|UK-Menu > Cancer Types > Lung Cancer|
Lung cancer is one of the most common types of cancer. The lungs are a pair of cone-shaped organs situated inside the chest, they bring oxygen into the body and take out waste carbon dioxide. There is a strong link between smoking and lung cancer. There are two main categories of lung cancer; Small Cell Lung Cancer (SCLC) , and Non-Small Cell Lung Cancer (NSCLC).
Around 42,000 people are diagnosed with lung cancer each year. (Source: Cancer Research UK)
This page shows only UK resources. For a more extensive list of resources from around the world see CancerIndex: Lung Cancer Information for Patients and the Public
Information for Health Professionals / Researchers
Latest Research Publications
Information Patients and the Public (7 links)
Information for Health Professionals / Researchers (5 links)
- PubMed search for publications about Lung Cancer - Limit search to: [Reviews]
PubMed Central search for free-access publications about Lung Cancer
MeSH term: Lung Neoplasms
US National Library of Medicine
PubMed has over 22 million citations for biomedical literature from MEDLINE, life science journals, and online books. Constantly updated.
Showing publications with corresponding authors from the UK (Source: PubMed).
Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer.
N Engl J Med. 2017; 376(7):629-640 [PubMed] Related Publications
Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer.
N Engl J Med. 2016; 375(19):1823-1833 [PubMed] Related Publications
Liquid Biopsy in Lung Cancer: A Perspective From Members of the Pulmonary Pathology Society.
Arch Pathol Lab Med. 2016; 140(8):825-9 [PubMed] Related Publications
First Clinical Investigation of Cone Beam Computed Tomography and Deformable Registration for Adaptive Proton Therapy for Lung Cancer.
Int J Radiat Oncol Biol Phys. 2016; 95(1):549-59 [PubMed] Related Publications
METHODS AND MATERIALS: The workflow was tested retrospectively for 20 consecutive lung cancer patients. A diffeomorphic Morphon algorithm was used to generate the lung vCT by deforming the average planning CT onto the CBCT scan. An additional correction step was applied to account for anatomic modifications that cannot be modeled by deformation alone. A set of clinical indicators for replanning were generated according to the water equivalent thickness (WET) and dose statistics and compared with those obtained on the rCT scan. The fast dose approximation consisted of warping the initial planned dose onto the vCT scan according to the changes in WET. The potential under- and over-ranges were assessed as a variation in WET at the target's distal surface.
RESULTS: The range-corrected dose from the vCT scan reproduced clinical indicators similar to those of the rCT scan. The workflow performed well under different clinical scenarios, including atelectasis, lung reinflation, and different types of tumor response. Between the vCT and rCT scans, we found a difference in the measured 95% percentile of the over-range distribution of 3.4 ± 2.7 mm. The limitations of the technique consisted of inherent uncertainties in deformable registration and the drawbacks of CBCT imaging. The correction step was adequate when gross errors occurred but could not recover subtle anatomic or density changes in tumors with complex topology.
CONCLUSIONS: A proton therapy workflow based on CBCT provided clinical indicators similar to those using rCT for patients with lung cancer with considerable anatomic changes.
Quantification of the smoking-associated cancer risk with rate advancement periods: meta-analysis of individual participant data from cohorts of the CHANCES consortium.
BMC Med. 2016; 14:62 [PubMed] Free Access to Full Article Related Publications
METHODS: This is a meta-analysis of 19 population-based prospective cohort studies with individual participant data for 897,021 European and American adults. For each cohort we calculated hazard ratios (HRs) for the association of smoking exposure with cancer outcomes using Cox regression adjusted for a common set of the most important potential confounding variables. RAPs (in years) were calculated as the ratio of the logarithms of the HRs for a given smoking exposure variable and age. Meta-analyses were employed to summarize cohort-specific HRs and RAPs.
RESULTS: Overall, 140,205 subjects had a first incident cancer, and 53,164 died from cancer, during an average follow-up of 12 years. Current smoking advanced the overall risk of developing and dying from cancer by eight and ten years, respectively, compared with never smokers. The greatest advancements in cancer risk and mortality were seen for lung cancer and the least for breast cancer. Smoking cessation was statistically significantly associated with delays in the risk of cancer development and mortality compared with continued smoking.
CONCLUSIONS: This investigation shows that smoking, even among older adults, considerably advances, and cessation delays, the risk of developing and dying from cancer. These findings may be helpful in more effectively communicating the harmful effects of smoking and the beneficial effect of smoking cessation.
Identification of Epigenetic Biomarkers of Lung Adenocarcinoma through Multi-Omics Data Analysis.
PLoS One. 2016; 11(4):e0152918 [PubMed] Free Access to Full Article Related Publications
Predicting death from surgery for lung cancer: A comparison of two scoring systems in two European countries.
Lung Cancer. 2016; 95:88-93 [PubMed] Related Publications
MATERIALS AND METHODS: We performed an internal validation using 2858 surgical patients from NLCA and an external validation using 3191 surgical patients from the Danish Lung Cancer Registry (DLCR). We calculated the proportion that died within 90 days of surgery. The discriminatory power of both scores was assessed by a receiver operating characteristic (ROC) and an area under the curve (AUC) calculation.
RESULTS: Ninety day mortality was 5% in both groups. AUC values for internal and external validation of NLCA score and validation of Thoracoscore were 0.68 (95% CI 0.63-0.72), 0.60 (95% CI 0.56-0.65) and 0.60 (95% CI 0.54-0.66) respectively. Post-hoc analysis was performed using NLCA records on 15554 surgical patients to derive summary tables for 30 and 90 day mortality, stratified by procedure type, age and performance status.
CONCLUSIONS: Neither score performs well enough to be advocated for individual risk stratification prior to lung cancer surgery. It may be that additional physiological parameters are required; however this is a further project. In the interim we propose the use of our summary tables that provide the real-life range of mortality for lobectomy and pneumonectomy.
Dataset for Reporting of Malignant Mesothelioma of the Pleura or Peritoneum: Recommendations From the International Collaboration on Cancer Reporting (ICCR).
Arch Pathol Lab Med. 2016; 140(10):1104-10 [PubMed] Free Access to Full Article Related Publications
OBJECTIVE: -To describe a dataset developed by the Expert Panel of the International Collaboration on Cancer Reporting for reporting malignant mesothelioma of both the pleura and peritoneum. The dataset is composed of "required" (mandatory) and "recommended" (nonmandatory) elements.
DESIGN: -Based on a review of the most recent evidence and supported by explanatory commentary.
RESULTS: -Eight required elements and 7 recommended elements were agreed upon by the Expert Panel to represent the essential information for reporting malignant mesothelioma of the pleura and peritoneum.
CONCLUSIONS: -In time, the widespread use of an internationally agreed upon, structured, pathology dataset for mesothelioma will lead not only to improved patient management but also provide valuable data for research and international benchmarks.
Cytochrome P450 Allele CYP3A7*1C Associates with Adverse Outcomes in Chronic Lymphocytic Leukemia, Breast, and Lung Cancer.
Cancer Res. 2016; 76(6):1485-93 [PubMed] Free Access to Full Article Related Publications
Percutaneous High-Energy Microwave Ablation for the Treatment of Pulmonary Tumors: A Retrospective Single-Center Experience.
J Vasc Interv Radiol. 2016; 27(4):474-9 [PubMed] Related Publications
MATERIALS AND METHODS: A retrospective review was undertaken of 44 patients (21 men, 23 women; median age, 66 y; range, 17-89 y) who underwent 62 sessions of high-energy MWA for 87 pulmonary tumors at a single tertiary referral center between June 2012 and June 2014. Primary tumor origin was sarcoma (n = 23), colorectal (n = 16), lung (n = 2), esophageal (n = 1), breast (n = 1), and bladder (n = 1). Median tumor size was 12 mm (range, 6-45 mm). Technical success was recorded contemporaneously, complication rate at 30 days was recorded prospectively, and technique effectiveness was assessed by longitudinal follow-up CT scan.
RESULTS: Primary technical success was achieved in 94% of ablation sessions. The median follow-up interval was 15 months (range, 6.2-29.5 mo) during which time local tumor progression was observed in two of 87 tumors (technique effectiveness 98%). Pneumothorax requiring chest tube insertion occurred in 19%; delayed pneumothorax occurred in four patients. No hemoptysis, infection, or other complications were recorded.
CONCLUSIONS: High-energy MWA is safe and effective for the destruction of lung tumors.
Non-Small Cell Lung Cancer, PD-L1, and the Pathologist.
Arch Pathol Lab Med. 2016; 140(3):249-54 [PubMed] Related Publications
OBJECTIVE: To discuss the possibility of biomarker selection of patients for these therapies. This is becoming a much debated issue, and the immunohistochemical detection of Programmed Death Ligand 1 (PD-L1), the ligand for the inhibitory Programmed Death receptor 1 (PD-1) checkpoint, is one possible biomarker. Data so far available show some conflicting results, but PD-L1 immunohistochemistry looks likely to be introduced into clinical use for selecting patients for treatment with anti-PD-1 or anti-PD-L1 therapies. Given that there are 4 such drugs rapidly approaching regulatory approval, each with its own independent PD-L1 immunohistochemistry biomarker test, both oncologists and pathologists face some significant challenges.
DATA SOURCES: Peer-reviewed literature and meeting proceedings, especially during the last 12 months, were used.
CONCLUSIONS: The biology of PD-1/PD-L1 is complex, the clinical data for these drugs show considerable variation, the selection performance of the PD-L1 biomarker test is not perfect, and the existence of 4 drug/test combinations adds significantly to the problems faced. This article addresses some of the background to this therapeutic problem and discusses some of the issues ahead.
Optimised Pre-Analytical Methods Improve KRAS Mutation Detection in Circulating Tumour DNA (ctDNA) from Patients with Non-Small Cell Lung Cancer (NSCLC).
PLoS One. 2016; 11(2):e0150197 [PubMed] Free Access to Full Article Related Publications
MATERIALS & METHODS: Peripheral blood and matched tumours were analysed from 45 NSCLC patients. We investigated the impact of pre-analytical variables on DNA yield and/or KRAS mutation detection: sample collection tube type, incubation time, centrifugation steps, plasma input volume and DNA extraction kits.
RESULTS: 2 hr incubation time and double plasma centrifugation (2000 x g) reduced overall DNA yield resulting in lowered levels of contaminating genomic DNA (gDNA). Reduced "contamination" and increased KRAS mutation detection was observed using cell-free DNA Blood Collection Tubes (cfDNA BCT) (Streck), after 72 hrs following blood draw compared to EDTA tubes. Plasma input volume and use of different DNA extraction kits impacted DNA yield.
CONCLUSION: This study demonstrated that successful ctDNA recovery for mutation detection in NSCLC is dependent on pre-analytical steps. Development of standardised methods for the detection of KRAS mutations from ctDNA specimens is recommended to minimise the impact of pre-analytical steps on mutation detection rates. Where rapid sample processing is not possible the use of cfDNA BCT tubes would be advantageous.
Accounting for the Multiple Natures of Missing Values in Label-Free Quantitative Proteomics Data Sets to Compare Imputation Strategies.
J Proteome Res. 2016; 15(4):1116-25 [PubMed] Related Publications
Characterization of FGFR1 Locus in sqNSCLC Reveals a Broad and Heterogeneous Amplicon.
PLoS One. 2016; 11(2):e0149628 [PubMed] Free Access to Full Article Related Publications
Perioperative Extracorporeal Membrane Oxygenation to Facilitate Lung Resection After Contralateral Pneumonectomy.
Ann Thorac Surg. 2016; 101(3):e71-3 [PubMed] Related Publications
Irradiation Decreases the Neuroendocrine Biomarker Pro-Opiomelanocortin in Small Cell Lung Cancer Cells In Vitro and In Vivo.
PLoS One. 2016; 11(2):e0148404 [PubMed] Free Access to Full Article Related Publications
RESULTS: Human SCLC cells (DMS 79) were established as subcutaneous xenograft tumours in CBA nude mice and then exposed to repeated 2Gy irradiation. In untreated animals, POMC in the blood closely mirrored tumour growth; an ideal characteristic for a circulating biomarker. Following repeated localised irradiation in vivo, circulating POMC decreased (p< 0.01), in parallel with a decrease in tumour size, but remained low even when the tumours re-established. The excised tumours displayed reduced and distinctly heterogeneous expression of POMC compared to untreated tumours. There was no difference in the epithelial marker, cytokeratin. However, there were significantly more N-cadherin positive cells in the irradiated tumours. To investigate the tumour response to irradiation, DMS79 cells were repeatedly irradiated in vitro and the surviving cells selected. POMC expression was reduced, while mesenchymal markers N-cadherin, β1-integrin, fibroblast-specific protein 1, β-catenin and Zeb1 expression were amplified in the more irradiation-primed cells. There were no consistent changes in epithelial marker expression. Cell morphology changed dramatically with repeatedly irradiated cells displaying a more elongated shape, suggesting a switch to a more mesenchymal phenotype.
CONCLUSIONS: In summary, POMC biomarker expression and secretion were reduced in SCLC tumours which regrew after irradiation and in repeatedly irradiation (irradiation-primed) cells. Therefore, POMC was no longer predictive of tumour burden. This highlights the importance of fully evaluating biomarkers during and after therapy to assess clinical utility. Furthermore, the gain in mesenchymal characteristics in irradiated cells could be indicative of a more invasive phenotype.
Registered report: Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET.
Elife. 2016; 5:e07383 [PubMed] Free Access to Full Article Related Publications
First-Line Afatinib versus Chemotherapy in Patients with Non-Small Cell Lung Cancer and Common Epidermal Growth Factor Receptor Gene Mutations and Brain Metastases.
J Thorac Oncol. 2016; 11(3):380-90 [PubMed] Related Publications
METHODS: For both LUX-Lung 3 and LUX-Lung 6, prespecified subgroup analyses of progression-free survival (PFS), overall survival, and objective response rate were undertaken in patients with asymptomatic brain metastases at baseline (n = 35 and n = 46, respectively). Post hoc analyses of clinical outcomes was undertaken in the combined data set (n = 81).
RESULTS: In both studies, there was a trend toward improved PFS with afatinib versus chemotherapy in patients with brain metastases (LUX-Lung 3: 11.1 versus 5.4 months, hazard ratio [HR] = 0.54, p = 0.1378; LUX-Lung 6: 8.2 versus 4.7 months, HR = 0.47, p = 0.1060). The magnitude of PFS improvement with afatinib was similar to that observed in patients without brain metastases. In combined analysis, PFS was significantly improved with afatinib versus with chemotherapy in patients with brain metastases (8.2 versus 5.4 months; HR, 0.50; p = 0.0297). Afatinib significantly improved the objective response rate versus chemotherapy in patients with brain metastases. Safety findings were consistent with previous reports.
CONCLUSIONS: These findings lend support to the clinical activity of afatinib in EGFR mutation-positive patients with NSCLC and asymptomatic brain metastases.
PROCLAIM: Randomized Phase III Trial of Pemetrexed-Cisplatin or Etoposide-Cisplatin Plus Thoracic Radiation Therapy Followed by Consolidation Chemotherapy in Locally Advanced Nonsquamous Non-Small-Cell Lung Cancer.
J Clin Oncol. 2016; 34(9):953-62 [PubMed] Related Publications
PATIENTS AND METHODS: Patients with stage IIIA/B unresectable nonsquamous non-small-cell lung cancer randomly received (1:1) pemetrexed 500 mg/m(2) and cisplatin 75 mg/m(2) intravenously every 3 weeks for three cycles plus concurrent TRT (60 to 66 Gy) followed by pemetrexed consolidation every 3 weeks for four cycles (arm A), or standard therapy with etoposide 50 mg/m(2) and cisplatin 50 mg/m(2) intravenously, every 4 weeks for two cycles plus concurrent TRT (60 to 66 Gy) followed by two cycles of consolidation platinum-based doublet chemotherapy (arm B). The primary objective was OS. The study was designed as a superiority trial with 80% power to detect an OS hazard ratio of 0.74 with a type 1 error of .05.
RESULTS: Enrollment was stopped early because of futility. Five hundred ninety-eight patients were randomly assigned (301 to arm A, 297 to arm B) and 555 patients (283 in arm A, 272 in arm B) were treated. Arm A was not superior to arm B in terms of OS (hazard ratio, 0.98; 95% CI, 0.79 to 1.20; median, 26.8 v 25.0 months; P = .831). Arm A had a significantly lower incidence of any drug-related grade 3 to 4 adverse events (64.0% v 76.8%; P = .001), including neutropenia (24.4% v 44.5%; P < .001), during the overall treatment period.
CONCLUSION: Pemetrexed-cisplatin combined with TRT followed by consolidation pemetrexed was not superior to standard chemoradiotherapy for stage III unresectable nonsquamous non-small-cell lung cancer.
A Novel Quantitative Computed Tomographic Analysis Suggests How Sirolimus Stabilizes Progressive Air Trapping in Lymphangioleiomyomatosis.
Ann Am Thorac Soc. 2016; 13(3):342-9 [PubMed] Free Access to Full Article Related Publications
OBJECTIVES: To prospectively determine the longitudinal computed tomographic lung imaging correlates of lung function change in MILES patients treated with placebo or sirolimus.
METHODS: We determined the baseline to 12-month change in computed tomographic image-derived lung volumes and the volume of the lung occupied by cysts in the 31 MILES participants (17 in sirolimus group, 14 in placebo group) with baseline and 12-month scans.
MEASUREMENTS AND MAIN RESULTS: There was a trend toward an increase in median expiratory cyst volume percentage in the placebo group and a reduction in the sirolimus group (+2.68% vs. +0.97%, respectively; P = 0.10). The computed tomographic image-derived residual volume and the ratio of residual volume to total lung capacity increased more in the placebo group than in the sirolimus group (+214.4 ml vs. +2.9 ml [P = 0.054] and +0.05 ml vs. -0.01 ml [P = 0.0498], respectively). A Markov transition chain analysis of respiratory cycle cyst volume changes revealed greater dynamic variation in the sirolimus group than in the placebo group at the 12-month time point.
CONCLUSIONS: Collectively, these data suggest that sirolimus attenuates progressive gas trapping in lymphangioleiomyomatosis, consistent with a beneficial effect of the drug on airflow obstruction. We speculate that a reduction in lymphangioleiomyomatosis cell burden around small airways and cyst walls alleviates progressive airflow limitation and facilitates cyst emptying.
In situ hybridisation: Technologies and their application to understanding disease.
Prog Histochem Cytochem. 2016; 50(4):37-48 [PubMed] Related Publications
A comparison between accelerated hypofractionation and stereotactic ablative radiotherapy (SABR) for early-stage non-small cell lung cancer (NSCLC): Results of a propensity score-matched analysis.
Radiother Oncol. 2016; 118(3):478-84 [PubMed] Related Publications
MATERIALS AND METHODS: From 1997-2007, 119 patients (T1-3N0M0 NSCLC) were treated with AH (48-60 Gy, 12-15 fractions). Prior to SABR, this represented our institutional standard. From 2008-2012, 192 patients (T1-3N0M0 NSCLC) were treated with SABR (48-52 Gy, 4-5 fractions). A total of 114 patients (57 per cohort) were matched (1:1 ratio, caliper: 0.10) using propensity scores.
RESULTS: Median follow-up (range) for the AH cohort was 36.3 (2.5-109.1) months, while that for the SABR group was 32.5 (0.3-62.6)months. Three-year overall survival (OS) and local control (LC) rates were 49.5% vs. 72.4% [p=0.024; hazard ratio (HR): 2.33 (1.28, 4.23), p=0.006] and 71.9% vs. 89.3% [p=0.077; HR: 5.56 (1.53, 20.2), p=0.009], respectively. On multivariable analysis, tumour diameter and PET staging were predictive for OS, while the only predictive factor for LC was treatment cohort.
CONCLUSIONS: OS and LC were improved with SABR, although OS is more closely related to non-treatment factors. This represents one of the few studies comparing AH to SABR for early-stage lung cancer.
ROS1 copy number alterations are frequent in non-small cell lung cancer.
Oncotarget. 2016; 7(7):8019-28 [PubMed] Free Access to Full Article Related Publications
METHODS: A total of 314 NSCLC patients were screened using ROS1 FISH break-apart probes. Of these, 47 surgical tumors were included in TMAs to analyze ROS1 heterogeneity assessed either by FISH and IHC, and chromosome 6 aneusomy. To characterize ROS1 partners, probes for CD74, EZR, SLC34A2 and SDC3 genes were developed. ROS1 positive FISH cases were screened also by IHC.
RESULTS: Five patients were ROS1 positive (1.8%). We identified two known fusion partners in three patients: CD74 and SLC34A2. Four out of five ROS1 rearranged patients were female, never smokers and with adenocarcinoma histology. Rearranged cases were also positive by IHC as well. According to ROS1 CNAs, we found a prevalence of 37.8% gains/amplifications and 25.1% deletions.
CONCLUSIONS: This study point out the high prevalence of ROS1 CNAs in a large series of NSCLC. ROS1 gains, amplifications and deletions, most of them due to chromosome 6 polysomy or monosomy, were heterogeneous within a tumor and had no impact on overall survival.
Programmed Death Ligand-1 Immunohistochemistry--A New Challenge for Pathologists: A Perspective From Members of the Pulmonary Pathology Society.
Arch Pathol Lab Med. 2016; 140(4):341-4 [PubMed] Related Publications
A Novel Clinical Prediction Model for Prognosis in Malignant Pleural Mesothelioma Using Decision Tree Analysis.
J Thorac Oncol. 2016; 11(4):573-82 [PubMed] Related Publications
METHODS: Between 2005 and 2014, all cases with pathologically confirmed MPM had routinely available histological, clinical, and laboratory characteristics recorded. Classification and regression tree analysis was performed using 29 variables with 18-month survival as the dependent variable. Risk groups were refined according to survival and clinical characteristics. The model was then tested on an external international cohort.
RESULTS: A total of 482 cases were included in the derivation cohort; the median survival was 12.6 months, and the median age was 69 years. The model defined four risk groups with clear survival differences (p < 0.0001). The strongest predictive variable was the presence of weight loss. The group with the best survival at 18 months (86.7% alive, median survival 34.0 months, termed risk group 1) had no weight loss, a hemoglobin level greater than 153 g/L, and a serum albumin level greater than 43 g/L. The group with the worst survival (0% alive, median survival 7.5 months, termed risk group 4d) had weight loss, a performance score of 0 or 1, and sarcomatoid histological characteristics. The C-statistic for the model was 0.761, and the sensitivity was 94.5%. Validation on 174 external cases confirmed the model's ability to discriminate between risk groups in an alternative data set with fair performance (C-statistic 0.68).
CONCLUSIONS: We have developed and validated a simple, clinically relevant model to reliably discriminate patients at high and lower risk of death using routinely available variables from the time of diagnosis in unselected populations of patients with MPM.
Problems of variable biomarker evaluation in stratified medicine research--A case study of ERCC1 in non-small-cell lung cancer.
Lung Cancer. 2016; 92:1-7 [PubMed] Free Access to Full Article Related Publications
MATERIALS AND METHODS: A systematic review of studies completed since 2007 and ongoing was undertaken. Questionnaires on details of ERCC1 evaluation procedures and the rationale for their choice were sent to contacts of identified studies.
RESULTS: Thirty-three studies of platinum-based chemotherapy in non-small-cell lung cancer using ERCC1 were identified. A reply to the questionnaire was received for 16 studies. Procedures for ERCC1 evaluation varied substantially and included reverse transcriptase quantitative polymerase chain reaction (nine studies), immunohistochemistry (five studies) and other methods (multiple methods-two studies, NER polymorphism-one study). In five studies ERCC1 use was planned, but not undertaken. In nine data was insufficient to identify the procedure. For each assay there was variation across studies in the details of the laboratory techniques, scoring systems and methods for obtaining samples.
CONCLUSIONS: We found large variation across studies in ERCC1 evaluation procedures. This will limit the future comparability of results between these different studies. To enable evidence-based clinical practice, consensus is needed on a validated procedure to assess a predictive biomarker in the early phase of research. We believe that ERCC1 is not untypical of biomarkers being investigated for stratified medicine.
The IASLC Lung Cancer Staging Project: Proposals for Revision of the TNM Stage Groupings in the Forthcoming (Eighth) Edition of the TNM Classification for Lung Cancer.
J Thorac Oncol. 2016; 11(1):39-51 [PubMed] Related Publications
RASSF1A Suppresses the Invasion and Metastatic Potential of Human Non-Small Cell Lung Cancer Cells by Inhibiting YAP Activation through the GEF-H1/RhoB Pathway.
Cancer Res. 2016; 76(6):1627-40 [PubMed] Related Publications
Programmed Death Ligand-1 Immunohistochemistry: Friend or Foe?
Arch Pathol Lab Med. 2016; 140(4):326-31 [PubMed] Related Publications
Pooled Analysis of the Prognostic and Predictive Value of KRAS Mutation Status and Mutation Subtype in Patients with Non-Small Cell Lung Cancer Treated with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors.
J Thorac Oncol. 2016; 11(3):312-23 [PubMed] Related Publications
METHODS: Data were pooled from four trials of EGFR TKIs versus placebo (National Cancer Institute of Canada Clinical Trials Group [NCIC CTG] trial BR.21, TOPICAL, NCIC CTG trial BR.26, and NCIC CTG trial BR.19). Analyses of the combined data were performed to determine relationships of MUT status/subtype to response and survival end points.
RESULTS: KRAS status was known for 1362 of 2624 patients (785 receiving EGFR TKIs and 577 receiving placebo); 275 (20%) had KRAS MUTs (248 at codon 12; 15 at codon 13; 12 at other codons). In the placebo arms there was no difference in overall survival (OS) for patients with KRAS MUTs or wild-type tumors (hazard ratio [HR] = 1.04, confidence interval [CI]: 0.81-1.33 for univariable analysis and HR = 1.09, CI: 0.85-1.41 for multivariable analysis). Patients with guanine-to-thymidine transversion MUTs had longer OS than did those with guanine-to-adenine transition MUTs or guanine-to-cytosine transversion MUTs (median OS 6.3, 1.8, and 3.9 months, respectively, p = 0.01). Patients with KRAS MUT tumors derived no benefit from EGFR TKIs (OS HR = 1.13, CI: 0.85-1.51; progression-free survival HR = 1.02, CI: 0.76-1.36). The interaction between KRAS status and EGFR TKI effect was significant for progression-free survival (p = 0.04) but not for OS (p = 0.17). For patients with G12V MUTs, EGFR TKI treatment was harmful (OS HR = 1.96, CI: 1.03-3.70, p = 0.04), whereas guanine-to-adenine transition MUTs were associated with an OS benefit from EGFR TKIs (HR = 0.49, CI: 0.24-1.00, p = 0.05).
CONCLUSIONS: Overall, KRAS MUT is neither prognostic nor predictive of benefit from EGFR TKIs. However, it appears that KRAS MUT subtypes are not homogeneous in terms of their prognostic and predictive effects. These observations require prospective validation.
See publications from around the world in CancerIndex: Lung Cancer