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Novel RT techniques for treating lung cancer 1403

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Novel RT techques for treating lung cancer

Novel RT techques for treating lung cancer


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  • 1. Novel RT Techniques For Lung Cancer Treatment Yong Chan Ahn, MD, PhD Dept. of Radiation Oncology Samsung Medical Center Sungkyunkwan University School of Medicine
  • 2. Fundamental of RT • To deliver high dose to tumor • To limit dose to normal tissues
  • 3. From Classic to Conformal • • • • Better local control Enhanced quality of life and reduced morbidity Improve accuracy of every step! Patient-specific: – Individualized – Customized – Adaptive
  • 4. RT Process Steps in RT that can be represented by links in a chain. Tx accuracy will be limited by the weakest link in the chain
  • 5. Preparation for Radiation Therapy • Acquisition of CT (MR, PET-CT) • Contouring
  • 6. Novel Technology in RT Image guided RT (IGRT) Stereotactic Ablative RT (SABR, SBRT) Intensity Modulated RT (IMRT) Particle Beam Therapy (Proton; Carbon)
  • 7. Image guided RT (IGRT) Stereotactic Ablative RT (SABR, SBRT) Intensity Modulated RT (IMRT) Particle Beam Therapy (Proton; Carbon)
  • 8. Image Guided RT (IGRT) If you can’t see it, you can’t hit it. If you can’t hit it, you can’t cure it.
  • 9. To identify and correct problems arising from inter- and intrafractional variations in patient setup and anatomy
  • 10. Electronic Portal Image (EPI)
  • 11. KV Cone-beam CT (CBCT)
  • 12. In-Room CT
  • 13. MV CT (Tomotherapy)
  • 14. Fluoroscopy-based IGRT
  • 15. CyberKnife (Synchrony)
  • 16. Image guided RT (IGRT) Stereotactic Ablative RT (SABR, SBRT) Intensity Modulated RT (IMRT) Particle Beam Therapy (Proton; Carbon)
  • 17. Ablative RT (by conventional technique)
  • 18. Stereotactic Ablative (Body) RT
  • 19. SABR
  • 20. Conventional RT SABR 1.8~3.0 Gy 10~20 Gy 10~30 fractions 1~5 fractions GTV, CTV, (ITV), PTV GTV, CTV, ITV, PTV (GTV  CTV) cm range mm range Need for mechanical accuracy Low to medium Very high Need for respiratory motion control Moderate High Radiobiology Well understood Still poorly understood Interaction with systemic therapy Currently active Will become active Dose/fraction Fraction number Target delineation Margins
  • 21. Rationale of SABR in Stage I NSCLC • RT is better than doing nothing. • (+) dose-response relationship in local control. • The smaller the tumor, the higher the local control and survival by RT. • LN metastasis incidence is very low. • Shorter RT is better than protracted RT in survival.
  • 22. Importance of tumor size Importance of RT duration
  • 23. SABR Indications at SMC • • • • cT1-2,N0 Single metastasis or recurrence ≤ 5 cm in size (preferably ≤ 3 cm) Location (peripheral > central, upper > lower)
  • 24. Respiratory Training (Respiratory Signal Analysis Program)
  • 25. Patients’ Characteristics I (116 Patients: ’01/Feb~’10/Nov) Characteristics # Pt (%) Age Median 69 (39~88) years Sex Male 98 (84.5%) Female 18 (15.5%) Tumor nature Primary 38 (32.8%) Metastatic 78 (67.2%) Lung 32 (41.0 %) GI Track 24 (30.8 %) Head & Neck 9 (11.5 %) Others 13 (16.7 %)
  • 26. Patients’ Characteristics II (116 Patients: ’01/Feb~’10/Nov) Characteristics # Pt (%) Tumor size ≤ 2.0 cm 58 (50.0%) > 2.0 cm 58 (50.0%) RT dose 50 Gy/5 Fx’s (’01/Jun~’02/May) 8 ( 6.9%) 60 Gy/5 Fx’s (’02/June~’09/Dec) 72 (62.1%) 60 Gy/4 Fx’s (’10/Jan~’10/Dec) 36 (31.0%)
  • 27. Survival Probability 66.4% 53.8% p = 0.036 Months
  • 28. Summary • SBRT to lung cancer at SMC: – High local control (90%) – Favorable 5 year survival (primary/metastatic – 66.4%/53.8%) – Very low risk of complication (Grade 2/3 – 3.4%/1.7%) – Highly effective and curative modality to patients who are unfit for surgery.
  • 29. Acta Oncologica, 2012
  • 30. Summary • SBRT for single or oligo-metastasis seems quite effective and safe. • Tumor size, disease-free interval, and presence of extrathoracic disease are prognosticators for survival.
  • 31. Image guided RT (IGRT) Stereotactic Ablative RT (SABR, SBRT) Intensity Modulated RT (IMRT) Particle Beam Therapy (Proton; Carbon)
  • 32. Multi-leaf Collimator
  • 33. LINAC-based IMRT • Static MLC (“step-and-shoot”) • Dynamic MLC (“sliding window”) • Volumetric modulated arc (VMAT)
  • 34. Tomotherapy
  • 35. Example Case: Sq, cT2N3
  • 36. SMC Experience of IMRT • May 2010~November 2012 • 77 patients with N3 (+) stage IIIB NSCLC • Definitive CCRT by 3DCRT or LINAC- IMRT – 66 Gy/33 Fx’s to CTV – 3DCRT (48); IMRT (29) – Weekly pacli-/docetaxel + cis-/carboplatin (67) – 3 weekly pemetrexed/etoposide + cisplatin (10)
  • 37. Characteristics Gender Male IMRT (29) p-value 62 (44-72) yrs Median age (range) 3D-CRT (48) 59 (40-80) yrs 0.7441 35 (72.9%) 18 (62.1%) 0.3904 Female 11 (37.9%) 34 (70.8%) Smoking history 13 (27.1%) 17 (58.6%) Yes 0.2722 No Median FEV1 (range) 2.49 (1.17-3.90) L 2.50 (1.46-3.71) L ECOG performance 0 10 (20.8%) 0.7909 6 (20.7%) 0.9880 1 Primary site lobe 38 (79.2%) 23 (79.3%) Upper/middle 39 (81.3%) 13 (44.8%) 0.0009 Lower 16 (55.2%) Adenoca 31 (64.6%) 22 (75.9%) Sq cell ca Histology 9 (18.7%) 15 (31.2%) 3 (10.3%) 2 (4.2%) 4 (13.8%) 3.8 (1.3-12.2) cm 3.7 (1.0-9.2) cm 34 (70.8%) 23 (79.3%) Others Median tumor size (range) cT stage cT1-2 0.0533 0.7852 0.4111 cT3-4 Involved N3 region 14 (29.2%) 6 (20.7%) Contralateral mediastinum 29 (60.4%) 7 (24.1%) 0.0020 Supraclavicular 26 (54.2%) 24 (82.8%) 0.0108
  • 38. Dosimetric Parameters Variable 3D-CRT (48) IMRT (29) p-value CTV Median 279.3 (89-1,543) cm3 357.5 (89-763) cm3 0.7064 <300 cm3 28 (59.3%) 10 (34.5%) ≥300 cm3 20 (41.7%) 19 (65.5%) 0.0425 Dose to lung Mean 18.4 (9.3-28.0) Gy 19.6 (14.6-25.2) Gy 0.0306 V5 57.2 (29.8-72.9)% 65.1 (48.4-90.0) % 0.0002 V10 48.6 (24.5-63.5)% 51.8 (41.8-62.9) % 0.1072 V15 40.6 (18.1-54.5)% 42.3 (34.7-53.6) % 0.0519 V20 32.8 (14.3-50.0)% 35.6 (28.2-45.9) % 0.0612
  • 39. Clinical Outcomes 3D-CRT (48) IMRT (29) Total (77) Disease progression 24 (50.0%) Failure pattern LR 4 (8.3%) Distant Both 17 (35.4%) 3 (6.3%) 21 (72.4%) 45 (58.4%) 2 (6.9%) 6 (7.8%) 15 (51.7%) 32 (41.6%) 4 (13.8%) 7 (9.1%) 9.1 months 6.0 months 8.2 months Grade ≤2 41 (85.4%) 21 (72.4%) 62 (80.5%) Grade 3 7 (14.6%) 8 (27.6%) 15 (19.5%) Grade 1 32 (66.7%) 22 (75.9%) 54 (70.1%) Grade ≥2 16 (33.3%) Median time to progression Esophagitis Pneumonitis 7 (24.1%) 23 (29.9%)
  • 40. Summary • Limitations: – Small number of patients – Heterogeneous patient population – Retrospective nature • IMRT group: – More extensive disease and larger CTV – More frequent early distant metastasis • Careful case selection and intensified systemic Tx maybe considered
  • 41. Image guided RT (IGRT) Stereotactic Ablative RT (SABR, SBRT) Intensity Modulated RT (IMRT) Particle Beam Therapy (Proton)
  • 42. Why Proton Beam Therapy? • Bragg peak (1946, Wilson et al. first proposed PBT) • RBE=1.1
  • 43. History of PBT • 1950: 1st clinical application to suppress pituitary function and to reduce metastases from breast ca • 1950’s: Uppsala Group (Sweden) pioneered proton RT for cancer • Early 1960’s: Harvard Cyclotron Group (US) developed most current techniques
  • 44. 50
  • 45. PBT for Stage I NSCLC
  • 46. PBT for Stage III NSCLC • Need for dose escalation: – RTOG trials (X-rays): 8311 (+) and 0617 (-) • Few dosimetric comparison studies: – Advantage of PBT over X-rays seems more significant in stage III than stage I • Recent on-going trials of high-dose PBT with concurrent chemotherapy – Safe and effective
  • 47. Dose-volume Histogram (DVH) 100 Proton PTV 90 Proton Spinal Cord Normalized volume (%) 80 Proton Both Lungs 70 IMRT PTV IMRT Spinal Cord 60 IMRT Both Lungs 50 3DCRT PTV 40 3DCRT Spinal Cord 30 3DCRT Both Lungs Tomo PTV 20 Tomo Spinal Cord 10 Tomo Both Lungs 0 0 10 20 30 40 50 Dose (Gy) 60 70 80
  • 48. Normal Tissue DVH
  • 49. Normalized volume (%) CTV DVH
  • 50. CTV DVH
  • 51. PBT for III NSCLC • Need for dose escalation: – RTOG trials (X-rays): 8311 (+) and 0617 (-) • Few dosimetric comparison studies: – Advantage of PBT over X-rays seems more significant in stage III than stage I • Recent on-going trials of high-dose PBT with concurrent chemotherapy – Safe and effective
  • 52. Summary • PBT can give excellent dose distribution using less ports (Bragg peak) • PBT maybe more widely applicable than SABR even with pulmonary comorbidity and difficult tumor location in stage I • PBT may save more normal tissue in stage III than in stage I • Pencil beam scanning seems promising • Dose-escalated PBT with concurrent CTx may be safe and effective
  • 53. Proton Therapy Center Samsung Medical Center
  • 54. Multidisciplinary approach
  • 55. Importance of Target Delineation • Target contouring errors generate systematic errors which no level of image guidance will eliminate. • Target delineation accuracy cannot be overemphasized!

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