Approaching early stage diseaseSurgery vs SBRT vs RFA

November 16, 2012

Ramesh Rengan MD PhDChief, Thoracic ServiceAssistant Director of Clinical OperationsDepartment of Radiation Oncology

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DISCLOSURES Speaker Honoraria

• Philips Healthcare

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Introduction: The Scope of the Problem

213,380 patients are diagnosed yearly with lung cancer in the US with approximately 160,390 deaths

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What is “Early Stage” Disease?

Technically resectable disease without evidence of mediastinal involvement

IA T1N0M0

IB T2aN0M0

IIAT2bN0M0T1N1M0

T2aN1M0

IIB T2bN1M0T3N0M0

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Prognosis

5yr OSStage IA 75%

Stage IB 55%

Stage IIA 50%

Stage IIB 40%

Stage IIIA 10-35%

Stage IIIB 5-8%

Stage IV <5%

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Medical Operability2007 ACCP Guidelines Age alone is not a reason to deny resection. Operative mortality for a lobectomy:

~2% for age < 60, ~8% for age > 70

General targets:• FEV1 > 1.5L• FEV1 > 80% pred• DLCO > 60-80% pred

Danger signs: • FEV1 or DLCO < 40% predicted• FEV1/FVC < 50%• PCO2 > 50mmHg• Cor pulmonale• VO2 < 15cc/kg/min• Or, ability to walk 1 flight of stairs

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Treatment for Early Stage Operable Disease

Lobectomy + Mediastinal LND or LNS Remains current standard of care

• ACOSOG Z0030

With appropriate pt selection, periop mortality rates are low• Pneumonectomy 5%• Lobectomy 1-3%• Smaller Resections < 1%

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Treatment for Early Stage Operable Disease: ACOSOG Z0030

1111 patients enrolled; 1023 randomized• Extensive MLNS followed by observation vs MLND

No difference in overall survival

Darling et al J Thoracic and CV Surgery, 2011

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Treatment for Early Stage Operable Disease: Is there a lumpectomy for the lung?

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LCSG showed trend towards increased likelihood of death with limited resection

LCSG showed three-fold increase in local failure with wedge resection vs. lobectomy

Treatment for Early Stage Operable Disease: Is there a lumpectomy for the lung?

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Cor pulmonale Severe coronary artery

disease Renal failure Poor pulmonary function

• DLCO <50%• FEV1/FVC ratio < 50 –

75% of predicted Impaired nutritional status

Medically Inoperable Early Stage: Role of RT

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StudyAuthor

n Dose (Gy)

5-yr survival

5-yr CSS

5-yr local

Dosoretz 152 60-69 10%

Krol 108 60-65 15% 31% 25%

Kaskowitz 53 63 6% 13% 0%

Sibley 141 55-70 13%

Rosenzweig 32 70.2 33% 39% 43%

Medically Inoperable Early Stage: Role of RT

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Medically Inoperable Early Stage: SBRT

Nyman et al Lung Cancer 2006

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Fractionation Options Conventionally fractionated radiotherapy

- small daily doses- go to very high cumulative doses

Ablative radiotherapy- very high daily doses (8-20 Gy)- overwhelm tumor repair- causes “late” effects that may be intolerable

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Dose Fractionation: Implications for Tumor Control

100

2 4 6 8

Sur

viva

l

Dose (Gy)

10-1

10-2

singlefraction

multiple 2 Gy fractions

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Early Stage Disease: Stereotactic Body Radiation Therapy

Pretreatment 6-weeks Post-treatment

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Medically Inoperable Early Stage: SBRT

Author # of Patients

Local Control

Overall Survival

Onishi et al. 245 85% 56% (3-yr)Timmerman 70 98% 55% (2-yr)Nyman 45 80% 71% (2-yr)Baumann 57 92% 60% (3-yr)Nagata 31 98% 79% (2-yr)Uematsu 50 94% 66% (3-yr)Koto 31 78% 72% (3-yr)Fakiris 70 88% 43% (3-yr)

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Dose Fractionation: Implications for Tumor Control

100

2 4 6 8

Sur

viva

l

Dose (Gy)

10-1

10-2

singlefraction

multiple 2 Gy fractions

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p = 0.003

Medically Inoperable Early Stage: Toxicity of SBRT

Corradetti et al NEJM 2012JCO 2006

RTOG 0813 is currently accruing Would not treat centrally located tumors with SBRT off-protocol Standard of care for peripheral medically inoperable NSCLC

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SBRT: Emerging toxicity data

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Treatment of Early Stage Inoperable Disease: RFA

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Treatment of Early Stage Inoperable Disease: RFA

Multicenter prospective trial of 106 patients with 183 lung tumors

33 patients with NSCLC 48% 2-year survival

• 73% 2-year CSS 10% pneumothorax rate Median hospital stay 3

daysLancioni Lancet Oncol 2008

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RFA: Emerging toxicity data

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Early Stage NSCLC: Conclusions

NCCN Guidelines, 2012

Lobectomy + MLNS or MLNDWith adjuvant chemotherapy+/- RT in high risk cases

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