Radiation Therapy in the Management of Lung Cancer
- 1. Radiation Therapy in the Management of Lung Cancer Bradford Hoppe MD, MPH James E. Lockwood, Jr Chair of Proton Therapy 11/5/2016
- 2. Disclosure • Employed by University of Florida
- 3. Content • Describe modern RT technology • Utilization of RT in treatment of lung cancer – NSCLC • Stage I • Stage II-III
- 4. Therapeutic Ratio RT dose needed for cure
- 5. Therapeutic Ratio Without exceeding the RT dose causing major toxicity
- 6. RT BASICS
- 7. Gross Tumor Volume (GTV)
- 8. Clinical Target Volume (CTV) “Microscopic disease” ~5 – 8 mm
- 9. Planned Target Volume (PTV) Set-up uncertainty Daily set-up errors Respiratory motion ~1.5 – 2 cm
- 10. Reducing Target Uncertainty IGRT Image Guided Radiotherapy
- 11. IGRT
- 12. IGRT- Image Guided Radiotherapy • Daily imaging to confirm accuracy of set up • Smaller margins for set up uncertainties
- 15. IGRT • IGRT is critical for: – Delivering high doses of RT – Stereotactic Ablative RT (SABR, previously called SBRT) • Increases patient treatment time
- 16. 3D Conformal RT
- 18. Highly Conformal XRT • Decrease the volume of normal tissue getting high dose RT (more conformal in high dose region) BUT… • Increase the volume getting low dose RT, which wouldn’t have been irradiated before
- 19. Highly Conformal XRT Type True Beam(Varian) Cyberknife Vero Infinity (Elekta) Novalis Tomotherapy • Intensity Modulated Radiotherapy (IMRT) • Non-coplanar 3DCRT (9+ beams) • Arc Therapy
- 20. Protons
- 21. Proton Therapy
- 22. Different Types of RT 3D IMRT PT
- 23. Modern RT Integration for Stage I NSCLC SABR/SBRT
- 24. Stage I Medically Inoperable - NSCLC Modality LC 5yr OS 5yr DFS Gd 3 pneumonitis 3DCRT (6-7 wks) 50-60% 20% 43% 0.2% Grutters et al Radiotherapy and Oncology 2010
- 25. Stage I Medically Inoperable - NSCLC Modality LC 5yr OS 5yr DFS Gd 3 pneumonitis 3DCRT (6-7 wks) 50-60% 20% 43% 0.2% Protons/Carbon 80-100% 41% 60% 1% Grutters et al Radiotherapy and Oncology 2010
- 26. Stereotactic Ablative RT • Utilizing highly conformal RT, IGRT, and controlling tumor motion • Deliver 7 weeks of RT in just 1 week • Daily dose of 6 – 20 Gy per fraction instead of the usual 2 Gy per fraction • Equivalent of 80-100 Gy at 2 Gy/fraction
- 27. Stage I Medically Inoperable - NSCLC Modality LC 5yr OS 5yr DFS Gd 3 pneumonitis 3DCRT (6-7 wks) 50-60% 20% 43% 0.2% Protons/Carbon 80-100% 41% 60% 1% SBRT 80-95% 42% 63% 2% Grutters et al Radiotherapy and Oncology 2010
- 28. SBRT versus Surgery? • Multiple Observational Studies using large databases (SEER, NCDB) • Shirvani et al IJROBP 2012, Yu et al Cancer 2015, Paul et al BMJ 2016, Ezer et al JTO 2015 – Hard to adjust for inherent differences – Toxicity lower for SBRT patients – No difference in survival between wedge resection and SBRT – Overall survival benefit for lobectomy patients over SBRT • Readjusted by propensity score analysis demonstrates similar OS
- 29. RCT: SBRT versus Surgery? • Chang et al Lancet Oncology 2015 – SBRT vs lobectomy with LN dissection • Combined STARS & ROSEL studies – 58 patients enrolled (31 SBRT, 27 surgery) – Median Follow up 40.2 months – Grade 3+ toxicity: SBRT (10%) versus lobectomy (48%)
- 30. Stage I NSCLC • Lobectomy is SOC for medically fit patients with long life expectancies • SBRT/SABR is the SOC for medically inoperable patients or those that refuse surgery • SBRT/SABR is reasonable option for patients with high surgical risk (can not tolerate lobectomy, age ≥75, poor lung function)
- 31. RT utilization for Stage III Lung Cancer
- 32. 40 Years of RTOG Studies Study “Winning Arm” RTOG 7301 60 Gy in 6 weeks with ENI RTOG 8808 Cisplatin/vinblastine then 60 Gy (sequential) RTOG 9410 Cisplatin/vinblastine + 60 Gy (concurrent) RTOG 0617 Carboplatin/paclitaxel + 60 Gy (concurrent) no ENI
- 33. Is Higher Dose Better? • RTOG 0617 (Bradley ASTRO 2011) R A N D O M I Z E Paclitaxel Carboplatin 60 Gy Paclitaxel Carboplatin 74 Gy R A N D O M I Z E Cetuximab No Cetuximab
- 34. RTOG 0617 Bradley et al Lancet Oncology 2015 Feb;16(2):187-99 Median OS 29 months 20 months Concurrent chemotherapy and 60 Gy vs 74 Gy RT in Stage 3 NSCLC Multivariate Analysis Grade 3 Esophagitis Heart dose (Cardiac V5)
- 35. 40 Years of RTOG Studies • Local control still remains a problem (~50%) • GI toxicities (Gd 3+: 10-20%) • Pulmonary toxicities (Gd 3+: 10-15%) • Bone marrow toxicities (Gd 3+: 43-52%) Study “Winning Arm” RTOG 7301 60 Gy in 6 weeks with ENI RTOG 8808 Cisplatin/vinblastine then 60 Gy (sequential) RTOG 9410 Cisplatin/vinblastine + 60 Gy (concurrent) RTOG 0617 Carboplatin/paclitaxel + 60 Gy (concurrent) no ENI
- 36. RTOG 1308
- 37. Addition of Surgery to Stage III Tx? • Three studies investigating the addition of surgery to chemoradiation in stage III NSCLC – Intergroup 0139- cis/etop +45 Gy then (16 Gy vs surgery) – EORTC- Chemo x 3 then ( 60 Gy vs surgery +/- PORT) – ESPATUE- Cis/Tax cis/vin +45 Gy (20Gy vs surgery)
- 38. Addition of Surgery to Stage III Tx? • Three studies investigating the addition of surgery to chemoradiation in stage III NSCLC – Intergroup 0139- cis/etop +45 Gy then (16 Gy vs surgery) – EORTC- Chemo x 3 then ( 60 Gy vs surgery +/- PORT) – ESPATUE- Cis/Tax cis/vin +45 Gy (20Gy vs surgery) Lobectomy Pneumonectomy
- 39. Modern RT for Stage III NSCL • Dose escalation with concurrent chemotherapy – Improve local control leading to increase overall survival – Increases dose to critical structures and toxicities • IGRT and highly conformal RT should allow for safer dose escalation – Lower dose to critical structures translating to less toxicity
- 40. Stage III NSCLC Recommendations • Surgically/Medically Inoperable – Concurrent chemotherapy and radiation • 60 – 70 Gy • Enrollment in NRG 1308 – IMRT versus Proton therapy • Operable, single station N2 – Induction chemotherapy then Lobectomy +/- PORT – Induction chemoradiation then Lobectomy – If unable to do just lobectomy, then avoid surgery and pursue RT option