Odd Terje Brustugun

• 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, p. 343–350. doi: 10.2340/1651-226X.2024.27572.
• 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. doi: 10.1016/j.cllc.2024.04.002.
• 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. ISSN 1471-2466. 24(1). doi: 10.1186/s12890-024-02918-w.
• Dyrbekk, Anne Pernille Harlem; Warsame, Abdirashid; Suhrke, Pål; Ludahl, Marianne Odnakk; Nermin, Zecic & Moe, Joakim Oliu [Show all 8 contributors for this article] (2024). Evaluation of NTRK expression and fusions in a large cohort of early-stage lung cancer. Clinical and Experimental Medicine. ISSN 1591-8890. 24(1). doi: 10.1007/s10238-023-01273-0.
• Nilssen, Yngvar; Solberg, Steinar; Brustugun, Odd Terje; Møller, Bjørn; Sundset, Arve & Wahl, Sissel Gyrid Freim [Show all 7 contributors for this article] (2023). Tracheal cancer: a rare and deadly but potentially curable disease that also affects younger people. European Journal of Cardio-Thoracic Surgery. ISSN 1010-7940. 64(1). doi: 10.1093/ejcts/ezad244. Full text in Research Archive
• Dyrbekk, Anne Pernille Harlem; Warsam, Abdirashid Ali; Suhrke, Pål; Ludahl, Marianne Odnakk; Moe, Joakim Oliu & Eide, Inger Johanne [Show all 8 contributors for this article] (2023). “Evaluation of ROS1 expression and rearrangements in a large cohort of early-stage lung cancer”. Diagnostic Pathology. ISSN 1746-1596. 18(1). doi: 10.1186/s13000-023-01357-1. Full text in Research Archive
• Eide, Inger Johanne; Nilssen, Yngvar; Stensland, Elin Marie & Brustugun, Odd Terje (2023). Real-World Data on EGFR and ALK Testing and TKI Usage in Norway—A Nation-Wide Population Study. Cancers. ISSN 2072-6694. 15(5). doi: 10.3390/cancers15051505. Full text in Research Archive
• Alexeyenko, Andrey; Brustugun, Odd Terje; Eide, Inger Johanne; Gencheva, Radosveta; Kosibaty, Zeinab & Lai, Yi [Show all 14 contributors for this article] (2022). Plasma RNA profiling unveils transcriptional signatures associated with resistance to osimertinib in EGFR T790M positive non-small cell lung cancer patients. Translational Lung Cancer Research (TLCR). ISSN 2218-6751. 11(10), p. 2064–2078. doi: 10.21037/tlcr-22-236. Full text in Research Archive Show summary

  Background: Targeted therapy with tyrosine kinases inhibitors (TKIs) against epidermal growth factor receptor (EGFR) is part of routine clinical practice for EGFR mutant advanced non-small cell lung cancer (NSCLC) patients. These patients eventually develop resistance, frequently accompanied by a gatekeeper mutation, T790M. Osimertinib is a third-generation EGFR TKI displaying potency to the T790M resistance mutation. Here we aimed to analyze if exosomal RNAs, isolated from longitudinally sampled plasma of osimertinib-treated EGFR T790M NSCLC patients, could provide biomarkers of acquired resistance to osimertinib. Methods: Plasma was collected at baseline and progression of disease from 20 patients treated with osimertinib in the multicenter phase II study TKI in Relapsed EGFR-mutated non-small cell lung cancer patients (TREM). Plasma was centrifuged at 16,000 g followed by exosomal RNA extraction using Qiagen exoRNeasy kit. RNA was subjected to transcriptomics analysis with Clariom D. Results: Transcriptome profiling revealed differential expression [log2(fold-change) >0.25, false discovery rate (FDR) P0.05] of 128 transcripts. We applied network enrichment analysis (NEA) at the pathway level in a large collection of functional gene sets. This overall enrichment analysis revealed alterations in pathways related to EGFR and PI3K as well as to syndecan and glypican pathways (NEA FDR 0.05 and NEA z-score exceeding 3 in at least one sample). Conclusions: Our study demonstrates a potential usability of plasma-derived exosomal RNAs to characterize molecular phenotypes of emerging osimertinib resistance. Furthermore, it highlights the involvement of multiple RNA species in shaping the transcriptome landscape of osimertinib-refractory NSCLC patients.

• Kosibaty, Zeinab; Brustugun, Odd Terje; Eide, Inger Johanne Zwicky; Tsakonas, Georgios; Grundberg, Oscar & De Petris, Luigi [Show all 9 contributors for this article] (2022). Ras-Related Protein Rab-32 and Thrombospondin 1 Confer Resistance to the EGFR Tyrosine Kinase Inhibitor Osimertinib by Activating Focal Adhesion Kinase in Non-Small Cell Lung Cancer. Cancers. ISSN 2072-6694. 14(14). doi: 10.3390/cancers14143430. Full text in Research Archive
• Eide, Inger Johanne; Stensgaard, Simone; Helland, Åslaug; Ekman, Simon; Mellemgaard, Anders & Hansen, Karin Holmskov [Show all 11 contributors for this article] (2022). Osimertinib in non-small cell lung cancer with uncommon EGFR-mutations: a post-hoc subgroup analysis with pooled data from two phase II clinical trials. Translational Lung Cancer Research (TLCR). ISSN 2218-6751. 11(6), p. 953–963. doi: 10.21037/tlcr-21-995. Full text in Research Archive
• Khadse, Anand; Haakensen, Vilde Drageset; Silwal-Pandit, Laxmi; Hamfjord, Julian; Micke, Patrick & Botling, Johan [Show all 10 contributors for this article] (2022). Prognostic Significance of the Loss of Heterozygosity of KRAS in Early-Stage Lung Adenocarcinoma. Frontiers in Oncology. ISSN 2234-943X. 12. doi: 10.3389/fonc.2022.873532. Show summary

  Lung cancer is a common disease with a poor prognosis. Genomic alterations involving the KRAS gene are common in lung carcinomas, although much is unknown about how different mutations, deletions, and expressions influence the disease course. The first approval of a KRAS-directed inhibitor was recently approved by the FDA. Mutations in the KRAS gene have been associated with poor prognosis for lung adenocarcinomas, but implications of the loss of heterozygosity (LOH) of KRAS have not been investigated. In this study, we have assessed the LOH of KRAS in early-stage lung adenocarcinoma by analyzing DNA copy number profiles and have investigated the effect on patient outcome in association with mRNA expression and somatic hotspot mutations. KRAS mutation was present in 36% of cases and was associated with elevated mRNA expression. LOH in KRAS was associated with a favorable prognosis, more prominently in KRAS mutated than in wild-type patients. The presence of both LOH and mutation in KRAS conferred a better prognosis than KRAS mutation alone. For wild-type tumors, no difference in prognosis was observed between patients with and without LOH in KRAS. Our study indicates that LOH in KRAS is an independent prognostic factor that may refine the existing prognostic groups of lung adenocarcinomas.

• Kaźmierczak, Dominika; Eide, Inger Johanne; Gencheva, Radosveta; Lai, Yi; Lewensohn, Rolf & Tsakonas, Georgios [Show all 12 contributors for this article] (2022). Elevated expression of miR-494-3p is associated with resistance to osimertinib in EGFR T790M-positive non-small cell lung cancer. Translational Lung Cancer Research (TLCR). ISSN 2218-6751. 11(5), p. 722–734. doi: 10.21037/tlcr-21-955. Full text in Research Archive Show summary

  Background: Non-small cell lung cancer (NSCLC) harboringactivating mutations in the gene encoding epidermal growth factor receptor (EGFR) is amenable for targeted therapy with tyrosine kinase inhibitors (TKIs). Eventually, resistance to TKI-therapy occurs resulting in disease progression. A substantial fraction of resistance mechanisms is unknown and may involve alterations in the RNA or protein landscape. MicroRNAs (miRNAs) have been frequently suggested to play roles in various forms of cancer including NSCLC. However, a role of miRNAs in acquired resistance to EGFR TKIs remains elusive. In this work, we aimed to investigate the potential involvement of miRNAs in acquired resistance to the third-generation EGFR TKI osimertinib in NSCLC. Methods: We combined miRNA expression profiling with miRNA-inhibitory screening to identify miRNAs involved in conferring resistance to osimertinib. Finally, we validated our top miRNA candidate by profiling longitudinal plasma exosomal RNA from patients receiving osimertinib as second-line therapy in a clinical trial. Results: Various miRNAs displayed differential expression in parental versus osimertinib-refractory NSCLC cells. miRNA-inhibitory screening revealed miR-494-3p to partially confer resistance to osimertinib in vitro. Expression of miR-494-3p was significantly elevated in plasma sampled at disease progression compared to plasma sampled at treatment baseline in a cohort of 21 EGFR T790M-mutation positive NSCLC patients receiving osimertinib. Conclusions: Our results highlight the need for further therapeutic exploration of miR-494-3p in in vivo models of EGFR-mutant NSCLC. Keywords: Non-small cell lung cancer (NSCLC); epidermal growth factor receptor (EGFR); osimertinib; microRNA (miRNA); resistance

• Eide, Inger Johanne; Nilssen, Yngvar; Lund-Iversen, Marius & Brustugun, Odd Terje (2022). Factors affecting outcome in resected EGFR-mutated lung cancer. Acta Oncologica. ISSN 0284-186X. 61(6), p. 749–756. doi: 10.1080/0284186X.2022.2066984.
• 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. Full text in Research Archive
• Sørensen, Jens Benn; Horvat, Pia; Rosenlund, Mats; Kejs, Anne Mette; Patel, Dony & Juarez-Garcia, Ariadna [Show all 12 contributors for this article] (2022). Initial treatment and survival in Danish patients diagnosed with non-small-cell lung cancer (2005-2015): SCAN-LEAF study. Future Oncology. ISSN 1479-6694. 18(2), p. 205–214. doi: 10.2217/fon-2021-0746.
• Agbarya, Abed; Shalata, Walid; Addeo, Alfredo; Charpidou, Andriani; Cuppens, Kristof & Brustugun, Odd Terje [Show all 12 contributors for this article] (2022). Real-World Journey of Unresectable Stage III NSCLC Patients: Current Dilemmas for Disease Staging and Treatment. Journal of Clinical Medicine. ISSN 2077-0383. 11(6). doi: 10.3390/jcm11061738.
• Killingberg, Kristin Toftaker; Halvorsen, Tarje Onsøien; Fløtten, Øystein; Brustugun, Odd Terje; Langer, Seppo W. & Nyman, Jan [Show all 13 contributors for this article] (2022). Patient-reported health-related quality of life from a randomized phase II trial comparing standard-dose with high-dose twice daily thoracic radiotherapy in limited stage small-cell lung cancer. Lung Cancer. ISSN 0169-5002. 166, p. 49–57. doi: 10.1016/j.lungcan.2022.02.002. Full text in Research Archive
• Nilssen, Yngvar; Brustugun, Odd Terje; Eriksen, Morten Tandberg; Guren, Marianne; Haug, Erik Skaaheim & Naume, Bjørn [Show all 8 contributors for this article] (2022). Compliance with recommended cancer patient pathway timeframes and choice of treatment differed by cancer type and place of residence among cancer patients in Norway in 2015–2016. BMC Cancer. ISSN 1471-2407. 22(220). doi: 10.1186/s12885-022-09306-9. Full text in Research Archive Show summary

  Background Cancer patient pathways (CPPs) were implemented in Norway to reduce unnecessary waiting times, regional variations, and to increase the predictability of cancer care for the patients. This study aimed to determine if 70% of cancer patients started treatment within the recommended time frames, and to identify potential delays. Methods Patients registered with a colorectal, lung, breast, or prostate cancer diagnosis at the Cancer Registry of Norway in 2015–2016 were linked with the Norwegian Patient Registry and Statistics Norway. Adjusting for sociodemographic variables, multivariable quantile (median) regressions were used to examine the association between place of residence and median time to start of examination, treatment decision, and start of treatment. Results The study included 20 668 patients. The proportions of patients who went through the CPP within the recommended time frames were highest among colon (84%) and breast (76%) cancer patients who underwent surgery and lung cancer patients who started systemic anticancer treatment (76%), and lowest for prostate cancer patients who underwent surgery (43%). The time from treatment decision to start of treatment was the main source of delay for all cancers. Travelling outside the resident health trust prolonged waiting time and was associated with a reduced odds of receiving surgery and radiotherapy for lung and rectal cancer patients, respectively. Conclusions Achievement of national recommendations of the CCP times differed by cancer type and treatment. Identified bottlenecks in the pathway should be targeted to decrease waiting times. Further, CPP guidelines should be re-examined to determine their ongoing relevance.

• Ekman, Simon; Horvat, Pia; Rosenlund, Mats; Kejs, Anne Mette; Patel, Dony & Juarez-Garcia, Ariadna [Show all 11 contributors for this article] (2021). Epidemiology and Survival Outcomes for Patients With NSCLC in Scandinavia in the Preimmunotherapy Era: A SCAN-LEAF Retrospective Analysis From the I-O Optimise Initiative. JTO Clinical and Research Reports. 2(5). doi: 10.1016/j.jtocrr.2021.100165.
• Frafjord, Astri; Buer, Linn; Hammarström, Clara Louise; Aamodt, Henrik; Woldbæk, Per R & Brustugun, Odd Terje [Show all 9 contributors for this article] (2021). The Immune Landscape of Human Primary Lung Tumors Is Th2 Skewed. Frontiers in Immunology. ISSN 1664-3224. 12:764596, p. 1–15. doi: 10.3389/fimmu.2021.764596. Full text in Research Archive
• Nilssen, Yngvar; Brustugun, Odd Terje & Møller, Bjørn (2021). Factors associated with emergency-related diagnosis, time to treatment and type of treatment in 5713 lung cancer patients. European Journal of Public Health. ISSN 1101-1262. 31(5), p. 967–974. doi: 10.1093/eurpub/ckab071.
• Lehtiö, Janne; Arslan, Taner; Siavelis, Ioannis; Pan, Yanbo; Socciarelli, Fabio & Berkovska, Olena [Show all 29 contributors for this article] (2021). Proteogenomics of non-small cell lung cancer reveals molecular subtypes associated with specific therapeutic targets and immune-evasion mechanisms. Cancer. ISSN 0008-543X. doi: 10.1038/s43018-021-00259-9.
• 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. Full text in Research Archive
• Bjaanæs, Maria Moksnes; Nilsen, Gro; Halvorsen, Ann Rita; Russnes, Hege Elisabeth Giercksky; Solberg, Steinar & Jørgensen, Lars [Show all 9 contributors for this article] (2021). Whole genome copy number analyses reveal a highly aberrant genome in TP53 mutant lung adenocarcinoma tumors. BMC Cancer. ISSN 1471-2407. 21(1). doi: 10.1186/s12885-021-08811-7. Full text in Research Archive
• Eide, Inger Johanne & Brustugun, Odd Terje (2021). Lungekreft behandlet med reseptortyrosinkinasehemmer i utlandet. Tidsskrift for Den norske legeforening. ISSN 0029-2001. 141(12), p. 1–4. doi: 10.4045/tidsskr.21.0147.
• Eide, Inger Johanne; Grut, Harald; Helland, Åslaug; Ekman, Simon; Sørensen, Jens Benn & Hansen, Karin Holmskov [Show all 11 contributors for this article] (2021). Intracranial effect of osimertinib in relapsed EGFR-mutated T790M-positive and -negative non-small cell lung cancer patients: results from a phase II study. Acta Oncologica. ISSN 0284-186X. doi: 10.1080/0284186X.2021.1973092. Full text in Research Archive Show summary

  Introduction Osimertinib is effective for relapsed T790M-positive patients with brain metastases. The high brain permeability suggests that also such patients without T790M could benefit. Therefore, we evaluated the effect of osimertinib on brain metastases in both T790M-positive and -negative patients. Methods The TREM-study was an investigator-initiated phase II, single-arm, multi-institutional clinical trial conducted in Northern Europe. Patients with resistance to prior EGFR-TKIs received osimertinib until radiological progression, unacceptable toxicity or death. Baseline brain scans were performed in patients with known or suspected brain metastases and repeated every 8–12 weeks. We assessed intracranial efficacy in patients with baseline brain metastases. Results Brain metastases were detected in 48/199 patients at baseline. Of these, 63% were T790M-positive, 27% -negative and 10% had unknown T790M-status. The majority (73%) of the patients had received prior whole brain radiotherapy and additionally 8% had received stereotactic radiosurgery (SRS). Brain scans were available for review for 42 patients. The intracranial progression free survival was 39.7 versus 3.5 months for T790M + and T790M- patients, respectively (p < 0.001). The overall intracranial disease control rate (iDCR) was 81%, and for T790M + and T790M- patients the DCR was 89% versus 55%, respectively. The estimated risk of CNS progression was 0.8% at 6 months and 6% at 12 months for T790M-positive patients, and 14% and 17% at 6 and 12 months, respectively, for the T790M-negative. Conclusion This subgroup analysis confirms CNS efficacy of osimertinib in patients with the T790M resistance mutation, while other treatment options should be considered for EGFR-TKI relapsed T790M-negative patients with brain metastases.

• Wahl, Sissel Gyrid Freim; Hong, Yan Dai; Emdal, Elisabeth Fritzke; Berg, Thomas; Halvorsen, Tarje Onsøien & Ottestad, Anine Larsen [Show all 14 contributors for this article] (2021). The prognostic effect of KRAS mutations in non-small cell lung carcinoma revisited: A norwegian multicentre study. Cancers. ISSN 2072-6694. 13(17), p. 1–19. doi: 10.3390/cancers13174294. Full text in Research Archive
• Bugge, Christoffer; Brustugun, Odd Terje; Sæther, Erik Magnus & Kristiansen, Ivar Sønbø (2021). Phase- and gender-specific, lifetime, and future costs of cancer: A retrospective population-based registry study. Medicine. ISSN 0025-7974. 100(26), p. 1–8. doi: 10.1097/MD.0000000000026523.
• Brustugun, Odd Terje; Nilssen, Yngvar & Eide, Inger Johanne (2021). Epidemiology and outcome of peritoneal and pleural mesothelioma subtypes in Norway. A 20 year nation-wide study. Acta Oncologica. ISSN 0284-186X. doi: 10.1080/0284186X.2021.1955971. Full text in Research Archive
• Grønberg, Bjørn Henning; Killingberg, Kristin Toftaker; Fløtten, Øystein; Brustugun, Odd; HORNSLIEN, KJERSTI & Madebo, Tesfaye [Show all 13 contributors for this article] (2021). High-dose versus standard-dose twice-daily thoracic radiotherapy for patients with limited stage small-cell lung cancer: an open-label, randomised, phase 2 trial. The Lancet Oncology. ISSN 1470-2045. 22(3), p. 321–331. doi: 10.1016/S1470-2045(20)30742-7. Full text in Research Archive Show summary

  Background Concurrent chemoradiotherapy is standard treatment for limited stage small-cell lung cancer (SCLC). Twice-daily thoracic radiotherapy of 45 Gy in 30 fractions is considered to be the most effective schedule. The aim of this study was to investigate whether high-dose, twice-daily thoracic radiotherapy of 60 Gy in 40 fractions improves survival. Methods This open-label, randomised, phase 2 trial was done at 22 public hospitals in Norway, Denmark, and Sweden. Patients aged 18 years and older with treatment-naive confirmed limited stage SCLC, Eastern Cooperative Oncology Group (ECOG) performance status 0–2, and measurable disease according to the Response Evaluation Criteria in Solid Tumors version 1.1 were eligible. All participants received four courses of intravenous cisplatin 75 mg/m2 or carboplatin (area under the curve 5–6 mg/mL × min, Calvert's formula) on day 1 and intravenous etoposide 100 mg/m2 on days 1–3 every 3 weeks. Participants were randomly assigned (1:1) in permuted blocks (sized between 4 and 10) stratifying for ECOG performance status, disease stage, and presence of pleural effusion to receive thoracic radiotherapy of 45 Gy in 30 fractions or 60 Gy in 40 fractions to the primary lung tumour and PET-CT positive lymph node metastases starting 20–28 days after the first chemotherapy course. Patients in both groups received two fractions per day, ten fractions per week. Responders were offered prophylactic cranial irradiation of 25–30 Gy. The primary endpoint, 2-year overall survival, was assessed after all patients had been followed up for a minimum of 2 years. All randomly assigned patients were included in the efficacy analyses, patients commencing thoracic radiotherapy were included in the safety analyses. Follow-up is ongoing. This trial is registered at ClinicalTrials.gov, NCT02041845. Findings Between July 8, 2014, and June 6, 2018, 176 patients were enrolled, 170 of whom were randomly assigned to 60 Gy (n=89) or 45 Gy (n=81). Median follow-up for the primary analysis was 49 months (IQR 38–56). At 2 years, 66 (74·2% [95% CI 63·8–82·9]) patients in the 60 Gy group were alive, compared with 39 (48·1% [36·9–59·5]) patients in the 45 Gy group (odds ratio 3·09 [95% CI 1·62–5·89]; p=0·0005). The most common grade 3–4 adverse events were neutropenia (72 [81%] of 89 patients in the 60 Gy group vs 62 [81%] of 77 patients in the 45 Gy group), neutropenic infections (24 [27%] vs 30 [39%]), thrombocytopenia (21 [24%] vs 19 [25%]), anaemia (14 [16%] vs 15 [20%]), and oesophagitis (19 [21%] vs 14 [18%]). There were 55 serious adverse events in 38 patients in the 60 Gy group and 56 serious adverse events in 44 patients in the 45 Gy group. There were three treatment-related deaths in each group (one neutropenic fever, one aortic dissection, and one pneumonitis in the 60 Gy group; one thrombocytic bleeding, one cerebral infarction, and one myocardial infarction in the 45 Gy group). Interpretation The higher radiotherapy dose of 60 Gy resulted in a substantial survival improvement compared with 45 Gy, without increased toxicity, suggesting that twice-daily thoracic radiotherapy of 60 Gy is an alternative to existing schedules.

• Brustugun, Odd & Heggelund, Lars (2021). Koronavaksinering av kreftpasienter. Tidsskrift for Den norske legeforening. ISSN 0029-2001. 141(3). doi: 10.4045/tidsskr.21.0026.
• Popat, Sanjay; Brustugun, Odd; Cadranel, Jacques; Felip, Enriqueta; Garassino, Marina Chiara & Griesinger, Frank [Show all 12 contributors for this article] (2021). Real-world treatment outcomes with brigatinib in patients with pretreated ALK+ metastatic non-small cell lung cancer. Lung Cancer. ISSN 0169-5002. 157, p. 9–16. doi: 10.1016/j.lungcan.2021.05.017. Full text in Research Archive Show summary

  Abstract Background The next-generation ALK inhibitor brigatinib is approved for use in patients with ALK inhibitor-naïve ALK-positive advanced NSCLC and in patients previously treated with crizotinib. A phase II trial showed that brigatinib is active in patients with ALK-positive metastatic NSCLC (mNSCLC) who had progressed on prior crizotinib (response rate 56 %, median PFS 16.7 months, median OS 34.1 months). We report final data from the UVEA-Brig study of brigatinib in ALK inhibitor-pretreated ALK-positive mNSCLC in clinical practice. Methods UVEA-Brig was a retrospective chart review of patients treated with brigatinib in Italy, Norway, Spain and the UK in an expanded access program. Adults with ALK-positive mNSCLC, including those with brain lesions, resistant to or intolerant of ≥1 prior ALK inhibitor and ECOG performance status ≤3 were eligible. Patients received brigatinib 180 mg once daily with a 7-day lead-in at 90 mg. The objectives were to describe patient characteristics, clinical disease presentation, treatment regimens used and clinical outcomes. Results Data for 104 patients (male: 43 %; median age: 53 [29–80] years; ECOG performance status 0/1/2/3: 41/41/10/5 %; brain/CNS metastases: 63 %) were analyzed. Patients had received a median of 2 (1–6) lines of systemic therapy prior to brigatinib (37.5 % received ≥3) and a median of 1 (1–5) lines of prior ALK inhibitor-containing therapy (crizotinib 83.6 %; ceritinib 50.0 %; alectinib 6.7 %; lorlatinib 4.8 %). At the time of analysis, 77 patients had discontinued brigatinib. Overall, the response rate was 39.8 %, median PFS was 11.3 (95 % CI:8.6–12.9) months and median OS was 23.3 (95 % CI: 16.0–NR) months. Four patients discontinued brigatinib treatment due to adverse events. 53 patients received systemic therapy after brigatinib, 42 with an ALK inhibitor (lorlatinib, n = 34). Conclusions These real-world data indicate the activity and tolerability of brigatinib in patients with ALK-positive mNSCLC who were more heavily pretreated than patients included in clinical trials.

• Bugge, Christoffer; Sæther, Erik Magnus; Brustugun, Odd & Kristiansen, Ivar Sønbø (2021). Societal cost of cancer in Norway –Results of taking a broader cost perspective. Health Policy. ISSN 0168-8510. doi: 10.1016/j.healthpol.2021.05.008.
• Berg, Janna; Ramberg, Christina; Haugstvedt, Jon Olav Sulheim; Bengtson, May-Bente; Gabrielsen, Anne Marie & Brustugun, Odd [Show all 8 contributors for this article] (2021). Lung Function After Stereotactic Body Radiation Therapy for Early-Stage Non-Small Cell Lung Cancer, Changes and Predictive Markers. Frontiers in Oncology. ISSN 2234-943X. 11. doi: 10.3389/fonc.2021.674731. Full text in Research Archive Show summary

  Introduction: The aim was to describe causal factors in children with postneonatal cerebral palsy (PNCP), compare clinical characteristics in children with PNCP to children with congenital CP, and compare congenital CP risk factors in children with PNCP to the general population. Patients and Methods: The Norwegian CP Registry was linked to the Medical Birth Registry for children born 1999 to 2013 (893,864 livebirths). Among 1710 children with CP, 67 (3.9%) had PNCP and 1643 congenital CP. Chi-Square tests were used to compare clinical characteristics in children with PNCP and congenital CP, and prevalence rates to compare risk factors in children with PNCP and the general population. Results: The leading causes of PNCP were cerebrovascular diseases (33%), accidents/trauma (22%) and infections (19%). More children with PNCP had spastic hemiplegic (54%) and quadriplegic/dyskinetic (31%) CP compared to congenital CP (42%; 20%, respectively) (p<0.001). More children with PNCP were unable to walk (GMFCS IV–V) (35%), had difficulty handling objects (MACS IV–V) (29%) compared to children with congenital CP (24%, p = 0.037; 19%, p = 0.008, respectively), and had significantly more associated impairments. Compared to the general population, children with PNCP were more likely to be born preterm, with a lower birthweight for gestational age and Apgar score, as a multiple, and with a congenital malformation.

• Haakensen, Vilde Drageset; Khadse, Anand; Sandhu, Vandana; Halvorsen, Ann Rita; Solberg, Steinar & Jørgensen, Lars Hilmar [Show all 9 contributors for this article] (2020). Molecular characterisation of TP53 mutated squamous cell carcinomas of the lung to identify putative targets for therapy. International Journal of Cancer. ISSN 0020-7136. 147(10), p. 2957–2966. doi: 10.1002/ijc.33121. Full text in Research Archive Show summary

  Personalised cancer treatment depends on identification of therapeutically relevant biological subgroups of patients for assessing effect of treatment and to discover new therapeutic options. By analyses in heterogeneous patient populations, the effects may be lost in noise. Squamous cell carcinoma of the lung is a major killer worldwide. Despite recent advances, mortality is high and response to therapies varies greatly from patient to patient. Target search in biologically relevant subgroups may identify treatment options not so far discovered. A total of 198 patients undergoing surgery for squamous cell carcinomas of the lung were included in the study. The tumours were analysed for copy number alterations (n = 152) and gene expression from tumour (n = 188) and normal lung (n = 21), with both data levels present in 140 patients. We studied alterations in tumours harbouring mutations in TP53 and in previously published gene expression subtypes. Genes with consistent alterations in both genomic levels were identified as putative biomarkers. Results were validated in TCGA. The most convincing biomarker in TP53 mutated squamous cell carcinomas of the lung was BIRC5 with amplification in 36% of mutated samples, 5% in wild‐type samples and a 17%‐fold change of expression between TP53 mutated tumours and normal lung tissue. BIRC5 was significantly altered in the classical and primitive subtypes. We suggest BIRC5 as a putative predictive biomarker and putative druggable target in squamous cell lung carcinomas harbouring TP53 mutation or classified as classical and primitive subtypes.

• Halvorsen, Ann Rita; Haugen, Mads Haugland; Øjlert, Åsa Kristina; Lund-Iversen, Marius; Jørgensen, Lars Hilmar & Solberg, Steinar [Show all 9 contributors for this article] (2020). Protein kinase C isozymes associated with relapse free survival in non-small cell lung cancer patients. Frontiers in Oncology. ISSN 2234-943X. 10:590755, p. 1–11. doi: 10.3389/fonc.2020.590755. Full text in Research Archive
• Yu, Hui; Brustugun, Odd Terje; Ekman, Simon; Botling, Johan; La Fleur, Linnea & Micke, Patrick [Show all 10 contributors for this article] (2020). Programmed cell death ligand 1 expression in resected non–small cell lung cancer. Clinical Lung Cancer. ISSN 1525-7304. p. 1–8. doi: 10.1016/j.cllc.2020.09.018.
• Øjlert, Åsa Kristina; Nebdal, Daniel J.H.; Lund-Iversen, Marius; Ellefsen, Renée Åstrøm; Brustugun, Odd Terje & Gran, Jon Michael [Show all 8 contributors for this article] (2020). Immune checkpoint blockade in the treatment of advanced non-small cell lung cancer–predictors of response and impact of previous radiotherapy. Acta Oncologica. ISSN 0284-186X. p. 1–9. doi: 10.1080/0284186X.2020.1854851. Full text in Research Archive
• Stankovic, Branislava; Aamodt, Henrik; Bjørhovde, Heidi Anine Korsmo; Müller, Elisabeth; Hammarström, Clara Louise & Brustugun, Odd Terje [Show all 9 contributors for this article] (2020). The immune microenvironment in typical carcinoid lung tumour, a brief report of four cases. Scandinavian Journal of Immunology. ISSN 0300-9475. 92:e12893(2), p. 1–12. doi: 10.1111/sji.12893. Full text in Research Archive
• Halvorsen, Tarje Onsøien; Stokke, Kristin; Killingberg, Kristin Toftaker; Raj, Sunil Xavier; Sørhaug, Sveinung & Brustugun, Odd Terje [Show all 12 contributors for this article] (2020). Randomized phase III trial comparing switch-maintenance pemetrexed with observation followed by pemetrexed at progression in advanced NSCLC. Acta Oncologica. ISSN 0284-186X. doi: 10.1080/0284186X.2020.1778179.
• Garon, Edward B.; Scagliotti, Giorgio Vittorio; Gautschi, Oliver; Reck, Martin; Thomas, Michael & Docampo, Lara Iglesias [Show all 20 contributors for this article] (2020). Exploratory analysis of front-line therapies in REVEL: A randomised phase 3 study of ramucirumab plus docetaxel versus docetaxel for the treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy. ESMO Open. ISSN 2059-7029. 5(1). doi: 10.1136/esmoopen-2019-000567.
• 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. Full text in Research Archive
• Eide, Inger Johanne; Helland, Åslaug; Ekman, Simon; Mellemgaard, Anders; Hansen, Karin Holmskov & Cicenas, Saulius [Show all 9 contributors for this article] (2020). Osimertinib in T790M-positive and -negative patients with EGFR-mutated advanced non-small cell lung cancer (the TREM-study). Lung Cancer. ISSN 0169-5002. 143, p. 27–35. doi: 10.1016/j.lungcan.2020.03.009. Full text in Research Archive
• Frafjord, Astri; Skarshaug, Renate; Hammarström, Clara Louise; Stankovic, Branislava; Dorg, Linda Trobe & Aamodt, Henrik [Show all 11 contributors for this article] (2020). Antibody combinations for optimized staining of macrophages in human lung tumours. Scandinavian Journal of Immunology. ISSN 0300-9475. 92:e12889(1), p. 1–24. doi: 10.1111/sji.12889. Full text in Research Archive
• Nilssen, Yngvar; Brustugun, Odd Terje; Eriksen, Morten Tandberg; Haug, Erik Skaaheim; Naume, Bjørn & Møller, Bjørn (2020). Patient and tumour characteristics associated with inclusion in Cancer patient pathways in Norway in 2015-2016. BMC Cancer. ISSN 1471-2407. 20(1), p. 1–11. doi: 10.1186/s12885-020-06979-y. Full text in Research Archive
• Alcala, Nicolas; Leblay, N; Gabriel, AAG; Mangiante, L; Hervas, D & Giffon, T [Show all 70 contributors for this article] (2019). Integrative and comparative genomic analyses identify clinically relevant pulmonary carcinoid groups and unveil the supra-carcinoids. Nature Communications. ISSN 2041-1723. 10:3407, p. 1–21. doi: 10.1038/s41467-019-11276-9.
• Menon, Usha; Vedsted, Peter; Zalounina Falborg, Alina; Jensen, Henry; Harrison, Samantha & Reguilon, Irene [Show all 26 contributors for this article] (2019). Time intervals and routes to diagnosis for lung cancer in 10 jurisdictions: Cross-sectional study findings from the International Cancer Benchmarking Partnership (ICBP). BMJ Open. ISSN 2044-6055. 9:e025895(11), p. 1–20. doi: 10.1136/bmjopen-2018-025895. Full text in Research Archive
• Halvorsen, Ann Rita; Aure, Miriam Ragle; Øjlert, Åsa Kristina; Brustugun, Odd Terje; Solberg, Steinar & Nebdal, Daniel J.H. [Show all 7 contributors for this article] (2019). Identification of microRNAs involved in pathways which characterize the expression subtypes of NSCLC. Molecular Oncology. ISSN 1574-7891. doi: 10.1002/1878-0261.12571. Full text in Research Archive
• Øjlert, Åsa Kristina; Halvorsen, Ann Rita; Nebdal, Daniel J.H.; Lund-Iversen, Marius; Solberg, Steinar & Brustugun, Odd Terje [Show all 8 contributors for this article] (2019). The immune microenvironment in non‐small cell lung cancer is predictive of prognosis after surgery. Molecular Oncology. ISSN 1574-7891. 13(5), p. 1166–1179. doi: 10.1002/1878-0261.12475. Full text in Research Archive
• 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. Full text in Research Archive
• Nilssen, Yngvar; Brustugun, Odd Terje; Eriksen, Morten Tandberg; Gulbrandsen, Johanne; Haug, Erik Skaaheim & Naume, Bjørn [Show all 7 contributors for this article] (2019). Decreasing waiting time for treatment before and during implementation of cancer patient pathways in Norway. Cancer Epidemiology. ISSN 1877-7821. 61, p. 59–69. doi: 10.1016/j.canep.2019.05.004. Full text in Research Archive
• Stankovic, Branislava; Bjørhovde, Heidi Anine Korsmo; Skarshaug, Renate; Aamodt, Henrik; Frafjord, Astri & Müller, Elisabeth [Show all 14 contributors for this article] (2018). Immune Cell Composition in Human Non-small Cell Lung Cancer. Frontiers in Immunology. ISSN 1664-3224. Feb(1), p. 1–21. doi: 10.3389/fimmu.2018.03101. Full text in Research Archive Show summary

  Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death in the world. Immunological analysis of the tumor microenvironment (immunoscore) shows great promise for improved prognosis and prediction of response to immunotherapy. However, the exact immune cell composition in NSCLC remains unclear. Here, we used flow cytometry to characterize the immune infiltrate in NSCLC tumors, non-cancerous lung tissue, regional lymph node, and blood. The cellular identity of >95% of all CD45+ immune cells was determined. Thirteen distinct immune cell types were identified in NSCLC tumors. T cells dominated the lung cancer landscape (on average 47% of all CD45+ immune cells). CD4+ T cells were the most abundant T cell population (26%), closely followed by CD8+ T cells (22%). Double negative CD4−CD8− T cells represented a small fraction (1.4%). CD19+ B cells were the second most common immune cell type in NSCLC tumors (16%), and four different B cell sub-populations were identified. Macrophages and natural killer (NK) cells composed 4.7 and 4.5% of the immune cell infiltrate, respectively. Three types of dendritic cells (DCs) were identified (plasmacytoid DCs, CD1c+ DCs, and CD141+ DCs) which together represented 2.1% of all immune cells. Among granulocytes, neutrophils were frequent (8.6%) with a high patient-to- patient variability, while mast cells (1.4%), basophils (0.4%), and eosinophils (0.3%) were less common. Across the cohort of patients, only B cells showed a significantly higher representation in NSCLC tumors compared to the distal lung. In contrast, the percentages of macrophages and NK cells were lower in tumors than in non-cancerous lung tissue. Furthermore, the fraction of macrophages with high HLA-DR expression levels was higher in NSCLC tumors relative to distal lung tissue. To make the method readily accessible, antibody panels and flow cytometry gating strategy used to identify the various immune cells are described in detail. This work should represent a useful resource for the immunomonitoring of patients with NSCLC.

• Halvorsen, Ann Rita; Sandhu, Vandana; Sprauten, Mette; Flote, Vidar Gordon; Kure, Elin Wenche Hegland & Brustugun, Odd Terje [Show all 7 contributors for this article] (2018). Circulating microRNAs associated with prolonged overall survival in lung cancer patients treated with nivolumab. Acta Oncologica. ISSN 0284-186X. 57(9), p. 1225–1231. doi: 10.1080/0284186X.2018.1465585. Full text in Research Archive
• Bugge, Anders; Lund, May-Brith; Valberg, Morten; Brustugun, Odd Terje; Solberg, Steinar & Kongerud, Johny (2018). Cause-specific death after surgical resection for early-stage non-small-cell lung cancer. European Journal of Cardio-Thoracic Surgery. ISSN 1010-7940. 53(1), p. 221–227. doi: 10.1093/ejcts/ezx274.
• George, Julie; Walter, Vonn; Peifer, Martin; Alexandrov, Ludmil B.; Seidel, Danila & Leenders, Frauke [Show all 62 contributors for this article] (2018). Integrative genomic profiling of large-cell neuroendocrine carcinomas reveals distinct subtypes of high-grade neuroendocrine lung tumors. Nature Communications. ISSN 2041-1723. 9:1048, p. 1–13. doi: 10.1038/s41467-018-03099-x. Full text in Research Archive
• Berg, Janna; Halvorsen, Ann Rita; Bengtson, May-Bente; Tasken, Kristin Austlid; Mælandsmo, Gunhild Mari & Yndestad, Arne [Show all 11 contributors for this article] (2018). Levels and prognostic impact of circulating markers of inflammation, endothelial activation and extracellular matrix remodelling in patients with lung cancer and chronic obstructive pulmonary disease. BMC Cancer. ISSN 1471-2407. 18(1). doi: 10.1186/s12885-018-4659-0.
• 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. Full text in Research Archive
• Eide, Hanne Astrid; Knudtsen, Ingerid Skjei; Sandhu, Vandana; Løndalen, Ayca; Halvorsen, Ann Rita & Abravan, Azadeh [Show all 12 contributors for this article] (2018). Serum cytokine profiles and metabolic tumor burden in patients with non-small cell lung cancer undergoing palliative thoracic radiation therapy. Advances in Radiation Oncology. ISSN 2452-1094. 3(2), p. 130–138. doi: 10.1016/j.adro.2017.12.007. Full text in Research Archive
• Lund-Iversen, Marius; Scott, Helge; Strøm, Erik Heyerdahl; Theiss, Noah; Brustugun, Odd Terje & Grønberg, Bjørn Henning (2018). Expression of estrogen receptor-α and survival in advanced-stage non-small cell lung cancer. Anticancer Research. ISSN 0250-7005. 38(4), p. 2261–2269. doi: 10.21873/anticanres.12470. Full text in Research Archive
• Valan, Christine Damgaard; Slagsvold, Jens Erik; Halvorsen, Tarje Onsøien; Herje, Martin; Bremnes, Roy M. & Brunsvig, Paal Fr. [Show all 11 contributors for this article] (2018). Survival in Limited Disease Small Cell Lung Cancer According to N3 Lymph Node Involvement. Anticancer Research. ISSN 0250-7005. 38(2), p. 871–876. doi: 10.21873/anticanres.12296. Full text in Research Archive Show summary

  We compared survival between subcategories of N3 disease in limited disease small cell lung cancer patients who received concurrent chemoradiotherapy (n=144). N3 disease was a negative prognostic factor, but there were no significant differences between the N3 subcategories. All patients had longer survival than in studies of extensive disease, suggesting that all N3 patients should be treated as limited disease.

• Mcgowan, Marc Kevin; Kleinberg, Lilach; Halvorsen, Ann Rita; Helland, Åslaug & Brustugun, Odd Terje (2017). NSCLC depend upon YAP expression and nuclear localization after acquiring resistance to EGFR inhibitors. Genes & cancer. ISSN 1947-6019. 8(3-4), p. 497–504. doi: 10.18632/genesandcancer.136. Full text in Research Archive Show summary

  Yes-associated protein (YAP) is a downstream target of the Hippo pathway and has been found to be oncogenic driving many cancers into developing metastatic phenotypes leading to poor survival outcomes. This study investigated if YAP expression is associated with drug resistance in two non-small cell lung cancer (NSCLC) lines (HCC827 and H1975) generated to become resistant to the EGFR tyrosine kinase inhibitors (EGFR TKI) erlotinib, gefitinib or the T790M-specific osimertinib. We found that acquired EGFR TKI resistance was associated with YAP over-expression (osimertinib-resistant cells) or YAP amplification (erlotinib- and gefitinib-resistant cells) along with EMT phenotypic changes. YAP was localized in the nucleus, indicative of active protein. siRNA-mediated silencing of YAP resulted in re-sensitizing the drug-resistant cells to EGFR TKI compared to the negative siRNA controls (p = <0.05). These results suggest YAP is a potential mechanism of EGFR-TKI resistance in NSCLC and may presents itself as a viable therapeutic target.

• Meyer, Mathias; Vliegenthart, Rozemarijn; Henzler, Thomas; Buergy, Daniel; Giordano, Frank A. & Kostrzewa, Michael [Show all 29 contributors for this article] (2017). Management of progressive pulmonary nodules found during and outside of CT lung cancer screening studies. Journal of Thoracic Oncology. ISSN 1556-0864. 12(12), p. 1755–1765. doi: 10.1016/j.jtho.2017.09.1956.
• Pedersen, Jesper Holst; Sørensen, Jens Benn; Saghir, Zaigham; Fløtten, Øystein; Brustugun, Odd Terje & Ashraf, Haseem [Show all 15 contributors for this article] (2017). Implementation of lung cancer CT screening in the Nordic countries. Acta Oncologica. ISSN 0284-186X. 56(10), p. 1249–1257. doi: 10.1080/0284186X.2017.1329592.
• Helland, Åslaug; Brustugun, Odd Terje; Nakken, Sigve; Halvorsen, Ann Rita; Dønnem, Tom & Bremnes, Roy M. [Show all 15 contributors for this article] (2017). High number of kinome-mutations in non-small cell lung cancer is associated with reduced immune response and poor relapse-free survival. International Journal of Cancer. ISSN 0020-7136. 141(1), p. 184–190. doi: 10.1002/ijc.30726. Full text in Research Archive
• Brustugun, Odd Terje; Sprauten, Mette & Helland, Åslaug (2017). Real-world data on nivolumab treatment of non-small cell lung cancer. Acta Oncologica. ISSN 0284-186X. 56(3), p. 438–440. doi: 10.1080/0284186X.2016.1253865.
• Brustugun, Odd Terje (2016). Stratification in advanced non-small cell lung cancer: precision medicine in practice. Expert Review of Precision Medicine and Drug Development. ISSN 2380-8993. 1(3), p. 279–287. doi: 10.1080/23808993.2016.1176861.
• Manegold, Christian; Dingemans, Anne-Marie C; Gray, Jhanelle E; Nakagawa, Kazuhiko; Nicolson, Marianne & Peters, Solange [Show all 27 contributors for this article] (2016). The Potential of Combined Immunotherapy and Antiangiogenesis for the Synergistic Treatment of Advanced NSCLC. Journal of Thoracic Oncology. ISSN 1556-0864. 12(2), p. 194–207. doi: 10.1016/j.jtho.2016.10.003.
• Weischenfeldt, Joachim; Dubash, Taronish; Drainas, Alexandros P.; Mardin, Balca R.; Chen, Yuanyuan & Stütz, Adrian M. [Show all 32 contributors for this article] (2016). Pan-cancer analysis of somatic copy-number alterations implicates IRS4 and IGF2 in enhancer hijacking. Nature Genetics. ISSN 1061-4036. 49(1), p. 65–74. doi: 10.1038/ng.3722.
• Mcgowan, Marc Kevin; Hoven, Aleksandra Silye; Lund-Iversen, Marius; Solberg, Steinar; Helland, Åslaug & Hirsch, Fred R [Show all 7 contributors for this article] (2016). PIK3CA mutations as prognostic factor in squamous cell lung carcinoma. Lung Cancer. ISSN 0169-5002. 103, p. 52–57. doi: 10.1016/j.lungcan.2016.11.018.
• Nyman, Jan; Hallqvist, Andreas; Lund, Jo-Åsmund; Brustugun, Odd Terje; Bergman, Bengt & Bergström, Per [Show all 10 contributors for this article] (2016). SPACE – A randomized study of SBRT vs conventional fractionated radiotherapy in medically inoperable stage I NSCLC. Radiotherapy and Oncology. ISSN 0167-8140. 121(1), p. 1–8. doi: 10.1016/j.radonc.2016.08.015.
• Halvorsen, Tarje Onsøien; Herje, Martin; Levin, Nina; Bremnes, Roy M.; Brustugun, Odd Terje & Fløtten, Øystein [Show all 9 contributors for this article] (2016). Tumour size reduction after the first chemotherapy-course and outcomes of chemoradiotherapy in limited disease small-cell lung cancer. Lung Cancer. ISSN 0169-5002. 102, p. 9–14. doi: 10.1016/j.lungcan.2016.10.003. Full text in Research Archive
• Eide, Hanne Astrid; Halvorsen, Ann Rita; Sandhu, Vandana; Fåne, Anne; Berg, Janna & Haakensen, Vilde Drageset [Show all 11 contributors for this article] (2016). Non-small cell lung cancer is characterised by a distinct inflammatory signature in serum compared with chronic obstructive pulmonary disease. Clinical & translational immunology. ISSN 2050-0068. 5. doi: 10.1038/cti.2016.65. Full text in Research Archive Show summary

  Development of lung cancer is closely related to smoking in a majority of patients. Most smokers, however, do not develop lung cancer in spite of a high mutational load accumulating in the lung tissue. Here we investigate whether a cancer-specific footprint can be revealed by investigating circulating inflammatory markers in patients with non-small cell lung cancer (NSCLC) compared with patients with chronic obstructive pulmonary disease (COPD), both cohorts characterised by similar smoking history. Serum concentrations of 57 cytokines and matrix metalloproteinases (MMPs) from 43 patients with advanced NSCLC were evaluated by multiplex immunoassays and compared with serum samples from 35 patients with COPD. Unsupervised hierarchical clustering and non-parametric analyses were performed. False discovery rate was used to adjust for multiple testing. Clustering of cytokine and MMP concentrations in the serum revealed a distinct separation of the NSCLC patients from the COPD group. Individual concentrations of thymus and activation-regulated cytokine (C-C motif chemokine ligand 17), Gro-b (C-X-C motif chemokine ligand 2 (CXCL2)), CXCL13, interleukin (IL)-1ra, IL-6, IL-8 (CXCL8), IL-16, IL-17A, macrophage migration inhibitory factor (MIF), granulocyte colony-stimulating factor, platelet-derived growth factor subunit B, MMP-2, MMP-8 and MMP-12 were significantly different in serum from NSCLC and COPD patients. Moreover, the interferon-γ/IL-10 ratio was lower in cancer patients compared with COPD patients, consistent with a cytokine milieu favouring tumour tolerance. Our results suggest that NSCLC is characterised by a distinct inflammatory signature in serum. The different cytokine profiles in NSCLC and COPD patients may represent tumour-promoting and tumour-suppressing immune responses developing in response to mucosal inflammation and mutations induced by smoking.

• Halvorsen, Tarje Onsøien; Sundstrøm, Stein Harald; Fløtten, Øystein; Brustugun, Odd Terje; Brunsvig, Paal Fr. & Aasebø, Ulf [Show all 9 contributors for this article] (2016). Comorbidity and outcomes of concurrent chemo- and radiotherapy in limited disease small cell lung cancer. Acta Oncologica. ISSN 0284-186X. 55(11), p. 1349–1354. doi: 10.1080/0284186X.2016.1201216. Full text in Research Archive
• Halvorsen, Ann Rita; Bjaanæs, Maria Moksnes; LeBlanc, Marissa; Holm, Are Martin; Bolstad, Nils & Rubio, Luis [Show all 12 contributors for this article] (2016). A unique set of 6 circulating microRNAs for early detection of non-small cell lung cancer. OncoTarget. ISSN 1949-2553. 7(24), p. 37250–37259. doi: 10.18632/oncotarget.9363.
• Rud, Ane Kristine Kongsgaard; Pedersen, Kjetil Boye; Fodstad, Øystein; Juell, Siri; Jørgensen, Lars Hilmar & Solberg, Steinar [Show all 9 contributors for this article] (2016). Detection of disseminated tumor cells in lymph nodes from patients with early stage non-small cell lung cancer. Diagnostic Pathology. ISSN 1746-1596. 11(50). doi: 10.1186/s13000-016-0504-4. Full text in Research Archive
• Joly-Battaglini, Albane; Hammarström, Clara Louise; Stankovic, Branislava; Aamodt, Henrik; Stjärne, Johan Folke Håkan & Brustugun, Odd Terje [Show all 9 contributors for this article] (2016). Rituximab efficiently depletes B cells in lung tumors and normal lung tissue. F1000. ISSN 1759-796X. 5. doi: 10.12688/f1000research.7599.1.
• Halvorsen, Ann Rita; Silwal-Pandit, Laxmi; Meza, Leonardo Zepeda; Vodak, Daniel; Vu, Phuong Ngoc Thi & Sagerup, Camilla Maria Troøien [Show all 11 contributors for this article] (2016). TP53 mutation spectrum in smokers and never smoking lung cancer patients. Frontiers in Genetics. ISSN 1664-8021. 7(MAY). doi: 10.3389/fgene.2016.00085. Show summary

  Background: TP53 mutations are among the most common mutations found in lung cancers, identified as an independent prognostic factor in many types of cancers. The purpose of this study was to investigate the frequency and prognostic impact of TP53 mutations in never-smokers and in different histological subtypes of lung cancer. Methods: We analyzed tumor tissue from 394 non-small cell carcinomas including adenocarcinomas (n = 229), squamous cell carcinomas (n = 112), large cell carcinomas (n = 30), and others (n = 23) for mutations in TP53 by the use of Sanger sequencing (n = 394) and next generation sequencing (n = 100). Results: TP53 mutations were identified in 47.2% of the samples, with the highest frequency (65%) of mutations among squamous cell carcinomas. Among never-smokers, 36% carried a TP53 mutation, identified as a significant independent negative prognostic factor in this subgroup. For large cell carcinomas, a significantly prolonged progression free survival was found for those carrying a TP53 mutation. In addition, the frequency of frameshift mutations was doubled in squamous cell carcinomas (20.3%) compared to adenocarcinomas (9.1%). Conclusion: TP53 mutation patterns differ between the histological subgroups of lung cancers, and are also influenced by smoking history. This indicates that the histological subtypes in lung cancer are genetically different, and that smoking-induced TP53 mutations may have a different biological impact than TP53 mutations occurring in never-smokers.

• Eide, Hanne Astrid; Halvorsen, Ann Rita; Bjaanæs, Maria Moksnes; Piri, Hossein; Holm, Ruth & Solberg, Steinar [Show all 10 contributors for this article] (2016). The MYCN-HMGA2-CDKN2A pathway in non-small cell lung carcinoma-differences in histological subtypes. BMC Cancer. ISSN 1471-2407. 16(1). doi: 10.1186/s12885-016-2104-9.
• Bjaanæs, Maria Moksnes; Fleischer, Thomas; Halvorsen, Ann Rita; Daunay, Antoine; Busato, Florence & Solberg, Steinar [Show all 14 contributors for this article] (2016). Genome-wide DNA methylation analyses in lung adenocarcinomas: Association with EGFR, KRAS and TP53 mutation status, gene expression and prognosis. Molecular Oncology. ISSN 1574-7891. 10(2), p. 330–343. doi: 10.1016/j.molonc.2015.10.021.
• Grønberg, Bjørn Henning; Halvorsen, Tarje Onsøien; Fløtten, Øystein; Brustugun, Odd Terje; Brunsvig, Paal Fr. & Aasebø, Ulf [Show all 12 contributors for this article] (2016). Randomized phase II trial comparing twice daily hyperfractionated with once daily hypofractionated thoracic radiotherapy in limited disease small cell lung cancer. Acta Oncologica. ISSN 0284-186X. 55(5), p. 591–597. doi: 10.3109/0284186X.2015.1092584. Full text in Research Archive
• Dønnem, Tom; Kilvær, Thomas Karsten; Andersen, Sigve; Richardsen, Elin; Paulsen, Erna-Elise & Hald, Sigurd [Show all 21 contributors for this article] (2016). Strategies for clinical implementation of TNM-Immunoscore in resected nonsmall-cell lung cancer. Annals of Oncology. ISSN 0923-7534. 27(2), p. 225–232. doi: 10.1093/annonc/mdv560.
• Nilssen, Yngvar; Strand, Trond-Eirik; Fjellbirkeland, Lars; Bartnes, Kristian; Brustugun, Odd Terje & O'Connell, Dianne L [Show all 8 contributors for this article] (2016). Lung cancer treatment is influenced by income, education, age and place of residence in a country with universal health coverage. International Journal of Cancer. ISSN 0020-7136. 138(6), p. 1350–1360. doi: 10.1002/ijc.29875.
• Berg, Janna; Fjellbirkeland, Lars; Suhrke, Pål; Jebsen, Peter Wilhelm; Lund-Iversen, Marius & Kleinberg, Lilach [Show all 9 contributors for this article] (2016). EGFR mutation testing of lung cancer patients - Experiences from Vestfold Hospital Trust. Acta Oncologica. ISSN 0284-186X. 55(2), p. 149–155. doi: 10.3109/0284186X.2015.1062537.
• Bjaanæs, Maria Moksnes; Nilsen, Gro; Solberg, Steinar; Brustugun, Odd Terje; Lingjærde, Ole Christian & Helland, Åslaug (2015). Whole-genome copy number analyses of NSCLC tumors reveal aberrations associated with EGFR mutations and may have prognostic impact. Journal of Thoracic Oncology. ISSN 1556-0864. 10(9), p. S581–S582.
• Lund-Iversen, Marius; Kotanska-Grøholt, Krystyna; Helland, Åslaug; Borgen, Elin & Brustugun, Odd Terje (2015). NUT expression in primary lung tumours. Diagnostic Pathology. ISSN 1746-1596. 10:156. doi: 10.1186/s13000-015-0395-9.

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• Brustugun, Odd Terje (2023). Håp når håpløsheten truer. Tidsskrift for Den norske legeforening. ISSN 0029-2001. 143(5). doi: 10.4045/tidsskr.23.0095.
• Tasken, Kjetil; Russnes, Hege Elisabeth Giercksky; Aas, Eline; Bjørge, Line; Blix, Egil Støre & Ahlquist, Terje C. [Show all 116 contributors for this article] (2022). A national precision cancer medicine implementation initiative for Norway. Nature Medicine. ISSN 1078-8956. 28(5), p. 885–887. doi: 10.1038/s41591-022-01777-4.
• Brustugun, Odd Terje (2022). Slik kan man få tilgang til legemidler uten vedtak i Beslutningsforum. Tidsskrift for Den norske legeforening. ISSN 0029-2001. 142(2). doi: 10.4045/tidsskr.21.0886.
• Brustugun, Odd Terje (2021). Kreft og koronarisiko. Tidsskrift for Den norske legeforening. ISSN 0029-2001. 141(2). doi: 10.4045/tidsskr.20.1044.
• Brustugun, Odd Terje; Sørhaug, Sveinung; Grønberg, Bjørn Henning; Aanerud, Marianne; Al-Zubaydi, Mohammed Modar & Fjellbirkeland, Lars [Show all 13 contributors for this article] (2020). Lungekreft: Forbedret prognose gir kapasitetsutfordringer. Tidsskrift for Den norske legeforening. ISSN 0029-2001. 140(5). doi: 10.4045/tidsskr.20.0014.
• Sørensen, J.B.; Ekman, S.; Brustugun, Odd Terje; Horvat, P.; Patel, D. & Rosenlund, M. [Show all 13 contributors for this article] (2019). Evolution of overall survival (OS) in patients (pts) with incident NSCLC in Denmark and Sweden: A SCAN-LEAF study analysis from the I-O Optimise initiative. Annals of Oncology. ISSN 0923-7534. 30, p. ii16–ii17. doi: 10.1093/annonc/mdz070.004.
• Ekman, S.; Sørensen, J.B.; Brustugun, Odd Terje; Horvat, P.; Patel, D. & Rosenlund, M. [Show all 13 contributors for this article] (2019). Treatment (Tx) patterns and overall survival (OS) in patients (pts) with NSCLC in Sweden: A SCAN-LEAF study analysis from the I-O Optimise initiative. Annals of Oncology. ISSN 0923-7534. 30, p. ii17–ii17. doi: 10.1093/annonc/mdz070.005.
• Berg, Janna; Lindberg, Morten; Bengtson, May-Bente; Brustugun, Odd Terje & Helland, Åslaug (2019). The Neutrophil and Platelet to Lymphocyte Ratios and Glasgow Prognostic Score as a Predictor for Relapse After Stereotactic Radiation for Lung Cancer. Journal of Thoracic Oncology. ISSN 1556-0864. 14. doi: 10.1016/j.jtho.2019.08.2457.
• Brustugun, Odd Terje (2019). A NOTCH added to metabolomics. British Journal of Cancer. ISSN 0007-0920. 121, p. 3–4. doi: 10.1038/s41416-019-0463-0.
• Knudtsen, Ingerid Søberg Skjei; Eide, Hanne Astrid; Løndalen, Ayca; Abravan, Azadeh; Bogsrud, Trond & Sprauten, Mette [Show all 9 contributors for this article] (2017). 18FDG-PET/CT for assessing short-term therapy response of advanced non-small cell lung cancer patients.
• Grønberg, Bjørn Henning; Sundstrøm, Stein Harald; Fløtten, Øystein; Brustugun, Odd Terje; Brunsvig, Paal Fr. & Bremnes, Roy M. [Show all 8 contributors for this article] (2015). Associations between Comorbidity, Treatment Toxicity and Overall Survival in Limited Disease Small-Cell Lung Cancer (LD-SCLC). Journal of Thoracic Oncology. ISSN 1556-0864. 10(9).
• Valan, Christine Damgaard; Halvorsen, Tarje Onsøien; Levin, Nina; Bremnes, Roy M.; Brunsvig, Paal Fr. & Fløtten, Øystein [Show all 9 contributors for this article] (2015). Survival of patients with N3 lymph node disease in a cohort with limited disease small-cell lung cancer receiving concurrent chemoradiotherapy. Journal of Thoracic Oncology. ISSN 1556-0864. 10(9).
• Valan, Christine Damgaard; Halvorsen, Tarje Onsøien; Levin, Nina; Bremnes, Roy M.; Brunsvig, Paal Fr. & Brustugun, Odd Terje [Show all 8 contributors for this article] (2015). Survival of patients with N3 lymph node disease in a cohort with limited disease small-cell lung cancer receiving concurrent chemoradiotherapy.
• Grønberg, Bjørn Henning; Levin, Nina; Sundstrøm, Stein Harald; Fløtten, Øystein; Brustugun, Odd Terje & Brunsvig, Paal Fr. [Show all 9 contributors for this article] (2015). Reduction in tumor size after the first course of cisplatin/etoposide (PE) in limited disease small-cell lung cancer (LD SCLC). Journal of Clinical Oncology. ISSN 0732-183X. 33.
• Grønberg, Bjørn Henning; Sundstrøm, Stein Harald; Fløtten, Øystein; Brustugun, Odd Terje; Brunsvig, Paal Fr. & Aasebø, Ulf [Show all 9 contributors for this article] (2015). Association between comorbidity, treatment toxicity and overall survival in limited disease small-cell lung cancer.

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