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1.
  • Koyi, Hirsh, et al. (författare)
  • A prospective study of a total material of lung cancer from a county in Sweden 1997-1999 : gender, symptoms, type, stage and smoking habits
  • 2002
  • Ingår i: Lung Cancer. - 0169-5002 .- 1872-8332. ; 36:1, s. 9-14
  • Recension (övrigt vetenskapligt/konstnärligt)abstract
    • The epidemiology of lung cancer is changing in many parts of the world. In the industrialized countries, there is a trend that the incidence in men is declining, while it is increasing for women. Also, adenocarcinomas are becoming relatively more common, especially among men. The purpose of this study was to investigate whether such trends also occur in Sweden and also to describe other aspects of an unselected lung cancer material today, such as symptoms, stage and smoking habits. In the county of Gaevleborg, Sweden, practically all patients with lung cancer are referred to the lung department, and thus a total material of lung cancer patients with only a minimal selection bias can be studied. All patients with lung cancer in the county from January 1, 1997 to December 31, 1999, were investigated prospectively regarding stage, type of cancer, and symptoms. In all, there were 364 patients, 237 (65.1%) men and 127 (34.9%) women. The mean age for men was 69.8 and for women, 68.1 years. 91.9% of the men and 78.6% of the women were smokers or ex-smokers. In general the men were heavier smokers than were the women (P<0.0001). Adenocarcinoma was the most common subtype found in women and squamous cell carcinoma in men. The excess of adenocarcinoma in women was due to never-smoking women; for smoking and ex-smoking men and women, the proportion of adenocarcinomas was the same. In all, 240 patients (68.0%) were diagnosed at Stage IIIb (27.2%) or IV (40.8%), with no significant differences between the sexes. The most common first symptom was cough. Only 7.0% of patients were asymptomatic. In conclusion, the trend of an increasing proportion of adenocarcinoma in lung cancer is seen also in Sweden. A depressingly high percentage of patients present in late stages and are thus inoperable.
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2.
  • Koyi, Hirsh, et al. (författare)
  • The 'reservoir' of undetected bronchial carcinomas in the generalpopulation
  • 2002
  • Ingår i: Lung Cancer. - 0169-5002 .- 1872-8332. ; 37:2, s. 137-142
  • Tidskriftsartikel (refereegranskat)abstract
    • Study objectives: Autopsy studies have shown that a sizeable portion of lung cancers are never diagnosed and thus not entered into any cancer registry.Design: In 1997, we decided to make all available efforts to find all patients with lung cancer who had not been registered previously.Setting: The local hospitals in the county of Gävleborg, Sweden.Patients: All patients with lung cancer diagnosed in the county from 1997 to 2000.Interventions: In meetings with all the general practitioners of the county, these were asked to refer all suspected cases as early as possible, including those with a seemingly dismal prognosis. This initiative was also covered by the newspapers and the local television station.Measurements and results: From 1997 onwards, the incidence of lung cancer in the county was found to be 40–50 per 100 000 inhabitants compared with an incidence of about 30 during the ten preceding years. This difference is significant in time (P<0.0001) and is compared with the incidence of lung cancers in four neighboring counties (P=0.002). Conclusions: There can be a considerable number of patients with lung cancer who are never diagnosed. This can explain differences in survival between various countries and this will also affect the results of screening programs, since the control groups will also include a number of lung cancer cases which will never be recognized.
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3.
  • Sjödin, Anna, et al. (författare)
  • Dysregulated secretoglobin expression in human lung cancers
  • 2003
  • Ingår i: Lung Cancer. - 0169-5002 .- 1872-8332. ; 41:1, s. 49-56
  • Tidskriftsartikel (refereegranskat)abstract
    • Lipophilins A, B, C, mammaglobin, and uteroglobin are members of the secretoglobin family of small, secreted, proteins. The functions of these proteins are not well understood but uteroglobin has been implicated in the development of cancers. Uteroglobin is known to be highly expressed in normal lung and down-regulated in lung cancers but expression of the other secretoglobins in normal lung and lung neoplasms have not been investigated. Therefore, we developed quantitative real-time reverse transcription (RT-) PCR assays for the different secretoglobins and evaluated their expression in normal and neoplastic lung tissues. The secretoglobin transcript levels were quantitated by real-time RT-PCR in samples from three normal lungs, 24 lung tumors including six small cell lung carcinomas, seven adenocarcinomas, and five squamous cell carcinomas, and in cell lines from three small cell lung carcinomas and one mesothelioma. Uteroglobin was confirmed to be abundantly expressed in normal lung and the different lung tumors showed down-regulated uteroglobin expression. Of the other secretoglobins, only lipophilin C was detected in normal lung, albeit at low levels. The lung tumors, however, frequently showed neo- or up-regulation of lipophilins A, B, C, and mammaglobin. The results constitute the first quantitative evaluation of secretoglobin expression in normal and neoplastic human lung tissues and demonstrate dysregulation in various human lung cancers. These findings could have important biological and diagnostic implications.
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4.
  • Bin, J., et al. (författare)
  • Lung cancer in systemic lupus erythematosus
  • 2007
  • Ingår i: Lung Cancer. - : Elsevier BV. - 1872-8332 .- 0169-5002. ; 56:3, s. 303-306
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Evidence points to a link between systemic lupus erythematosus (SLE) and an increased risk of lung cancer. Our objective was to provide a brief report of the lung cancer cases from an SLE cohort, with respect to demographics, histology, and exposures to smoking and immunosuppressive medications. Methods: Data were obtained from a multi-site international cohort study of over 9500 SLE patients from 23 centres. Cancer cases were ascertained through linkage with regional tumor registries. Results: We analyzed information on histology subtype for 30 lung cancer cases that had occurred across five countries. Most (75%) of these 30 cases were female, with a median age of 61 (range 27-91) years. In eight cases, the histological type was not specified. In the remainder, the most common histological type reported was adenocarcinoma (N = 8; two of the adenocarcinomas were bronchoalveolar carcinoma) followed by small cell carcinoma (N = 6), and squamous cell carcinoma (N = 6) with one case each of large cell carcinoma and carcinoid tumor. Most (71%) of the lung cancer cases were smokers; only the minority (20%) had been previously exposed to immunosuppressive agents. Conclusions: The histological distribution of the lung cancers from the SLE sample appeared similar to that of lung cancer patients in the general population, though the possibility of a higher proportion of more uncommon tumors (such as bronchoalveolar and carcinoid) cannot be excluded. A large proportion of the cancer cases were smokers, which is also not surprising. However, only a minority appeared to have been exposed to immunosuppressive agents. A large case-cohort study currently in progress should help shed light on the relative importance of these exposures in lung cancer risk for SLE patients. (c) 2007 Elsevier Ireland Ltd. All rights reserved.
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5.
  • Brattström, Daniel, et al. (författare)
  • Serum VEGF and bFGF adds prognostic information in patients with normal platelet counts when sampled before, during and after treatment for locally advanced non-small cell lung cancer
  • 2003
  • Ingår i: Lung Cancer. - : Elsevier BV. - 0169-5002 .- 1872-8332. ; 43:1, s. 55-62
  • Tidskriftsartikel (refereegranskat)abstract
    • Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) have both been implicated to have roles in tumour angiogenesis. In the present retrospective study, serum VEGF and bFGF from patients with locally advanced non-small cell lung cancer (NSCLC) were analysed before, during and after treatment. Seventy-three patients and a total of 460 serum samples were analysed for VEGF and 443 serum samples were analysed for bFGF. Pre-treatment bFGF levels in patients with normal platelet counts, were correlated to poorer survival, P-value = 0.047. During chemotherapy, each rise of one unit bFGF corresponded to a hazard ratio of 4.06 (P=0.022). In patients with normal platelet counts, VEGF levels after radiotherapy significantly correlated to good prognosis (P=0.023), during radiotherapy VEGF levels indicated the same correlation (P=0.085). We conclude that serum VEGF and especially bFGF are of clinical interest as prognostic factors, especially in patients presenting with normal platelet counts.
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6.
  • Brenner, Darren R, et al. (författare)
  • Leisure-time physical activity and lung cancer risk : a systematic review and meta-analysis
  • 2016
  • Ingår i: Lung Cancer. - : Elsevier. - 0169-5002 .- 1872-8332. ; 95, s. 17-27
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: We conducted a systematic review and meta-analysis of the association between recreational physical activity and lung cancer risk to update previous analyses and to examine population subgroups of interest defined by smoking status and histology.MATERIALS AND METHODS: We searched the PubMed database for studies up to May 2015. Individual study characteristics were abstracted including study design, number of cases, assessment of recreational physical activity and type and level of adjustment for confounding factors. Combined effect estimates were calculated for the overall associations and across subgroups of interest.RESULTS: We identified 28 studies that were eligible for inclusion in the meta-analysis. The overall analysis indicated an inverse association between recreational physical activity and lung cancer risk (Relative Risk (RR), 0.76; 95% Confidence Interval (CI), 0.69-0.85, p-value: <0.001). Similar inverse associations with risk were also noted for all evaluated histological subtypes, including adenocarcinoma (RR, 0.80; 95% CI, 0.72-0.88), squamous (RR, 0.80; 95% CI, 0.71-0.90) and small cell (RR, 0.79; 95% CI, 0.66-0.94). When we examined effects by smoking status, inverse associations between recreational physical activity and lung cancer risk were observed among former (RR, 0.77; 95% CI, 0.69-0.85) and current smokers (RR, 0.77; 95% CI, 0.72-0.83), but not among never smokers (RR, 0.96; 95% CI, 0.79-1.18).CONCLUSION: Results from this meta-analysis suggest that regular recreational physical activity may be associated with reduced risk of lung cancer. Only four studies examining never smokers were identified, suggesting the need for additional research in this population.
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  • Brocki, Barbara Cristina, 1957-, et al. (författare)
  • Short and long-term effects of supervised versus unsupervised exercise training on health-related quality of life and functional outcomes following lung cancer surgery : a randomized controlled trial
  • 2014
  • Ingår i: Lung Cancer. - : Elsevier. - 0169-5002 .- 1872-8332. ; 83:1, s. 102-108
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE:Surgical resection enhances long-term survival after lung cancer, but survivors face functional deficits and report on poor quality of life long time after surgery. This study evaluated short and long-term effects of supervised group exercise training on health-related quality of life and physical performance in patients, who were radically operated for lung cancer.METHODS:A randomized, assessor-blinded, controlled trial was performed on 78 patients undergoing lung cancer surgery. The intervention group (IG, n=41) participated in supervised out-patient exercise training sessions, one hour once a week for ten weeks. The sessions were based on aerobic exercises with target intensity of 60-80% of work capacity, resistance training and dyspnoea management. The control group (CG, n=37) received one individual instruction in exercise training. Measurements consisted of: health-related quality of life (SF36), six minute walk test (6MWT) and lung function (spirometry), assessed three weeks after surgery and after four and twelve months.RESULTS:Both groups were comparable at baseline on demographic characteristic and outcome values. We found a statistically significant effect after four months in the bodily pain domain of SF36, with an estimated mean difference (EMD) of 15.3 (95% CI:4 to 26.6, p=0.01) and a trend in favour of the intervention for role physical functioning (EMD 12.04, 95% CI: -1 to 25.1, p=0.07) and physical component summary (EMD 3.76, 95% CI:-0.1 to 7.6, p=0.06). At 12 months, the tendency was reversed, with the CG presenting overall slightly better measures. We found no effect of the intervention on 6MWT or lung volumes at any time-point.CONCLUSION:Supervised compared to unsupervised exercise training resulted in no improvement in health-related quality of life, except for the bodily pain domain, four months after lung cancer surgery. No effects of the intervention were found for any outcome after one year.
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  • Crona, Joakim, et al. (författare)
  • Treatment, prognostic markers and survival in thymic neuroendocrine tumours : A study from a single tertiary referral centre
  • 2013
  • Ingår i: Lung Cancer. - : Elsevier BV. - 0169-5002 .- 1872-8332. ; 79:3, s. 289-293
  • Tidskriftsartikel (refereegranskat)abstract
    • Thymic neuroendocrine tumours (TNETs) are uncommon but malignant neoplasms, usually associated with a poor prognosis. The number of cases reported is limited to a few hundreds and there are few prognostic factors available. All 28 patients (22 male, 6 female; median age 46.5 years) with thymic neuroendocrine tumour, treated at the Department of Endocrine Oncology, Uppsala University Hospital, Uppsala, Sweden between 1985 and 2011 were studied. The overall 3, 5 and 10-year survival was 89%, 79% and 41% respectively. Ki67<10% (p=0.018) as well as surgical resection (p=0.001) and macroscopically radical primary surgery (p=0.034) was associated with increased survival. Staging & grading according to Masaoka and ENETS systems did not correlate with survival. However, a modified ENETS grading showed a positive correlation (p=0.015). Median time to progression was 20.5 months with Temozolomide and 18 months with platinum based therapy. Partial responses were noted in three patients (38%) treated with platinum based therapy and in two patients (20%) treated with Temozolomide based therapy. High proliferative rate, measured by Ki67 index, and absence of macroscopically radical primary resection as well as no surgical resection are three negative prognostic factors in patients with TNETs. Temozolomide or Platinum based chemotherapy should be considered as first-line medical therapy in patients with metastatic or non-resectable tumours.
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10.
  • Dietel, M., et al. (författare)
  • Real-world prevalence of programmed death ligand 1 expression in locally advanced or metastatic non small-cell lung cancer : The global, multicenter EXPRESS study
  • 2019
  • Ingår i: Lung Cancer. - : Elsevier BV. - 0169-5002 .- 1872-8332. ; 134, s. 174-179
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectivesTumor programmed death ligand 1 (PD-L1) expression is associated with improved clinical benefit from immunotherapies targeting the PD-1 pathway. We conducted a global, multicenter, retrospective observational study to determine real-world prevalence of tumor PD-L1 expression in patients with NSCLC.Materials and methodsPatients ≥18 years with histologically confirmed stage IIIB/IV NSCLC and a tumor tissue block (≤5 years old) obtained before treatment were identified in 45 centers across 18 countries. Tumor samples from eligible patients were selected consecutively, when possible. PD-L1 expression was evaluated at each center using the PD-L1 IHC 22C3 pharmDx kit (Agilent, Santa Clara, CA, USA).ResultsOf 2617 patients who met inclusion criteria, 2368 (90%) had PD-L1 data; 530 (22%) patients had PD-L1 TPS ≥ 50%, 1232 (52%) had PD-L1 TPS ≥ 1%, and 1136 (48%) had PD-L1 TPS < 1%. The most common reason for not having PD-L1 data (n = 249) was insufficient tumor cells (<100) on the slide (n = 170 [6%]). Percentages of patients with PD-L1 TPS ≥ 50% and TPS ≥ 1%, respectively were: 22%/52% in Europe; 22%/53% in Asia Pacific; 21%/47% in the Americas, and 24%/55% in other countries. Prevalence of EGFR mutations (19%) and ALK alterations (3%) was consistent with prior reports from metastatic NSCLC studies. Among 1064 patients negative for both EGFR mutation and ALK alteration, the percentage with PD-L1 TPS ≥ 50% and TPS ≥ 1%, respectively, were 27% and 53%.ConclusionsThis is the largest real-world study in advanced NSCLC to date evaluating PD-L1 tumor expression using the 22C3 pharmDx kit. Testing failure rate was low with local evaluation of PD-L1 TPS across a large number of centers. Prevalence of PD-L1 TPS ≥ 50% and TPS ≥ 1% among patients with stage IIIB/IV NSCLC was similar across geographic regions and broadly consistent with central testing results from clinical trial screening populations.
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11.
  • Djureinovic, Dijana, et al. (författare)
  • Detection of autoantibodies against cancer-testis antigens in non-small cell lung cancer
  • 2018
  • Ingår i: Lung Cancer. - : Elsevier BV. - 0169-5002 .- 1872-8332. ; 125, s. 157-163
  • Tidskriftsartikel (refereegranskat)abstract
    • Cancer testis antigens (CTAs) are defined as proteins that are specifically expressed in testis or placenta and their expression is frequently activated in cancer. Due to their ability to induce an immune response, CTAs may serve as suitable targets for immunotherapy. The aim of this study was to evaluate if there is reactivity against CTAs in the plasma of non-small cell lung cancer (NSCLC) patients through the detection of circulating antibodies. To comprehensively analyse auto-antibodies against CTAs the multiplexing capacities of suspension bead array technology was used. Bead arrays were created with 120 protein fragments, representing 112 CTAs. Reactivity profiles were measured in plasma samples from 133 NSCLC patients and 57 cases with benign lung diseases. Altogether reactivity against 69 antigens, representing 81 CTAs, was demonstrated in at least one of the analysed samples. Twenty-nine of the antigens (45 CTAs) demonstrated exclusive reactivity in NSCLC samples. Reactivity against CT47A genes, PAGE3, VCX, MAGEB1, LIN28B and C12orf54 were only found in NSCLC patients at a frequency of 1%-4%. The presence of autoantibodies towards these six antigens was confirmed in an independent group of 34 NSCLC patients.In conclusion, we identified autoantibodies against CTAs in the plasma of lung cancer patients. The reactivity pattern of autoantibodies was higher in cancer patients compared to the benign group, stable over time, but low in frequency of occurrence. The findings suggest that some CTAs are immunogenic and that these properties can be utilized as immune targets.
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  • Ekberg, Marie, et al. (författare)
  • Socio-economic status and lung cancer risk including histologic subtyping-A longitudinal study.
  • 2006
  • Ingår i: Lung Cancer. - : Elsevier BV. - 1872-8332 .- 0169-5002. ; 51:1, s. 21-29
  • Tidskriftsartikel (refereegranskat)abstract
    • We investigated prospectively the risk of lung cancer in relation to socioeconomic status (SES) in 22387 middle-aged individuals who attended a screening program in the city of Malmo, Sweden between 1974 and 1992. We also examined the relationship between SES and histologic subtype in smokers. By 2003, a total of 550 lung cancer cases had been identified. Relative risks (RR) were calculated with adjustment for age, current smoking, inhalation habits and marital status at baseline in the low SES group compared to high SES group. Among smokers, the RR (95% confidence interval (Cl)) for lung cancer in the tow SES group of men was 1.39 (1.11-1.73), and women 1.56 (1.04-2.34). Also among smokers, low SES was associated with an increased risk of squamous cell carcinoma in men; RR 1.89 (1.16-2.81) and women; RR 7.10 (1.63-30.86), and with an increased risk of mesothelioma in men RR 9.97 (1.29-76.96). We conclude that Low SES groups run an increased risk of lung cancer despite accounting for smoking habits. Furthermore, tow SES was positively associated with squamous cell carcinoma and mesothelioma. Our results suggest that the association between low SES and lung cancer could be mediated by unaccounted for smoking exposure, Lifestyle or occupational hazards. (C) 2005 Elsevier Ireland Ltd. All rights reserved.
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14.
  • Elfving, Hedvig, et al. (författare)
  • Evaluation of NTRK immunohistochemistry as a screening method for NTRK gene fusion detection in non-small cell lung cancer
  • 2021
  • Ingår i: Lung Cancer. - : Elsevier. - 0169-5002 .- 1872-8332. ; 151, s. 53-59
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: The small molecule inhibitors larotrectinib and entrectinib have recently been approved as cancer agnostic drugs in patients with tumours harbouring a rearrangement of the neurotrophic tropomyosin receptor kinase (NTRK). These oncogenic fusions are estimated to occur in 0.1-3 % of non-small cell lung cancers (NSCLC). Although molecular techniques are most reliable for fusion detection, immunohistochemical analysis is considered valuable for screening. Therefore, we evaluated the newly introduced diagnostic immunohistochemical assay (clone EPR17341) on a representative NSCLC cohort.Methods: Cancer tissue from 688 clinically and molecularly extensively annotated NSCLC patients were comprised on tissue microarrays and stained with the pan-TRK antibody clone EPR17341. Positive cases were further analysed with the TruSight Tumor 170 RNA assay (Illumina). Selected cases were also tested with a NanoString NTRK fusion assay. For 199 cases, NTRK RNA expression data were available from previous RNA sequencing analysis.Results: Altogether, staining patterns for 617 NSCLC cases were evaluable. Of these, four cases (0.6 %) demonstrated a strong diffuse cytoplasmic and membranous staining, and seven cases a moderate staining (1.1 %). NanoString or TST170-analysis could not confirm an NTRK fusion in any of the IHC positive cases, or any of the cases with high mRNA levels. In the four cases with strong staining intensity in the tissue microarray, whole section staining revealed marked heterogeneity of NTRK protein expression.Conclusion: The presence of NTRK fusion genes in non-small cell lung cancer is exceedingly rare. The use of the immunohistochemical NTRK assay will result in a small number of false positive cases. This should be considered when the assay is applied as a screening tool in clinical diagnostics.
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  • Hallqvist, Andreas, 1973, et al. (författare)
  • Concurrent cetuximab and radiotherapy after docetaxel-cisplatin induction chemotherapy in stage III NSCLC : Satellite-A phase II study from the Swedish Lung Cancer Study Group
  • 2011
  • Ingår i: Lung Cancer. - : Elsevier BV. - 0169-5002 .- 1872-8332. ; 71:2, s. 166-172
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Several attempts to increase the locoregional control in locally advanced lung cancer including concurrent chemotherapy, accelerated fractionation and dose escalation have been made during the last years. As the EGFR directed antibody cetuximab has shown activity concurrent with radiotherapy in squamous cell carcinoma of the head and neck, as well as in stage IV NSCLC combined with chemotherapy, we wanted to investigate radiotherapy with concurrent cetuximab in locally advanced NSCLC, a tumour type often over expressing the EGF-receptor. Methods: Between February 2006 and August 2007 75 patients in stage Ill NSCLC with good performance status (PS 0 or 1) and adequate lung function (FEV1 > 1.0) were enrolled in this phase II study at eight institutions. Treatment consisted of 2 cycles of induction chemotherapy, docetaxel 75 mg/m(2) and cisplatin 75 mg/m(2) with 3 weeks interval. An initial dose of cetuximab 400 mg/m(2) was given before start of 3D-CRT to 68 Gy with 2 Gy per fraction in 7 weeks concurrent with weekly cetuximab 250 mg/m(2). Toxicity was scored weekly during radiotherapy (CTC 3.0), and after treatment the patients were followed every third month with CT-scans, toxicity scoring and QLQ. Results: Seventy-one patients were eligible for analysis as four were incorrectly enrolled. Histology: adenocarcinoma 49%, squamous cell carcinoma 39% and other NSCLC 12%. The majority had PS 0 (62.5%), median age 62.2 (42-81), 50% were women and 37% had a pre-treatment weight loss > 5%. Toxicity: esophagitis grade 1-2: 72%; grade 3:1.4%. Hypersensitivity reactions grade 3-4: 5.6%. Febrile neutropenia grade 3-4: 15.4%. Skin reactions grade 1-2: 74%; grade 3: 4.2%. Diarrhoea grade 1-2: 38%; grade 3: 11.3%. Pneumonitis grade 1-2: 26.8%; grade 3: 4.2%; grade 5:1.4%. The median follow-up was 39 months for patients alive and the median survival was 17 months with a 1-, 2- and 3-year OS of 66%, 37% and 29% respectively. Until now local or regional failure has occurred in 20 patients and 22 patients have developed distant metastases. Weight loss, PS and stage were predictive for survival in univariate as well as in multivariate analysis. Conclusion: Induction chemotherapy followed by concurrent cetuximab and RT to 68 Gy is clearly feasible with promising survival. Toxicity, e.g. pneumonitis and esophagitis is low compared to most schedules with concurrent chemotherapy. This treatment strategy should be evaluated in a randomised manner vs. concurrent chemoradiotherapy to find out if it is a valid treatment option.
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19.
  • Hallqvist, Andreas, 1973, et al. (författare)
  • Dose escalation to 84 Gy with concurrent chemotherapy in stage III NSCLC appears excessively toxic: Results from a prematurely terminated randomized phase II trial
  • 2018
  • Ingår i: Lung Cancer. - : Elsevier BV. - 0169-5002 .- 1872-8332. ; 122, s. 180-186
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Concurrent chemoradiotherapy is the mainstay treatment for NSCLC stage III disease. To investigate whether radiation dose escalation based on individual normal tissue constraints can improve outcome, the Swedish lung cancer study group launched this randomized phase II trial. Materials and Methods: NSCLC patients with stage III disease, good performance status (0-1) and adequate lung function (FEV1 > 1.0 L and CO diffusion capacity > 40%) received three cycles of cisplatin (75 mg/m(2) day 1) and vinorelbine (25 mg/m(2) day 1 and 8) every third week. Radiotherapy started concurrently with the second cycle, with either 2 Gy daily, 5 days a week, to 68 Gy (A) or escalated therapy (B) based on constraints to the spinal cord, esophagus and lungs up to 84 Gy by adding an extra fraction of 2 Gy per week. Results: A pre-planned safety analysis revealed excessive toxicity and decreased survival in the escalated arm, and the study was stopped. Thirty-six patients were included during 2011-2013 (56% male, 78% with adenocarcinoma, 64% with PS 0 and 53% with stage IIIB). The median progression-free survival (PFS) and overall survival (OS) were 11 and 17 months in arm B compared to the encouraging results of 28 and 45 months in the standard arm. The 1- and 3-year survival rates were 56% and 33% (B) and 72% and 56% (A), respectively. There were seven toxicity-related deaths due to esophageal perforations and pneumonitis: five in the escalated group and two with standard treatment. Conclusion: Dose-escalated concurrent chemoradiotherapy to 84 Gy to primary tumor and nodal disease is hazardous, with a high risk of excessive toxicity, whereas modern standard dose chemoradiotherapy with proper staging given in the control arm shows a promising outcome with a median survival of 45 months and a 3-year survival of 56% (NCT01664663).
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  • Karlsson, Terese, 1979-, et al. (författare)
  • LMO7 and LIMCH1 interact with LRIG proteins in lung cancer, with prognostic implications for early-stage disease
  • 2018
  • Ingår i: Lung Cancer. - : Elsevier BV. - 0169-5002 .- 1872-8332. ; 125, s. 174-184
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: The human leucine-rich repeats and immunoglobulin-like domains (LRIG) protein family comprises the integral membrane proteins LRIG1, LRIG2 and LRIG3. LRIG1 is frequently down-regulated in human cancer, and high levels of LRIG1 in tumor tissue are associated with favorable clinical outcomes in several tumor types including non-small cell lung cancer (NSCLC). Mechanistically, LRIG1 negatively regulates receptor tyrosine kinases and functions as a tumor suppressor. However, the details of the molecular mechanisms involved are poorly understood, and even less is known about the functions of LRIG2 and LRIG3. The aim of this study was to further elucidate the functions and molecular interactions of the LRIG proteins.Materials and methods: A yeast two-hybrid screen was performed using a cytosolic LRIG3 peptide as bait. In transfected human cells, co-immunoprecipitation and co-localization experiments were performed. Proximity ligation assay was performed to investigate interactions between endogenously expressed proteins. Expression levels of LMO7 and LIMCH1 in normal and malignant lung tissue were investigated using qRT-PCR and through in silico analyses of public data sets. Finally, a clinical cohort comprising 355 surgically treated NSCLC cases was immunostained for LMO7.Results: In the yeast two-hybrid screen, the two paralogous proteins LMO7 and LIMCH1 were identified as interaction partners to LRIG3. LMO7 and LIMCH1 co-localized and co-immunoprecipitated with both LRIG1 and LRIG3. Endogenously expressed LMO7 was in close proximity of both LRIG1 and LRIG3. LMO7 and LIMCH1 were highly expressed in normal lung tissue and down-regulated in malignant lung tissue. LMO7 immunoreactivity was shown to be a negative prognostic factor in LRIG1 positive tumors, predicting poor patient survival.Conclusion: These findings suggest that LMO7 and LIMCH1 physically interact with LRIG proteins and that expression of LMO7 is of clinical importance in NSCLC.
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  • Kerr, Keith M., et al. (författare)
  • The evolving landscape of biomarker testing for non-small cell lung cancer in Europe
  • 2021
  • Ingår i: Lung Cancer. - : Elsevier. - 0169-5002 .- 1872-8332. ; 154, s. 161-175
  • Forskningsöversikt (refereegranskat)abstract
    • The discovery of oncogenic driver mutations rendering non-small cell lung cancer (NSCLC) targetable by small molecule inhibitors, and the development of immunotherapies, have revolutionised NSCLC treatment. Today, instead of non-selective chemotherapies, all patients with advanced NSCLC eligible for treatment (and increasing numbers with earlier, less extensive disease) require fast and comprehensive screening of biomarkers for first-line patient selection for targeted therapy, chemotherapy, or immunotherapy (with or without chemotherapy). To avoid unnecessary re-biopsies, biomarker screening before first-line treatment should also include markers that are actionable from second-line onwards; PD-L1 expression testing is also mandatory before initiating treatment.& nbsp; Population differences exist in the frequency of oncogenic driver mutations: EGFR mutations are more frequent in Asia than Europe, whereas the converse is true for KRAS mutations. In addition to approved first-line therapies, a number of emerging therapies are being investigated in clinical trials. Guidelines for biomarker testing vary by country, with the number of actionable targets and the requirement for extensive molecular screening strategies expected to increase. To meet diagnostic demands, rapid screening technologies for single driver mutations have been implemented. Improvements in DNA-and RNA-based next-generation sequencing & nbsp;technologies enable analysis of a group of genes in one assay; however, turnaround times remain relatively long. Consequently, rapid screening technologies are being implemented alongside next-generation sequencing.& nbsp; Further challenges in the evolving landscape of biomarker testing in NSCLC are actionable primary and secondary resistance mechanisms to targeted therapies. Therefore, comprehensive testing on re-biopsies, collected at the time of disease progression, in combination with testing of circulating tumour DNA may provide important information to guide second-or third-line therapies. Furthermore, longitudinal biomarker testing can provide insights into tumour evolution and heterogeneity during the course of the disease. We summarise best practice strategies for Europe in the changing landscape of biomarker testing at diagnosis and during treatment.
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24.
  • Killingberg, K. T., et al. (författare)
  • 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
  • 2022
  • Ingår i: Lung Cancer. - : Elsevier BV. - 0169-5002 .- 1872-8332. ; 166, s. 49-57
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: In a randomized phase II trial, twice daily (BID) thoracic radiotherapy (TRT) of 60 Gy/40 frac-tions improved survival compared with 45 Gy/30 fractions in limited stage small-cell lung cancer (LS SCLC). Notably, the higher dose did not cause more toxicity. Here we present health related quality of life (HRQoL) reported by the trial participants during the first 2 years.& nbsp;Materials and methods: 170 patients were randomized 1:1 to TRT of 45 Gy or 60 Gy concurrently with cisplatin/etoposide chemotherapy. The 150 patients who commenced TRT and completed a minimum of one HRQoL-questionnaire were included in the present study. Patients reported HRQoL on the European Organization for Research and Treatment of Cancer Core 30 and Lung Cancer 13 Quality of Life Questionnaires. Questionnaires were completed weeks 0, 4 (before TRT), 8 (end of TRT), 12 (response evaluation after chemoradiotherapy) and 16 (end of prophylactic cranial irradiation), then every 10 weeks year one, and every 3 months year two. Primary HRQoL endpoints were dysphagia and dyspnea. A difference in mean score of >= 10 was defined as clinically significant.& nbsp;Results: Maximum dysphagia was reported on week 8, with no significant difference between treatment arms (mean scores 45 Gy: 44.2, 60 Gy: 51.1). The 60 Gy arm had more dysphagia in the convalescence period, but dysphagia scores returned to baseline levels at week 16 in both arms. For dyspnea there were no significant changes, or differences between treatment arms, at any timepoint. There were no significant differences between treatment arms for any other HRQoL-scales.& nbsp;Conclusion: TRT of 60 Gy did not cause significantly higher maximum dysphagia, though patients on the 60 Gy arm reported more dysphagia the first 8 weeks of convalescence. The higher dose was well tolerated and is an attractive alternative to current TRT schedules in LS SCLC.& nbsp;
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25.
  • Koukourakis, Michael I., et al. (författare)
  • C2028T polymorphism in exon 12 and dinucleotide repeat polymorphism in intron 13 of the HIF-1 alpha gene define HIF-1 alpha protein expression in non-small cell lung cancer
  • 2006
  • Ingår i: Lung Cancer. - : Elsevier BV. - 1872-8332 .- 0169-5002. ; 53:3, s. 257-262
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: In this study, we investigated whether polymorphisms of the HIF-1 alpha gene may account for the patterns of HIF-1 alpha protein expression in non-small cell lung carcinomas (NSCLC) and the expression of HIF-1 alpha down-stream proteins. Methods: Specific HIF-1 alpha polymorphisms were assessed in a series of patients with NSCLC: (a) the C to T transition at nucleotide 1744 (position 2028 according to sequence with accession number NM_001530, which gives rise to Pro/Ser variation at codon 582), (b) the G to A nucleotide substitution at point 1790 (position 2046 according to sequence with accession number NM_001530, which gives rise to Ala/Thr variation at codon 588), and (c) the dinucleotide GT repeat polymorphism in intron 13. Immunohistochemistry for HIF-1 alpha and down-stream proteins (VEGF, LDH-5, GLUT-1) was also performed in tumor material. Results: A strong association of the P582S polymorphism and of GT repeat polymorphism higher than 14/14 with increased HIF-1 alpha expression was noted. HIF-1 alpha polymorphism did not relate to the expression of the HIF-1 alpha downstream proteins analysed, but significant association of HIF-1 alpha expression with LDH-5 was confirmed (p=0.008). Conclusions: HIF-1 alpha polymorphisms may have an important impact on HIF-protein stability and, eventually, function. (C) 2006 Elsevier Ireland Ltd. All rights reserved.
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26.
  • Kuemmel, Andreas, et al. (författare)
  • TA-MUC1 epitope in non-small cell lung cancer
  • 2009
  • Ingår i: Lung Cancer. - : Elsevier BV. - 0169-5002 .- 1872-8332. ; 63:1, s. 98-105
  • Tidskriftsartikel (refereegranskat)abstract
    • MUC1 (CD227), an established tumor marker, is expressed on glandular epithelia and on epithelial tumors. Tumor MUC1 differs from normal MUC1 by modified glycan side chains. Recently, a novel carbohydrate-induced conformational tumor-associated MUC1 epitope (TA-MUC1) was described, whose clinical relevance in lung cancer is not known. Eighty-five paraffin embedded tissue sections of non-small cell lung cancer (NSCLC) patients (73% male; mean age 64+/-9 years) were stained with the monoclonal antibody PankoMab (against TA-MUC1) and compared with the established antibodies E29 and 214D4 regarding prognostic relevance. TA-MUC1 is virtually absent in bronchial epithelium. As shown by multivariate analysis, only staining with PankoMab, but not with E29 or 214D4, was correlated with patients' survival (p=0.029). Moreover, when regarding interactions of MUC1 antibody staining results and clinico-pathological parameters, patients with lymph node metastasis lacking PankoMab staining were attributed the highest risk by far (Hazard ratio=4.6, 95% CI: 2.1-9.7, p=0.000). In summary, the presence of TA-MUC1 is a favorable prognostic factor in this cohort of NSCLC patients, in particular if lymph node metastases are present. This is in contrast to the results for E29 and 214D4, which recognize less or not glycosylation dependent epitopes. As this is the first report on a well-defined MUC1 epitope associated with improved survival in NSCLC, a more differentiated view on MUC1 may be mandatory.
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27.
  • La Fleur, Linnea, et al. (författare)
  • Mutation patterns in a population-based non-small cell lung cancer cohort and prognostic impact of concomitant mutations in KRAS and TP53 or STK11
  • 2019
  • Ingår i: Lung Cancer. - : Elsevier BV. - 0169-5002 .- 1872-8332. ; 130, s. 50-58
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: Non-small cell lung cancer (NSCLC) is a heterogeneous disease with unique combinations of somatic molecular alterations in individual patients, as well as significant differences in populations across the world with regard to mutation spectra and mutation frequencies. Here we aim to describe mutational patterns and linked clinical parameters in a population-based NSCLC cohort.MATERIALS AND METHODS: Using targeted resequencing the mutational status of 82 genes was evaluated in a consecutive Swedish surgical NSCLC cohort, consisting of 352 patient samples from either fresh frozen or formalin fixed paraffin embedded (FFPE) tissues. The panel covers all exons of the 82 genes and utilizes reduced target fragment length and two-strand capture making it compatible with degraded FFPE samples.RESULTS: We obtained a uniform sequencing coverage and mutation load across the fresh frozen and FFPE samples by adaption of sequencing depth and bioinformatic pipeline, thereby avoiding a technical bias between these two sample types. At large, the mutation frequencies resembled the frequencies seen in other western populations, except for a high frequency of KRAS hotspot mutations (43%) in adenocarcinoma patients. Worse overall survival was observed for adenocarcinoma patients with a mutation in either TP53, STK11 or SMARCA4. In the adenocarcinoma KRAS-mutated group poor survival appeared to be linked to concomitant TP53 or STK11 mutations, and not to KRAS mutation as a single aberration. Similar results were seen in the analysis of publicly available data from the cBioPortal. In squamous cell carcinoma a worse prognosis could be observed for patients with MLL2 mutations, while CSMD3 mutations were linked to a better prognosis.CONCLUSION: Here we have evaluated the mutational status of a NSCLC cohort. We could not confirm any survival impact of isolated driver mutations. Instead, concurrent mutations in TP53 and STK11 were shown to confer poor survival in the KRAS-positive adenocarcinoma subgroup.
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28.
  • Lal, R., et al. (författare)
  • Feasibility of home delivery of pemetrexed in patients with advanced non-squamous non-small cell lung cancer
  • 2015
  • Ingår i: Lung Cancer. - : Elsevier. - 0169-5002 .- 1872-8332. ; 89:2, s. 154-160
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To evaluate the feasibility and adherence to home delivery (HD) of pemetrexed maintenance treatment in patients with advanced non-squamous non-small cell lung cancer (nsqNSCLC). Materials and methods: Exploratory, prospective, single-arm, Phase II study in advanced nsqNSCLC patients, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0/1 that did not progress after 4 first-line induction cycles of a platinum doublet. The first cycle of pemetrexed (500 mg/m(2)) was hospital administered, further cycles were HD until progressive disease or discontinuation. Feasibility was assessed by the adherence rate to HD (probability of reversion to hospital administration or treatment discontinuation due to HD) as primary endpoint, and by health-related quality-of-life (HRQoL: EQ-5D, lung cancer symptom scale [LCSS]), satisfaction with HD, overall survival (OS), and safety. Results: 52 patients (UK and Sweden) received a median of 4 (range 1-19) pemetrexed maintenance cycles. Adherence rate up to Cycle 6 was 98.0% (95% confidence interval [CI]: 86.4%, 99.7%). All but 2 patients remained on HD. 1 patient discontinued after Cycle 1 (patient decision), and 1 after Cycle 6 (noncompliance with oral dexamethasone). 87% (33/38) of the patients preferred home to hospital treatment and in 90% (28/31) of cases, physicians were satisfied with distant management of patients. During HD Cycles 2-4 mean change from baseline ranged from 3.0 to 7.7 for EQ-5D visual analog scale. The 6-month OS rate was 73% (95% CI: 58%, 83%). 1 patient had an HD-related adverse event (device-related infection, Grade 2) and 1 patient died after Cycle 1, before HD, due to a possibly drug-related atypical pneumonia. Conclusion: HD of pemetrexed maintenance treatment in patients with advanced nsqNSCLC was feasible, safe, and preferred by patients, while maintaining HRQoL. Physicians were satisfied with distant patient management. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
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29.
  • Lindqvist, Jonatan, et al. (författare)
  • Effect of adherence to treatment guidelines on overall survival in elderly non-small-cell lung cancer patients
  • 2022
  • Ingår i: Lung Cancer. - : Elsevier. - 0169-5002 .- 1872-8332. ; 171, s. 9-17
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Mean age at diagnosis of lung cancer is increasing with increasing age in Western populations. The present study was designed to evaluate the effect of adherence to first-line treatment guidelines on overall survival (OS) in elderly patients with non-small-cell lung cancer (NSCLC) and reasons for non-adherence to treatment guidelines.Materials and methods: All patients aged ≥ 65 years diagnosed with NSCLC in Ostrobothnia, Finland, during the years 2016 to 2020 were identified from hospital registries. Adherence of first-line treatment to contemporary treatment guidelines was analysed based on diagnosis, tumour stage and performance status (PS), as was the effect of adherence on OS.Results: A review of hospital registries identified 238 NSCLC patients aged ≥ 65 years. Guideline adherence by stage decreased significantly with age, with 66.4% of patients aged 65 to 74 years, but only 33.3% of those aged > 80 years treated according to guidelines (p < 0.001). Other factors associated with non-adherence to guidelines included poor PS, frailty, and limited lung function. Of the patients with PS 0–2, 26.9% were under-treated according to guidelines. Reasons for under-treatment included comorbidities, decreased lung function, physician decision to reduce treatment intensity or recommend best supportive care, patient choice and PS decline before treatment initiation. Guideline adherence increased overall OS of elderly NSCLC patients in all stages. Elderly PS 2 patients appear to benefit from guideline adherence and active treatment. In contrast, active treatment did not benefit patients with PS 3–4.Conclusions: Guideline adherence was associated with increased OS in elderly NSCLC patients. Almost 10% of elderly and otherwise fit NSCLC patients were not treated according to guidelines and could have benefitted from more intensive treatment.
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30.
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31.
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32.
  • Lövgren, Malin, et al. (författare)
  • Symptoms and problems with functioning among women and men with inoperable lung cancer : A longitudinal study.
  • 2008
  • Ingår i: Lung Cancer. - : Elsevier BV. - 0169-5002 .- 1872-8332. ; 60:1, s. 113-124
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study is to compare the prevalence and intensity of symptoms and problems with functioning between women and men with inoperable lung cancer (LC) during 3 months post-diagnosis. One hundred and fifty-nine patients completed the EORTC QLQ C-30+LC13 at three time points: close to diagnosis and prior to treatment, and one, and 3 months later. Descriptive cross-sectional analyses and longitudinal analyses using repeated measure ANOVA were conducted. These patients reported many and intense symptoms and problems with functioning. The most salient finding from the cross-sectional analysis was that women reported both more, and more intense problems with emotional functioning close to diagnosis. Statistically significant improvements over time were found in both men and women with regard to emotional functioning, dyspnea, insomnia, cough, pain in arm/shoulder, while physical functioning, fatigue, constipation, dysphagia, peripheral neuropathy and alopecia deteriorated significantly over time. The longitudinal analyses suggest that, with the exception of emotional functioning, gender differences were not only related to biological sex alone, but were also found to be related to other components of the patients' life situation, such as education, age, civil status and type of LC. Sensitivity to different symptom experiences and responses to those experiences between and within women and men is also necessary in the management of symptoms in patients with inoperable LC.
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33.
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34.
  • Meyer, Ralf G., et al. (författare)
  • An open-label, prospective phase I/II study evaluating the immunogenicity and safety of a ras peptide vaccine plus GM-CSF in patients with non-small cell lung cancer
  • 2007
  • Ingår i: Lung Cancer. - : Elsevier BV. - 0169-5002 .- 1872-8332. ; 58:1, s. 88-94
  • Tidskriftsartikel (refereegranskat)abstract
    • Mutations of the ras gene have been reported in 20-40% of NSCLC patients. If present, they are critical for the malignant phenotype of these tumors. Therefore, targeting them by specific vaccination is a promising therapeutic approach. In a clinical trial we screened for ras mutations in patients with NSCLC. Patients with ras-positive tumors were immunized six times intradermally with a mixture of seven peptides representing the most common ras mutations. Objectives of the study were the feasibility, efficacy and safety of the vaccination. In addition, the induction of a specific immune reaction was investigated by DTH tests, and the induction of peptide-specific T cells was tested in ex vivo IFN-gamma-ELISPOT assays. Five of 18 patients had ras mutations at codon 12. Four of these patients, all with adenocarcinomas (stage I: n=3, stage IV: n=1) entered the study. The patient with stage IV disease withdrew prematurely after the third application because of disease progression associated with pulmonary embolism. Ras-specific T cells were not detected ex vivo. However, one patient developed a positive DTH reaction after the fifth vaccination that increased after the sixth vaccination. Our results are in line with earlier trials reporting ras mutations in 20-40% of NSCLC patients. Vaccination with mutated ras peptides is feasible and well tolerated. One patient revealed a positive DTH test. An ex vivo detectable T cell response was not induced in any of the patients.
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35.
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36.
  • Moreno-Ruiz, Pablo, et al. (författare)
  • Stromal FAP is an independent poor prognosis marker in non-small cell lung adenocarcinoma and associated with p53 mutation
  • 2021
  • Ingår i: Lung Cancer. - : Elsevier. - 0169-5002 .- 1872-8332. ; 155, s. 10-19
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectivesFibroblasts regulate tumor growth and immune surveillance. Here, we study FAP, PDGFβR and α-SMA fibroblast markers in a well-annotated clinical cohort of non–small-cell lung cancer (NSCLC) for analyses of associations with immune cell infiltration, mutation status and survival.Materials and MethodsA well-annotated NSCLC cohort was subjected to IHC analyses of stromal expression of FAP, PDGFβR and α-SMA and of stromal CD8 density. Fibroblast markers-related measurements were analyzed with regard to potential associations with CD8 density, cancer genetic driver mutations, survival and PD-L1 expression in the whole NSCLC cohort and in subsets of patients.ResultsHigh stromal FAP expression was identified as an independent poor prognostic marker in the whole study population (HR 1.481; 95 % CI, 1.012–2.167, p = 0.023) and in the histological subset of adenocarcinoma (HR 1.720; 95 % CI, 1.126–2.627, p = 0.012). Among patients with adenocarcinoma, a particularly strong association of FAP with poor survival was detected in patients with low stromal CD8 infiltration, and in other subpopulations identified by specific clinical characteristics; elderly patients, females, non-smokers and patients with normal ECOG performance status. α-SMA expression was negatively associated with CD8 infiltration in non-smokers, but none of the fibroblast markers expression was associated with CD8 density in the whole study population. Significant associations were detected between presence of p53 mutations and high α-SMA (p = 0.003) and FAP expression (p < 0.001).ConclusionThe study identifies FAP intensity as a candidate independent NSCLC prognostic biomarker. The study also suggests continued analyses of the relationships between genetic driver mutations and the composition of tumor stroma, as well as continued probing of marker-defined fibroblasts as NSCLC subset-specific modifiers of immune surveillance and outcome.
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37.
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38.
  • Mousavi, Seyed Mohsen, et al. (författare)
  • Risk of lung cancer by histology among immigrants to Sweden
  • 2012
  • Ingår i: Lung Cancer. - : Elsevier BV. - 1872-8332 .- 0169-5002. ; 76:2, s. 159-164
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: We wanted to define lung cancer incidence rates by histological subtype among immigrants in Sweden to explore the effect of new environments on the incidence of lung cancer by histological subtype in different ethnic populations. Methods: The nationwide Swedish Family-Cancer Database w used to calculate age-standardized incidence rates (ASR) (per 100,000) and standardized incidence ratios (SIRs). The patient series covered 19,255 male and 14,601 female Swedes, and 3236 male and 1751 female immigrants. Results: By time since immigration, Former Yugoslavian (ASR = 46.4) and Asian Arab (38.8) men, and Danish (23.3), Norwegian (19.5) and Finnish (14.5) women had the highest rates for lung cancer, while the lowest rate was seen among Asian Arab women (5.8). The highest adenocarcinoma rates were seen among South European men (11.5), and Danish (7.4) and Norwegian (6.9) women, while squamous cell (SCC) and small cell carcinomas rates were the highest among former Yugoslavian (16.0) and Baltic (8.8) men, respectively. Former Yugoslavian men (2.6) had the highest rate for large cell carcinoma. Compared to Swedes, former Yugoslavian men had the highest significant risk for SCC (SIR = 3.62), small cell (3.14) and large cell (4.21) carcinomas, whereas the highest adenocarcinoma risk was seen among Asian Arabs (2.35). Danish women had the highest risks for SCC (1.91) and small cell carcinoma (2.56). Conclusion: The ethnic-specific lung cancer rates by histology followed the rates in the countries of origin. Our findings may suggest that preservation of smoking habits in the host country is linked to the ethnic diversity of lung cancer incidence by histology. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
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39.
  • Myrdal, Gunnar, et al. (författare)
  • Regional differences in treatment and outcome in non-small cell lung cancer : a population-based study (Sweden)
  • 2009
  • Ingår i: Lung Cancer. - : Elsevier BV. - 0169-5002 .- 1872-8332. ; 63:1, s. 16-22
  • Tidskriftsartikel (refereegranskat)abstract
    • In the recent decade uniform treatment guidelines for non-small cell lung cancer (NSCLC) have been introduced in Sweden. The objective of this study was to examine time trends and differences in treatment intensity for NSCLC between county clinical centres in Central Sweden. A second aim was to investigate whether any differences in treatment of NSCLC were associated with differences in survival. 4345 patients with a diagnosis of NSCLC between 1995 and 2003 were identified in the population-based Lung Cancer Register of Central Sweden. Multivariate logistic regression was used to estimate odds ratios to analyse the likelihood of receiving different treatment modalities for NSCLC. Cox proportional hazard models estimating relative hazard ratios were used to identify factors related to death (by any cause). Of all patients, 33.4% received no treatment, and 17.5% underwent surgery. Between 1995 and 2003, the proportion of patients receiving chemotherapy rose from 14.6% to 55%. There were pronounced differences between county centres in treatment policies, especially concerning surgery and radiotherapy. The likelihood of receiving treatment for NSCLC was highest at county centre A where both surgical treatment and chemotherapy were given more often. Compared to this reference county, the risk of death was between 20% and 40% higher in the other counties after adjusting for age, stage, gender, time period, smoking status and histopathological type. When analyses were adjusted for treatment, county of residence was no longer a prognostic factor. Despite common guidelines there were marked differences in treatment activity between the counties. Treatment activity was associated with survival. Survival benefits may follow improvement in compliance to guidelines.
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40.
  • Mörth, Charlott, et al. (författare)
  • Single-agent versus combination chemotherapy as first-line treatment for patients with advanced non-small cell lung cancer and performance status 2 : A literature-based meta-analysis of randomized studies
  • 2014
  • Ingår i: Lung Cancer. - : Elsevier BV. - 0169-5002 .- 1872-8332. ; 84:3, s. 209-214
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The purpose of this study was to compare the efficacy and tolerability of first-line treatment with combination versus single agent chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) and performance status (PS) 2.METHODS: A systematic literature search was performed to identify randomized trials comparing combination versus single agent chemotherapy in patients with advanced NCSLC. Both trials dedicated to PS 2 patients and trials that performed a subset analysis according to PS were included in the meta-analysis. Standard meta-analytic procedures were used to analyze the study outcomes.RESULTS: Twelve trials were considered eligible and were further analyzed. The use of combination chemotherapy resulted in a statistically significant better overall survival compared to single agent chemotherapy (11 trials, 1114 patients; hazard ratio (HR), 0.79, 95% confidence interval (CI): 0.71-0.88). The survival benefit was pronounced when platinum-based combination was used (HR: 0.71, 95% CI: 0.61-0.81) while no survival benefit was observed in non-platinum based combinations (HR: 0.96, 95% CI: 0.80-1.15). Grade 3/4 anemia (OR: 3.12, 95% CI: 1.55-6.27), thrombocytopenia (OR: 12.81, 95% CI: 4.65-33.10), and neutropenia (OR: 7.91, 95% CI: 3.97-15.78) but not febrile neutropenia were significantly more frequent with combination chemotherapy.CONCLUSION: This meta-analysis provides evidence supporting the use of combination chemotherapy in patients with NSCLC and PS 2. However, the patients should be informed about the higher risk for toxicity with the combination chemotherapy and the final treatment strategy should be individualized.
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41.
  • Nyman, Jan, 1956, et al. (författare)
  • How to improve loco-regional control in stages IIIa-b NSCLC? Results of a three-armed randomized trial from the Swedish Lung Cancer Study Group.
  • 2009
  • Ingår i: Lung cancer (Amsterdam, Netherlands). - : Elsevier BV. - 1872-8332 .- 0169-5002. ; 65:1, s. 62-7
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: A combination of chemotherapy and radiotherapy is the treatment base for locally advanced non-small cell lung cancer (NSCLC). However, both loco-regional and distant failure is frequent. Attempts to improve the loco-regional control were made in three separate phase II studies in Swedish University Hospitals, where accelerated radiotherapy or concurrent daily or weekly chemotherapy with conventional radiotherapy were tested. Comparatively good results from these studies lead to this national randomized phase II study, the RAKET-study, where the different concepts were investigated on a wider basis for further phase III studies. METHODS: Inoperable stage III non-small cell lung cancer patients in good performance status (PS<2) were equally randomized to either of three arms in eight institutions. All arms started with two cycles of induction chemotherapy: paclitaxel 200 mg/m2 and carboplatin AUC6. Arm A: a third identical cycle was given concomitant with start of accelerated radiotherapy, 1.7 Gy BID to 64.6 Gy in 4.5 weeks. Arm B consisted of daily concomitant paclitaxel 12 mg/m2 with conventionally fractionated radiotherapy: 2 Gy to 60 Gy in 6 weeks. Arm C: weekly concomitant paclitaxel 60 mg/m2 and identical radiotherapy to 60 Gy. Primary endpoint: TTP. Secondary: OS, toxicity, QL and relapse pattern. RESULTS: Between June 2002 and May 2005 152 patients were randomized and of them 151 were evaluable: 78 men and 73 women, median age 62 years (43-78), 55% had performance status 0 and 45% PS 1. Thirty-four percent had stage IIIa and 66% IIIb. Histology: adenocarcinoma 48%, squamous cell carcinoma 32% and 20% non-small cell carcinoma. The three arms were well balanced. Toxicity was manageable with 12% grades 3-4 esophagitis, 1% grades 3-4 pneumonitis and there was no clear difference between the arms. The QL data did not differ either. Median time to progression was 9.8 (8.3-12.7) months (8.8, 10.3 and 9.3 months for arms A, B and C, respectively). Median survival was 17.8 (14.4-23.7) months (17.7, 17.7 and 20.6 months for A, B and C, respectively). The 1-, 3- and 5-year overall survival was 63, 31 and 24%. Sixty-nine percent of the patients relapsed with distant metastases initially and 31% had loco-regional tumor progression, without significant differences between treatment arms. Thirty-four percent developed brain metastases. CONCLUSIONS: Treatment results are quite equal by intensifying the loco-regional treatment either by accelerated fractionated radiotherapy or daily or weekly concomitant chemo-radiotherapy both in terms of survival, toxicity and quality of life. The optimal treatment schedule for patients with locally advanced NSCLC is still to be decided and investigated in future clinical studies. Relapse pattern with distant metastases and especially brain metastases is a great problem and need further research for better therapy options and higher cure rate for this patient group.
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42.
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43.
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44.
  • Pallari, E., et al. (författare)
  • Lung cancer research and its citation on clinical practice guidelines
  • 2021
  • Ingår i: Lung Cancer. - : Elsevier Ireland Ltd. - 0169-5002 .- 1872-8332. ; 154, s. 44-50
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The impact of medical research is usually judged on the basis of citations in the serial literature. A better test of its utility is through its contribution to clinical practice guidelines (CPGs) on how to prevent, diagnose, and treat illness. This study aimed to compare the parameters of lung cancer research papers with those cited as references in lung cancer CPGs from 16 countries, and the Cochrane Collaboration. These comparisons were mainly based on bibliographic data compiled from the Web of Science (WoS).Methodology: We examined 7357 references (of which 4491 were unique) cited in a total of 77 lung cancer CPGs, and compared them with 73,214 lung cancer papers published in the WoS between 2004 and 2018.Results: References used by lung CPGs were much more clinical than the overall body of research papers on this cancer, and their authors predominantly came from smaller northern European countries. However, the leading institutions whose papers were cited the most on these CPGs were from the USA, notably the MD Anderson Cancer Center in Texas, the Memorial Sloan Kettering Cancer Center, New York, and the Mayo Clinic in Rochester, Minnesota. The types of research cited by the CPGs were primarily clinical trials, as well as three treatment modalities (chemotherapy, radiotherapy and surgery). Genetics, palliative care and quality of life were largely neglected. The median time gap between papers cited on a lung CPG and its publication was 3.5 years longer than for WoS citations.Conclusions: Analysis of the references on CPGs allows an alternative means of research evaluation, and one that may be more appropriate for clinical research than citations in academic journals. Own-country references show the direct contribution of research to a country's health care, and other-country references show the esteem in which this research has been held internationally. © 2021 King's College London
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45.
  • Riihimäki, Matias, et al. (författare)
  • Metastatic sites and survival in lung cancer.
  • 2014
  • Ingår i: Lung Cancer. - : Elsevier BV. - 1872-8332 .- 0169-5002. ; 86:1, s. 78-84
  • Tidskriftsartikel (refereegranskat)abstract
    • Population-based data on metastatic sites and survival in site-specific metastases are lacking for lung cancer and for any cancer because most cancer registries do not record metastases. This study uses a novel population-based approach to identify metastases from both death certificates and national inpatient data to describe metastatic pathways in lung cancer patients.
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46.
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47.
  • Salander, Pär, 1948-, et al. (författare)
  • Severely diseased lung cancer patients narrate the importance of being included in a helping relationship
  • 2005
  • Ingår i: Lung Cancer. - Amsterdam : Elsevier. - 0169-5002 .- 1872-8332. ; 50:2, s. 155-162
  • Tidskriftsartikel (refereegranskat)abstract
    • Because patients with advanced lung cancer have a poor prognosis, healthcare staff should treat and support them with sensitivity without placing them under necessary strain. A common way of revealing patients’ psychological needs is to rely on questionnaires where predefined potential problem areas are examined. Another and less common way of detecting their needs is to focus on the patients’ concrete everyday-experiences in their contacts with health care. In this study, 23 consecutive patients with advanced non-small cell lung cancer were asked to describe their experiences in dealing with their healthcare providers. Data were analysed qualitatively by categorising the incidents according to content. It emerged that ‘being connected to health care’ and being ‘acknowledged as a person’ were by far the most prominent dimensions. Very few incidents were directly related to ‘information’. The results suggest that in oncology it is important to call attention to the fact that the patient-physician relationship cannot be reduced to the communication of information. Other dimensions are worth considering.  
  •  
48.
  • Salander, Pär, 1948-, et al. (författare)
  • To carry on as before : a meta-synthesis of qualitative studies in lung cancer
  • 2016
  • Ingår i: Lung Cancer. - : Elsevier BV. - 0169-5002 .- 1872-8332. ; 99, s. 88-93
  • Tidskriftsartikel (refereegranskat)abstract
    • As a complement to quantitative studies, qualitative studies give us a better understanding of how persons affected by lung cancer live their everyday lives and how they deal with the obvious strain of having lung cancer. Because qualitative studies are based on only a few participants in specific contexts, the purpose of the present study is to synthesize knowledge from these qualitative studies to get a more general picture of the everyday lives of patients with lung cancer. A search on PubMed, CINAHL, Medline and PsychInfo yielded 383 hits. After exclusion we found 16 studies that focused on how these patients lived, reflected, and dealt with their new life situation. These studies comprised 393 interviews with 283 patients with primary lung cancer, and the findings from these studies were synthesized into a core process with subcategories. The overarching process was that the patients were eager "to carry on as before". They wanted to resume their former everyday life, and their views on their relationships with their bodies and side effects of treatments, their families, the health care staff, and with dying and death were very much related to how these could assist the core process. The synthesis presented here suggests that health care in consultations with patients with lung cancer should defer to the importance of the patient's core idea that life carries on despite the fact that it will probably soon come to an end.
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49.
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50.
  • Sanjinez, Claudia, et al. (författare)
  • Antimuscarinics and lung cancer survival : A Norwegian population-based cohort study
  • 2023
  • Ingår i: Lung Cancer. - : ELSEVIER IRELAND LTD. - 0169-5002 .- 1872-8332. ; 179
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Epidemiological studies have reported an association between antimuscarinics and reduced risk of cancer, including lung cancer (LC). However, the potential association between antimuscarinic use and LC prognosis has not previously been assessed. In a large population-based cohort, we aimed to investigate the association between the use of antimuscarinics and LC-specific survival.Materials and Methods: Norwegian residents, aged >= 50 years, and diagnosed with LC between 2005 and 2018, were identified in the Cancer Registry of Norway, and information on filled prescriptions was obtained from the Norwegian Prescription Database. We used Cox proportional hazard models to estimate hazard ratios (HR) and 95 % confidence intervals (CI) for the association between peri-diagnostic and post-diagnostic use of anti-muscarinics and LC-specific survival.Results: We included 26,693 patients with incident primary invasive LC. Of these, 466 (1.7 %) were peri-diag-nostic users, and 877 (3.3 %) were post-diagnostic users of antimuscarinics, respectively. During a median follow-up of nine months, 18,088 (67.8 %) patients died due to LC. In the overall LC population, the HRs for the association between the use of antimuscarinics, compared to no use, were estimated at 1.01 (95 %CI: 0.90-1.12) for peri-diagnostic use, and 0.84 (95 %CI: 0.77-0.92) for post-diagnostic use. The association with post-diagnostic use was observed in many subgroups defined by sex, age, smoking status, histopathology, and stage, except for patients with unspecified or other histopathology than small cell LC and non-small cell LC, and for patients with local disease. The association was observed in patients treated with chemotherapy (HR = 0.75, 95 %CI: 0.64-0.88), but not in those not treated with chemotherapy (HR = 1.00, 95 %CI: 0.86-1.17; p for interaction: 0.007).Conclusion: Our results suggest a possible association between use of antimuscarinics and longer LC-specific survival. More studies are warranted to investigate the use of antimuscarinics to possibly prolong LC prognosis.
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