scholarly journals A computational modeling approach for dosing endoscopic intratumoral chemotherapy for advanced non-small cell lung cancer

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Vitor Mori ◽  
Jason H. T. Bates ◽  
Michael Jantz ◽  
Hiren J. Mehta ◽  
C. Matthew Kinsey
Keyword(s):  
Lung Cancer ◽  
Computational Modeling ◽  
Small Cell Lung Cancer ◽  
Power Law ◽  
Cell Lung Cancer ◽  
Lung Tumor ◽  
Small Cell ◽  
Small Cell Lung ◽  
Actual Patient ◽  
Clinical Responses

AbstractWe recently developed a computational model of cisplatin pharmacodynamics in an endobronchial lung tumor following ultrasound-guided transbronchial needle injection (EBUS-TBNI). The model suggests that it is more efficacious to apportion the cisplatin dose between injections at different sites rather than giving it all in a single central injection, but the model was calibrated only on blood cisplatin data from a single patient. Accordingly, we applied a modified version of our original model in a set of 32 patients undergoing EBUS-TBNI for non-small cell lung cancer (NSCLC). We used the model to predict clinical responses and compared them retrospectively to actual patient outcomes. The model correctly predicted the clinical response in 72% of cases, with 80% accuracy for adenocarcinomas and 62.5% accuracy for squamous-cell lung cancer. We also found a power-law relationship between tumor volume and the minimal dose needed to induce a response, with the power-law exponent depending on the number of injections administered. Our results suggest that current injection strategies may be significantly over- or under-dosing the agent depending on tumor size, and that computational modeling can be a useful planning tool for EBUS-TBNI of cisplatin in lung cancer.

Serum Antibody Against NY-ESO-1 and XAGE1 Predicts Clinical Responses to Anti-PD-1 Therapy in Non-Small-Cell Lung Cancer

2018 ◽  
Author(s):  
Yoshihiro Ohue ◽  
Koji Kurose ◽  
Takahiro Karasaki ◽  
Midori Isobe ◽  
Takaaki Yamaoka ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Serum Antibody ◽  
Small Cell ◽  
Small Cell Lung ◽  
Clinical Responses

Prognostic impact of c-Met/phospho-Met, and topoisomerase I in small cell lung cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e17540-e17540
Author(s):  
Hideko Ikeda ◽  
Hayato Koba ◽  
Koji Kurokawa ◽  
Shingo Nishikawa ◽  
Tomoyuki Araya ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Prognostic Factor ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Lung Tumor ◽  
Small Cell ◽  
Independent Prognostic Factor ◽  
High Expression ◽  
Prognostic Impact ◽  
Small Cell Lung

e17540 Background: The hepatocyte growth factor/MET pathway has been shown to cause tumor progression in several types of carcinomas. We reported that c-Met up-regulated topoisomease I (Topo I) in non-small cell lung cancer cell lines (submitted for publication). The aims of this study were 1) to examine the prognostic influence of c-MET/phospho-MET (p-Met), or Topo I expression and 2) to elucidate correlation between c-Met/p-Met expression and Topo I expression in small cell lung cancer (SCLC). Methods: This retrospective study included 72 SCLC patients (pts) with available tumor tissue from primary lung tumor or metastatic lesions and clinical data including survival. We performed immunohistochemistry to detect c-MET/phospho-MET and Topo I expression. Results: Tumor tissues were obtained from 72 SCLC pts. Sixty-six pts, (51 male, 15 female, median age 67.5 range 43-91, LD/ED 38/28, PS0,1/2,3,4 57/9) were evaluated. c-Met overexpression was seen in 40.9%, p-Met in 74.2%, and Topo I expression in 59.1%, respectively. High expression of Topo I associated with lower response rate (RR) (96.7% in low group vs 78.4% in high group, p=0.029) and shorter progression-free survival (PFS) (65W vs 39W, p=0.040) but did not correlate with overall survival (OS). Phosphorylation of Met protein did not correlate with RR, PFS or OS. Interestingly, intensity of p-Met significantly correlated with Topo I expression (p=0.048). High expression of c-Met protein did not associated with RR or PFS but significantly associated with shorter OS (high 53W, low 95W, p=0.018). Multivariate analysis which included c-Met, stage, PS, and age resulted that c-Met was an independent prognostic factor for OS of pts with SCLC (HR; 2.144, 95% confidence interval 1.162-3.956, p=0.015). Conclusions: This study suggested c-Met high expression was an independent prognostic factor, and Topo I was up-regulated by Met in SCLC.

Significance of EGFR and KRAS gene mutation in small cell lung cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e18564-e18564 ◽  
Author(s):  
Koji Kurokawa ◽  
Tomoharu Matsui ◽  
Hideko Ikeda ◽  
Shingo Nishikawa ◽  
Takashi Sone ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kras Mutation ◽  
Egfr Mutation ◽  
Kinase Inhibitor ◽  
Lung Tumor ◽  
Small Cell ◽  
Driver Mutations ◽  
Small Cell Lung

e18564 Background: In non-small cell lung cancer, epidermal growth factor receptor (EGFR) and KRAS are known as driver mutations. However the association between these gene alteration and small cell lung cancer (SCLC) has been unclear. The aim of this study is to investigate the gene status of EGFR and Kras in SCLC. Methods: This retrospective study included 66 SCLC patients with available tumor tissue from primary lung tumor or metastatic and clinical data including survival. We evaluated for the presence of EGFR and KRAS mutation those patients using Scorpion-ARMS method. This study was approved by IRB. Results: Sixty-six patients (52 male,14 female median age 68 range 49-89, LD/ED 34/32, PS0-1/2-3 57/9, smoker/never smoker 64/2) were evaluated. Their median overall survival (OS) were 484 days, progression-free survival (PFS) were 217 days. Sixty-six samples were evaluated EGFR mutation test and 61 were evaluated KRAS mutation test by Scorpion-ARMs methods. SCLC patients with EGFR mutation were the only one patients (1.5%,1/66). KRAS mutation were also the only one patients (1.6%,1/61). A 54 years-old nevere-smoker female was already treated with EGFR tyrosine kinase inhibitor for non-small cell lung cancer, the patients with EGFR mutation had a transformation into SCLC. The KRAS mutation patient was combined SCLC with adenocarcinoma. Conclusions: This study suggested that EGFR and KRAS patients associated with SCLC is poor, these driver mutation is unnecessary for common SCLC.

O-152 Immunotherapy with gene-modified allogenic cells successfully induced CD8 T cell and clinical responses in patients with advanced non-small cell lung cancer (NSCLC)

Lung Cancer ◽  
2003 ◽  
Vol 41 ◽  
pp. S46-S47
Author(s):  
Luis E. Raez ◽  
Peter A. Cassileth ◽  
James Schlesselman ◽  
Swaminathan Padmanabhan ◽  
Eva Fisher ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cell ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Cd8 T Cell ◽  
Small Cell ◽  
Small Cell Lung ◽  
Clinical Responses

scholarly journals Cost-Efficient and Easy to Perform PCR-Based Assay to Identify Met Exon 14 Skipping in Formalin-Fixed Paraffin-Embedded (FFPE) Non-Small Cell Lung Cancer (NSCLC) Samples

Diagnostics ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 13
Author(s):  
Odharnaith O’Brien ◽  
Mark Wright ◽  
Cathal O’Brien ◽  
Orla Geoghegan ◽  
Niamh Leonard ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Diagnostic Testing ◽  
Small Cell ◽  
Small Cell Lung ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Clinical Responses ◽  
Cost Efficient

MET is a receptor tyrosine kinase (RTK) that plays important roles in carcinogenesis. Despite being frequently overexpressed in cancer, clinical responses to targeting this receptor have been limited. Recently novel splicing mutations involving the loss of exon 14 (called METex14 skipping) have emerged as potential biomarkers to predict for responsiveness to targeted therapies with Met inhibitors in non-small cell lung cancer (NSCLC). Currently, the diverse genomic alterations responsible for METex14 skipping pose a challenge for routine clinical diagnostic testing. In this report, we examine three different methodologies to detect METex14 and assess their potential utility for use as a diagnostic assay for both the identification of METex14 and intra-tumoural distribution in NSCLC.

Clinical observation of next-generation photodynamic therapy (NGPDT) for advanced non-small cell lung cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19028-e19028
Author(s):  
Li Jun Li
Keyword(s):  
Lung Cancer ◽  
Photodynamic Therapy ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Clinical Observation ◽  
Lung Tumor ◽  
Remission Rate ◽  
Small Cell ◽  
Next Generation ◽  
Small Cell Lung

e19028 Background: Clinical observation of next-generation photodynamic therapy (NGPDT) for advanced non-small cell lung cancer (NSCLC). Methods: Through pathology or cytology diagnosis, 66 cases of advanced non-small cell lung cancer patients were selected and randomly divided into two groups. The Next Generation Photodynamic Therapy (NGPDT) group had 32 patients. Photosensitizer was administered on a dosage of 2 mg per kilogram of body weight, wherein two-thirds via ultrasonic atomization inhalation and one-third via oral intake. After the irradiation target(s) were determined, optical fiber for laser treatment purposes was guided into lung tumor(s) via interstitial procedure, percutaneous puncture under precious laser navigation, irradiation light intensity was 200 J/cm2, irradiation power was 1,000 mw, activation was then started and lasted for eight to ten minutes, laser irradiation into tumor was two to five centimeters in length, irradiation could be performed phase by phase (sub-paragraph treatment) based on tumor size or irradiations could be performed repeatedly. While in the mean time in the chemotherapy/radiotherapy group (external beam radiotherapy + whole body chemotherapy) 34 cases were observed, 15 MV X ray radiation therapy irradiation field covers primary lung tumor lesion(s) and mediastinal lymphatic drainage area, dosage was 65-70 Gy, on every first day in a week of radiotherapy, 20 mg cisplatin was administered via intravenous application. Results: In the NGPDT group and simultaneous radiotherapy/chemotherapy group, one and two years survival rate were 93.75%, 70.60% and 68.75, 32.35% respectively (P <0.05). The complete remission rate and partial remission rate were 56.20% and 21.30%, rate of the NGPDT group was significantly higher than that of the corresponding radiotherapy and chemotherapy group, the difference was statistically significant (P <0.05). Conclusions: NGPDT can prolong survival in patients with advanced NSCLC, improving their quality of life; it is one of the most effective measures for advanced non-small cell lung cancer treatment.

Comparative T-cell oligoclonality in lung, tumor and lymph nodes in human non-small cell lung cancer

2005 ◽  
Author(s):  
Sophie Derniame ◽  
Jean-Michel Vignaud ◽  
Gilbert Faure ◽  
Marie Béné ◽  
Frédéric Massin
Keyword(s):  
Lung Cancer ◽  
T Cell ◽  
Lymph Nodes ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Lung Tumor ◽  
Small Cell ◽  
Small Cell Lung
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