Publications by authors named "Odd Terje Brustugun"

94 Publications

Lungekreft behandlet med reseptortyrosin=kinasehemmer i utlandet.

Tidsskr Nor Laegeforen 2021 Sep 24;141. Epub 2021 Aug 24.

Background: Activating RET fusions are oncogenic drivers in multiple cancers and are identified in 1-2 % of non-small cell lung cancers (NSCLC). Selpercatinib and pralsetinib are tyrosine kinase inhibitors selectively targeting RET and with clinical activity in RET-positive NSCLC.

Case Presentation: A male never-smoker in his forties was diagnosed with advanced lung adenocarcinoma. With negative tests for EGFR mutations, ROS1 and ALK rearrangements, he was treated with a combination of chemotherapy and an immune checkpoint inhibitor. Upon progression a rebiopsy analysed by next generation sequencing (NGS) revealed a KIF5B-RET fusion. He received treatment with pralsetinib through a compassionate use programme, with relief of symptoms within weeks, and radiological partial response after two months of treatment. He has not experienced side effects after six months of treatment.

Interpretation: Precision medicine is dependent on diagnostic methods such as NGS to identify patients who might benefit from targeted therapies. Selective inhibitors of molecular oncogenic drivers are usually effective and well tolerated.
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http://dx.doi.org/10.4045/tidsskr.21.0147DOI Listing
September 2021

Kolangiokarsinom behandlet med tumoragnostisk legemiddel.

Tidsskr Nor Laegeforen 2021 Sep 31;141. Epub 2021 Aug 31.

Background: Precision medicine with genomic analyses of tumour tissue has introduced tumour-agnostic therapies in oncology.

Case Presentation: A previously healthy woman in her thirties was diagnosed with advanced cholangiocarcinoma. She received four courses of cisplatin and gemcitabine, but her disease progressed. RNA-based next-generation sequencing revealed a fusion transcript involving RBPMS-NTRK3. She commenced entrectinib 600 mg OD and after five days reported clinical improvement. CT scans after five weeks of treatment confirmed response. She experienced some toxicities, such as mild chest pain with slight increase in troponin, urinary retention (successfully treated with mirabegron 50 mg daily), dysaesthesia, constipation and dysgeusia. Echocardiography and coronary angiography were performed without pathology. Dosing was reduced to 400 mg daily after six weeks, and she has received treatment without significant side effects and with normal troponin for five months.

Interpretation: This example shows the importance of implementing next-generation sequencing of tumours and access to tumour-agnostic cancer treatment.
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http://dx.doi.org/10.4045/tidsskr.21.0064DOI Listing
September 2021

The Prognostic Effect of Mutations in Non-Small Cell Lung Carcinoma Revisited: A Norwegian Multicentre Study.

Cancers (Basel) 2021 Aug 26;13(17). Epub 2021 Aug 26.

Department of Clinical Pathology, University Hospital of North Norway, N-9038 Tromsø, Norway.

Background: due to emerging therapeutics targeting G12C and previous reports with conflicting results regarding the prognostic impact of and G12C in non-small cell lung cancer (NSCLC), we aimed to investigate the frequency of mutations and their associations with clinical characteristics and outcome. Since mutation subtypes have different preferences for downstream pathways, we also aimed to investigate whether there were differences in outcome according to mutation preference for the Raf, PI3K/Akt, or RalGDS/Ral pathways.

Methods: retrospectively, clinicopathological data from 1233 stage I-IV non-squamous NSCLC patients with known status were reviewed. ' associations with clinical characteristics were analysed. Progression free survival (PFS) and overall survival (OS) were assessed for the following groups: wild type (wt) versus mutated, wt versus G12C versus non-G12C, among mutation subtypes and among mutation subtypes grouped according to preference for downstream pathways.

Results: a total of 1117 patients were included; 38% had mutated tumours, 17% had G12C. Among mutated, G12C was the most frequent mutation in former/current smokers (45%) and G12D in never smokers (46%). There were no significant differences in survival according to status, G12C status, among mutation subtypes or mutation preference for downstream pathways.

Conclusion: status or mutation subtype did not have any significant influence on PFS or OS.
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http://dx.doi.org/10.3390/cancers13174294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8428342PMC
August 2021

Intracranial effect of osimertinib in relapsed -mutated T790M-positive and -negative non-small cell lung cancer patients: results from a phase II study.

Acta Oncol 2021 Sep 6:1-7. Epub 2021 Sep 6.

Section of Oncology, Vestre Viken Hospital Trust, Drammen, Norway.

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 ( < 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.
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http://dx.doi.org/10.1080/0284186X.2021.1973092DOI Listing
September 2021

Epidemiology and outcome of peritoneal and pleural mesothelioma subtypes in Norway. A 20 year nation-wide study.

Acta Oncol 2021 Oct 27;60(10):1250-1256. Epub 2021 Jul 27.

Section of Oncology, Drammen Hospital, Vestre Viken Hospital Trust, Drammen, Norway.

Background: Mesothelioma of the pleural or peritoneal cavities is one of the deadliest cancer types. The incidence of pleural subtypes has decreased over time due to decrease in asbestos exposure, and the current treatment landscape is changing due to introduction of novel therapies. In this study we have analysed contemporary epidemiological data of mesothelioma on a national level before the advent of immunotherapy.

Material And Methods: Complete national data on 1509 pleural and peritoneal malignant mesothelioma from the Cancer Registry of Norway from 2000 to 2019 are presented. Age standardised incidence and median survival were calculated.

Results: The age-standardised incidence of pleural mesothelioma among males has decreased from 1.7 per 100 000 in 2000-2004 to 1.1 in 2015-2019, whereas the incidence for females has been stable, lower than 0.3 per 100 000 throughout the period. Incidence of peritoneal mesotheliomas remained low, below 0.08 per 100 000. The female to male ratio among pleural mesotheliomas was 1:7 with no differences among morphological subtypes, whereas this ratio was 1:1.2 in peritoneal mesotheliomas. Median age at diagnosis for pleural mesothelioma was 73 years and 76 years for females and males respectively in the last 5-year period, and 67 years for peritoneal mesotheliomas of both sexes. Median survival among pleural mesotheliomas has been stable, with significantly worse prognosis among sarcomatoid subtype (5.4 months) compared to epithelioid subtype (15.8 months). Peritoneal mesothelioma of the epithelioid subtype, representing 38% of cases, had a median survival of 43.3 months, contrasting the non-epithelioid subtype of 5.1 months.

Discussion: Mesothelioma is still a significant disease with a dismal prognosis. Improvement in treatment is warranted.
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http://dx.doi.org/10.1080/0284186X.2021.1955971DOI Listing
October 2021

Phase- and gender-specific, lifetime, and future costs of cancer: A retrospective population-based registry study.

Medicine (Baltimore) 2021 Jul;100(26):e26523

Department of Health Management and Health Economics, University of Oslo.

Abstract: Valid estimates of cancer treatment costs are import for priority setting, but few studies have examined costs of multiple cancers in the same setting.We performed a retrospective population-based registry study to evaluate phase-specific (initial, continuing, and terminal phase) direct medical costs and lifetime costs for 13 cancers and all cancers combined in Norway. Mean monthly cancer attributable costs were estimated using nationwide activity data from all Norwegian hospitals. Mean lifetime costs were estimated by combining phase-specific monthly costs and survival times from the national cancer registry. Scenarios for future costs were developed from the lifetime costs and the expected number of new cancer cases toward 2034 estimated by NORDCAN.For all cancers combined, mean discounted per patient direct medical costs were Euros (EUR) 21,808 in the initial 12 months, EUR 4347 in the subsequent continuing phase, and EUR 12,085 in the terminal phase (last 12 months). Lifetime costs were higher for cancers with a 5-year relative survival between 50% and 70% (myeloma: EUR 89,686, mouth/pharynx: EUR 66,619, and non-Hodgkin lymphoma: EUR 65,528). The scenario analyses indicate that future cancer costs are highly dependent on future cancer incidence, changes in death risk, and cancer-specific unit costs.Gender- and cancer-specific estimates of treatment costs are important for assessing equity of care and to better understand resource consumption associated with different cancers.Cancers with an intermediate prognosis (50%-70% 5-year relative survival) are associated with higher direct medical costs than those with relatively good or poor prognosis.
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http://dx.doi.org/10.1097/MD.0000000000026523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257845PMC
July 2021

Lung Function After Stereotactic Body Radiation Therapy for Early-Stage Non-Small Cell Lung Cancer, Changes and Predictive Markers.

Front Oncol 2021 24;11:674731. Epub 2021 May 24.

Department of Cancer Genetics, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.

Introduction: The present study explores changes in pulmonary function, symptoms and radiological signs of pneumonitis after curatively intended stereotactic body radiation therapy (SBRT).

Methods: All inoperable, early-stage non-small cell lung cancer patients treated with stereotactic body radiation therapy (SBRT) from 2014-2017 were included in this single-centre study. They were followed regularly for 12 months after treatment. The patients were classified into three groups based on radiology and symptomatology: no radiation pneumonitis, asymptomatic and symptomatic radiation pneumonitis.

Results: Forty-four patients with stage IA-IIB disease were treated with 45-56 Gy in 3-8 fractions. The median age was 75 years, 43% of the patients were female; 60% of the patients had a COPD in GOLD grade of 2-4, and 95.5% were active or former smokers. Symptomatic radiation pneumonitis occurred in 18% of the patients and asymptomatic pneumonitis as defined by radiology, in 39%. The mean of forced expiratory volume in 1 second (FEV1) and diffusion capacity for carbon monoxide (DLCO) decreases for all patients during the first years were higher than one would expect from physiologic ageing. FEV1 and DLCO in percent decrease 7-8% at 1-1.5 months in the symptomatic radiation pneumonitis group. CT scan findings consistent with radiation pneumonitis occurred after a median of 2.9 months in the symptomatic and 5.4 months in the asymptomatic radiation pneumonitis groups. In the group with symptomatic radiation pneumonitis, symptoms, as measured by the Clinical COPD questionnaire score, significantly increased at 3 and 6 months. Significant higher maximum doses to the critical lung volumes DC1000cm (1000 cm of lung receiving a given dose or less) and DC 1500cm (1500 cm of lung receiving a given dose or less) were observed in patients who developed radiation pneumonitis.

Conclusion: Early decrease in measured FEV1 and DLCO occurred before imaging changes and symptoms and might indicate the development of symptomatic radiation pneumonitis. The dose to critical lung volumes of DC1000 cm and DC1500 cm may predict the risk for the development of symptomatic radiation pneumonitis.
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http://dx.doi.org/10.3389/fonc.2021.674731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8181743PMC
May 2021

Societal cost of cancer in Norway -Results of taking a broader cost perspective.

Health Policy 2021 08 24;125(8):1100-1107. Epub 2021 May 24.

Department of Health Management and Health Economics, University of Oslo, Forskningsveien 3A, 0317 Oslo, Norway; Oslo Economics, Kronprinsesse Märthas plass 1, 0160 Oslo, Norway; Institute of Public Health, University of Southern Denmark, Campusvej 55, 5230 Odense, Danmark.

Background: The broader cost consequences of diseases may be of interest for a wide range of stakeholders. We aimed to estimate all relevant societal costs of cancer and to provide insight into the relative magnitude of the different cost categories.

Method: We used data from eight different health and work-related registries in Norway. Direct, indirect, and intangible costs (value of lost life years) were estimated over a period of one year with a combination of a top-down and a bottom-up costing approach.

Results: The indirect costs (EUR 1,997 million per year) are almost as high as direct costs (EUR 2,154 million), and the value of lost life years and quality of life represents the greatest cost related to cancer (EUR 18,200 million). In addition, cancer is associated with other costs which are commonly omitted from cost-of-illness analyses, including informal nursing (EUR 306 million), patient time costs (EUR 85 million), and excess costs of using public funds (EUR 439 million). Breast and cervical cancer had relatively high work absenteeism costs, while pancreatic and lung cancer had relatively high production costs due to premature deaths.

Discussion: Direct health care costs represent small proportions of the total societal costs of cancer. Costs commonly omitted in cost-of-illness analyses represent a significant cost and should be measured and valued in these analyses.
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http://dx.doi.org/10.1016/j.healthpol.2021.05.008DOI Listing
August 2021

Real-world treatment outcomes with brigatinib in patients with pretreated ALK+ metastatic non-small cell lung cancer.

Lung Cancer 2021 07 24;157:9-16. Epub 2021 May 24.

Oncology Department, University of Turin, AOU San Luigi, 10043, Orbassano, Turin, Italy. Electronic address:

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.
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http://dx.doi.org/10.1016/j.lungcan.2021.05.017DOI Listing
July 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.

Lancet Oncol 2021 03;22(3):321-331

Department of Clinical and Molecular Medicine, NTNU, Norwegian University of Science and Technology, Trondheim, Norway; Department of Oncology, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.

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/m or carboplatin (area under the curve 5-6 mg/mL × min, Calvert's formula) on day 1 and intravenous etoposide 100 mg/m 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.

Funding: The Norwegian Cancer Society, The Liaison Committee for Education, Research and Innovation in Central Norway, the Nordic Cancer Union, and the Norwegian University of Science and Technology.
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http://dx.doi.org/10.1016/S1470-2045(20)30742-7DOI Listing
March 2021

COVID-19 vaccination of cancer patients.

Tidsskr Nor Laegeforen 2021 02 15;141(3). Epub 2021 Jan 15.

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http://dx.doi.org/10.4045/tidsskr.21.0026DOI Listing
February 2021

Cancer and coronavirus risk.

Tidsskr Nor Laegeforen 2021 02 1;141(2). Epub 2021 Feb 1.

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http://dx.doi.org/10.4045/tidsskr.20.1044DOI Listing
February 2021

Immune checkpoint blockade in the treatment of advanced non-small cell lung cancer - predictors of response and impact of previous radiotherapy.

Acta Oncol 2021 Feb 24;60(2):149-156. Epub 2020 Dec 24.

Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway.

Background: The implementation of immune checkpoint inhibitors (ICI) into the standard care of advanced non-small cell lung cancer (NSCLC) has improved prognosis for this group of patients. However, long-term survival is rare. The aim of the study was to identify predictors of response and, especially, to investigate the impact radiotherapy might have on duration of response.

Material And Methods: The association between pretreatment patient/tumor characteristics and progression-free survival (PFS), overall survival (OS), and lung cancer-specific survival was investigated in 78 patients receiving an ICI as ≥2nd line treatment for advanced NSCLC, using Cox regression analysis. Due to competing risk, cause-specific deaths were also examined with cumulative incidence plots.

Results: Median OS was 12.6 months (95% CI 7.8-18.2) and median PFS 4.1 months (95% CI 3.0-6.2), after median follow-up time of 49.7 months (range 20.9-51.5). Increasing CRP and neutrophil/lymphocyte ratio (NLR), were associated with poor PFS (CRP: HR 1.49, 95% CI 1.12-1.98; NLR: HR 1.59, 95% CI 1.22-1.85) and OS (CRP: HR 1.94, 95% CI 1.47-2.56; NLR: HR 1.54, 95% CI 1.27-1.87). Radiotherapy prior to immunotherapy was not significantly associated with patient outcome. However, when the dataset was split at 6 months of follow-up, to be able to identify early and late predictors of prognosis, we found that patients receiving radiotherapy <6 months prior to immunotherapy had better PFS (HR: 0.27, 95% CI 0.09-0.84) and lung cancer-specific survival (HR: 0.41, 95% CI 0.18-0.95) after the first 6 months of follow-up, while increasing CRP (PFS: HR1.61, 95% CI 1.21-2.14; OS: HR2.04, 95% CI 1.51-2.74) and NLR (PFS: HR 1.57, 95% CI 1.29-1.91; OS: HR 1.63, 95% CI 1.35-1.97) were predictors of poor short-term prognosis.

Conclusions: Radiotherapy may be of importance to achieve a long-lasting response to immunotherapy, while indicators of systemic inflammation can help in identifying patients with poor short-term prognosis.
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http://dx.doi.org/10.1080/0284186X.2020.1854851DOI Listing
February 2021

Protein Kinase C Isozymes Associated With Relapse Free Survival in Non-Small Cell Lung Cancer Patients.

Front Oncol 2020 25;10:590755. Epub 2020 Nov 25.

Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital-Radiumhospitalet, Oslo, Norway.

Introduction: Protein expression is deregulated in cancer, and the proteomic changes observed in lung cancer may be a consequence of mutations in essential genes. The purpose of this study was to identify protein expression associated with prognosis in lung cancers stratified by smoking status, molecular subtypes, and , , and -mutations.

Methods: We performed profiling of 295 cancer-relevant phosphorylated and non-phosphorylated proteins, using reverse phase protein arrays. Biopsies from 80 patients with operable lung adenocarcinomas were analyzed for protein expression and association with relapse free survival (RFS) were studied.

Results: Spearman's rank correlation analysis identified 46 proteins with significant association to RFS (p<0.05). High expression of protein kinase C (PKC)-α and the phosporylated state of PKC-α, PKC-β, and PKC-δ, showed the strongest positive correlation to RFS, especially in the wild type samples. This was confirmed in gene expression data from 172 samples. Based on protein expression, unsupervised hierarchical clustering separated the samples into four subclusters enriched with the molecular subtypes terminal respiratory unit (TRU), proximal proliferative (PP), and proximal inflammatory (PI) (p=0.0001). Subcluster 2 contained a smaller cluster (2a) enriched with samples of the subtype PP, low expression of the PKC isozymes, and associated with poor RFS (p=0.003) compared to the other samples. Low expression of the PKC isozymes in the subtype PP and a reduced relapse free survival was confirmed with The Cancer Genome Atlas (TCGA) lung adenocarcinoma (LUAD) samples.

Conclusion: This study identified different proteins associated with RFS depending on molecular subtype, smoking- and mutational-status, with PKC-α, PKC-β, and PKC-δ showing the strongest correlation.
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http://dx.doi.org/10.3389/fonc.2020.590755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725872PMC
November 2020

Programmed Cell Death Ligand 1 Expression in Resected Non-Small Cell Lung Cancer.

Clin Lung Cancer 2021 07 15;22(4):e555-e562. Epub 2020 Oct 15.

Mount Sinai Cancer, Mount Sinai Health System, Icahn School of Medicine, New York, NY.

Background: Recently, anti-programmed cell death 1 (PD-1) and anti-programmed cell death ligand 1 (PD-L1) immunotherapies have yielded promising outcomes for patients with advanced non-small cell lung cancer (NSCLC) and led to great interest in applying these agents to treat resectable early-stage NSCLC. The objective of our study was to evaluate PD-L1 protein expression in resectable early-stage NSCLC specimens from a large Northern European cohort, examine the relationship to clinical characteristics, and demonstrate the prognostic role in resected NSCLC.

Materials And Methods: A large cohort of 875 NSCLC tumors consisted of 337 patients from Sweden and 538 patients from Norway was studied. All the patients had undergone pulmonary resection, and most patients had had early-stage NSCLC. PD-L1 protein expression was assessed by immunohistochemistry using the Dako PD-L1 22C3 pharmDx kit. The tumor proportion score for PD-L1 protein expression was compared with comprehensive demographic and clinicopathologic data.

Results: The overall prevalence of PD-L1 protein expression in the resectable NSCLC cohort was 9.5% at a tumor proportion score cutoff of ≥ 50%. Stage I NSCLC had lower PD-L1 expression compared with that of the other stages (P = .0012). PD-L1 expression correlated with wild-type EGFR gene expression (P = .0156) and mutated KRAS gene expression (P = .0004). No significant association was found between PD-L1 expression and mortality after multivariable adjustment for clinical characteristics, although the survival curves showed PD-L1 expression significantly correlated with a poor prognosis in the total NSCLC cohort and in the adenocarcinoma subgroup.

Conclusion: PD-L1 expression in the present large cohort of resectable NSCLC was relatively low compared with data from clinical trials of advanced NSCLC. PD-L1 expression correlated positively with tumor stage, wild-type EGFR, and KRAS mutation. PD-L1 expression was not found as an independent prognostic factor in the present study. These findings could be important in the future when evaluating the role of anti-PD-1/PD-L1 immunotherapy in the setting of neoadjuvant or adjuvant trials for early-stage resectable NSCLC.
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http://dx.doi.org/10.1016/j.cllc.2020.09.018DOI Listing
July 2021

Randomized phase III trial comparing switch-maintenance pemetrexed with observation followed by pemetrexed at progression in advanced NSCLC.

Acta Oncol 2020 Sep 16;59(9):1051-1057. Epub 2020 Jun 16.

Department of Clinical and Molecular Medicine, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.

Two phase III trials show that maintenance pemetrexed therapy after platinum-doublet chemotherapy prolongs overall survival (OS) and progression free survival (PFS) in advanced non-squamous non-small-cell lung cancer (NSCLC). However, few patients in the control arms received pemetrexed at progression in these trials, performance status (PS) two patients were ineligible and few of the participants were elderly. Thus, we designed this study comparing immediate switchmaintenance pemetrexed therapy with pemetrexed at progression after platinum-doublet chemotherapy. Patients with stage IIIB/IV non-squamous NSCLC, ≥18 years, PS 0-2, and non-progression after four courses of carboplatin/vinorelbine were randomized to receive immediate maintenance pemetrexed therapy or observation followed by pemetrexed at progression. The primary endpoint was OS, secondary endpoints were PFS, toxicity and health related quality of life (HRQoL). 105 patients were randomized between May 2014 and September 2017. Median age was 67 years, 36% were >70 years, 9% had PS 2, 91% stage IV and 47% were women. In the observation arm, 73% received pemetrexed at progression. Patients in the maintenance arm had a numerically longer OS (median 12.0 vs. 10.0 months;  = .10) and a statistically significant longer PFS (median 3.1 vs. 1.9 months;  < .01). In multivariable analyses adjusting for baseline characteristics, there was a trend toward improved OS (HR 0.65, 95% CI 0.42-1.01);  = .05), and a significantly improved PFS (HR 0.53, 95% CI 0.35-0.80;  < .01). There were no significant differences in toxicity or HRQoL between the treatment arms. There was a trend toward prolonged OS and significantly longer PFS from switch maintenance pemetrexed therapy when 73% of patients in the control arm received pemetrexed at progression. NCT02004184.
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http://dx.doi.org/10.1080/0284186X.2020.1778179DOI Listing
September 2020

Patient and tumour characteristics associated with inclusion in Cancer patient pathways in Norway in 2015-2016.

BMC Cancer 2020 May 30;20(1):488. Epub 2020 May 30.

Department of Registration, Cancer Registry of Norway, Oslo, Norway.

Background: Cancer patient pathways (CPPs) were implemented in 2015 to reduce waiting time, regional variation in waiting time, and to increase the predictability of cancer care for the patients. The aims of this study were to see if the national target of 70% of all cancer patients being included in a CPP was met, and to identify factors associated with CPP inclusion.

Methods: All patients registered with a colorectal, lung, breast or prostate cancer diagnosis at the Cancer Registry of Norway in the period 2015-2016 were linked with the Norwegian Patient Registry for CPP information and with Statistics Norway for sociodemographic variables. Multivariable logistic regression examined if the odds of not being included in a CPP were associated with year of diagnosis, age, sex, tumour stage, marital status, education, income, region of residence and comorbidity.

Results: From 2015 to 2016, 30,747 patients were diagnosed with colorectal, lung, breast or prostate cancer, of whom 24,429 (79.5%) were included in a CPP. Significant increases in the probability of being included in a CPP were observed for colorectal (79.1 to 86.2%), lung (79.0 to 87.3%), breast (91.5 to 97.2%) and prostate cancer (62.2 to 76.2%) patients (p < 0.001). Increasing age was associated with an increased odds of not being included in a CPP for lung (p < 0.001) and prostate cancer (p < 0.001) patients. Colorectal cancer patients < 50 years of age had a two-fold increase (OR = 2.23, 95% CI: 1.70-2.91) in the odds of not being included in a CPP. The odds of no CPP inclusion were significantly increased for low income colorectal (OR = 1.24, 95%CI: 1.00-1.54) and lung (OR = 1.52, 95%CI: 1.16-1.99) cancer patients. Region of residence was significantly associated with CPP inclusion (p < 0.001) and the probability, adjusted for case-mix ranged from 62.4% in region West among prostate cancer patients to 97.6% in region North among breast cancer patients.

Conclusions: The national target of 70% was met within 1 year of CPP implementation in Norway. Although all patients should have equal access to CPPs, a prostate cancer diagnosis, older age, high level of comorbidity or low income were significantly associated with an increased odds of not being included in a CPP.
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http://dx.doi.org/10.1186/s12885-020-06979-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7260744PMC
May 2020

Molecular characterisation of TP53 mutated squamous cell carcinomas of the lung to identify putative targets for therapy.

Int J Cancer 2020 11 17;147(10):2957-2966. Epub 2020 Jun 17.

Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.

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.
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http://dx.doi.org/10.1002/ijc.33121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7540694PMC
November 2020

The immune microenvironment in typical carcinoid lung tumour, a brief report of four cases.

Scand J Immunol 2020 Aug 9;92(2):e12893. Epub 2020 Jun 9.

Tumor Immunology Lab, Department of Pathology, Rikshospitalet, Oslo University Hospital and University of Oslo, Oslo, Norway.

Pulmonary typical carcinoid (TC) is a low-grade, rare lung cancer of neuroendocrine origin. Currently, there is very little information available about the immune cell composition in TC tumours. Here, we analysed by flow cytometry resected tumours from four never-smoker female patients with TC. Twelve distinct immune cell types were identified in TC tumours. The most abundant immune cells were CD8 T cells, CD4 T cells, B cells and macrophages, which represented 19.8%, 17.7%, 11.5% and 11% of all tumour-infiltrating CD45 leucocytes, respectively. Natural killer (NK) cells (8.8%) and neutrophils (3.9%) were also common. Three types of dendritic cells (DCs) were identified (plasmacytoid DCs, CD1c  DCs, and CD141  DCs) which together constituted 1.4% of all immune cells in TC tumours. Small populations of basophils (1.2%), mast cells (0.8%) and eosinophils (0.6%) were also present. Notably, the percentage of leucocytes (of all living cells) was much lower in TC tumours compared to high-grade non-small cell lung cancer (NSCLC) tumours and also compared to non-cancerous lung tissue. We conclude that TC tumours are relatively non-inflammatory, although the immune landscape was found to be very complex.
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http://dx.doi.org/10.1111/sji.12893DOI Listing
August 2020

Cancer treatment and COVID-19.

Tidsskr Nor Laegeforen 2020 05 3;140(7). Epub 2020 Apr 3.

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http://dx.doi.org/10.4045/tidsskr.20.0280DOI Listing
May 2020

Antibody combinations for optimized staining of macrophages in human lung tumours.

Scand J Immunol 2020 Jul 10;92(1):e12889. Epub 2020 May 10.

Tumor Immunology Lab, Department of Pathology, Rikshospitalet, Oslo University Hospital and University of Oslo, Oslo, Norway.

The analysis of tumour-associated macrophages (TAMs) has a high potential to predict cancer recurrence and response to immunotherapy. However, the heterogeneity of TAMs poses a challenge for quantitative and qualitative measurements. Here, we critically evaluated by immunohistochemistry and flow cytometry two commonly used pan-macrophage markers (CD14 and CD68) as well as some suggested markers for tumour-promoting M2 macrophages (CD163, CD204, CD206 and CD209) in human non-small cell lung cancer (NSCLC). Tumour, non-cancerous lung tissue and blood were investigated. For immunohistochemistry, CD68 was confirmed to be a useful pan-macrophage marker although careful selection of antibody was found to be critical. The widely used anti-CD68 antibody clone KP-1 stains both macrophages and neutrophils, which is problematic for TAM quantification because lung tumours contain many neutrophils. For TAM counting in tumour sections, we recommend combined labelling of CD68 with a cell membrane marker such as CD14, CD163 or CD206. In flow cytometry, the commonly used combination of CD14 and HLA-DR was found to not be optimal because some TAMs do not express CD14. Instead, combined staining of CD68 and HLA-DR is preferable to gate all TAMs. Concerning macrophage phenotypic markers, the scavenger receptor CD163 was found to be expressed by a substantial fraction (50%-86%) of TAMs with a large patient-to-patient variation. Approximately 50% of TAMs were positive for CD206. Surprisingly, there was no clear overlap between CD163 and CD206 positivity, and three distinct TAM sub-populations were identified in NSCLC tumours: CD163 CD206 , CD163 CD206 and CD163 CD206 . This work should help develop macrophage-based prognostic tools for cancer.
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http://dx.doi.org/10.1111/sji.12889DOI Listing
July 2020

Osimertinib in T790M-positive and -negative patients with EGFR-mutated advanced non-small cell lung cancer (the TREM-study).

Lung Cancer 2020 05 12;143:27-35. Epub 2020 Mar 12.

Vestre Viken Hospital Trust, Drammen, Norway; Department of Cancer Genetics, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.

Objectives: In non-small cell lung cancer patients with acquired resistance to first- or second-generation EGFR-TKIs, osimertinib is approved in the presence of the T790 M resistance mutation. We assessed the efficacy of osimertinib in both T790M-positive and T790M-negative patients.

Materials And Methods: The TREM-study is an investigator-initiated, multi-centre, single-arm, phase 2 clinical trial conducted in five Northern European countries. Patients with progression on at least one previous EGFR-TKI were assigned to treatment with 80 mg of osimertinib daily until radiological progression or death. Patients were included regardless of the presence of T790 M. The primary endpoint was objective response rate (ORR).

Results: Of 199 included patients, 120 (60 %) were T790M-positive, 52 (26 %) were T790M-negative and 27 (14 %) had unknown T790M-status. 24 % had brain metastases and 15 % had an ECOG performance status of 2. Overall ORR was 48 % (95 % CI, 41 %-55 %), 60 % (51 %-69 %) for T790M-positive patients and 28 % (15 %-41 %) for T790M-negative patients, p < 0.001. ORR for patients with co-occurring del19 vs L858R was 61 % vs 32 %, p = 0.001. Duration of response was similar between the T790M-positive and -negative groups (11.8 vs 10.7 months, p = 0.229). Overall median progression-free survival (PFS) was 8.9 months (95 % CI, 7.4-10.5), and 10.8 vs 5.1 months for T790M-positive vs -negative patients (HR 0.62, p = 0.007). Median overall survival (OS) was 17.9 months (95 % CI, 14.4-21.3). For T790M-positive vs -negative median OS was 22.5 vs 13.4 months, (HR 0.55, p = 0.002).

Conclusions: This study confirms the efficacy of osimertinib for T790M-positive patients. There was also clinically significant activity of osimertinib in a proportion of T790M-negative patients.

Clinical Trial Registration: This trial is registered with ClinicalTrials.gov (NCT02504346).
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http://dx.doi.org/10.1016/j.lungcan.2020.03.009DOI Listing
May 2020

Reduced delays in diagnostic pathways for non-small cell lung cancer after local and National initiatives.

Cancer Treat Res Commun 2020 Jan 22;23:100168. Epub 2020 Jan 22.

Department of Respiratory Medicine, Oslo University Hospital, University of Oslo, Oslo, Norway.

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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http://dx.doi.org/10.1016/j.ctarc.2020.100168DOI Listing
January 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 2020 01;5(1)

Medical Oncology, Centre Leon Berard, Lyon, France.

Introduction: Non-small-cell lung cancer (NSCLC) is a heterogeneous disease. Front-line therapy may affect responses to subsequent treatment regimens, thus influencing second-line therapy decision making. In the randomised phase 3 REVEL study, second-line ramucirumab plus docetaxel (ram+doc) versus docetaxel (doc) improved survival of patients with metastatic NSCLC. We explore efficacy, safety and quality-of-life (QoL) in REVEL based on front-line therapy.

Methods: Patients were grouped by specific front-line therapy received. Overall survival (OS), progression-free survival (PFS), objective response rate, safety and QoL were assessed descriptively. Kaplan-Meier estimation and Cox proportional hazards modelling were used; frequencies reported in percentages.

Results: Baseline characteristics of 1253 patients were generally well balanced between treatment arms within each front-line therapy subgroup. For patients with non-squamous disease (n=912), induction therapies included platinum-based chemotherapy plus a taxane (n=227; 25%) or pemetrexed (n=449; 49%), with (n=172; 19%) or without bevacizumab. For patients with squamous disease (n=328), induction therapies included platinum-based chemotherapy plus gemcitabine (n=176; 54%) or a taxane (n=69; 21%). A highly selected subgroup (n=127; 14%) received pemetrexed continuation maintenance therapy. Ram+doc improved median OS and PFS versus doc across front-line therapy subgroups, as reflected by HRs ranging from 0.78 to 0.91 and 0.66 to 0.92, respectively, similar to results in the overall intention-to-treat cohort (HRs: 0.86 and 0.76, respectively). High-grade treatment-emergent adverse events of special interest (including neutropenia, febrile neutropenia, leucopenia and hypertension) were generally higher in ram+doc-treated patients relative to doc-treated patients regardless of front-line therapy. No clear differences in safety or QoL were seen across front-line therapy subgroups; outcomes were consistent with those reported in the overall intention-to-treat cohort.

Conclusions: Results of this exploratory analysis suggest that second-line ram+doc may be effective regardless of prior treatment with platinum-based chemotherapy plus a taxane, pemetrexed, gemcitabine or bevacizumab. Overall, ram+doc is clinically beneficial across a wide range of patients with metastatic NSCLC who have progressed after various front-line therapies.

Trial Registration Number: NCT01168973.
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http://dx.doi.org/10.1136/esmoopen-2019-000567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003392PMC
January 2020

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 2019 11 27;9(11):e025895. Epub 2019 Nov 27.

Centre for Population Health Sciences, Edinburgh University, Edinburgh, UK.

Objective: Differences in time intervals to diagnosis and treatment between jurisdictions may contribute to previously reported differences in stage at diagnosis and survival. The International Cancer Benchmarking Partnership Module 4 reports the first international comparison of routes to diagnosis and time intervals from symptom onset until treatment start for patients with lung cancer.

Design: Newly diagnosed patients with lung cancer, their primary care physicians (PCPs) and cancer treatment specialists (CTSs) were surveyed in Victoria (Australia), Manitoba and Ontario (Canada), Northern Ireland, England, Scotland and Wales (UK), Denmark, Norway and Sweden. Using Wales as the reference jurisdiction, the 50th, 75th and 90th percentiles for intervals were compared using quantile regression adjusted for age, gender and comorbidity.

Participants: Consecutive newly diagnosed patients with lung cancer, aged ≥40 years, diagnosed between October 2012 and March 2015 were identified through cancer registries. Of 10 203 eligible symptomatic patients contacted, 2631 (27.5%) responded and 2143 (21.0%) were included in the analysis. Data were also available from 1211 (56.6%) of their PCPs and 643 (37.0%) of their CTS.

Primary And Secondary Outcome Measures: Interval lengths (days; primary), routes to diagnosis and symptoms (secondary).

Results: With the exception of Denmark (-49 days), in all other jurisdictions, the median adjusted total interval from symptom onset to treatment, for respondents diagnosed in 2012-2015, was similar to that of Wales (116 days). Denmark had shorter median adjusted primary care interval (-11 days) than Wales (20 days); Sweden had shorter (-20) and Manitoba longer (+40) median adjusted diagnostic intervals compared with Wales (45 days). Denmark (-13), Manitoba (-11), England (-9) and Northern Ireland (-4) had shorter median adjusted treatment intervals than Wales (43 days). The differences were greater for the 10% of patients who waited the longest. Based on overall trends, jurisdictions could be grouped into those with trends of reduced, longer and similar intervals to Wales. The proportion of patients diagnosed following presentation to the PCP ranged from 35% to 75%.

Conclusion: There are differences between jurisdictions in interval to treatment, which are magnified in patients with lung cancer who wait the longest. The data could help jurisdictions develop more focused lung cancer policy and targeted clinical initiatives. Future analysis will explore if these differences in intervals impact on stage or survival.
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http://dx.doi.org/10.1136/bmjopen-2018-025895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6886977PMC
November 2019

Identification of microRNAs involved in pathways which characterize the expression subtypes of NSCLC.

Mol Oncol 2019 12 22;13(12):2604-2615. Epub 2019 Sep 22.

Department of Cancer Genetics, Institute for Cancer Research, OUS Radiumhospitalet, Oslo, Norway.

Dysregulation of microRNAs is a common mechanism in the development of lung cancer, but the relationship between microRNAs and expression subtypes in non-small-cell lung cancer (NSCLC) is poorly explored. Here, we analyzed microRNA expression from 241 NSCLC samples and correlated this with the expression subtypes of adenocarcinomas (AD) and squamous cell carcinomas (SCC) to identify microRNAs specific for each subtype. Gene set variation analysis and the hallmark gene set were utilized to calculate gene set scores specific for each sample, and these were further correlated with the expression of the subtype-specific microRNAs. In ADs, we identified nine aberrantly regulated microRNAs in the terminal respiratory unit (TRU), three in the proximal inflammatory (PI), and nine in the proximal proliferative subtype (PP). In SCCs, 1, 5, 5, and 9 microRNAs were significantly dysregulated in the basal, primitive, classical, and secretory subtypes, respectively. The subtype-specific microRNAs were highly correlated to specific gene sets, and a distinct pattern of biological processes with high immune activity for the AD PI and SCC secretory subtypes, and upregulation of cell cycle-related processes in AD PP, SCC primitive, and SCC classical subtypes were found. Several in silico predicted targets within the gene sets were identified for the subtype-specific microRNAs, underpinning the findings. The results were significantly validated in the LUAD (n = 492) and LUSC (n = 380) TCGA dataset (False discovery rates-corrected P-value < 0.05). Our study provides novel insight into how expression subtypes determined with discrete biological processes may be regulated by subtype-specific microRNAs. These results may have importance for the development of combinatory therapeutic strategies for lung cancer patients.
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http://dx.doi.org/10.1002/1878-0261.12571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6887593PMC
December 2019

Increase in curative treatment and survival of lung cancer in Norway 2001-2016.

Eur J Epidemiol 2019 Oct 16;34(10):951-955. Epub 2019 Jul 16.

Department of Pulmology, Rikshospitalet, Oslo University Hospital and Faculty of Medicine, University of Oslo, Oslo, Norway.

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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http://dx.doi.org/10.1007/s10654-019-00536-zDOI Listing
October 2019

Decreasing waiting time for treatment before and during implementation of cancer patient pathways in Norway.

Cancer Epidemiol 2019 08 27;61:59-69. Epub 2019 May 27.

Department of Registration, Cancer Registry of Norway, Oslo, Norway.

Background: In 2015, Norway implemented cancer patient pathways to reduce waiting times for treatment. The aims of this paper were to describe patterns in waiting time and their association with patient characteristics for colorectal, lung, breast and prostate cancers.

Methods: National, population-based data from 2007 to 2016 were used. A multivariable quantile regression examined the association between treatment period, age, stage, sex, place of residence, and median waiting times.

Results: Reduction in median waiting times for radiotherapy among colorectal, lung and prostate cancer patients ranged from 14 to 50 days. Median waiting time for surgery remained approximately 21 days for both colorectal and breast cancers, while it decreased by 7 and 36 days for lung and prostate cancers, respectively. The proportion of lung and prostate cancer patients with metastatic disease at the time of diagnosis decreased, while the proportion of colorectal patients with localised disease and patients with stage I breast cancer increased (p < 0.001). After adjusting for case-mix, a patient's place of residence was significantly associated with waiting time for treatment (p < 0.001), however, differences in waiting time to treatment decreased over the study period.

Conclusions: Between 2007 and 2016, Norway experienced improved stage distributions and consistently decreasing waiting times for treatment. While these improvements occurred gradually, no significant change was observed from the time of cancer patient pathway implementation.
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http://dx.doi.org/10.1016/j.canep.2019.05.004DOI Listing
August 2019

A NOTCH added to metabolomics.

Br J Cancer 2019 07 22;121(1):3-4. Epub 2019 May 22.

Section of Oncology, Drammen Hospital, Vestre Viken Health Trust, Dronninggata 28, N-3004, Drammen, Norway.

Deregulated metabolism is a hallmark of cancer. In the accompanying study by Sellers et al. published in the British Journal of Cancer, metabolism-related transcriptomics data from in silico data sets are analysed, with the findings being further investigated in the experiments on tumour tissue slices and finally validated in patients. The study adds to our growing understanding of therapeutically accessible metabolic reprogramming in malignancies.
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http://dx.doi.org/10.1038/s41416-019-0463-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6738034PMC
July 2019
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