1. |
- Holgersson, Georg, et al.
(author)
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The prognostic value of pre-treatment thrombocytosis in two cohorts of patients with non-small cell lung cancer treated with curatively intended chemoradiotherapy
- 2017
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In: Neoplasma (Bratislava). - Bratislava : AEPress. - 0028-2685 .- 1338-4317. ; 64:6, s. 909-915
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Journal article (peer-reviewed)abstract
- Chemoradiotherapy is the standard of care for inoperable stage III non-small cell lung cancer (NSCLC). This treatment, however, offers only a small chance of cure and is associated with many side effects. Little research has been made concerning which patients benefit most/least from the treatment. The present study evaluates the prognostic value of anemia, leukocytosis and thrombocytosis at diagnosis in this treatment setting. In the present study, data were collected retrospectively for 222 patients from two different phase II studies conducted between 2002-2007 in Sweden with patients treated with chemoradiotherapy for stage IIIA-IIIB NSCLC. Clinical data and the serum values of hemoglobin (Hgb), White blood cells (WBC) and Platelets (Plt) at enrollment were collected for all patients and studied in relation to overall survival using Kaplan-Meier product-limit estimates and a multivariate Cox proportional hazards regression model. The results showed that patients with thrombocytosis (Plt > 350 x 109 /L) had a shorter median overall survival (14.5 months) than patients with normal Plt at baseline (23.7 months). Patients with leukocytosis (WBC > 9 x 109 /L) had a shorter median survival (14.9 months) than patients with a normal WBC at baseline (22.5 months). However, in a multivariate model including all lab parameters and clinical factors, only thrombocytosis and performance status displayed a prognostic significance. In Conclusion, thrombocytosis showed to be an independent prognostic marker associated with shorter overall survival in stage III NSCLC treated with curatively intended chemoradiotherapy. This knowledge can potentially be used together with established prognostic factors, such as performance status when choosing the optimal therapy for the individual patient in this clinical setting
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2. |
- Berglund, Åke, et al.
(author)
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The response to vaccination against influenza A(H1N1) 2009, seasonal influenza and Streptococcus pneumoniae in adult outpatients with ongoing treatment for cancer with and without rituximab
- 2014
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In: Acta Oncologica. - : Taylor & Francis Group. - 0284-186X .- 1651-226X. ; 53:9, s. 1212-1220
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Journal article (peer-reviewed)abstract
- It is debated whether cancer patients treated with chemotherapy can mount an adequate response to vaccination.Material and methods: Ninety-six adult outpatients with cancer, who were undergoing chemotherapy and/or monoclonal antibody, tyrosine kinase inhibitor, irradiation or corticosteroid treatments, were studied. Two doses of the pandemic infl uenza A(H1N1)/09 AS03-adjuvanted split virion vaccine, one dose of the seasonal infl uenza vaccine and one dose of the 23-valent pneumococcal polysaccharide vaccine were given. Serum haemagglutination inhibition (HI) assays were used to determine antibody titres against the infl uenza strains. For the pneumococcal vaccine 14 different serotypespecifi c anti-capsular antibodies were measured by bead assay xMAP ® .Results: Patients treated with rituximab did not respond to vaccination. For patients without rituximab treatment 4% had putatively protective antibodies before vaccination (HI 40) to the pandemic-like strain A/California7/2009HINI. After the fi rst and second dose of vaccine, seroprotection rates (SPR) were 62% and 87%, and seroconversion rates (SCR) 62% and 84%, respectively. Before seasonal fl u vaccination SPR against infl uenza A/Brisbane/59/2007H1N1 and A/Uruguay/10/2007H3N2 were 19% and 17%, respectively. After vaccination, SPR were 70% and 59% and SCR 42% and 50%, respectively. For the pneumococcal vaccine protective antibodies were found to 40% of the 14 strains before and to 68% after vaccination. The mean response to pneumococcal vaccination was to 44% of the 14 serotypes. A response to at least 50% of the 14 serotypes was found in 49% of the patients. No serious adverse events were reported.Conclusion: A substantial number of adult cancer patients with ongoing chemotherapy treatment could mount an adequate serological response to infl uenza and pneumococcal vaccination without severe adverse events. Thus, vaccination should be recommended. Adjuvanted vaccines may improve the vaccine response among this patient group. Patients recently treated with rituximab do not respond to vaccination.
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3. |
- Isaksson, Johan, et al.
(author)
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Highly elevated systemic inflammation is a strong independent predictor of early mortality in advanced non-small cell lung cancer
- 2022
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In: Cancer Treatment and Research Communications. - : Elsevier. - 2468-2942. ; 31
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Journal article (peer-reviewed)abstract
- BackgroundAmple evidence support inflammation as a marker of outcome in non-small cell lung cancer (NSCLC). Here we explore the outcome for a subgroup of patients with advanced disease and substantially elevated systemic inflammatory activity.MethodsThe source cohort included consecutive patients diagnosed with NSCLC between January 2016 – May 2017 (n = 155). Patients with active infection were excluded. Blood parameters were examined individually, and cut-offs (ESR > 60 mm, CRP > 20 mg/L, WBC > 10 × 109, PLT > 400 × 109) were set to define the group of hyperinflamed patients. A score was developed by assigning one point for each parameter above cut-off (0–4 points).ResultsHigh systemic inflammation was associated with advanced stage and was seldom present in limited NSCLC. However, the one year survival of patients in stage IIIB-IV (n = 93) with an inflammation score of ≥2 was 0% compared to 33% and 50% among patients with a score of 1 and 0 respectively. The effect of a high inflammation score on overall survival remained significant in multi-variate analysis adjusted for confounding factors. The independent hazard ratio of an inflammation score ≥ 2 in multi-variate analysis (HR 3.43, CI 1.76–6.71) was comparable to a change in ECOG PS from 0 to 2 (HR 2.42, CI 1.13–5.18).ConclusionOur results show that high level systemic inflammation is a strong independent predictor of poor survival in advanced stage NSCLC. This observation may indicate a need to use hyperinflammation as an additional clinical parameter for stratification of patients in clinical studies and warrants further research on underlying mechanisms linked to tumor progression.
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4. |
- Isaksson, Johan, et al.
(author)
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KRAS G12C mutant non-small cell lung cancer linked to female sex and high risk of CNS metastasis : Population-based demographics and survival data from the National Swedish Lung Cancer Registry
- 2023
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In: Clinical Lung Cancer. - : Elsevier. - 1525-7304 .- 1938-0690. ; 24:6, s. 507-518
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Journal article (peer-reviewed)abstract
- BackgroundReal-world data on demographics related to KRAS mutation subtypes are crucial as targeted drugs against the p.G12C variant have been approved.MethodWe identified 6183 NSCLC patients with reported NGS-based KRAS status in the Swedish national lung cancer registry between 2016 and 2019. Following exclusion of other targetable drivers, three cohorts were studied: KRAS-G12C (n = 848), KRAS-other (n = 1161), and driver negative KRAS-wild-type (wt) (n = 3349).ResultsThe prevalence of KRAS mutations and the p.G12C variant respectively was 38%/16% in adenocarcinoma, 28%/13% in NSCLC-NOS and 6%/2% in squamous cell carcinoma. Women were enriched in the KRAS-G12C (65%) and KRAS-other (59%) cohorts versus KRAS-wt (48%). A high proportion of KRAS-G12C patients in stage IV (28%) presented with CNS metastasis (vs. KRAS-other [19%] and KRAS-wt [18%]). No difference in survival between the mutation cohorts was seen in stage I-IIIA. In stage IV, median overall survival (mOS) from date of diagnosis was shorter for KRAS-G12C and KRAS-other (5.8 months/5.2 months) vs. KRAS wt (6.4 months). Women had better outcome in the stage IV cohorts, except in KRAS-G12C subgroup where mOS was similar between men and women. Notably, CNS metastasis did not impact survival in stage IV KRAS-G12C, but was associated with poorer survival, as expected, in KRAS-other and KRAS-wt.ConclusionThe KRAS p.G12C variant is a prevalent targetable driver in Sweden and significantly associated with female sex and presence of CNS metastasis. We show novel survival effects linked to KRAS p.G12C mutations in these subgroups with implications for clinical practice.
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5. |
- Isaksson, Johan, et al.
(author)
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Predictors of long-term survival and recurrence patterns after definitive chemoradiotherapy in stage III NSCLC – a multicenter cohort study from Mid Sweden
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Other publication (other academic/artistic)abstract
- Background: Stage III NSCLC is heterogeneous but often recurs despite intensive treatment with curative intent. Clinical tools to predict the risk and pattern of recurrence and long-term survival in individual patients are largely lacking. Methods: NSCLC stage III patients (N=193) treated 2009-2018 with definitive, curatively intended chemoradiotherapy (CRT, 60Gy+) were retrospectively identified from three healthcare regions in Mid Sweden. Outcome variables included overall survival (OS), progression-free survival (PFS) and recurrence patterns. Results: Median follow-up of patients alive was 52 months. 1, 2 and 5-year OS was 80%, 63% and 34% with a mOS of 32 months. Pre-treatment serum inflammatory markers were associated with inferior OS, including leukocyte count > 10 (HR 1.58, 95% CI 1.08-2.31, p=0.018) and CRP > 5 (HR 1.81, 95% CI 1.16-2.83, p=0.009). CRP remained independently associated with OS in multivariable analysis, HR 1.67 (1.05-2.65, p=0.029). No other pre-treatment variable was significantly associated with OS. Progressive disease (PD) was documented in 65% of patients after a median time of 9.5 months, 96% within 3 years from CRT, and was typically either distant or locoregional (12% mixed). Distant PD developed earlier (6.3 months) than locoregional PD (11.5 months; p=0.052). N3 disease (OR 2.7, 95% CI 1.2-6.3,; p=0.022) and presence of driver mutations (OR 4.6, 95% CI 1.5-14.0; p=0.0076) increased the risk of distant PD, while ≥2 concurrent chemotherapy courses was protective of locoregional PD (OR 0.38, 9% CI 0.1-1.0; p=0.049). Brain metastases were the first indication of PD in 22 patients (12%) and were in all cases isolated without synchronous extracranial PD. A post-CRT 18F-FDG-PET SUVmax of ≥7 was associated with a shorter time to PD (HR 0.41, 95% CI 0.21-0.79, p=0.008). Conclusions: The study reinforces the prognostic role of systemic inflammation in stage III NSCLC and provides clinically useful indicators of relapse pattern as a basis for rational disease monitoring following CRT.
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6. |
- Willén, Linda, 1979-, et al.
(author)
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Are older patients with non-small cell lung cancer receiving optimal care? A population-based study
- 2022
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In: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 61:3, s. 309-317
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Journal article (peer-reviewed)abstract
- Background: Results from studies addressing age-related patterns of cancer care have found evidence of unjustified differences in management between younger and older patients.Methods: We examined associations between age and clinical presentation, management and mortality in patients diagnosed with non-small cell lung cancer (NSCLC) between 2002 and 2016. Analyses were adjusted for comorbidity and other factors that may have affected management decisions and outcomes.Results: The study population encompassed 40,026 patients with NSCLC. Stage at diagnosis did not differ between age groups ≤ 84. The diagnostic intensity was similar in age groups <80 years. In patients with stage IA–IIB disease and PS 0–2, surgery was more common in the youngest age groups and decreased with increasing age, and was rarely performed in those ≥ 85 years. The use of stereotactic body radiotherapy (SBRT) increased with age (≤69 years 5.4%; ≥85 years 35.8%). In patients with stage IIIA disease and PS 0–2, concurrent chemoradiotherapy was more common in younger patients (≤69 years 55.3%; ≥85 years 2.2%). In stage IA–IIIA disease, no major differences in treatment-related mortality was observed. In stage IIIB–IV and PS 0–2, chemotherapy was more common in patients <80 years. However, 58.1% of patients 80–84 years and 30.3% ≥ 85 years received treatment. In stage IA–IIIA, overall and cause-specific survival decreased with increasing age. No age-differences in survival were observed in patients with stage IIIB-IV NSCLC.Conclusion: Treatments were readily given to older patients with metastatic disease, but to a lesser degree to those with early stage disease. Significant differences in cause specific survival were observed in early, but not late stage disease. Our findings underscore the importance of individualized assessment of health status and life expectancy. Our results indicate that older patients with early stage lung cancer to a higher extent should be considered for curative treatment.
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7. |
- Willén, Linda, 1979-, et al.
(author)
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Depression, anxiety, intoxication and suicide following a diagnosis of non-small cell lung cancer : A population-based study (Sweden)
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Other publication (other academic/artistic)abstract
- Introduction: Cancer affects quality of life, including psychological wellbeing. The risk of depression and suicide have been found to be increased in cancer patients, especially in cancers with poor prognosis. The aim of this study was to examine rates of indicators of psychological distress in patients with non-small cell lung cancer (NSCLC). Methods: We used data in a population-based research database to assess post-diagnostic events of depression, anxiety, intoxication (alcohol, opioids, sedatives and hypnotics) and suicide in patients with non-small cell lung cancer (NSCLC) in comparison to individuals free of lung cancer (comparators) matched on age, sex and area of residence, representing the background population. Results: The study population encompassed 38,454 patients diagnosed with NSCLC between 2002 and 2016 and 184,090 lung cancer free individuals. Compared to the comparators, patients with NSCLC were more likely to have an immigrant background (14.9 % vs 12.6 %), a lower educational level (42.9 % vs 36.7 %) and a higher comorbidity burden (28.3 % vs 16.4 %). Post diagnostic rates of depression, anxiety intoxication and suicide were higher in NSCLC patients compared to individuals free of lung cancer. While the risk of depression, anxiety and suicide decreased over time, the risk of intoxication remained elevated throughout the follow-up period. Conclusion: We found evidence of increased rates of indicators of psychological distress after a diagnosis of NSCLC. Our findings underscore the importance of symptom monitoring post-diagnosis and preparedness to provide adequate support and treatment.
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8. |
- Willén, Linda, 1979-, et al.
(author)
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Educational level and management and outcomes in non-small cell lung cancer. A nationwide population-based study
- 2019
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In: Lung Cancer. - : ELSEVIER IRELAND LTD. - 0169-5002 .- 1872-8332. ; 131, s. 40-46
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Journal article (peer-reviewed)abstract
- Objectives: We examined associations between educational level and clinical presentation, patterns of management and mortality in patients with non-small cell lung cancer (NSCLC) in Sweden, a country with a National Health Care System. Materials and Methods: We identified 39,671 patients with a NSCLC diagnosis 2002-2016 in Lung Cancer Data Base Sweden (LCBaSe), a population-based research database. In analyses adjusted for comorbidity and other prognostic factors, odds Ratios (OR) and hazard Ratios (HR) were estimated to examine associations between patients' educational level and aspects of management and mortality. Results: Stage at diagnosis and waiting times did not differ between educational groups. In multivariable analysis, the likelihood to undergo PET/CT and assessment in a multidisciplinary team setting were higher in patients with high compared to low education (aOR 1.14; CI 1.05-1.23 and aOR 1.22; CI 1.14-1.32, respectively). In patients with early stage IA-IIB disease, the likelihood to undergo stereotactic radiotherapy was elevated in patients with high education (aOR 1.40; CI 1.03-1.91). Both all-cause (aHR 0.86; CI 0.77-0.92) and cause specific mortality (aHR 0.83; CI 0.74-0.92) was lower in patients with high compared to low education in early stage disease (IA-IIB). In higher stage NSCLC no differences were observed. Patterns were similar in separate assessments stratified by sex and histopathology. Conclusions: While stage at diagnosis and waiting times did not differ between educational groups, we found socioeconomic differences in diagnostic intensity, multidisciplinary team assessment, stereotactic radiotherapy and mortality in patients with NSCLC. These findings may in part reflect social gradients in implementation and use of novel diagnostic and treatment modalities. Our findings underscore the need for improved adherence to national guidelines.
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9. |
- Willén, Linda, 1979-
(author)
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Factors influencing management and outcome in non-small cell lung cancer : the role of socioeconomic status, age, geographic region of origin and aspects of quality of life
- 2023
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Doctoral thesis (other academic/artistic)abstract
- Yearly, 4,200 individuals in Sweden are diagnosed with lung cancer, of which 85 % are non-small cell lung cancer (NSCLC). The aims of this thesis were to investigate aspects of equality of care and outcomes in patients with NSCLC and to examine indicators of quality of life. All studies used data in Lung Cancer Database Sweden (LCBaSe), a research database generated by record linkages between the National Lung Cancer Register and other population-based registers. We identified 40,000 patients with NSCLC diagnosed between 2002 and 2016.Paper I examined influence of socioeconomic status. Patients with a high educational level were more often offered PET-CT, assessed in a multidisciplinary team setting, treated with stereotactic body radiotherapy and had better survival in early-, but not in late-stage disease.Paper II investigated elderly NSCLC patients. No difference in stage was seen in patients ≤ 84 years, nor in diagnostic intensity <80 years. Treatment intensity was adapted according to age. Survival differed across age groups in early-, but not late-stage disease.Paper III examined immigrants. We found evidence of a “healthy migrant effect”. There were only small differences in management and outcome. If anything, non-Nordic immigrants had better survival in early-stage disease. Paper IV assessed psychological impact following a NSCLC diagnosis. Higher rates of depression, anxiety, intoxication and suicide were seen in NSCLC patients compared to lung cancer free individuals. The risk of depression, anxiety and suicide decreased over time but the increased risk of intoxication remained throughout the follow-up period.In summary, we found equal access of care and only minor differences in patterns of management and outcomes according to socioeconomic status, age and geographic region of origin. New diagnostics and treatment modalities need to be quickly introduced to enable equal access across socioeconomic groups. A careful assessment of older patients is important to avoid age-biased clinical decision-making. A diagnosis of NSCLC impacts psychological aspects of quality of life and active measures to identify and treat depression and anxiety as well as to identify patients at risk of intoxication and suicide is necessary.
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10. |
- Willén, Linda, 1979-, et al.
(author)
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Patterns of care and outcomes in immigrants with non-small cell lung cancer : a population-based study (Sweden)
- 2022
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In: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 17:12
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Journal article (peer-reviewed)abstract
- Objectives: While studies have found lower cancer risks and better cancer survival in immigrant populations, it is debated whether cancer care is offered on equal terms to all residents regardless of background. Our aim was to study patterns of care and outcomes in immigrants in a country with a tax-financed universal health care system.Material and methods: We used a population-based database to compare clinical presentation, management and mortality between Swedish-born and immigrant patients with non-small cell lung cancer (NSCLC). Analyses were adjusted for potential confounders.Results: We identified 40,075 patients diagnosed with NSCLC of which 84% were born in Sweden, 7% in Nordic and 9% in Non-Nordic countries. Non-Nordic immigrants were to a higher extent male, smokers, younger at diagnosis, had a better performance status and a higher educational level. No differences were seen regarding comorbidity burden or stage at diagnosis. Non-Nordic immigrants more often underwent positron emission tomography (PET) (aHR 1.32; 95% CI 1.19-1.45) and were more often discussed in a multidisciplinary team setting (aHR 1.30; 95% CI 1.17-1.44). There were no differences in treatment modalities following adjustment for age, with the exception of concurrent chemoradiotherapy in stage IIIA disease which was more common in Non-Nordic immigrants (aOR 1.34; 95% CI 1.03-1.74). Both overall and cause specific survival in non-metastatic disease were higher among Non- Nordic immigrants. Overall mortality in stage I-II: HR 0.81; 95% CI 0.73-0.90 and stage IIIA: HR 0.75; 95% CI 0.65-0.86. Following full adjustments, cause-specific mortality in stage I-II was aHR 0.86, 95% CI 0.75-0.98.Conclusion: Taken together, only minor differences in management and outcomes were observed between Swedish-born and immigrant patients. We conclude that lung cancer care is offered on equal terms. If anything, outcomes were better in Non-Nordic immigrants with early stage NSCLC.
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