| 1. |
- Koyi, Hirsh, et al.
(författare)
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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
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Ingår i: Lung Cancer. - 0169-5002 .- 1872-8332. ; 36:1, s. 9-14
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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)
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The 'reservoir' of undetected bronchial carcinomas in the generalpopulation
- 2002
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Ingår i: Lung Cancer. - 0169-5002 .- 1872-8332. ; 37:2, s. 137-142
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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. |
- Brattström, Daniel, et al.
(författare)
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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
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Ingår i: Lung Cancer. - : Elsevier BV. - 0169-5002 .- 1872-8332. ; 43:1, s. 55-62
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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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| 4. |
- Crona, Joakim, et al.
(författare)
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Treatment, prognostic markers and survival in thymic neuroendocrine tumours : A study from a single tertiary referral centre
- 2013
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Ingår i: Lung Cancer. - : Elsevier BV. - 0169-5002 .- 1872-8332. ; 79:3, s. 289-293
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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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| 5. |
- Dietel, M., et al.
(författare)
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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
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Ingår i: Lung Cancer. - : Elsevier BV. - 0169-5002 .- 1872-8332. ; 134, s. 174-179
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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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| 6. |
- Djureinovic, Dijana, et al.
(författare)
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Detection of autoantibodies against cancer-testis antigens in non-small cell lung cancer
- 2018
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Ingår i: Lung Cancer. - : Elsevier BV. - 0169-5002 .- 1872-8332. ; 125, s. 157-163
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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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| 7. |
- Elfving, Hedvig, et al.
(författare)
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Evaluation of NTRK immunohistochemistry as a screening method for NTRK gene fusion detection in non-small cell lung cancer
- 2021
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Ingår i: Lung Cancer. - : Elsevier. - 0169-5002 .- 1872-8332. ; 151, s. 53-59
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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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| 8. |
- Hallqvist, Andreas, 1973, et al.
(författare)
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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
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Ingår i: Lung Cancer. - : Elsevier BV. - 0169-5002 .- 1872-8332. ; 71:2, s. 166-172
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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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| 9. |
- Karlsson, Terese, 1979-, et al.
(författare)
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LMO7 and LIMCH1 interact with LRIG proteins in lung cancer, with prognostic implications for early-stage disease
- 2018
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Ingår i: Lung Cancer. - : Elsevier BV. - 0169-5002 .- 1872-8332. ; 125, s. 174-184
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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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| 10. |
- Kerr, Keith M., et al.
(författare)
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The evolving landscape of biomarker testing for non-small cell lung cancer in Europe
- 2021
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Ingår i: Lung Cancer. - : Elsevier. - 0169-5002 .- 1872-8332. ; 154, s. 161-175
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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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