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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
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
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2012 (English)In: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 29, no 5, 3176-3182 p.Article in journal (Refereed) Published
Abstract [en]

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 (> 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 < 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 > 9.0 x 10(9)/L and < 9.0 x 10(9)/L, the median survival was 11.6 and 15.4 months, respectively (p < 0.0001). For Plt > 350 x 10(9)/L and < 350 x 10(9)/L, the median survival was 11.2 and 14.9 months, respectively (p < 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 < 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.

Place, publisher, year, edition, pages
2012. Vol. 29, no 5, 3176-3182 p.
Keyword [en]
Non-small cell lung cancer, Prognosis, Biomarker, Anaemia, Thrombocytosis, Leukocytosis
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-189133DOI: 10.1007/s12032-012-0247-3ISI: 000311513800027OAI: oai:DiVA.org:uu-189133DiVA: diva2:582496
Available from: 2013-01-04 Created: 2012-12-25 Last updated: 2017-12-06Bibliographically approved
In thesis
1. Prognosis, Prediction and Risk Assessment in the Prevention and Treatment of Non-Small Cell Lung Cancer
Open this publication in new window or tab >>Prognosis, Prediction and Risk Assessment in the Prevention and Treatment of Non-Small Cell Lung Cancer
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: Lung cancer causes more deaths than any other cancer. Smoking causes roughly 90% of lung cancer cases. Concurrent chemoradiation therapy is the standard of care for stage IIIb patients with performance status (PS) 0-1. A less toxic approach is warranted for less fit patients. To optimize care, the understanding of common clinical variables such as haematological responses to inflammation could be much improved. Adherence to guidelines for proper clinical work-up is vital to ensure patients’ optimal care, especially for predictive assays. Screening of high-risk patients is now being implemented internationally. Chronic pulmonary obstructive disease (COPD) patients, a group at high risk to develop lung cancer, could be of interest for screening.

Methods: Patient cohorts collected nationally and regionally by manual search in patient records or automated search in electronic patient records and national registries were analysed in relation to overall survival, comorbidities, medication, treatment, smoking status, biomarkers and adherence to guidelines. Standard statistics were applied to adjust for confounding factors.

Results: Induction chemotherapy results in longer overall survival than radiotherapy alone (15.6 and 11.6 months respectively). The overall survival for patients with combined anaemia, leucocytosis and thrombocytosis at diagnosis is half of what could be anticipated if blood samples are normal (8.0 and 16.0 months respectively). Fifty percent of patients were overlooked in the routine work-up with EGFR analysis. Less than 40% of the patients received EGFR-tyrosine kinase inhibitors in first-line therapy. The frequency of EGFR mutation was 9.9%. COPD patients with asthma and medicating with inhaled corticosteroids, specific serotonin reuptake inhibitors (SSRI) or beta-blockers have a significantly decreased risk of lung cancer.

Conclusions: Patients unfit to receive chemoradiation therapy should be considered for induction chemotherapy sequentially to radiotherapy. A patient that presents with pathological blood samples is likely to have poor prognosis and diagnostic work-up should be thorough to optimize outcome. Inadequate adherence to the national guidelines regarding treatment and EGFR analysis was shown. COPD patients medicating with ICS, beta-blockers or SSRI and with a concurrent asthma diagnosis have a decreased risk of lung cancer. 

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2015. 71 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1141
Keyword
chemoradiation therapy, induction chemotherapy, thrombocytosis, anaemia, leucocytosis, EGFR, guidelines, molecular pathology, ACOS, COPD, risk assessment, comorbidities
National Category
Cancer and Oncology Respiratory Medicine and Allergy
Research subject
Lung Medicine
Identifiers
urn:nbn:se:uu:diva-261554 (URN)978-91-554-9364-6 (ISBN)
Public defence
2015-11-27, Enghoffsalen, Ing 50, Akademiska Sjukhuset, Uppsala, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2015-11-04 Created: 2015-09-01 Last updated: 2015-11-10
2. Prognostic Factors in Non-Small Cell Lung Cancer (NSCLC)
Open this publication in new window or tab >>Prognostic Factors in Non-Small Cell Lung Cancer (NSCLC)
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: Non-small cell lung cancer (NSCLC) is the cancer disease with the highest mortality globally. About 75% of NSCLC patients are diagnosed in an advanced stage where surgical treatment is not possible. For patients with locally advanced disease without distant metastases, the treatment of choice is curatively intended radiotherapy. However, this treatment has considerable side effects and many patients relapse. To individualize the treatment strategy for these patients, it is essential to have as much prognostic information as possible. The aim of this thesis was to investigate the prognostic significance of histology and pre-treatment hematopoietic blood parameters.

Material and Methods: Data were collected retrospectively for NSCLC patients treated between 1990 and 2000 with curatively intended radiotherapy. The data were obtained by manually searching patient records from all radiation oncology departments in Sweden. The prognostic significance of histology, and pre-treatment levels of hemoglobin (Hgb), white blood cells (WBC) and platelets (Plt) were analyzed in relation to overall survival using univariate and multivariate statistical methods. These prognostic factors were further analyzed in a chemoradiation patient cohort and in a cohort of patients with recurrent NSCLC treated with palliative docetaxel, or the insulin-like growth factor 1 receptor (IGF-1R) modulator AXL1717.

Results: In the cohort of NSCLC patients treated between 1990 and 2000, squamous cell carcinoma (SCC) histology and pre-treatment anemia (Hgb <110 g/L), leukocytosis (WBC > 9.0 x109/L), and thrombocytosis (Plt >350 x109/L) were independent prognostic factors for shorter overall survival. However, in the chemoradiation cohort only thrombocytosis retained independent prognostic significance in a multivariate analysis. In the cohort of patients with recurrent disease treated with palliative systemic therapy, only leukocytosis was significantly associated with worse survival.

Conclusions: Routine pre-treatment hematopoietic blood parameters—together with other prognostic factors such as disease stage and performance status—can provide decision-making support when individualizing treatment of NSCLC. The prognostic role of histology is unclear and further research is warranted to determine its significance. 

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2017. 84 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1359
Keyword
NSCLC, prognostic factors, survival, histology, anemia, leukocytosis, thrombocytosis
National Category
Medical and Health Sciences
Research subject
Oncology
Identifiers
urn:nbn:se:uu:diva-327925 (URN)978-91-513-0043-6 (ISBN)
Public defence
2017-10-27, Rudbecksalen, Rudbecklaboratoriet, Dag Hammarskjölds väg 20, Uppsala, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2017-10-02 Created: 2017-08-22 Last updated: 2017-10-17

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Sandelin, MartinLamberg, Kristina LundströmJanson, ChristerBergqvist, Michael

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