1509 webinar oligometa lung

Management of Oligometastatic

Lung Cancer

Yong Chan Ahn, MD/PhD Dept. of Radiation Oncology

Samsung Medical Center, Sungkyunkwan University School of Medicine

• 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

Oligometastasis

Nat Rev Clin Oncol, 2011

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

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

Nat Rev Clin Oncol, 2011

Single & DFI 36 months

Multiple or DFI < 36 months

Multiple and DFI < 36 months

Lung meta

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

Oligometastasis in NSCLC

Lung Cancer, 2013

Lung Cancer, 2013

Lung Cancer, 2013

Lung Cancer, 2013

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.

SMC Experience of SBRT for

Oligometastasis to Lung

Acta Oncol, 2012

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

Acta Oncol, 2012

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

Acta Oncol, 2012

59.7% 56.2%

at 2 years at 5 years

Acta Oncol, 2012

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

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

Local Treatment for

Oligometastasis

Clinical Lung Cancer, 2014

Clinical Lung Cancer, 2014

Clinical Lung Cancer, 2014

Clinical Lung Cancer, 2014

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

Clinical Studies/Review

• 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.

• 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.

Survey

Am J Clin Oncol, 2015

• 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

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

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

Ongoing Trials

Metachronous meta ≤ 5 sites NCT01446744

Canada/Netherlands

DFI 3 months

≤ 3 mets in any single organ

≤ 5 total mets

NCT01446744

Canada/Netherlands Metachronous meta ≤ 5 sites

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/Netherlands Metachronous meta ≤ 5 sites

NCT01725165

MDACC Synchronous meta ≤ 3 sites

NCT02045446

UTSWMC Synchronous meta ≤ 6 sites

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.

Staging Project

16th WCLC at Denver

Paradigm has changed, is changing, and will change!

Don’t give up easily!

Thank your for your attention!