Used at IASLC Webinar on Sept 25, 2015.

1. Management of Oligometastatic
Lung Cancer
Yong Chan Ahn, MD/PhD
Dept. of Radiation Oncology
Samsung Medical Center, Sungkyunkwan University School of Medicine

2. • Oligometastasis
• Oligometastasis in NSCLC
• SMC Experience of SBRT for
Oligometastasis to Lung
• Local Treatment for Oligometastasis
• Clinical Studies/Review
• Survey
• Ongoing Trials
• Take Home Messages

3. Oligometastasis

4. Nat Rev Clin Oncol, 2011

5. Oligometastasis
• Theory 1st proposed by Hellman and
Weichselbaum in 1995.
• Along spectrum of locally confined to widely
metastatic cancer, there exists intermediate
“oligometastatic state” where metastases are
limited in number and location.
Paradigm Stages
Old Early vs Metastatic
New Early ~ Oligometastatic ~ Systemic
Nat Rev Clin Oncol, 2011

6. Oligometastasis
• Eradication of “oligometastases” with local
ablative Tx could be curative in select patients.
• Cure is achieved following curative surgical
resection in:
– Liver metastases from colon cancer
– Lung metastases from various sites
– Adrenal metastases from lung cancer
Nat Rev Clin Oncol, 2011

7. Nat Rev Clin Oncol, 2011
Single & DFI  36 months
Multiple or DFI < 36 months
Multiple and DFI < 36 months
Lung meta

8. Oligometastasis
• Oligometastases have long been recognized as
potentially curable, but were considered rare
exceptions to cancer metastasis paradigm.
• Oligometastatic state, however, is becoming
more frequently identified with more
sensitive methods.
• Clinicians will be able to limit ablative local
Tx to only those with true oligometastases.
Nat Rev Clin Oncol, 2011

10. Oligometastasis in NSCLC

11. Lung Cancer, 2013

12. Lung Cancer, 2013

13. Lung Cancer, 2013

14. Lung Cancer, 2013

15. Lung Cancer, 2013
Conclusion
• Patient selection is key determinant:
– Definitive Tx of primary tumor
– Long disease-free interval
– Lack of intra-thoracic nodal metastasis
• These should be utilized to guide clinical
decision making and design of future studies.

17. SMC Experience of SBRT for
Oligometastasis to Lung

18. Acta Oncol, 2012

19. SBRT for Lung Metastasis
• SBRT to 57 patients, 67 metastatic lesions
• Sep. 2001~Nov. 2010
• Lung toxicity:
– Grade 2 in 4 patients (6.0%)
– Grade 5 in 1
Acta Oncol, 2012

20. Acta Oncol, 2012

21. Response at 1 month:
- CR in 17 (25%)
- PR in 40 (60%)
- SD in 10 (15%)
Local progression in 3 (5%)
94.5% at 3 years
Acta Oncol, 2012

22. Acta Oncol, 2012

23. 59.7% 56.2%
at 2 years at 5 years
Acta Oncol, 2012

24. Presence of extrathoracic disease was
the only significant factor (p=0.049)
on multivariate analysis.
64.0% vs 38.9%
at 3 years
66.1% vs 0%
at 3 years 71.1% vs 51.1%
at 3 years
Acta Oncol, 2012

25. Conclusion
• 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.
Acta Oncol, 2012

26. Local Treatment for
Oligometastasis

27. Clinical Lung Cancer, 2014

28. Clinical Lung Cancer, 2014

29. Clinical Lung Cancer, 2014

30. Clinical Lung Cancer, 2014

31. Clinical Practice Points
• Select oligometastatic NSCLC Pts might benefit
from aggressive Tx to all disease sites:
– Pts with controlled primary lung cancer are
most likely to experience long-term survival.
– Pts with metachronous meta experienced the
longest survivals.
– Pts with synchronous meta and N1-2 disease
had the poorest survivals.
Clinical Lung Cancer, 2014

32. Clinical Studies/Review

33. • Radiation therapy for oligometastatic non-small cell lung cancer.
Salama JK, Schild SE. Cancer Metastasis Rev. 2015;34(2):183-93.
• Stereotactic body radiation therapy for oligometastases to the lung: a
phase 2 study. Nuyttens JJ et al. Int J Radiat Oncol Biol Phys. 2015;91(2):337-43.
• Stereotactic body radiotherapy for oligometastatic disease. Hanna GG et
al. Clin Oncol (R Coll Radiol). 2015;27(5):290-7.
• Predictive factors for local control in primary and metastatic lung
tumours after four to five fraction stereotactic ablative body
radiotherapy: a single institution's comprehensive experience. Thibault
I et al. Clin Oncol (R Coll Radiol). 2014;26(11):713-9.
• Outcomes and toxicities of stereotactic body radiation therapy for
non-spine bone oligometastases. Owen D et al. Pract Radiat Oncol.
2014;4(2):e143-9.
• Management of pulmonary oligometastases by stereotactic body
radiotherapy. Gamsiz H et al. Tumori. 2014;100(2):179-83.
• Radical treatment of synchronous oligometastatic non-small cell
lung carcinoma (NSCLC): patient outcomes and prognostic factors.
Griffioen GH et al. Lung Cancer. 2013;82(1):95-102.

34. • Reviews:
• SABR for aggressive local therapy of metastatic cancer: A new
paradigm for metastatic non-small cell lung cancer. Westover KD et al.
Lung Cancer. 2015;89(2):87-93.
• Stereotactic ablative radiotherapy for pulmonary oligometastases
and oligometastatic lung cancer. Shultz DB et al. J Thorac Oncol.
2014;9(10):1426-33.

35. Survey

36. Am J Clin Oncol, 2015

37. • 25-question survey
• 1,007 respondents from 43
countries
• SBRT users:
• Length of practice
• # patients treated
• Organs treated
• Primary reason
• Dose schedules
• Future intentions
• SBRT non-users:
• Reason for not using SBRT
• Future intentions
83%
>1/3
Am J Clin Oncol, 2015

38. Reasons for adopting SBRT to treat OM
84%
• Commonly treated organs: lung (90%), liver
(75%), and spine (70%).
• Most would offer second SBRT to new OM.
• 99% planned to continue and 66% planned to
increase SBRT use.
Various dose schedules!
Am J Clin Oncol, 2015

39. Reasons for planning to adopt SBRT
• The most common reasons for not using SBRT were lack of
clinical efficacy (48%) and/or lack of necessary image guidance
equipment (34%).  need for prospective clinical trials!
• Of those not using SBRT, 59% plan to start soon.
Am J Clin Oncol, 2015

40. Ongoing Trials

41. Metachronous meta ≤ 5 sites
NCT01446744
Canada/Netherlands

42. DFI  3 months
≤ 3 mets in any single organ
≤ 5 total mets
NCT01446744
Canada/NetherlandsMetachronous meta ≤ 5 sites

43. Arm 1
Lung 8 Gy/1 Fx; 20 Gy/5 Fx’s; 30 Gy/10 Fx’s
Bone 8 Gy/1 Fx; 20 Gy/5 Fx’s; 30 Gy/10 Fx’s
Brain 20 Gy/5 Fx’s; 30 Gy/10 Fx’s
Liver 20 Gy/5 Fx’s
NCT01446744
Canada/NetherlandsMetachronous meta ≤ 5 sites

44. NCT01725165
MDACCSynchronous meta ≤ 3 sites

45. NCT02045446
UTSWMCSynchronous meta ≤ 6 sites

46. Take Home Messages
• Proportion of patients with OM has been increasing.
• Management of OM has become challenging.
• Patients selection is very important:
– Controlled primary
– Long DFI (metachronous >> synchronous)
– Initially low cN stages
• Consider high dose aggressive local RT (SBRT,
IMRT, IGRT, Particle…) to favorable subgroups.

47. Staging Project
16th WCLC at Denver
Paradigm has changed, is changing, and will change!

51. Don’t give up easily!
Thank your for your attention!