Optimization of radiotherapy in locally advanced lung cancer

摘要: Lung cancer is the leading cause of death worldwide as well in Sweden, where incidence around 3500 new cases per year. About 50% have distant metastases by time diagnosis and are treated with palliative intent. Early stages tumour confined to lung without regional spread constitute 20% may be candidates for surgery aiming cure. The remaining 30% represent an intermediate group patients metastasized lymph nodes thorax making them inappropriate surgery. They do not however this group, often referred locally advanced or stage III cancer, suitable oncologic treatment radiotherapy chemotherapy curative It established that a combination these two modalities should used, but since long term survival still poor 5-year 5-25%, there many questions on how further improve strategies. This thesis aims evaluate different approaches optimize patient analysing one retrospective study, prospective trials also looking into clinical genetic prognostic factors studying Health Related Quality Life (HRQL) during intense combined therapy. In first study we analyse protocol limited Small Cell Cancer (SCLC), was initiated 1997, consisting concurrent chemoradiotherapy, delivered 1.5 Gy, twice day, five days week total dose 60 45 Gy depending function, performance status burden. Complete responders good partial were given prophylactic cranial irradiation 30 15 fractions. results show it clearly feasible give population. Median 20.8 months 3and 25% 16%. There no difference between groups even if negative selection low group. second evaluates RAKET trial, three-armed randomized phase II trial which compares three ways intensifying local Non (NSCLC); either hyperfractionated accelerated weekly daily basis. median 17.8 31% 24% respectively. strategies equal regard efficacy toxicity. third outcome Satellite one-armed addressing same population i.e. NSCLC III, receiving induction followed antibody cetuximab. had previously showed head neck been studied together thoracic irradiation. comparable data previous chemotherapy. 17 3-year 29%. Furthermore found less toxicity regimen compared what usually described chemoradiation. We observed immense impact regarding basic factor (IIIA IIIB), (0, 1) pre diagnostic weight loss. fourth paper prevalence important alterations NSCLC, namely EGFR mutations, FISH positivity KRAS mutations investigate their possible disease. figures expected unselected Caucasians being present 7.5%, 19.7% 28.8% positive (paper III) trend towards inferior most importantly mutated independent marker multivariate analysis. Finally fifth HRQL high done using EORTC QLQ C30 LC14 questionnaires therapy at follow-up. experience gradual decline nearly all functional scales. Treatment related side effects return base-line majority persistent worsening dyspnoea fatigue. Patients IIIA and/or 0 seem tolerate better HRQL, cetuximab influences than ISBN 978-91-628-8372-0