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Prognostic Factors in Non-Small Cell Lung Cancer (NSCLC)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
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. , p. 84
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1359
Keyword [en]
NSCLC, prognostic factors, survival, histology, anemia, leukocytosis, thrombocytosis
National Category
Medical and Health Sciences
Research subject
Oncology
Identifiers
URN: urn:nbn:se:uu:diva-327925ISBN: 978-91-513-0043-6 (print)OAI: oai:DiVA.org:uu-327925DiVA, id: diva2:1135309
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
List of papers
1. Swedish Lung Cancer Radiation Study Group: Predictive value of histology for radiotherapy response in patients with non-small cell lung cancer
Open this publication in new window or tab >>Swedish Lung Cancer Radiation Study Group: Predictive value of histology for radiotherapy response in patients with non-small cell lung cancer
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2011 (English)In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 47, no 16, p. 2415-2421Article in journal (Refereed) Published
Abstract [en]

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.

Keyword
Lung cancer, Non-small cell lung cancer, Histology, Predictive value, Adenocarcinoma, Squamous cell carcinoma
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-166077 (URN)10.1016/j.ejca.2011.06.011 (DOI)000297452000007 ()
Available from: 2012-01-12 Created: 2012-01-10 Last updated: 2017-12-08Bibliographically approved
2. 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
Open this publication in new window or tab >>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
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2012 (English)In: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 29, no 5, p. 3176-3182Article 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.

Keyword
Non-small cell lung cancer, Prognosis, Biomarker, Anaemia, Thrombocytosis, Leukocytosis
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-189133 (URN)10.1007/s12032-012-0247-3 (DOI)000311513800027 ()
Available from: 2013-01-04 Created: 2012-12-25 Last updated: 2017-12-06Bibliographically approved
3. The Prognostic Value of Pre-treatment Thrombocytosis in Two Cohorts of Patients with Non-small Cell Lung Cancer Treated with Curatively Intended Chemoradiotherapy
Open this publication in new window or tab >>The Prognostic Value of Pre-treatment Thrombocytosis in Two Cohorts of Patients with Non-small Cell Lung Cancer Treated with Curatively Intended Chemoradiotherapy
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(English)In: Neoplasma (Bratislava), ISSN 0028-2685, E-ISSN 1338-4317Article in journal (Refereed) Accepted
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-327924 (URN)
Available from: 2017-08-12 Created: 2017-08-12 Last updated: 2017-08-22
4. The Prognostic Value of Pre-Treatment Leukocytosis in Patients with Previously Treated, Stage IIIB/IV Non-Small Cell Lung Cancer Treated with the IGF-1R Pathway Modulator AXL1717 or Docetaxel; a Retrospective Analysis of a Phase II Trial
Open this publication in new window or tab >>The Prognostic Value of Pre-Treatment Leukocytosis in Patients with Previously Treated, Stage IIIB/IV Non-Small Cell Lung Cancer Treated with the IGF-1R Pathway Modulator AXL1717 or Docetaxel; a Retrospective Analysis of a Phase II Trial
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2017 (English)In: Asian Pacific Journal of Cancer Prevention, ISSN 1513-7368, Vol. 18, no 6, p. 1555-1560Article in journal (Refereed) Published
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-327923 (URN)
Available from: 2017-08-12 Created: 2017-08-12 Last updated: 2017-08-22

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