This document discusses modern radiation therapy techniques for lung cancer, focusing on non-small cell lung cancer (NSCLC). It summarizes that stereotactic ablative radiotherapy (SABR) is now the standard of care for inoperable stage I NSCLC, providing local control and survival rates comparable or superior to surgery with less toxicity. For stage III NSCLC, concurrent chemotherapy and radiation improves survival compared to sequential treatment, though local control remains challenging and toxicities can be significant. Ongoing studies are exploring dose escalation using intensity-modulated radiation therapy (IMRT) and proton therapy to improve outcomes while reducing normal tissue damage.

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

13. Daily Conebeam CT

14. Daily Conebeam CT

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

17. Highly 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