivariate model, the best response was observed in pts with performance status (PS) 0, low ERCC1 levels, and XRCC3 241 SNP ( Table ). Conclusions: Further research is warranted to define the role of theTGFBR1 Int7G24A gene in customized treatments. No significant financial relationships to disclose. [Table: see text]
Phase II trial of oxaliplatin, pemetrexed, and bevacizumab in previously-treated advanced non-small cell lung cancer (NSCLC)
Authors: Heist R. S. , Fidias P. , Huberman M. , Temel J. , Sequist L. , Lynch T. J. 
Published: March 2020

7700 Background: Single agent chemotherapy is standard for second and third line therapy of NSCLC. Combination therapy has to date not proven to be superior to single agents –often adding additional toxicity without any additional efficacy. We investigated whether the combination of oxaliplatin, pemetrexed, and bevacizumab was an active and tolerable regimen in the pre-treated advanced NSCLC setting. Methods: In this two-stage phase II trial, patients received pemetrexed (500 mg/m2), oxaliplatin (120 mg/m2), and bevacizumab (15 mg/kg) on day 1 of every 21 day cycle, for a total of 6 cycles or until disease progression. Eligibility criteria included PS 0–1, non-squamous histology, and at least one prior chemotherapy regimen. Patients with treated brain metastases were allowed on this trial. The primary endpoint was response rate, with secondary endpoints of TTP, PFS, and OS. Results: 36 patients were enrolled on this study. Patient characteristics for 32 for which data is available were: 16 (50%) women, 16 (50%) men, 26 (81%) adenocarcinoma, 6 (19%) large cell or NSCLC, 6 (19%) treated brain metastases. Of the 31 patients evaluable for tumor response, 0 had CR, 8 (25%) had PR, 14 (44%) had SD, and 9 (28%) had PD. One patient experienced Grade V hemoptysis after cycle 2 before restaging. Nine patients experienced a Grade III/IV serious adverse event. These Grade III/IV toxicities included: cardiac ischemia (1), sensory neuropathy (1), dyspnea (1), anemia (1), constipation (1), fatigue (1), colitis (1), face pain (1), hyperglycemia (1), elevated ALT (1). Among the 6 patients with treated brain metastases, there was 1 PR, 2 SD, 2 PD, and one patient with Grade V hemoptysis whose response could not be assessed; there were no brain hemorrhage events. Data for PFS and OS are preliminary; estimated median PFS is 5.8 months (95% CI 3.8 - 8.9 mo), and estimated OS is 10.9 mo (95% CI 6.4 - 20 mo). Updated data will be presented at the time of the meeting. Conclusions: This data suggests that the combination of pemetrexed, oxaliplatin, and bevacizumab is tolerable and has a promising response rate. Updated data will be presented at the meeting. No significant financial relationships to disclose.
Up-regulation of inflammatory and thrombotic mediators in lung cancer and their modulation by oral anticoagulantion
Authors: Fareed J. , Ciftci A. , Demir M. , Hoppensteadt D. , Altiay G. , Tobu M. , Iqbal O. , Fareed D. , Bick R. , Sheikh A. 
Published: March 2020

7705 Background: Venous thromboembolic events (VTE) are associated with lung cancer and significantly contributes to the increased mortality in these patients. While the increased prevalence of VTE is fully recognized in lung cancer, its pathogenesis is not fully understood at this time. Even the patients undergoing therapeutic interventions are at high risk to develop VTE. Profiling of surrogate markers of thrombosis and inflammation provides an opportunity to understand the pathogenesis of thrombosis in these patients. Methods: In a prospective, randomized, controlled study patients with inoperable lung cancer (n=100) were randomized to receive chemotherapy, radiation and warfarin (INR 1.5–2.5) or chemotherapy, radiation without warfarin (n=50). Blood samples were drawn prior to and after the second treatment cycle with warfarin. All samples were analyzed for such inflammation markers as the tumor necrosis factor alpha (TNF a), CD 40 ligand (CD 40L), C-reactive protein (CRP), interleukin 1 beta (IL-1β), asymmetric dimethylarginine (ADMA) and nitric oxide (NO). In addition, prothrombin fragment F1.2 (F1.2) and thrombin antithrombin complex (TAT) were also measured. Results: The results are summarized in the following table . All of the surrogate markers of inflammation showed a decreased trend (13–50%) in the warfarin treated group, whereas the non-warfarin treated group exhibited an increase (18–46%) in all markers except CRP and ADMA. The markers of thrombin generation were down regulated in the warfarin treated group. Conclusions: The levels of various inflammatory markers are upregulated in lung cancer suggesting a pathogenic role of this process in lung cancer. Warfarin down regulated the inflammatory and thrombogenic processes in contrast to the non-warfarin treated group. The clinical relevance of these observations require additional analysis. No significant financial relationships to disclose. [Table: see text]
Impact of induction chemotherapy and adjuvant radiation therapy on outcome after extrapleural pneumonectomy for malignant pleural mesothelioma
Authors: de Perrot M. , Feld R. , Anraku M. , Bezjak A. , Burkes R. , Roberts H. , Cho J. , Visbal A. , Leighl N. , Keshavjee S. , Johnston M. 
Published: March 2020

7708 Background: Examine the results of tri-modality therapy for malignant pleural mesothelioma (MPM). Methods: Protocol consisted of induction cisplatin-based chemotherapy, followed by extrapleural pneumonectomy (EPP) and adjuvant hemithoracic radiation therapy (RT) to 54 Gy. Results: A total of 60 patients were suitable candidates for tri-modality therapy between 01/2001 and 01/2007. Induction chemotherapy was administered to 56 patients; 4 patients underwent EPP without induction chemotherapy because of patient refusal (n=2), previous chemotherapy (n=1) and sarcomatoid MPM (n=1). Chemotherapy included vinorelbine/cisplatin (n=26), pemetrexed/cisplatin (n=26) and gemcitabine/cisplatin (n=4). EPP was performed in 47 patients; 13 patients did not undergo EPP because of tumor progression during chemotherapy (n=2), extensive chest wall involvement at surgery (n=6), or involvement of mediastinal lymph nodes at mediastinoscopy (n=5). Three patients (6%) died within 30 days of surgery. Pathological stage was II (n=6), III (n=35), and IV (n=6). Adjuvant RT was administered postoperatively to 36 patients and is ongoing in 5 patients; 6 patients did not receive adjuvant RT because of fatigue (n=5) or previous RT (n=1), and 4 patients did not complete RT up to 54 Gy. Overall survival for the 23 patients who completed the tri-modality therapy was 37% at 3 years with a median survival of 15 months. Eleven of the 23 patients had recurrence after a median of 8 months (range, 2–13 months). Recurrences were locoregional (n=2), in contralateral chest (n=3), abdomen (n=3), contralateral chest and abdomen (n=2), or pericardium (n=1). Among patients undergoing EPP, disease-free survival was longer in patients undergoing adjuvant high dose hemithoracic RT (p=0.07), in epithelial tumors (p=0.03), and in early stage (p=0.07). Overall survival was influenced by histology (p=0.007) and stage (p=0.05), but not by adjuvant high dose hemithoracic RT (p=0.5). The type of chemotherapy had no impact on disease-free and overall survival. Conclusions: Aggressive tri-modality therapy is feasible in selected patient with MPM. Adjuvant high dose hemithoracic RT can improve disease free survival and achieve good local control. No significant financial relationships to disclose.
Effect of family history on lung cancer outcomes
Authors: Ganti A. , Loberiza F. R. , Kessinger A. 
Published: March 2020

7711 Background: Risk factors for development of lung cancer includes a family history of the disease, especially if younger and multiple family members are affected. The effect of family history on lung cancer outcomes is unknown. A study was conducted to investigate this question. Methods: The following data were abstracted from the medical records of patients with lung cancer seen in the Medical Oncology clinic by one of the authors (AK, AG) between 1999 and 2006: age, gender, smoking history, family history, stage, treatment and survival. χ2 test and Wilcoxon test were used for univariate comparisons based on family history of lung cancer. Cox Proportional Hazards regression analysis was used to evaluate the adjusted risk of death by family history. Univariate probability of survival was computed using Kaplan Meier estimate and compared using the log rank test. Results: Two hundred and eighty-nine of the 560 patients studied (51%) were male and 519 (93%) had a smoking history. Median age at diagnosis was 63 years (range: 16 - 89 yrs). Of the 148 patients (26%) with a family history of lung cancer, 115 had an affected first degree relative. The histology of the patients’ malignancy was: adenocarcinoma - 227 (41%), squamous cell - 103 (18%), small cell - 93 (17%) and other non-small cell carcinoma - 137 (24%). There was no effect of family history on histology or stage at diagnosis. Median survival in patients with a family history was 53 months compared to 58 months in patients without such a history (p = 0.06). On multivariate analysis, after adjusting for age, histology, stage at diagnosis, and smoking history, patients with a family history of lung cancer had a relative risk of death of 1.65 (95% CI: 1.07 - 2.56) (p = 0.02) compared to those without a family history ( Table ). This risk was especially increased in those who had an affected first degree relative (RR: 1.72; 95% CI: 1.08 - 2.75, p = 0.02). Conclusions: Lung cancer patients who have a first degree relative with lung cancer appear to have a worse outcome than those without a family history of lung cancer. No significant financial relationships to disclose. [Table: see text]
Activated Src kinase is expressed in malignant pleural mesothelioma tumors; dasatinib inhibition leads to cytotoxicity, cell cycle inhibition, and prevention of invasion and migration
Authors: Tsao A. S. , He D. D. , Saigal B. , Liu S. , Lee J. , Bakkannagari S. , Ordonez N. , Hong W. , Wistuba I. , Johnson F. 
Published: March 2020

7713 Background: Malignant pleural mesothelioma (MPM) is a lethal disease with few effective therapeutic options. We sought to determine whether Src, a non-receptor tyrosine kinase, could be a new therapeutic target in MPM and to establish the potential therapeutic use of pharmacologic Src inhibitors in this disease. Methods: We analyzed four MPM cell lines (MSTO-211H, NCI-H28, NCI-H2052, and NCI- H2452) for immunohistochemical (IHC) expression of total and phosphorylated Src (Tyr 419, Tyr 530). These cell lines were treated with dasatinib, a Src inhibitor, and evaluated for apoptosis, cell cycle analysis, and migration and invasion. Downstream signaling events were studied by Western blot analysis. We also conducted IHC analyses with total Src, phosphorylated Src Tyr 419 (p-Src Tyr 419), and phosphorylated Src Tyr 530 on 46 archived MPM tumor specimens and correlated the biomarker results with the clinical outcome. Results: All four MPM cell lines expressed total and activated Src (p-Src Tyr 419). Three of the four cell lines were sensitive in vitro to cytotoxicity by dasatinib with inhibition of migration and invasion, cell cycle inhibition, and apoptosis. Treatment with dasatinib inhibited several pathways downstream of Src. In the archived MPM tumor specimens, Src protein was highly expressed on IHC analysis in tumor cells, but that expression did not correlate with overall or progression-free survival. However, expression of activated Src (p-Src Tyr 419) on the tumor cell membrane was higher in patients with stage 4 disease; the presence of metastasis correlated with higher membrane (P = 0.03) and cytoplasmic (P = 0.04) expression of p-Src Tyr 419. MPM nodal involvement at N1 was associated with the highest membrane expression of inactive Src (p-Src Tyr 530) (P = 0.02), whereas N2 disease was associated with the lowest expression. No gene mutations in Src exon 12 were found in the cell lines or tumor specimens. Conclusions: Activated Src may have an important role in survival, metastasis, and invasion in MPM, and targeting Src may be an important therapeutic strategy. No significant financial relationships to disclose.
Clinical outcomes of adjuvant treatments for invasive thymoma: Dose chemotherapy influence prognosis?
Authors: Jeong S. , Cho B. , Jung J. , Im C. , Kim Y. , Choi H. , Park M. , Kim S. , Chung K. , Kim J. 
Published: March 2020

7715 Background: The aim of this study was to evaluate therapeutic outcomes and to validate prognostic factors, including adjuvant chemotherapy, in resected thymoma patients who received adjuvant treatment. Methods: One hundred thymoma patients who received post-surgical adjuvant therapy from 1995 to 2005 were retrospectively reviewed. 55 patients received only radiotherapy for the adjuvant therapy, while 45 patients received both radiotherapy and chemotherapy. The total radiation dose was 45–63 Gy, with a median dose of 50.4 Gy. The chemotherapy consisted of 6 cycles of doxorubicin, cisplatin, vincristine, and cyclophosphamide. Treatments were applied every 3–4 weeks. The median follow-up duration was 65 months (range, 5–200 months). Results: The 5-year overall survival (OS) and disease- free survival (DFS) rates were 75.7% (89.2% in stage II, 67.9% in stage III, and 52.1% in stage IVA) and 70.3% (83% in stage II, 62.4% in stage III, and 33.6% in stage IVA) respectively. According to multivariate analysis, the prognostic factors for OS were age, WHO histology, Masaoka stage, and recurrence, while pleural involvement and WHO histology had statistically significant impacts on DFS. Higher radiation dosage, positive resection margins, and adjuvant chemotherapy did not influence survival outcomes. The most common relapse site was the pleura (15 patients, 53.6%). The toxicity from chemotherapy and radiotherapy was manageable, with no deaths due to toxicity. Conclusion: The prognosis of invasive thymoma was poor despite adjuvant treatments with radiotherapy and chemotherapy. In addition to WHO histology, pleural involvement was the most important prognostic factor for recurrence. The pleura was the most common relapse site. Therefore, new modalities to reduce pleural recurrence are warranted. No significant financial relationships to disclose.