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  • 1. Principles of Radiation Oncology in (advanced stage) NSCLC Stephan Bodis Kantonsspital Aarau
  • 2. The Tools for the Radiation Oncologist
    • Sophisticated treatment machines
    • (dual energies, multileaf-collimator, 3 paired laser beams for patient set-up, integrated CT, IMRT, stereotactic treatment)
    • Tumor volume definition : CT-MRI-PET fusion imaging, dedicated planing CT (lasersystem, large diameter)
    • Treatment planing : Standardized dose prescription to tumor (maximal) and to normal tissue (minimal), dose-volume histogram for tumor and each organ at risk
    • Treatment delivery : fix RT-field, moving RT-field (infield movement = IMRT), image guidance, respiration correction
    • Fractionated (daily) radiotherapy to a defined total dose
  • 3. Integration of Molecular Biology
    • Biology, Physics and Clinical Oncology
    • are the 3 pillars of Radiation Oncology
    • Defined biologic model systems available :
    • > 20 years experience in classic radiobiology
    • Molecular key targets for radiosensitization : (search) for novel RT-sensitizers
    • Stem cell research, human genome project, microarray technology : Implications for clinical radiation oncology
  • 4. Life inside a LINAC Prototype
  • 5. Ionizing Radiation: The physical tools
    • Photons: - High energy X-rays (MV for LINAC)
    • - Skin sparing effect
    • - Dose decrease 2-5% /cm tissue
    • Electrons: - Charged light particles
    • - No skin sparing effect, limited depth
    • - Steep dose decrease after a few cm‘s
    • Protons: - Charged heavy particles
    • - unique dose distribution (matterhorn like – Bragg Peak)
  • 6. Imaging for RT Planing (incl. CT-MRI/PET) Stage shift up to 30%
  • 7. Preclinical research: Metabolic image guided RT (mIGRT) with repeated FDG-PET during RT?
  • 8. Intensity modulated RT (IMRT) Voxel by voxel RT for complex volumes (high/low dose)
  • 9. IMRT: Maximal dose in the tumor (red), minimal dose in the adjacent normal tissue (blue)
  • 10. Therapeutic Index of RT: Reason for fractionated radiotherapy (daily low dose)
  • 11. There is nothing magic about fractionation Small fractions (daily dose) = high total dose Large fractions (daily dose) = low total dose Equivalent effect: 5 x 8 Gy = 30 x 2 Gy (Various math. models for „effective dose“ (NSD, E/alpha) E.g.: Large, radioresistant tumors with radiosensitive adjacent normal tissue need a small daily dose and high total dose
  • 12. Radiotherapy in NSCLC 75 % of lung cancer patients need radiotherapy Primary radical radiotherapy (Stage I – IIIB) Adjuvant, radical radiotherapy (Stage IIB – IIIA) Radical radiotherapy in local recurrence (Stage I – III) Palliative radiotherapy (Any stage)
  • 13. NSCLC Stage I/II The role of radical radiotherapy
    • - Radical surgery: Gold-standard
    • Radical RT: 10-30% less effective (historic)
    • - Is „state of the art“ radical RT more effective ?
    • (e.g. CT-PET, stereotactic RT, IMRT, image guided RT, breath-triggered RT)
    • Assumption: better therapeutic index with smaller RT- volume, higher total dose, higher daily dose)
  • 14. NSCLC Stage I/II The role of adjuvant radiotherapy
    • R0-resection: No proven benefit of adjuvant radiotherapy
    • R1/R2-resection and no 2nd surgery: Postoperative RT indicated (meta-analysis)
    • Small volume radiotherapy (involved field)
    • Dose 50 to > 60 Gy (if 2 Gy/day and 5x/week )
  • 15. NSCLC Stage IIIA The role of radiation oncology
    • Multimodality therapy (patients should be enrolled in international clinical trials)
    • Heterogeneous patient population: often lack of subststaging (IIIA1/2; IIIA3; IIIA4 and biology)
    • Optimal RT is still controversial: IIIA1/2 adj. CT+ (RT), IIIA3 (?), IIIA4 (CT-RT?)
    • Historical toxicity of RT has to be re-considered with current state of the art RT
  • 16. NSCLC Stage IIIA The role of radiation oncology
    • Phase III trials: RT + Surgery OR Surgery + RT vs. Surgery: same or worse OS, more toxicity (NCI; LCSG-Weisenberger 1985, Dautzenberg 1999)
    • Benefit for preop. RT for Pancoast Tumors ( Paulson 1995)
    • Postop. phase III trials (EORTC, Villejuif)
    • S w/wo CT + RT vs. S w/wo CT: lower OS with older trials using RT, same OS with recent trials; more toxity - „reason“ for lower OS in metanalyis; better LC with most recent studies )
  • 17. NSCLC Stage IIIB The role of radiation oncology
    • Multimodality therapy (patients should be enrolled in international clinical trials)
    • Optimal combination and sequence is controversial: Too many small studies
    • Survival benefit of additional chemotherapy modest: max 5% in 2 meta-analysis (2y, 5y OS) ( BMJ 1995 ; Auperin, Annals Onc. 2006)
  • 18. NSCLC Stage IIIB The role of radiation oncology
    • Phase III trials: CT-RT vs. RT (data from 5 rand. trials):
    • CT-RT (2y OS of 14-26%) vs. RT (2 y OS 6% to 17%)
    • (e.g. leChevalier, Dillmann)
    • Phase III trials: conc. CT-RT vs. sequential CT-RT
    • (3 rand. trials): concurrent CT better (modest gain in OS)
    • (e.g. Furuse, Curran)
    • median survial 17 months vs. 14 months, higher toxicity
    • (grade ¾ acute non-hem 40% vs. 0%!)
    • Metaanalysis: a) conc. CT-RT vs. RT: OS at 2y. (25 / 21%) b) conc. vs. seq. CT-RT: cc CT-RT better OS, more toxic deaths
    • (Auperin, Ann. Onc. 2006; Rowell Cochrane Library 2005
  • 19. NSCLC advance stage palliative/elective local therapy
    • Published RT-concepts: 10x3 or 5x4 Gy (3-4x/week)
    • Immediate vs. deferred local RT in low symptom patients: no difference (Falk, BMJ 2002)
    • Elective whole brain RT for stage III NSCLC in CR (PR/metabolic CR sufficient?)
  • 20. Pre-clinical research: Potential molecular targets for RT-sensitizers in lung cancer 1970 Radiobiology 2008