Publications
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Nyen, Johanne Elise; Booth, Anja Ødegård; Husby, Øyvind; Bugge, Christoffer; Engebretsen, Ingrid & Oteiza, Francisco
[Show all 10 contributors for this article]
(2025).
Targeted treatment and survival in advanced non-squamous non-small cell lung cancer patients – a nationwide and longitudinal study.
Frontiers in Oncology.
15.
doi:
10.3389/fonc.2025.1506041.
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Objectives: We aimed to describe treatment patterns, time on treatment (ToT) and overall survival (OS) for patients with advanced non-squamous, EGFR+, ALK+ and ROS1+ NSCLC in Norway.
Materials and methods: We extracted data on patients ≥ 18 years diagnosed with advanced non-squamous NSCLC between 2015 and 2022 from the Cancer Registry of Norway and data on cancer drug therapy from the Norwegian Patient Registry and the Norwegian Prescribed Drug Registry. ToT was measured from the date treatment was collected or administered until the last dispensing was depleted or last hospital drug administration. OS was measured from date of diagnosis until death.
Results: In total, 5,279 patients were included, of whom 449 EGFR+, 131 ALK+ and 38 ROS1+. 75% of EGFR+ patients, 88% of ALK+ patients, and 58% of ROS1+ patients received at least one systemic treatment within the first three months after diagnosis. Median follow-up was 13, 19, and 4 months for EGFR+, ALK+, and ROS1+, respectively. The median ToT in first line (1L) for EGFR+ patients was 11 months for osimertinib (CI: 10.1-NA) and 9 months (CI: 8.2-11.2) for afatinib, dacomitinib, erlotinib and gefitinib. For ALK+ patients, median ToT in 1L was 20 months (CI: 14.7-23.7for alectinib, 11 months (CI: 4.7-NA) for brigatinib, and 7 months (CI: 2.9-21.6) for crizotinib. For the five ROS1+ patients treated with crizotinib in 1L, median ToT was 5 months (CI: 2.4-NA). For all patients with a targetable genomic alteration, unadjusted median OS was higher (p-value = 0.025) for patients diagnosed in 2020-2022 (median OS: 23 months, CI: 19.5-NA) compared to patients diagnosed in 2015-2019 (median: 19 months, CI: 16.5-21.2).
Conclusions: ToT for targeted therapies was shorter than progression-free survival in clinical trials. However, patients eligible for targeted therapy still had a survival improvement during the study period.
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Nilssen, Yngvar; Brustugun, Odd Terje; Fjellbirkeland, Lars; Helland, Åslaug; Møller, Bjørn & Wahl, Sissel Gyrid Freim
[Show all 7 contributors for this article]
(2024).
Distribution and characteristics of malignant tumours by lung lobe.
BMC Pulmonary Medicine.
24(1).
doi:
10.1186/s12890-024-02918-w.
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Background The main focus on the characteristics of malignant lung tumours has been the size, position within the lobe, and infiltration into neighbouring structures. The aim of this study was to investigate the distribution and characteristics of malignant tumours between the lung lobes and whether the diagnosis, treatment, and outcome differed based on location. Methods This study is based on 10,849 lung cancer patients diagnosed in 2018–2022 with complete data on the location and characteristics of the tumours. The proportions of tumours in each lobe divided by its volume were termed the relative proportion. Results The right upper lobe comprised 31.2% of the tumours and 17.6% of the lung volume. The relative proportion of 1.77 was higher than in the other lobes (p < 0.001). The right middle lobe had a relative proportion of 0.64 but the highest proportion of neuroendocrine tumours (26.1% vs. 15.3 on average). Surgical resection was more often performed in patients with tumours in the lower lobes, and curative radiotherapy was more often performed in the upper lobes. After adjusting for age, sex, stage, and histology, the location of the tumour was found to be a significant independent predictor for resection but not for survival. Conclusion The main finding of the right upper lobe as a site of predilection for lung cancer is similar to tuberculosis and pneumoconiosis. This may be explained that most of the inhaled air, containing bacilli, inorganic particles or tobacco smoke goes to the upper and right parts of the lung.
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Hektoen, Helga; Tsuruda, Kaitlyn; Fjellbirkeland, Lars; Nilssen, Yngvar; Brustugun, Odd Terje & Kulle, Bettina
(2024).
Real-world evidence for pembrolizumab in non-small cell lung cancer: a nationwide cohort study.
British Journal of Cancer.
ISSN 0007-0920.
132,
p. 93-102–93-102.
doi:
10.1038/s41416-024-02895-1.
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Background Based on favourable results from clinical trials, immune checkpoint inhibitors (ICI) have become the standard first line (1 L) systemic anticancer treatment (SACT) for advanced stage non-small cell lung cancer (NSCLC) without targetable mutations. We evaluate whether these results are generalizable to everyday clinical practice and compare overall survival (OS) of patients treated with ICI to a historical cohort of patients treated with chemotherapy and results from clinical trials. Methods Our study comprised all advanced NSCLC patients initiating SACT in 2012–21 in Norway. Clinical characteristics and treatment information was retrieved from Norwegian Health Registries. Results Survival for all 8416 advanced NSCLC patients treated with SACT increased concurrently with the gradual implementation of ICIs. Median OS of patients treated with 1 L pembrolizumab after 2017 was better (mono-/combination therapy: 13.8/12.8 months) than for patients treated with chemotherapy before 2017 (8.0 months). Although median OS for patients treated with pembrolizumab was lower in clinical practice than clinical trials (Keynote-024/189: 26.3/22.0 months), the survival benefit relative to chemotherapy was similar. Conclusion Our nationwide study demonstrated a survival benefit over conventional chemotherapy of a similar magnitude as observed in clinical trials and confirms the effectiveness of pembrolizumab in routine clinical practice.
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Nilssen, Yngvar; Brustugun, Odd Terje; Fjellbirkeland, Lars; Grønberg, Bjørn Henning; Haram, Per Magnus & Helbekkmo, Nina
[Show all 10 contributors for this article]
(2024).
Small Cell Lung Cancer in Norway: Patterns of Care by Health Region and Survival Trends.
Clinical Lung Cancer.
ISSN 1525-7304.
25(5),
p. e221–e228.e3.
doi:
10.1016/j.cllc.2024.04.002.
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Introduction/Background: There has been a marked survival improvement for patients with non–small-cell lung cancer. We describe the national trends in characteristics and survival, and geographical differences in diagnostic workup, treatment, and survival for patients with small-cell lung cancer (SCLC). Materials and Methods: Patients registered with SCLC at the Cancer Registry of Norway in 2002 to 2022 were included. Trends in overall survival were estimated for all SCLC patients, patients with limited stage SCLC, patients undergoing surgery, and by health region. Adjusting for case-mix, a multivariable Cox regression was performed examining the association between health region and death. Results: The study included 8374 patients. The stage distribution remained unchanged during the study period. The 5-year overall survival increased from 7.7% to 22.8% for patients with limited stage. The use of multidisciplinary team meetings varied from 62.5% to 85.7%, and the use of positron emission tomography-computer tomography varied from 70.4% to 86.2% between the health regions. Treatment patterns differed markedly between the health regions, with the proportion dying without any registered treatment ranging from 1.2% to 10.9%. For limited stage patients in 2018 to 2022, the median overall survival ranged from 16.5 to 25.5 months across health regions, and the 5-year overall survival ranged from 18.7% to 28.7% (P = .019). Conclusion: The survival for patients with SCLC remains poor. The use of diagnostic procedures, treatment modalities, and survival differed between regions, warranting investigations to further explore the reasons.
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Lærum, Dan; Strand, Trond-Eirik; Brustugun, Odd Terje; Gallefoss, Frode; Falk, Ragnhild Sørum & Durheim, Michael Thomas
[Show all 7 contributors for this article]
(2024).
Evaluation of sex inequity in lung-cancer-specific survival.
Acta Oncologica.
ISSN 0284-186X.
63(1),
p. 343–350.
doi:
10.2340/1651-226X.2024.27572.
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Background: Whether sex is an independent prognostic factor in lung cancer survival is the subject of ongoing debate. Both large national registries and single hospital studies have shown conflicting findings. In this study, we explore the impact of sex on lung-cancer-specific survival in an unselected population that is well-characterized with respect to stage and other covariates. Material and methods: All patients diagnosed with lung cancer at a single hospital serving a whole and defined region in Southern Norway during the 10 years 2007–2016 were included. Follow-up data were available for at least 56 months for all patients. Analyses were adjusted for stage, treatment, performance status, smoking, age, histology, epidermal growth factor receptor/anaplastic lymphoma kinase/immunotherapy treatment and period. Differences in lung-cancer-specific survival by sex were explored using restricted mean survival times (RMST). Results: Of the 1,261 patients diagnosed with lung cancer, 596 (47%) were females and 665 (53%) males, with mean ages of 68.5 and 69.5 years, respectively. The observed 5-year lung-cancer-specific survival rate was 27.4% (95% CI 23.7, 31.2) in females and 21.4% (95% CI 18.2, 24.8) in males. However, after adjustment for covariates, no significant differences by sex were observed. The 5-year RMST was 0.9 months shorter (95% CI −2.1, 0.31, p = 0.26) in males compared to females. Interpretation: In this cohort, sex was not associated with a difference in lung-cancer-specific survival after adjusting for clinical and biological factors. Imbalance in stage at diagnosis was the main contributor to the observed difference in lung-cancer-specific survival by sex.
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Rakaee, Mehrdad; Andersen, Sigve; Giannikou, K.; Paulsen, Erna-Elise; Kilvær, Thomas Karsten & Busund, Lill-Tove Rasmussen
[Show all 25 contributors for this article]
(2023).
Machine learning-based immune phenotypes correlate with STK11/KEAP1 co-mutations and prognosis in resectable NSCLC: a sub-study of the TNM-I trial.
Annals of Oncology.
ISSN 0923-7534.
doi:
10.1016/j.annonc.2023.04.005.
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Background We aim to implement an immune cell score model in routine clinical practice for resected non-small-cell lung cancer (NSCLC) patients (NCT03299478 ). Molecular and genomic features associated with immune phenotypes in NSCLC have not been explored in detail. Patients and methods We developed a machine learning (ML)-based model to classify tumors into one of three categories: inflamed, altered, and desert, based on the spatial distribution of CD8+ T cells in two prospective (n = 453; TNM-I trial) and retrospective (n = 481) stage I-IIIA NSCLC surgical cohorts. NanoString assays and targeted gene panel sequencing were used to evaluate the association of gene expression and mutations with immune phenotypes. Results Among the total of 934 patients, 24.4% of tumors were classified as inflamed, 51.3% as altered, and 24.3% as desert. There were significant associations between ML-derived immune phenotypes and adaptive immunity gene expression signatures. We identified a strong association of the nuclear factor-κB pathway and CD8+ T-cell exclusion through a positive enrichment in the desert phenotype. KEAP1 [odds ratio (OR) 0.27, Q = 0.02] and STK11 (OR 0.39, Q = 0.04) were significantly co-mutated in non-inflamed lung adenocarcinoma (LUAD) compared to the inflamed phenotype. In the retrospective cohort, the inflamed phenotype was an independent prognostic factor for prolonged disease-specific survival and time to recurrence (hazard ratio 0.61, P = 0.01 and 0.65, P = 0.02, respectively). Conclusions ML-based immune phenotyping by spatial distribution of T cells in resected NSCLC is able to identify patients at greater risk of disease recurrence after surgical resection. LUADs with concurrent KEAP1 and STK11 mutations are enriched for altered and desert immune phenotypes.
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Solberg, Steinar; Nilssen, Yngvar; Brustugun, Odd Terje; Haram, Per Magnus; Helland, Åslaug & Møller, Bjørn
[Show all 9 contributors for this article]
(2022).
Concordance between clinical and pathology TNM-staging in lung cancer.
Lung Cancer.
ISSN 0169-5002.
171,
p. 65–69.
doi:
10.1016/j.lungcan.2022.07.014.
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Objectives - A prerequisite for utilizing the tumour, lymph-nodes, and metastases (TNM) for the staging of lung cancer patients is a high quality of the reported data on which the staging is based. The aim of this study was to investigate the concordance between the clinical, cTNM and the pathology, pTNM staging for lung cancer, version 8 as reported to the Cancer Registry of Norway (CRN). Materials and Methods - A total of 1284 patients who underwent surgery 2018–2019 with sufficient data regarding both clinical and pathology T and N descriptors were included. Results - The differences in tumour diameter reported in the clinical and the pathology notifications were ≤5 mm and ≤10 mm in 65.9 % and in 84.4 % of the cases, respectively. For the c- and pT categories, there was concordance in 53.4 % while 28.4 % were upstaged and 18.2 % were downstaged. For N categories there was concordance in 83.3 % while 13.7 % were upstaged and 3.0 % were downstaged. Unforeseen pN2 was found in 6.2 % of the cases. For TNM staging groups there was concordance in 48.1 % of the cases, while 33.4 % were upstaged and 18.5 % were downstaged. The calculated sensitivity and specificity for reported cTNM staging as diagnostic test for being eligible for adjuvant treatment (stage II–IIIA) were 0.65 and 0.91, respectively. Conclusions - These data on staging for lung cancer, as reported to the CRN, shows a disappointingly low precision and concordance in c- and pTNM staging. This urges a strategy for a marked improvement.
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Lærum, Dan; Brustugun, Odd Terje; Gallefoss, Frode; Falk, Ragnhild Sørum; Strand, Trond-Eirik & Fjellbirkeland, Lars
(2021).
Factors associated with delayed treatment initiation in an unselected cohort of patients with small-cell lung cancer.
Cancer Treatment and Research Communications.
ISSN 2468-2942.
29.
doi:
10.1016/j.ctarc.2021.100477.
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Background Small-cell lung cancer (SCLC) is an aggressive, rapidly progressive malignancy. Thus, expedient diagnosis and treatment initiation is important. This study identifies and quantifies factors associated with delayed diagnosis and treatment initiation in patients with SCLC and compares time to treatment in SCLC with a cohort of patients with non-small cell lung cancer (NSCLC). Materials and Methods The study included all patients diagnosed with SCLC at a hospital in southern Norway in a ten-year period (2007–2016), and all NSCLC patients during the period 2013–2016. Total time to treatment (TTT), was defined as the number of days from date of referral due to suspicion of lung cancer to first day of treatment. Factors associated with prolonged TTT were estimated using multivariate median regression analysis. Results The median TTT and interquartile range (IQR) for the 183 patients with SCLC was 16 (10–23) days. Factors associated with delayed TTT included outpatient versus inpatient evaluation (+8.4 days), number of diagnostic procedures (+4.3 days per procedure), stage I-III versus stage IV (+3.6 days) and age (+2.1 days per 10 years). In 2013–16, TTT in SCLC was 3.5 days shorter than in the period before and less than half that of NSCLC in the same period, 15 (9–22) versus 33 (22–50) days (p = 0.001). Conclusion Shorter TTT is seen in higher stage, while longer TTT is a result of increasing complexity of the diagnostic process and treatment decisions of patients with curative intent treatment. Knowledge on delaying factors can shorten TTT and improve clinical practice.
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Lærum, Dan; Brustugun, Odd Terje; Gallefoss, Frode; Falk, Ragnhild Sørum; Strand, Trond-Eirik & Fjellbirkeland, Lars
(2020).
Reduced delays in diagnostic pathways for non-small cell lung cancer after local and National initiatives.
Cancer Treatment and Research Communications.
ISSN 2468-2942.
23.
doi:
10.1016/j.ctarc.2020.100168.
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Objectives Patients with non-small cell lung cancer (NSCLC) may experience progression and stage shift due to delays in a complex and time-consuming diagnostic work-up. We have analyzed the impact of both a local and national intervention on total time to treatment (TTT). Material and Methods All patients diagnosed with NSCLC at a Norwegian county hospital from 2007 to 2016 were reviewed. Logistic bottlenecks and delays were identified (2007–12) resulting in implementation of a local initiative with new diagnostic algorithm introduced by the beginning of 2013. In 2015, national diagnostic cancer pathways were implemented. TTT defined as time from received referral from the primary physician to start of treatment was compared in the three diagnostic time periods; baseline (2007–12), local (2013–14) and national (2015–16). Results A total of 780 patients were included. Among patients treated with curative intent the median TTT decreased by 21 days, from 64 to 43 days (p < 0.001) while the mean number of diagnostic procedures increased from 3.5 to 3.9. In median regression analysis, the local initiative was associated with a reduction of estimated 7.8 days (95% CI 3.2, 12.3) in TTT, while the national initiative correlated with a reduction of estimated 14.9 days (95% CI 10.2, 19.6) compared to time at baseline. Covariates associated with longer TTT were stage I, use of PET-CT, diagnostic procedure at external hospital, and number of diagnostic procedures. Conclusion Local and national initiatives significantly reduced TTT in NSCLC. The effect was most pronounced among patients with disease available for curative treatment.
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Solberg, Steinar; Nilssen, Yngvar; Brustugun, Odd Terje; Grimsrud, Tom Kristian; Haram, Per Magnus & Helbekkmo, Nina
[Show all 15 contributors for this article]
(2019).
Increase in curative treatment and survival of lung cancer in Norway 2001-2016.
European Journal of Epidemiology (EJE).
ISSN 0393-2990.
34(10),
p. 951–955.
doi:
10.1007/s10654-019-00536-z.
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We have studied the alterations in the use of curative treatment and the outcome for lung cancer patients in Norway 2001–2016. The Cancer Registry of Norway has a practically complete registration of all cancer diagnoses, treatments given and deaths. For the years 2001–2016, 43,137 patients were diagnosed with lung cancer. Stereotactic radiotherapy was established nationwide from 2008 and its use has increased, and in 2016, 8.8% were given this treatment. In addition 20.6% were operated and 8.5% were treated with conventional radiotherapy. Thus 37.9% of those diagnosed were treated with intention to cure, compared to 22.9% in 2001 (p < 0.0001). Further, the median survival for the whole group diagnosed with lung cancer increased from 6.0 (95% CI 5.6–6.7) months in 2001 to 11.8 (95% CI 10.9–12.7) in 2016. The 5 year survival increased from 9.4 (95% CI 8.1–10.8)% to 19.9 (95% CI 19.2–20.6)% in the same period. In 2016 the age adjusted incidence rate was 59.5 per 100,000 (Norwegian standard) and had increased significantly in both sexes. There had also been an increase in mean age at diagnosis and the proportion diagnosed in an early stage. The increase in curative treatment has been paralleled with a doubling in both the median and 5-year survival. The present results are used for surveillance and as a benchmark, and we are looking forward to reaching a proportion of 40% of patients given curative treatment.
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Brustugun, Odd Terje; Grønberg, Bjørn Henning; Fjellbirkeland, Lars; Helbekkmo, Nina; Aanerud, Marianne & Grimsrud, Tom Kristian
[Show all 11 contributors for this article]
(2018).
Substantial nation-wide improvement in lung cancer relative survival in Norway from 2000 to 2016.
Lung Cancer.
ISSN 0169-5002.
122,
p. 138–145.
doi:
10.1016/j.lungcan.2018.06.003.
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Introduction There have been significant changes in both diagnostic procedures and therapy for lung cancer since the beginning of the millennium. National incidence and survival data from 2000 through 2016 are studied. Methods National data on cancer incidence and vital status are virtually complete. Changes in incidence and survival are described by absolute numbers, percentages, and calculation of relative survival (period analysis). Results A total of 44,825 individuals were diagnosed with lung cancer in Norway in the study period. The number of incident cases increased with 49% whereas the prevalence increased with 136% from 2000 to 2016. Age-standardised rates rose markedly for women and levelled off for men. In 2016, adenocarcinoma accounted for about 50% of all lung cancers, slightly more for women than for men. The entity “NSCLC not otherwise specified” declined from 24% to 13%, and the fraction of patients with metastatic disease decreased from 54% to 46% during the period, for both sexes combined. The overall median survival time doubled for women and men, reaching 14.3 months and 11.4 months, respectively. For patients with metastatic disease, median survival time showed a small increase but remained less than 6 months. The overall 5-year relative survival increased from 16% to 26% in women and from 16% to 22% in men. The corresponding improvements for the subgroup of non-surgically treated cases with localised disease, were up from 25% to more than 40% in females, and from 10% to almost 40% in males. Conclusion There have been notable changes in incidence patterns and a remarkable improvement in survival for lung cancer over the last 17 years, most markedly for patients without distant metastases at the time of diagnosis. Hopefully, survival will improve even more when immunotherapy is implemented.
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Nilssen, Yngvar; Strand, Trond-Eirik; Fjellbirkeland, Lars; Bartnes, Kristian & Møller, Bjørn
(2016).
Lung cancer survival in Norway, 1997-2011: From nihilism to optimism.
European Respiratory Journal.
ISSN 0903-1936.
47(1),
p. 275–287.
doi:
10.1183/13993003.00650-2015.
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Brustugun, Odd Terje; Helland, Åslaug; Fjellbirkeland, Lars; Kleinberg, Lilach; Ariansen, Sarah Louise & Jebsen, Peter Wilhelm
[Show all 15 contributors for this article]
(2012).
Mutasjonstesting ved ikke-småcellet lungekreft.
Tidsskrift for Den norske legeforening (Tidsskriftet).
ISSN 0029-2001.
132(8),
p. 952–955.
doi:
10.4045/tidsskr.11.1017.
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BAKGRUNN. Epidermal vekstfaktor-reseptor (EGFR) tyrosinkinasehemmere (EGFR-TKI) er en relativt ny klasse legemidler til behandling av ikke-småcellet lungekreft. Den nasjonale faggruppen for lungekreft, Norsk Lunge Cancer Gruppe, anbefaler at pasienter med ikke-småcellet lungekreft testes for mutasjoner i EGFR-genet. Vi rapporterer her erfaringene som er gjort etter at slik testing ble innført i Norge i 2010. MATERIALE OG METODE. Opplysninger om hvor mange som er testet, kjønnsfordeling, histopatologiske data og analyseresultater er samlet inn fra de molekylærpatologiske laboratorier ved universitetssykehusene i Tromsø, Trondheim, Bergen og Oslo for perioden mai 2010 til mai 2011. RESULTATER. 1 058 pasienter med lungekreft ble testet for mutasjoner i EGFR-genet i denne perioden, hvilket svarer til ca. halvdelen av alle som fikk diagnosen ikke-småcellet lungekreft. Mutasjon ble påvist hos 123 pasienter (11,6 %). Det var en høyere andel mutasjonspositive kvinner enn menn (17,6 % mot 6,3 %, p < 0,001), og lavere andel ved plateepitelkarsinom enn ved andre histopatologiske undertyper (3,0 % mot 12,9 %, p = 0,001). Av 80 cytologiske prøver var ni (11,3 %) positive. FORTOLKNING. På bakgrunn av den relativt høye mutasjonsfrekvensen og et ikke ubetydelig antall positive i plateepitelkarsinomgruppen, anbefaler vi videreføring av mutasjonstesting av alle pasienter med ikke-småcellet lungekreft.
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Lund-Iversen, Marius; Kleinberg, Lilach; Fjellbirkeland, Lars; Helland, Åslaug & Brustugun, Odd Terje
(2012).
Clinicopathological Characteristics of 11 NSCLC Patients with EGFR-Exon 20 Mutations.
Journal of Thoracic Oncology.
ISSN 1556-0864.
7(9),
p. 1471–1473.
doi:
10.1097/JTO.0b013e3182614a9d.
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Fjellbirkeland, Lars; Laerum, Ole Didrik; Eide, Geir Egil & Bjerkvig, Rolf
(1998).
Invasiveness by lacZ transfected non-small cell lung cancer cells into human bronchial tissues in vitro.
Lung Cancer.
ISSN 0169-5002.
21(1),
p. 7–19.
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Gismarvik, Marit Enny & Fjellbirkeland, Lars
(2026).
Årsrapport 2025 med resultater og forbedringstiltak fra Nasjonalt kvalitetsregister for lungekreft.
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Nyen, Johanne Elise; Booth, Anja Ødegård; Husby, Øyvind; Bugge, Christoffer; Engebretsen, Ingrid & Oteiza, Francisco
[Show all 10 contributors for this article]
(2025).
Corrigendum: Targeted treatment and survival in advanced non-squamous non-small cell lung cancer patients – a nationwide and longitudinal study (Frontiers in Oncology, (2025), 15, (1506041), 10.3389/fonc.2025.1506041).
Frontiers in Oncology.
15.
doi:
10.3389/fonc.2025.1595028.
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Published
Apr. 13, 2011 2:54 PM
- Last modified
May 27, 2011 4:07 PM