Precise delivery Accurate positioning Cone beam verification
TABLE WITH SURVIVAL-SEE PAPER ON PATTERNS OF RECURRENCE Despite patient selection Low rates of acute toxicity Low rates of pneumonitis Main side effects Fatigue Chest pain Rib fracture Lack of long term data-late toxicity?
In the interest of time I could not detail all trial that have established the role of CT and RT in locally advanced NSCLC The findings from these trials are summarised on this slide NSCLCCG BMJ 1995-The meta-analysis did not provide an answer to the question of the optimal radiotherapy or chemotherapy regimen. HR 0.87-reduction in risk of death of 13% Auperin metaA conc vs seq Toxicity Increased risk of grades 3 et 4 œsophagitis with conc CTRT HR = 4.9 (CI 95 %: 3.1-7.8 ; p < 0.0001) No increase in risk of acute pneumonitis HR = 0,69 (CI 95 % : 0.42-1.12; p = 0.13) Long term toxicity?
(A) Survival curves and (B) progression-free survival curves. The numbers of person-years and of deaths observed each year during the first 4 years and after are given. RT, radiation therapy; HR, hazard ratio; conc, concurrent; CT, chemotherapy; seq, sequential.
Show CT William Parkinson
Poumon atelectatique Volume large (>15 cm cranio-caudale)
Conc>seq but not for all patients Short overall treatment time- reduces risk of repopulation and better for patient convenience
Terminated early on the basis of futility after an interim analysis febrile neutropenia (10.9%) and pneumonitis (9.6%); 28.8% of patients were hospitalized during docetaxel ( v 8.1% in observation arm), and 5.5% died as a result of docetaxel.
In this unselected population, gefitinib did not improve survival. Decreased survival was a result of tumor progression and not gefitinib toxicity.
Ongoing Dutch trial
below the age of 75 (patients above 75 have not been included in clinical trials), Currently, there is no consensus on the optimal chemotherapy regimen when combined with radiotherapy. There is clinical trial data to support the combination of cisplatin based chemotherapy. A number of regimens have been reported showing acceptable outcome and toxicity profiles. (EL: Refs 264-267 268-271) The choice of chemotherapy regimen with concurrent thoracic radiotherapy should be considered based on individual patient characteristics, toxicity profile and local experience
CTRT alone 23 months survival Hoosier study 26 months Kuira study
Addition of targeted agents With RT or CTRT? Consolidation treatment? Dissapointing in Swog
Update Cochrane Review 2005 (10 studies) adding the Trodella study in stage I NSCLC 2-year Survival: 58% 2-year Survival: 52% ‘ Thoracic RT is deleterious for pN0 and pN1 pts due to an excess of treatment-related toxicity in the PORT group’ ‘ Role of PORT in N2 tumours less clear and may warrant further research with newer techniques’
Stratification factors : Center, Administration of CT (no CT vs Post-op CT vs pre-op CT alone), Histology (SCC vs other), Extent of lymph node involvement (0 vs 1 vs2+), Histology (SCC vs others), use of pre- treatment PET-scan (yes/no)
NSCLC R adiotherapy 10 th ESO ESMO masterclass 6 th April 2011 Dr Corinne Faivre-Finn Manchester Radiotherapy Related Research Group Manchester Cancer Research Centre The Christie, Manchester, UK
Induction CT CALGB 39801 Vokes et al. J Clin Oncol 2007 ns 36% 32% Oesophagitis (grade 3-4) ns 10% 4% Pneumonitis (grade 3-4) 0.3 14 months 12 months Median survival 31% 29% 2 year survival 170 161 N p CT CTRT CTRT
Consolidation CT HOG 01-24 Docetaxel 75 mg/m²/3 w x 3 cycles Stage IIIAN2/IIIB 203 pts Cisplatin 50mg/m² D1,8,29,36 Etoposide 50mg/m² D1-5 and D29-33 RT 59.4 Gy/6w Observation Hanna et al. J Clin Oncol 2008 R < 0.001 8.1% 28.8% Hospitalisations 23.2 21.2 Median survival (months) 0.88 0.058 < 0.001 0.003 p 26.1% 27.1% 3 yr survival 1.4% 9.6% Radiation pneumonitis 0% 5.5% Deaths attributed to RT 0% 11% Infections Observation n=74 Docetaxel n=73 After randomisation
Kelly et al. JCO 2008; 26: 2450-56 Consolidation CT SWOG 0023 1% of patients died as a consequence of pneumonitis R Docetaxel 75mg/m 2 / 3 w (3 cycles) Cisplatin 50mg/m 2 D1, 8, 29, 36 Etoposide 50 mg/m 2 D1-5, D29-33 RT 61 Gy Gefitinib 500 mg/d 250 mg/d Placebo 59% 46% 2 yr survival 0 2 (2%) Toxic deaths after randomisation 42 (78%) 61 (86%) Cancer deaths 54 71 Deaths 35 months 23 months Median survival Placebo n = 125 Gefitinib n = 118
RTOG 0214 PCI in stage III NSCLC PCI 30 Gy 2 Gy/fraction NSCLC Stage IIIA/IIIB No PD after radical treatment Observation Target-1058 patients 356 patients included 340 patients evaluable Gore et al. J Clin Oncol 2009 Abstract 7506 p = 0.86 24.8 25.8 Median (months) PCI Control 1 year survival 75.6% 76.9% Brain mets 7.7% 18% p = 0.004 R