Trattamenti ipofrazionati ed ipofrazionati-accelerati: effetti sul controllo tumorale e sulla tossicità (inclusa consequential late-toxicity)
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24° CORSO RESIDENZIALE DI AGGIORNAMENTO con il patrocinio dell’Associazione Italiana di Radioterapia Oncologica (AIRO) Moderna Radioterapia, Nuove Tecnologie e Ipofrazionamento della Dose 17 marzo 2014: Trattamenti ipofrazionati ed ipofrazionati-accelerati: effetti sul controllo tumorale e sulla tossicità (inclusa consequential late-toxicity)
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Trattamenti ipofrazionati ed ipofrazionati-accelerati: effetti sul controllo tumorale e sulla tossicità (inclusa consequential late-toxicity)
- 1. Trattamenti ipofrazionati ed ipofrazionati-accelerati: effetti sul controllo tumorale e sulla tossicità (inclusa consequential late-toxicity) A.G. Morganti – A.R. Alitto
- 2. Preambles
- 3. • Damage’s DNA Repair Systems • Time required: 6-8 hours • These systems become“saturated” • Cell die when it attempted mitosis Preambles
- 4. Slow proliferation tissue Time for damage repair Sublethal damage reparation “small” fraction: healing “big”fraction: not healing FRACTIONATION DEPENDENCE “ shoulder “ Late cellular death LATE CLINICAL EFFECTS LATE RESPONDERS
- 5. Fast proliferation tissue no time for damage reparation No sublethal damage healing “small” fraction: not healing “big” fraction: not healing FRACTIONATION INDIPENDET no “shoulder“ Early cellular death ACUTE CLINICAL EFFECTS repopulation OVERALL TREATMENT TIME ACUTE RESPONDERS
- 6. L.G. Marcu / Cancer Treatment Reviews 36 (2010) 606–614 Fractionation:Rationale
- 7. Dose/fraction Dose/week Conventional 180-200 900-1000 Hypofractionation (ex: 400 cGy/fr, alter. day) > = Hyperfractionation (ex: 100 cGy/fr x 2/die) < = Accelerated (ex: 200 cGy/fr x 2/die) = > Split course (ex: 200 cGy/fr, with split) = < Fractionation
- 8. Dose/fraction Dose/week Conventional 180-200 900-1000 Hypof.-accel. (ex: 300 cGy x 10 fr) > > Hyperf.-accelerato (ex: 150 cGy x 2/die) < > CHART (ex: 150 cGy x 3/die, without pause in week end) < >>> Fractionation
- 9. L.G. Marcu / Cancer Treatment Reviews 36 (2010) 606–614 Hypofractionation:Rationale
- 10. Basic Clinical Radiobiology-Joiner & van der Kogel- 4° edition Hypofractionation:Rationale
- 11. E: effect D, T --> ARD, T --> AR D, F --> LRD, F --> LR
- 12. L.G. Marcu / Cancer Treatment Reviews 36 (2010) 606–614 E.C. Ko et al. / Cancer/Radiothérapie 15 (2011) 221–229 Accelerated-Hypofractionation • Tumor cell population heterogenous • Different effect on cancer stem cells • Effect on stromal cells (including endothelium) • Immunological cascades • Prostate, Breast… • TOXICITY
- 13. Toxicity
- 14. Toxicity Basic Clinical Radiobiology-Joiner & van der Kogel- 4° edition
- 15. Basic Clinical Radiobiology-Joiner & van der Kogel- 4° edition Early Toxicity Vascular effects, inflammation
- 16. Early Toxicity Basic Clinical Radiobiology-Joiner & van der Kogel- 4° edition
- 17. Basic Clinical Radiobiology-Joiner & van der Kogel- 4° edition Early Toxicity
- 18. MacrophagesMacrophages Basic Clinical Radiobiology-Joiner & van der Kogel- 4° edition Late Toxicity Parenchyma Endothelium Fibroblasts Parenchyma Endothelium Fibroblasts Induction Progression Manifestation
- 19. Late Toxicity Basic Clinical Radiobiology-Joiner & van der Kogel- 4° edition
- 20. Late Toxicity Basic Clinical Radiobiology-Joiner & van der Kogel- 4° edition
- 21. Consequential Late Toxicity Basic Clinical Radiobiology-Joiner & van der Kogel- 4° edition LATE RADIATION EFFECTS, which are influenced by the extent (severity, duration) of the corresponding early effect in the same organ/tissue.
- 22. Consequential Late Toxicity Stone HB et al/ The Lancet Oncology (2003); 4: 529-36
- 23. Consequential Late Toxicity W. Dorr, J.H. Hendry / Radiotherapy and Oncology 61 (2001) 223–231 CLECLE
- 24. W. Dorr, J.H. Hendry / Radiotherapy and Oncology 61 (2001) 223–231
- 25. W. Dorr, J.H. Hendry / Radiotherapy and Oncology 61 (2001) 223–231 Consequential Late Toxicity
- 26. Factors Stone HB et al/ The Lancet Oncology (2003); 4: 529-36
- 27. Factors Stone HB et al/ The Lancet Oncology (2003); 4: 529-36
- 28. Factors Stone HB et al/ The Lancet Oncology (2003); 4: 529-36
- 29. Factors Basic Clinical Radiobiology-Joiner & van der Kogel- 4° edition
- 30. • EARLY EFFECTS • Turnover tissue-proliferating cells • Latent time: ≠dose;≈tissue biology • Maximum severity: ≈dose • Time to restoration: ≈dose • LATE EFFECTS • All tissues • Complex pathogenesis (parenchyma, fibroblast, endothelium, macrophages) • Irreversible • Dose-dependent latency • Dose-dependent progressione rate incidence (tolerance) ≈follow up • CONSEQUENTIAL LATE EFFECTS • Radiobiological characteristics of early effects (fractionation, overall treatment time) • Correlate with markers for early effects • Modulated by treatment of early effects • LATE EFFECT General considerations Basic Clinical Radiobiology-Joiner & van der Kogel- 4° edition
- 31. • Long term follow-up for Hypof • Linear Quadratic Models • Others factors (molecular, biological, tissue effects) • Clinical applications of hypofractionation • Technological innovation General considerations Seminars in Radiation Oncology- Issue 18-2008