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1.
  • Brodszki, Nicholas, et al. (författare)
  • A novel treatment approach for paediatric Gorham-Stout syndrome with chylothorax
  • 2011
  • Ingår i: Acta Pædiatrica. - : Wiley. - 1651-2227 .- 0803-5253. ; 100:11, s. 1448-1453
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: To expand the treatment options in paediatric Gorham-Stout syndrome (GSS) when conventional therapy is ineffective. Method: Two children with biopsy confirmed GSS, a rare disorder with progressive lymphangiomatosis, were treated with a combination of interferon-alpha-2b, low anticoagulant, low molecular weight heparin, radiotherapy and surgery. Results: The combined therapy resolved the symptoms in the acute phase, and both patients have since been free of symptoms for >2 years. Conclusion: The successful addition of a low anticoagulant, low molecular weight heparin ( tafoxiparin) to the treatment protocol in two paediatric cases of the GSS may justify the use of this approach in similar cases.
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2.
  • 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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3.
  • Holgersson, Georg, et al. (författare)
  • Swedish Lung Cancer Radiation Study Group: Predictive value of age at diagnosis for radiotherapy response in patients with non-small cell lung cancer
  • 2012
  • Ingår i: Acta Oncologica. - London : Informa Healthcare. - 0284-186X .- 1651-226X. ; 51:6, s. 759-767
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction. The aim of the present study was to investigate the impact of age at diagnosis on prognosis in patients treated with curatively intended radiotherapy for NSCLC. Material and methods. This is a joint effort among all the Swedish Oncology Departments that includes all identified patients with a diagnosed non-small cell lung cancer that have been subjected to curatively intended irradiation (andgt;= 50 Gy) treated during 1990 to 2000. Included patients had a histopathological/cytological diagnosis date as well as a death date or a last follow-up date. The following variables were studied in relation to overall and disease-specific survival: age, gender, histopathology, time period, smoking status, stage and treatment. Results. The median overall survival of all 1146 included patients was 14.7 months, while the five-year overall survival rate was 9.5%. Younger patients (andlt;55 years), presented with a more advanced clinical stage but had yet a significantly better overall survival compared with patients in the age groups 55-64 years (p = 0.035) and 65-74 years (p = 0.0097) in a multivariate Cox regression analysis. The overall survival of patients aged andgt;= 75 years was comparable to those aged andlt;55 years. Conclusion. In this large retrospective study we describe that patients younger than 55 years treated with curatively intended radiotherapy for NSCLC have a better overall survival than patients aged 55-64 and 65-74 years and that younger patients seem to benefit more from the addition of surgery and/or chemotherapy to radiotherapy. Due to the exploratory nature of the study, these results should be confirmed in future prospective trials.
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4.
  • Holgersson, Georg, et al. (författare)
  • Swedish Lung Cancer Radiation Study Group: Predictive value of histology for radiotherapy response in patients with non-small cell lung cancer
  • 2011
  • Ingår i: European Journal of Cancer. - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 47:16, s. 2415-2421
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of the present study was to evaluate the potential predictive value of histology in non-small cell lung cancer (NSCLC) treated with curatively intended radiotherapy. In a collaborative effort among all the Swedish Oncology Departments, clinical data were collected for 1146 patients with a diagnosed non-small cell lung cancer subjected to curatively intended irradiation (>= 50 Gy) during the years 1990 to 2000. The included patients were identified based on a manual search of all medical and radiation charts at the oncology departments from which the individual patient data were collected. Only patients who did not have a histological diagnosis date and death date/last follow-up date were excluded (n = 141). Among the 1146 patients with non-small cell carcinoma eligible for analysis, 919 were diagnosed with either adenocarcinoma (n = 323) or squamous cell carcinoma (n = 596) and included in this study. The median survival for the 919 patients was 14.8 months, while the 5-year survival rate was 9.5%. Patients with adenocarcinoma had a significantly better overall survival compared with patients with squamous cell carcinoma (p = 0.0062, log-rank test). When comparing different stages, this survival benefit was most pronounced for stages IIA-IIB (p<0.0001, log-rank test). The difference in survival between the two histological groups was statistically significant in a univariate Cox analysis (p = 0.0063) as well as in two multivariate Cox analyses including demographic and treatment variables (p = 0.037 and p = 0.048, respectively). In this large population based retrospective study we describe for the first time that patients with adenocarcinoma have a better survival after curatively intended radiation therapy in comparison with squamous cell carcinoma patients, particularly those with clinical stages IIA-IIB. (C) 2011 Elsevier Ltd. All rights reserved.
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5.
  • Holgersson, Georg, et al. (författare)
  • Swedish lung cancer radiation study group: the prognostic value of anaemia, thrombocytosis and leukocytosis at time of diagnosis in patients with non-small cell lung cancer
  • 2012
  • Ingår i: Medical Oncology. - : Humana Press (Springer Imprint). - 1357-0560 .- 1559-131X. ; 29:5, s. 3176-3182
  • Tidskriftsartikel (refereegranskat)abstract
    • There is a need to improve the prognostic and predictive indicators in non-small cell lung cancer (NSCLC). At present, the main focus is on genetic predictive markers while the prognostic value of the standard blood variables related to haematopoiesis has been subjected to relatively limited attention. To study the prognostic potential of haemoglobin (Hgb), platelet (Plt) and white blood cell (WBC) levels at time of diagnosis in NSCLC patients, 835 NSCLC patients, stage I-IV, who received radiotherapy with curative intention (andgt; 50 Gy), were included in the study. WBC, Plt, Hgb, gender, age at diagnosis, stage, surgery and first-line chemotherapy were studied in relation to overall survival. For patients with Hgb andlt; 110 g/L and Hgb a parts per thousand yen 110 g/L), the median survival was 11.2 and 14.5 months, respectively (p = 0.0032). For WBC andgt; 9.0 x 10(9)/L and andlt; 9.0 x 10(9)/L, the median survival was 11.6 and 15.4 months, respectively (p andlt; 0.0001). For Plt andgt; 350 x 10(9)/L and andlt; 350 x 10(9)/L, the median survival was 11.2 and 14.9 months, respectively (p andlt; 0.0001). The median survival in patients with pathological results in all three markers was half of that in patients with normal levels of all three markers (8.0 and 16.0 months, respectively (p andlt; 0.0001). The level of the three studied haematological biomarkers corresponds significantly to outcome in NSCLC. These results indicate that standard haematological variables may be used as guidance for the clinician in the decision-making regarding treatment intensity and patient information.
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6.
  • Holgersson, Georg, et al. (författare)
  • The impact of hyperfractionated radiotherapy regimen in patients with non-small cell lung cancer
  • 2013
  • Ingår i: Medical Oncology. - : Humana Press. - 1357-0560 .- 1559-131X. ; 30:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The prognosis for patients with lung cancer is poor with an average of 5-year overall survival rate of only 10-15 % taking all clinical stages together. The aim of this study was to elucidate the impact of the radiotherapy regimen on survival. Clinical data were collected from all the Swedish Oncology Departments for 1,287 patients with a diagnosed non-small cell lung cancer (NSCLC) subjected to curatively intended irradiation (andgt;= 50 Gy) during the years 1990 to 2000. The included patients were identified based on a manual search of all medical and radiation charts at the oncology departments from which the individual patient data were collected. Patients who did not have a histopathological diagnosis date and/or death date/last follow-up date as well as patients being surgically treated were excluded from the study (n = 592). Thus, 695 patients were included in the present study. Patients who received hyperfractionated radiotherapy (HR) had a higher local control rate compared with patients receiving conventional fractionation (CF) (38 vs. 49 % local relapse). The difference in survival between the two radiotherapy regimens was statistically significant in a univariate Cox analysis (p = 0.023) in favor of HR. This significance was, however, not retained in a multivariate Cox analysis (p = 0.56). Thus, the possible beneficial effects of hyperfractionation are still unclear and need to be further investigated in well-controlled prospective clinical trials, preferably including systemic treatment with novel drugs.
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7.
  • Holgersson, Georg, et al. (författare)
  • The value of induction chemotherapy for survival in patients with non-small cell lung cancer treated with radiotherapy.
  • 2012
  • Ingår i: Anticancer research. - : The International Institute of Anticancer Research. - 1791-7530 .- 0250-7005. ; 32:4, s. 1339-46
  • Tidskriftsartikel (refereegranskat)abstract
    • AIM: The aim of the present study was to retrospectively investigate the impact of induction chemotherapy on treatment outcome in patients treated with curatively intended radiotherapy for non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with a diagnosed NSCLC that have been subjected to curatively intended irradiation (≥50 Gy) and treated in an oncology department in Sweden during the years 1990-2000 were included in the study. Operated patients and patients having received concomitant chemotherapy were excluded. The included patients were localised by a manual search of all the oncology departments' medical records and radiation charts. RESULTS: Patients treated with induction chemotherapy (n=79) had a significantly better overall survival compared with patients treated with radiotherapy alone (p=0.0097) in a univariate Cox regression analysis. A platinum/taxane combination produced the greatest survival benefit; hazard ratio=0.49 (95% confidence interval=0.31 to 0.75). CONCLUSION: We found that patients treated with induction chemotherapy in addition to radiotherapy for NSCLC have a better overall survival than patients treated with radiotherapy alone and that the best results are achieved using a platinum/taxane combination.
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8.
  • Staaf, Johan, et al. (författare)
  • Relation between smoking history and gene expression profiles in lung adenocarcinomas
  • 2012
  • Ingår i: BMC Medical Genomics. - : Springer Science and Business Media LLC. - 1755-8794. ; 5
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Lung cancer is the worldwide leading cause of death from cancer. Tobacco usage is the major pathogenic factor, but all lung cancers are not attributable to smoking. Specifically, lung cancer in never-smokers has been suggested to represent a distinct disease entity compared to lung cancer arising in smokers due to differences in etiology, natural history and response to specific treatment regimes. However, the genetic aberrations that differ between smokers and never-smokers' lung carcinomas remain to a large extent unclear. Methods: Unsupervised gene expression analysis of 39 primary lung adenocarcinomas was performed using Illumina HT-12 microarrays. Results from unsupervised analysis were validated in six external adenocarcinoma data sets (n=687), and six data sets comprising normal airway epithelial or normal lung tissue specimens (n=467). Supervised gene expression analysis between smokers and never-smokers were performed in seven adenocarcinoma data sets, and results validated in the six normal data sets. Results: Initial unsupervised analysis of 39 adenocarcinomas identified two subgroups of which one harbored all never-smokers. A generated gene expression signature could subsequently identify never-smokers with 79-100% sensitivity in external adenocarcinoma data sets and with 76-88% sensitivity in the normal materials. A notable fraction of current/former smokers were grouped with never-smokers. Intriguingly, supervised analysis of never-smokers versus smokers in seven adenocarcinoma data sets generated similar results. Overlap in classification between the two approaches was high, indicating that both approaches identify a common set of samples from current/former smokers as potential never-smokers. The gene signature from unsupervised analysis included several genes implicated in lung tumorigenesis, immune-response associated pathways, genes previously associated with smoking, as well as marker genes for alveolar type II pneumocytes, while the best classifier from supervised analysis comprised genes strongly associated with proliferation, but also genes previously associated with smoking. Conclusions: Based on gene expression profiling, we demonstrate that never-smokers can be identified with high sensitivity in both tumor material and normal airway epithelial specimens. Our results indicate that tumors arising in never-smokers, together with a subset of tumors from smokers, represent a distinct entity of lung adenocarcinomas. Taken together, these analyses provide further insight into the transcriptional patterns occurring in lung adenocarcinoma stratified by smoking history.
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9.
  • Svensson, Gunnar A, et al. (författare)
  • Prognostic factors in lung cancer in a defined geographical area over two decades with a special emphasis on gender.
  • 2013
  • Ingår i: Clinical Respiratory Journal. - 1752-6981. ; 7:1, s. 91-100
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Many studies over recent decades report an increasing incidence of lung cancer in female patients. Female gender is often reported as a good prognostic factor. Objectives: The aim of the present study was to investigate prognostic factors with a special emphasis on gender. Methods: During 1989-2008, 1497 patients in eastern Scania, a part of southern Sweden with 202 000 inhabitants, were referred to one Central Hospital and prospectively registered. All patients were grouped into four 5-year periods and analysed for occurrence of lung cancer, patient performance status, types and stages of lung cancer and the relation to gender. Results: The incidence of lung cancer more than doubled in women. The proportion of adenocarcinomas increased in females and males to 57 % (p=0.028) and 42 % (p=0.001), respectively, while the frequency of small cell lung carcinomas (SCLCs) decreased in both genders to approximately 14 %. Females had significantly more frequent stage 1 (16.6 %) and higher surgery rate (23.1 %) than males (12 % and 18.2 %, respectively). Females showed a higher 5-year survival rate than males (20.1 % and 11.5 %, respectively; p<0.001). Patients with non-small cell lung carcinoma (NSCLC) had a higher 5-year survival rate than those with SCLC (16.5 % and 7.5 %, respectively; p<0.01); however there was no significant survival difference in females between NSCLC and SCLC. Conclusion: Female patients exhibited longer survival than males for both NSCLC and SCLC, and this was not explained by a higher frequency of stage 1 or surgery in NSCLC. © 2012 Blackwell Publishing Ltd.
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10.
  • SVENSSON, GUNNAR, et al. (författare)
  • Gender-Related Survival in Different Stages of Lung Cancer—A Population Study over 20 Years
  • 2014
  • Ingår i: Open Journal of Internal Medicine. - : Scientific Research Publishing, Inc.. - 2162-5980 .- 2162-5972. ; 4:3, s. 47-58
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Tumour stage is the most important prognostic factor in non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). The aim of this study was to evaluate if female gender was a prognostic factor in different tumour stages in relation to histology and given therapy. Methods: From 1989-2008, 1497 patients in eastern Scania, in southern Sweden with 202,000 inhabitants, were referred and prospectively registered. Tumour stage, performance status, lung cancer type and primary therapy were registered. Results: In NSCLC, female patients in stages 1 and 2 who were treated with surgery had a better 5-year survival rate (79.4%), compared to males (60.6%; p = 0.0004). Female patients in stage 3 with active therapy (surgery and/or radiotherapy and/or chemotherapy) had a better 5-year survival than males (20.6% vs. 10.5%, respectively, p = 0.0006). Female patients with adenocarcinoma were favourable in stages 1-3. In stage 4, there was no survival difference between females and males. In SCLC, females with limited disease (LD) and active therapy (chemotherapy ± radiotherapy ± surgery) had a higher 5-year survival rate (28%) than males (5.6%); p = 0.001. Females with extensive disease (ED) and active therapy (chemotherapy ± radiotherapy) had a better 5-year survival (3.9%) compared to males (0.7%); p = 0.023. In multivariate analyses, patient performance status at diagnosis was also an independent prognostic factor in all tumour stages of lung cancer. Conclusions: This population-based study corroborates a female survival advantage in NSCLC stages 1-3, but not in metastatic stage 4, and this is also demonstrated for the adenocarcinoma subgroup. The study also confirms better prognosis in females with SCLC in both LD and ED. The study also demonstrates the importance of patient performance status as a prognostic factor in all stages of lung cancer.
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