1. Approaching early stage disease
Surgery vs SBRT vs RFA
Ramesh Rengan MD PhD
Chief, Thoracic Service
Assistant Director of Clinical Operations
Department of Radiation Oncology
November 16, 2012

2. DISCLOSURES
Speaker Honoraria
Philips Healthcare

3. Introduction: The Scope of the Problem
213,380 patients are diagnosed yearly with lung cancer in the US with approximately 160,390 deaths

4. What is “Early Stage” Disease?IA
T1N0M0 IB
T2aN0M0
IIA
T2bN0M0
T1N1M0
T2aN1M0
IIB
T2bN1M0
T3N0M0
Technically resectable disease without evidence of mediastinal involvement

5. Prognosis 5yr OS Stage IA 75% Stage IB 55% Stage IIA 50% Stage IIB 40%
Small Cell Ca: Limited Stage 15-25% 5yr OS, Extended stage 3% 5yr OS
5yr OS
Stage IA
75%
Stage IB
55%
Stage IIA
50%
Stage IIB
40%
Stage IIIA
10-35%
Stage IIIB
5-8%
Stage IV
<5%

6. Medical Operability 2007 ACCP Guidelines
Colice GL. Physiologic Evaluation of the Patient With Lung Cancer Being Considered for Resectional Surgery*: ACCP Evidenced-Based Clinical Practice Guidelines (2nd Edition).
The preoperative physiologic assessment should begin with a cardiovascular evaluation and spirometry to measure the FEV1. If diffuse parenchymal lung disease is evident on radiographic studies or if there is dyspnea on exertion that is clinically out of proportion to the FEV1, the diffusing capacity of the lung for carbon monoxide (Dlco) should also be measured. In patients with either an FEV1 or Dlco < 80% predicted, the likely postoperative pulmonary reserve should be estimated by either the perfusion scan method for pneumonectomy or the anatomic method, based on counting the number of segments to be removed, for lobectomy. An estimated postoperative FEV1 or Dlco < 40% predicted indicates an increased risk for perioperative complications, including death, from a standard lung cancer resection (lobectomy or greater removal of lung tissue). Cardiopulmonary exercise testing (CPET) to measure maximal oxygen consumption (V̇o2max) should be performed to further define the perioperative risk of surgery; a V̇o2max of < 15 mL/kg/min indicates an increased risk of perioperative complications. Alternative types of exercise testing, such as stair climbing, the shuttle walk, and the 6-min walk, should be considered if CPET is not available. Although often not performed in a standardized manner, patients who cannot climb one flight of stairs are expected to have a V̇o2max of < 10 mL/kg/min. Data on the shuttle walk and 6-min walk are limited, but patients who cannot complete 25 shuttles on two occasions will likely have a V̇o2max of < 10 mL/kg/min. Desaturation during an exercise test has not clearly been associated with an increased risk for perioperative complications. Lung volume reduction surgery (LVRS) improves survival in selected patients with severe emphysema. Accumulating experience suggests that patients with extremely poor lung function who are deemed inoperable by conventional criteria might tolerate combined LVRS and curative-intent resection of lung cancer with an acceptable mortality rate and good postoperative outcomes. Combining LVRS and lung cancer resection should be considered in patients with a cancer in an area of upper lobe emphysema, an FEV1 of > 20% predicted, and a Dlco of > 20% predicted.
2007 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

7. Treatment for Early Stage Operable Disease
NSLCL, if resectable, should be treated surgically.
Contradindications to surger:
Spread of tumor beyond the hemithorax incl SCV node involvement, malig pleural effusion, recurrent laryn nerve paralysis, medical inoperability, patient refusal, presence of med LN mets
However, some patients with limited mediastinal LN mets remain surgical candidates
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%

8. 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

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

10. Treatment for Early Stage Operable Disease: Is there a lumpectomy for the lung?
LCSG showed trend towards increased likelihood of death with limited resection
LCSG showed three-fold increase in local failure with wedge resection vs. lobectomy

11. Medically Inoperable Early Stage: Role of RT
Cor pulmonale
Severe coronary artery disease
Renal failure
Poor pulmonary function
DLCO <50%
FEV1/FVC ratio < 50 – 75% of predicted
Impaired nutritional status

12. Medically Inoperable Early Stage: Role of RT
Study
Author 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
Rosenzweig 32
70.2
33%
39%
43%

13. Medically Inoperable Early Stage: SBRT
Nyman et al Lung Cancer 2006

14. 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

15. Dose Fractionation: Implications for Tumor Control
100 2 4
Survival
Dose (Gy)
10-1
10-2
single
fraction
multiple 2 Gy
fractions

16. Early Stage Disease: Stereotactic Body Radiation Therapy
Pretreatment
6-weeks Post-treatment

17. 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
79% (2-yr)
Uematsu 50
94%
66% (3-yr)
Koto
78%
72% (3-yr)
Fakiris
88%
43% (3-yr)

18. Dose Fractionation: Implications for Tumor Control
100
multiple 2 Gy
fractions
Survival
10-1
single
fraction
10-2 2 4
Dose (Gy)

19. Medically Inoperable Early Stage: Toxicity of SBRT
Corradetti et al NEJM 2012
JCO 2006
RTOG 0813 is currently accruing
Would not treat centrally located tumors with SBRT off-protocol
Standard of care for peripheral medically inoperable NSCLC
p = 0.003

20. SBRT: Emerging toxicity data

21. Treatment of Early Stage Inoperable Disease: RFA

22. Treatment of Early Stage Inoperable Disease: RFA
Multicenter prospective trial of 106 patients with lung tumors
33 patients with NSCLC
48% 2-year survival
73% 2-year CSS
10% pneumothorax rate
Median hospital stay 3 days
Lancioni Lancet Oncol 2008

23. RFA: Emerging toxicity data

24. Early Stage NSCLC: Conclusions
Lobectomy + MLNS or MLND
With adjuvant chemotherapy
+/- RT in high risk cases
NCCN Guidelines, 2012