This document discusses controversies around treating oligometastatic non-small cell lung cancer (NSCLC) with systemic therapy versus surgery. It reviews evidence that local ablative therapies like surgery and stereotactic body radiotherapy (SBRT) may cure a minority of patients with oligometastatic NSCLC, especially those with few metastases, longer disease-free intervals, and complete resection of metastases. However, the evidence is limited and does not allow for clear recommendations. The decision to use local ablative therapies depends on a case-by-case clinical judgment weighing factors like patient health, number/location of metastases, and whether ablation can render all visible disease.

1. CONTROVERSIAS: CANCER DE PULMON
OLIGOMETASTÁSICO
(TRATAMIENTO SISTÉMICO Vs CIRUGÍA)
Mauricio Lema Medina MD – Clínica de oncología Astorga,
Clínica SOMA, Medellín
ACHO, Bogotá, 29.07.2016

2. Mauricio Lema Medina
Conflicts of interest
Consulting and honoraria as a speaker: Pfizer, MSD, Novartis, ROCHE,
Aztra-Zeneca, Boehringer-Ingelheim.
Harrisons’s, 19th Ed.

3. Page  3
@onconerd

4. CONTROVERSIAS: CANCER DE PULMON
OLIGOMETASTÁSICO
(TRATAMIENTO SISTÉMICO Vs CIRUGÍA)
Mauricio Lema Medina MD – Clínica de oncología Astorga,
Clínica SOMA, Medellín
ACHO, Bogotá, 29.07.2016
TERAPIA ABLATIVA

5. Oligometastases
“A clinical state of metastasis termed ‘oligometastases’ that refers to
restricted tumor metastatic capacity”
“The implication of this concept is that local cancer treatments are
curative in a proportion of patients with metastases.”
“Usually reserved to 1-3 discreet metastases (1-6 in some cohorts).
Ralph R. Weichselbaum and Samuel Hellman (1995)

Weichselbum RR, Nature Review Clin Oncol, 2011

6. Local ablative therapy for oligometastatic NSCLC
Feasibility: Can it be (safely) done? Crop: What is the yield?
Profit: Is it worth it?

7. Local ablative therapy for oligometastatic NSCLC
Feasibility: Can it be (safely) done?

8. Page  8
Colon cancer literature
Liver resection
Pulmonary resection

9. Weichselbum RR, Nature Review Clin Oncol, 2011
In colorectal cancer, liver metastasectomy for both, synchronous
and metachronous, resectable hepatic metastases is a standard
of care.

10. Long-term results of lung metastasectomy: prognostic
analyses based on 5206 cases
Pastorino U, J Thorac Cardiovasc Surg. 1997 Jan;113(1):37-49.
Study design Internationa Registry
Patient population Lung metastasectomy
Enrolled 5206
Complete surgical resection 4572 (88%)
Epithelial 2260
Actuarial 5-yr OS for complete resection 36%
Actuarial 10-yr OS for complete resection 26%
Actuaial 5-yr OS for incomplete resection 13%
5-yr OS for 0-11 months disease-free interval 33%
5-yr OS for disease-free interval longer than 36 months 45
5-yr OS for single lesion 43%
5-yr OS for more than 4 lesions 27%
These results confirm that lung metastasectomy is a safe and potentially curative
procedure.

11. Weichselbum RR, Nature Review Clin Oncol, 2011
Lung metastasectomy

12. Lung metastasectomy
Lung metastasectomy may cure some
patients with lung metastases,
especially those with single-lesion
metastatic disease, longer disease-free
interval, and in those in which
complete resection was achieved.
Weichselbum RR, Nature Review Clin Oncol, 2011

13. Laparoscopic transperitoneal lateral adrenalectomy
for malignant and potentially malignant adrenal
tumours
Pedziwiater, M, BMC Surg. 2015; 15: 101.
52 patients, 7 with NSLC

14. The American Society of Radiation
Oncology defines SBRT as external
beam radiotherapy used to deliver
a high dose of radiation very
precisely to an extracranial target
within the body, as a single dose or
a small number of fractions

15. Stereotactic body radiotherapy for oligometastases
The Lancet Oncology 2013 14, e28-e37DOI: (10.1016/S1470-2045(12)70510-7)
Copyright © 2013 Elsevier Ltd Terms and Conditions
Disease-free survival in patients with oligometastatic disease at 17–48 months' follow-up
Tree A, Lancet Oncol, 2013

16. Stereotactic body radiotherapy for oligometastases
The Lancet Oncology 2013 14, e28-e37DOI: (10.1016/S1470-2045(12)70510-7)
Copyright © 2013 Elsevier Ltd Terms and Conditions
Lymph-node or adrenal oligometastases
Tree A, Lancet Oncol, 2013

17. Stereotactic body radiotherapy for oligometastases
The Lancet Oncology 2013 14, e28-e37DOI: (10.1016/S1470-2045(12)70510-7)
Copyright © 2013 Elsevier Ltd Terms and Conditions
Mixed oligometastatic sites
Tree A, Lancet Oncol, 2013

18. Stereotactic body radiotherapy for oligometastases
The Lancet Oncology 2013 14, e28-e37DOI: (10.1016/S1470-2045(12)70510-7)
Copyright © 2013 Elsevier Ltd Terms and Conditions
Spinal oligometastases
Tree A, Lancet Oncol, 2013

19. Stereotactic body radiotherapy for oligometastases
Stereotactic body radiotherapy results in a high control rate of treated
metastases (∼80%)
About 20% of patients are progression free at 2–3 years after stereotactic body
radiotherapy
Toxicity is low
Stereotactic body radiotherapy should be considered in patients with isolated
metastases, especially if the disease-free interval is longer than 6 months
Randomised trials are needed to establish whether stereotactic body
radiotherapy improves progression free and/or overall survival
Patients most likely to benefit from stereotactic body radiotherapy have:
Long disease-free interval
Breast histology
One to three metastases
Small metastases
Higher radiation dose delivered (biologic effective dose >100 Gy)
The Lancet Oncology 2013 14, e28-e37DOI: (10.1016/S1470-2045(12)70510-7)
Copyright © 2013 Elsevier Ltd Terms and Conditions
Evidence-based practice for extracranial oligometastases
Tree A, Lancet Oncol, 2013

20. Stereotactic body radiotherapy (SBRT) for high-
risk central pulmonary metastases
Lischalk JW et al. Radiat Oncol. 2016; 11: 28.
Study design Cohort
Patient population “High-risk” central pulmonary metastases treated with
SBRT
Enrolled 20
NSCLC 7/20
Isolated intrathoracic disease 35%
Surgery and CT 60% and 75%
1-yr local control rate 70%
1-yr overall survival 75%
Bone (mOS, mo) 4.3 (* poor prognosis by MVA)
Five-fraction SBRT to a total dose of 35 or 40 Gy appears to be a safe and effective
management strategy for high-risk central pulmonary metastatic lesions, though
care should be taken to limit the maximum point dose to the mainstem bronchus.

21. CyberKnife robotic image-guided stereotactic
radiotherapy for oligometastic cancer : A
prospective evaluation of 95 patients/118 lesions.
Jereczek-Fossa BA. Strahlenther Onkol. 2013; 448-55.
Study design Cohort
Patient population Metastatic cancer with 1-5 metastases, amenable to
SBRT
Enrolled 95 patients /118 lesions
Evaluable lesions 87
3-yr In-field PFS 67.5%
3-yr PFS 18.4%
3-yr OS 31.2%
CBK-SRT is a feasible therapeutic approach for oligometastastic cancer patients that
provides long-term in-field tumor control with a low toxicity profile. Further
investigations should focus on dose escalation and optimization of the combination
with systemic therapies.

22. Local ablative therapy for oligometastatic NSCLC
Feasibility: Can it be (safely) done?

23. Local ablative therapy for oligometastatic NSCLC
Crop: What is the yield?
Lung cancer literature

24. Surgical Treatment of Extrapulmonary
Oligometastatic Non-small Cell Lung Cancer
Plones T, Indian J Surgery, 2012
Study design Retrospective chart review
Patient population NSCLC + resected synchronous metastases
Screened 56
Evaluable 50
Median OS (mo) 14.6
Soft-tissue metastases (mOS, mo) 23.4
Brain metastases (mOS, mo) 16.7
Adrenal gland (mOS, mo) 9.5
Bone (mOS, mo) 4.3 (* poor prognosis by MVA)

25. Surgical Treatment of Estrapulmonary
Oligometastatic Non-small Cell Lung Cancer
Plones T, Indian J Surgery, 2012
Study design Retrospective chart review
Patient population NSCLC + resected synchronous metastases
Screened 56
Evaluable 50
Median OS (mo) 14.6
Soft-tissue metastases (mOS, mo) 23.4
Brain metastases (mOS, mo) 16.7
Adrenal gland (mOS, mo) 9.5
Bone (mOS, mo) 4.3 (* poor prognosis by MVA)

26. Phase II Trial of Stereotactic Body Radiation Therapy Combined
With Erlotinib for Patients With Limited but Progressive
Metastatic Non–Small-Cell Lung Cancer
Conclusion Use of SBRT with erlotinib for unselected patients with stage IV NSCLC as a second- or
subsequent line therapy resulted in dramatic changes in patterns of failure, was well tolerated, and resulted
in high PFS and OS, substantially greater than historical values for patients who only received systemic
agents.
Iyegar, P, JCO, 2014
Study design Phase II Trial
Patient population NSCLC after 1st-Line CT failure, 1-6non-CNS metastases,
ALL amenable to SBRT
Intervention Erlotinib + SBRT
Endpoint 6-mo PFS of 20%, or more
Patients enrolled 24
Number of metastatic sites 52
# with more than 1 site 16/24
Median PFS (mo) 14.7
Median OS (mo) 20.4
In-field recurrence 3/47 (evaluable) lesions
Grade 4 toxicities (n) 0
EGFR mutation + 0/13

27. Phase II Trial of Stereotactic Body Radiation Therapy Combined
With Erlotinib for Patients With Limited but Progressive
Metastatic Non–Small-Cell Lung Cancer
Iyegar, P, JCO, 2014

28. Phase II Trial of Stereotactic Body Radiation Therapy Combined
With Erlotinib for Patients With Limited but Progressive
Metastatic Non–Small-Cell Lung Cancer
Iyegar, P, JCO, 2014

29. Metastasectomy in Lung Cancer
The evidence of ablative therapies for
metastases in lung cancer is limited,
restricted to (very) small cohorts.

30. Local ablative therapy for oligometastatic NSCLC
Crop: What is the yield?
Lung cancer literature

31. Local ablative therapy for oligometastatic NSCLC
Profit: Is it worth it?

32. Age 56
Histology Adenocarcinoma
EGFR/ALK EGFR+
Metastases Single lesion
Disease-free interval (PFS) 3-years
Resectability Surgical / SBRT
Comorbidities None-minimal
PS 0
Age 75
Histology Squamous
EGFR/ALK Unmutated
Metastases Single lesion
Disease-free interval 2-months
Resectability SBRT
Comorbidities COPD-oxygen-dependent
PS 1
Good patient, good disease
Could be better patient, good disease

33. Age 56
Histology Adenocarcinoma
EGFR/ALK Unmutated
Metastases 2-3 lesions
Disease-free interval 3-years
Resectability Surgical / SBRT
Comorbidities None-minimal
PS 0
Age 75
Histology Squamous
EGFR/ALK Unmutated
Metastases 2-3 lesions
Disease-free interval 2-months
Resectability SBRT
Comorbidities COPD-oxygen-dependent
PS 1
Good patient, so-so disease
Could be better patient, so-so disease

34. Age 56
Histology Adenocarcinoma
EGFR/ALK Unmutated
Metastases More than 3 lesions
Disease-free interval 3-years
Resectability Surgical / SBRT
Comorbidities None-minimal
PS 0
Age 75
Histology Squamous
EGFR/ALK Unmutated
Metastases More than 3 lesions
Disease-free interval 2-months
Resectability SBRT
Comorbidities COPD-oxygen-dependent
PS 1
Good patient, bad disease
Could be better patient, bad disease

35. Age 56
Histology Adenocarcinoma
EGFR/ALK EGFR+
Metastases Single lesion
Disease-free interval 3-years
Resectability Surgical / SBRT
Comorbidities None-minimal
PS 0
Good patient, good disease
Surgery
SBRT + Erlotinib
Anti EGFR

36. Age 75
Histology Squamous
EGFR/ALK Unmutated
Metastases Single lesion
Disease-free interval 2-months
Resectability SBRT
Comorbidities COPD-oxygen-dependent
PS 1
Could be better patient, good disease
SBRT + Erlotinib

37. Good patient, so-so disease
Could be better patient, so-so disease
56, adenocarcinoma, unmutated, 2-3 lesions, DFI interval, No
comorbidities, PS 0
75, squamous, unmutated, 2-3 lesions, 2 moth DFI interval,
Severe COPD, PS 1
Surgery
SBRT
CT: 1-yr OS

38. Good patient, bad disease
Could be better patient, bad disease
56, adenocarcinoma, unmutated, more than 3 lesions, DFI
interval, No comorbidities, PS 0
75, squamous, unmutated, more than 3 lesions, 2 moth DFI
interval, Severe COPD, PS 1
CT: 1-yr OS
Sandler A, et al. N Engl J Med. 2006;355:2542-2550.
Scagliotti et al., J Clin Oncol 2008; 26:3543-3551

39. Local ablative therapy for oligometastatic NSCLC
Profit: Is it worth it?

40. Local ablative therapy for oligometastatic NSCLC
Feasibility: Can it be (safely) done? Crop: What is the yield?
Profit: Is it worth it?

41. Ablative therapies for
metastatic NSCLC may
help a minority of
patients.
Poor evidence precludes
clear-cut recommendations
It boils down to clinical judgement, availability
and patient preference in those few patients
with 1-3 oligometastases that can be rendered
R0 with surgery of SBRT.