| 41. |
- Moreira, Andre L., et al.
(författare)
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A Grading System for Invasive Pulmonary Adenocarcinoma : A Proposal From the International Association for the Study of Lung Cancer Pathology Committee
- 2020
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Ingår i: Journal of Thoracic Oncology. - : ELSEVIER SCIENCE INC. - 1556-0864 .- 1556-1380. ; 15:10, s. 1599-1610
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: A grading system for pulmonary adenocarcinoma has not been established. The International Association for the Study of Lung Cancer pathology panel evaluated a set of histologic criteria associated with prognosis aimed at establishing a grading system for invasive pulmonary adenocarcinoma. Methods: A multi-institutional study involving multiple cohorts of invasive pulmonary adenocarcinomas was conducted. A cohort of 284 stage I pulmonary adenocarcinomas was used as a training set to identify histologic features associated with patient outcomes (recurrence-free survival [RFS] and overall survival [OS]). Receiver operating characteristic curve analysis was used to select the best model, which was validated (n = 212) and tested (n = 300, including stage I-III) in independent cohorts. Reproducibility of the model was assessed using kappa statistics. Results: The best model (area under the receiver operating characteristic curve [AUC] = 0.749 for RFS and 0.787 for OS) was composed of a combination of predominant plus high-grade histologic pattern with a cutoff of 20% for the latter. The model consists of the following: grade 1, lepidic predominant tumor; grade 2, acinar or papillary predominant tumor, both with no or less than 20% of high-grade patterns; and grade 3, any tumor with 20% or more of high-grade patterns (solid, micropapillary, or complex gland). Similar results were seen in the validation (AUC = 0.732 for RFS and 0.787 for OS) and test cohorts (AUC = 0.690 for RFS and 0.743 for OS), confirming the predictive value of the model. Interobserver reproducibility revealed good agreement (k = 0.617). Conclusions: A grading system based on the predominant and high-grade patterns is practical and prognostic for invasive pulmonary adenocarcinoma. (C) 2020 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.
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| 42. |
- Nicholson, Andrew G., et al.
(författare)
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Interobserver Variation among Pathologists and Refinement of Criteria in Distinguishing Separate Primary Tumors from Intrapulmonary Metastases in Lung
- 2018
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Ingår i: Journal of Thoracic Oncology. - : ELSEVIER SCIENCE INC. - 1556-0864 .- 1556-1380. ; 13:2, s. 205-217
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Tidskriftsartikel (refereegranskat)abstract
- Multiple tumor nodules are seen with increasing frequency in clinical practice. On the basis of the 2015 WHO classification of lung tumors, we assessed the reproducibility of the comprehensive histologic assessment to distinguish second primary lung cancers (SPLCs) from intrapulmonary metastases (IPMs), looking for the most distinctive histologic features. An international panel of lung pathologists reviewed a scanned sequential cohort of 126 tumors from 48 patients and recorded an agreed set of histologic features, including tumor typing and predominant pattern of adenocarcinoma, thereby opining whether the case was SPLC, IPM, or a combination thereof. Cohen kappa statistics of 0.60 on overall assessment of SPLC or IPM indicated a good agreement. Likewise, there was good agreement (kappa score 0.64, p < 0.0001) between WHO histologic pattern in individual cases and SPLC or IPM status, but the proportions diversified for histologic pattern and SPLC or IPM status (McNemar test, p < 0.0001). The strongest associations for distinguishing between SPLC and IPM were observed for nuclear pleomorphism, cell size, acinus formation, nucleolar size, mitotic rate, nuclear inclusions, intraalveolar clusters, and necrosis. Conversely, the associations for lymphocytosis, mucin content, lepidic growth, vascular invasion, macrophage response, clear cell change, acute inflammation keratinization, and emperipolesis did not reach significance with tumor extent. Comprehensive histologic assessment is recommended for distinguishing SPLC from IPM with good reproducibility among lung pathologists. In addition to main histologic type and predominant patterns of histologic subtypes, nuclear pleomorphism, cell size, acinus formation, nucleolar size, and mitotic rate strongly correlate with pathologic staging status.
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| 43. |
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| 44. |
- Nisman, Benjamin, et al.
(författare)
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Serum Thymidine Kinase 1 Activity in the Prognosis and Monitoring of Chemotherapy in Lung Cancer Patients : A Brief Report
- 2014
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Ingår i: Journal of Thoracic Oncology. - 1556-0864 .- 1556-1380. ; 9:10, s. 1568-1572
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Thymidine kinase 1 (TK1) is a metabolic enzyme involved in DNA synthesis. Most standard treatment protocols for lung cancer (LC) include cytotoxic agents, which are potential modulators of TK1. We aimed to assess the prognostic significance of serum TK1 activity and its role in monitoring chemotherapy in LC patients. Methods: TK1 activity was measured using the DiviTum (Biovica) assay in sera from 233 patients with non-small-cell lung cancer (NSCLC), 91 with small-cell lung cancer (SCLC), and 90 with benign lung disease. Results: TK1 activity was significantly associated with age, performance status, and stage in NSCLC and with stage and weight loss in SCLC. In multivariate analysis, pretreatment TK1 activity, adjusted for performance status, stage, and weight loss, independently affected survival in NSCLC (relative risk = 1.45, p = 0.031) and SCLC (relative risk = 2.49, p = 0.001). In NSCLC patients, adjusted elevated TK1 activity (>100 Du/L) at pretreatment was a significant predictor of treatment failure (odds ratio = 2.55, p = 0.01). A small (less than twofold) increase in TK1 activity after the first and second cycle of chemotherapy was significantly associated with treatment failure and poor overall survival. Conclusions: Elevated pretreatment serum TK1 activity was an independent, adverse prognostic factor, based on survival, in the two main histological types of LC. A small (less than twofold) increase in TK1 activity after the first and second cycle of chemotherapy was associated with treatment failure and poor overall survival.
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| 45. |
- Nyman, J., et al.
(författare)
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Dose Escalated Chemo-RT to 84 Gy in Stage III NSCLC Appears Excessively Toxic : Results from a Randomized Phase II Trial
- 2018
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Ingår i: Journal of Thoracic Oncology. - : Elsevier. - 1556-0864 .- 1556-1380. ; 13:10, s. S373-S373
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Concurrent chemoradiotherapy is the mainstay treatment for NSCLC stage III disease, however, with a rather high probability of locoregional and metastatic recurrence further treatment optimization is warranted. Based on previous one-armed trials with dose escalated radiotherapy, showing feasibility, the Swedish Lung Cancer Study Group aimed to investigate whether dose escalation based on individual normal tissue constraints could improve outcome in this randomized phase II trial.Method: NSCLC patients with stage III disease, good performance status (0-1), adequate lung function (FEV1 > 1.0 L and CO diff. > 40%) received three cycles of cisplatin (75 mg/m2 day 1) and vinorelbine (25 mg/m2 day 1 and 8) every third week. The radiotherapy started concurrently with the second cycle, with either 2 Gy daily, 5 days a week, to a total dose of 68 Gy (standard arm A) or escalated therapy (B) based on constraints to the spinal cord, esophagus and lungs up to 84 Gy by adding an extra fraction of 2 Gy per week while keeping the total treatment time constant at seven weeks with the same dose to involved nodes and primary tumor.Result: A pre-planned safety analysis revealed excessive toxicity and decreased survival in the escalated arm, and the study was stopped. Thirty-six patients were included during 2011-2013 (56% male, 78% with adenocarcinoma, 64% with PS 0 and 53% with stage IIIB). The median progression-free survival (PFS) and overall survival (OS) were 11 and 17 months in the dose escalated group compared to 28 and 45 months in the standard group. The 1-, 3- and 5-year survival rates were 56%, 33% and 17% in the escalated arm and 72%, 61% and 34% in the standard arm. There were four toxicity-related deaths due to esophageal perforations (one in arm A and three in arm B) and three deaths due to pneumonitis (one in arm A and two in arm B).Conclusion: Dose-escalated concurrent chemoradiotherapy to 84 Gy to primary tumor and nodal disease is hazardous, with a high risk of excessive toxicity, whereas modern standard dose chemoradiotherapy with proper staging given in the control arm shows a promising outcome with a median survival of 45 months and a 5-year survival of 34%. A possible step forward will be to improve systemic therapy, but future approaches with escalated radiotherapy may include boost techniques to remaining PET positive areas or different escalation schedules to the primary tumor and mediastinal nodes.
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| 46. |
- Osarogiagbon, RU, et al.
(författare)
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Early-Stage NSCLC: Advances in Thoracic Oncology 2018
- 2019
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Ingår i: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer. - : Elsevier BV. - 1556-1380. ; 14:6, s. 968-978
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Tidskriftsartikel (refereegranskat)
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| 47. |
- Qvick, Alvida, 1990-, et al.
(författare)
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Circulating miRNA : a biomarker for classification of lung cancer and benign lung disease
- 2019
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Ingår i: Journal of Thoracic Oncology. - : Elsevier. - 1556-0864 .- 1556-1380. ; 14:10, s. 311-311
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background Circulating biomarkers for cancer have great potential for diagnosis as well as follow up of treatment. MicroRNAs (miRNA) are involved in the expression of a majority of proteins with different cell types having different miRNA expression. The aim of this study was to create a circulating miRNA-based model to discriminate patients with lung cancer from patients with benign lung disease. Methods Samples were collected from patients under investigation for lung cancer at Örebro University hospital. Patients were then divided into groups based on diagnosis, which resulted in NSCLC adenocarcinoma (n=24), NSCLC squamous cell carcinoma (n=13), SCLC (n=4) and a heterogeneous group consisting of different benign lung diseases (n=19). Healthy controls were collected separately (n=17). Circulating miRNA was processed using the extraction-free library preparation miRNA Whole Transcriptome Assay with probes for 2083 human mature miRNAs and analyzed with massive parallel sequencing. Differential expression between groups was estimated using edgeR. MiRNAs that had the highest impact on patient grouping were used in a sPLS discriminant analysis. The resulting classification model was validated using the leave-one-out method. Results The final model for comparison between patients with benign lung disease and patients with lung cancer contained 19 miRNAs. The model had an error rate of 15 % with errors distributed evenly between groups. A sub-analysis of patients with mutations in EGFR (n=5) and KRAS (n=6) was performed showing two distinct patterns in miRNA expression. Conclusion MiRNA shows promise as a circulating biomarker for lung cancer but may not be sufficient as an independent classifier. The predictive power may be improved by using several biomarkers in combination. The difference in expression between tumors with different mutations may be derived from alternate driving processes in these tumors.Sequencing results were standardized as counts per million (cpm), miRNA with cpm < 100 was filtered out and quantile normalization and log2 transformation was performed. Differential expression was analyzed using regression model (R software v. 3.5.1, package edgeR v. 3.24.1) with Benjamini-Hochberg correction. The miRNAs that, after correction, had a significant impact on sample groups were kept and analyzed with sparse partial least squares-regression. The resulting model was validated using leave-one-out method.
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| 48. |
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| 49. |
- Rittmeyer, Achim, et al.
(författare)
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Health-Related Quality of Life in Patients with Advanced Nonsquamous Non-Small-Cell Lung Cancer Receiving Bevacizumab or Bevacizumab-Plus-Pemetrexed Maintenance Therapy in AVAPERL (MO22089)
- 2013
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Ingår i: Journal of Thoracic Oncology. - : Lippincott, Williams and Wilkins. - 1556-0864 .- 1556-1380. ; 8:11, s. 1409-1416
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: In the phase III AVAPERL trial, patients with advanced nonsquamous non-small-cell lung cancer receiving bevacizumab-plus-pemetrexed maintenance after first-line induction had a significant progression-free survival benefit relative to those treated with single-agent bevacizumab maintenance but with an increase in grade 3 adverse events. Here, we compare health-related quality of life (HRQOL) between AVAPERL maintenance arms. less thanbrgreater than less thanbrgreater thanMethods: Patient-reported outcomes were collected at designated intervals from preinduction to final visits. HRQOL was assessed using the self-administered European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and the Quality of Life Lung Cancer-Specific Module 13. Differences in scores of 10 points or more between arms were above the minimum important difference threshold and considered clinically meaningful. less thanbrgreater than less thanbrgreater thanResults: During induction, patient-reported coughing symptoms improved slightly, whereas fatigue and appetite loss scores worsened relative to preinduction baseline. During maintenance, changes in mean global health status and the majority of Quality of Life Questionnaire Core 30 and Quality of Life Lung Cancer-Specific Module 13 subscale scores did not differ between trial arms by the minimum important difference defining clinically meaningful (better or worse) patient-reported outcomes. Exceptions were patient-reported role functional status, fatigue symptoms and appetite loss symptoms (favoring bevacizumab), and pain in arm or shoulder symptoms (favoring bevacizumab-plus-pemetrexed maintenance), which differed by clinically meaningful amounts at more than one maintenance assessment. less thanbrgreater than less thanbrgreater thanConclusions: In AVAPERL, HRQOL remained relatively stable throughout maintenance and was generally similar in both arms. Despite an increase in adverse event rates, the addition of pemetrexed to bevacizumab maintenance resulted in similar stabilization of disease symptoms with improved efficacy outcomes.
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