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Prognosis, Prediction and Risk Assessment in the Prevention and Treatment of Non-Small Cell Lung Cancer
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology. (Professor Christer Janson)ORCID iD: 0000-0002-0370-8819
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 [en]
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: urn:nbn:se:uu:diva-261554ISBN: 978-91-554-9364-6 (print)OAI: oai:DiVA.org:uu-261554DiVA: diva2:859347
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
List of papers
1. The Value of Induction Chemotherapy for Survival in Patients with Non-small Cell Lung Cancer Treated with Radiotherapy
Open this publication in new window or tab >>The Value of Induction Chemotherapy for Survival in Patients with Non-small Cell Lung Cancer Treated with Radiotherapy
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2012 (English)In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 32, no 4, 1339-1346 p.Article in journal (Refereed) Published
Abstract [en]

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.

Keyword
NSCLC, lung cancer, radiotherapy, predictive value, age
National Category
Respiratory Medicine and Allergy Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-173639 (URN)000302492600028 ()
Available from: 2012-05-09 Created: 2012-05-02 Last updated: 2017-12-07Bibliographically 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, 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.

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. Patients with Non-small Cell Lung Cancer Analyzed for EGFR: Adherence to Guidelines, Prevalence and Outcome
Open this publication in new window or tab >>Patients with Non-small Cell Lung Cancer Analyzed for EGFR: Adherence to Guidelines, Prevalence and Outcome
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2015 (English)In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 35, no 7, 3979-3985 p.Article in journal (Refereed) Published
Abstract [en]

Background: Epidermal growth factor receptor (EGFR) analysis is the first molecular test introduced in the routine care of patients with non-small cell lung cancer (NSCLC). In the present study, we describe the prevalence of EGFR mutations and the adherence to testing and treatment guidelines in a population-based Swedish NSCLC cohort. Materials and Methods: Patients with NSCLC analyzed for EGFR mutations were identified and their characteristics and survival data were retrieved. We compared the study cohort to a matched lung cancer population. Results: The EGFR mutation frequency was 10%. Mutations were enriched in women and in adenocarcinoma cases. Out of patients with advanced-stage NSCLC with non-squamous histology, only 49% were referred for EGFR analysis. Out of the patients with EGFR mutation and advanced disease, only 38% received EGFR-tyrosine kinase inhibitor (TKI) in first-line therapy. Conclusion: The EGFR-mutated NSCLC population studied is similar to other Western populations. Surprisingly, a large proportion of patients were not referred for EGFR analysis. Out of the patients with EGFR mutation, fewer than 40% received EGFR-TKI as first-line treatment. Our results highlight the need for follow-up of treatment and diagnostic algorithms in routine healthcare.

Keyword
Non-small cell lung cancer, EGFR, mutation, outcome, population, prevalence
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-259096 (URN)000357116400029 ()26124345 (PubMedID)
Available from: 2015-07-28 Created: 2015-07-27 Last updated: 2017-12-04Bibliographically approved
4. Factors Associated With Risk Alteration Of Lung Cancer Development In Chronic Obstructive Pulmonary Disease Patients
Open this publication in new window or tab >>Factors Associated With Risk Alteration Of Lung Cancer Development In Chronic Obstructive Pulmonary Disease Patients
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(English)Manuscript (preprint) (Other academic)
Keyword
COPD, lung cancer, risk, epidemiology, comorbidity, ICS
National Category
Respiratory Medicine and Allergy
Research subject
Lung Medicine; Oncology
Identifiers
urn:nbn:se:uu:diva-261552 (URN)
Available from: 2015-09-01 Created: 2015-09-01 Last updated: 2015-11-10

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