Tissue Diagnosis and Staging for SBRT

2012 Lung Cancer Summit – Focus on Thoracic Surgery: Lung Cancer

Kazuhiro Yasufuku Director, Interventional Thoracic Surgery ProgramAssistant Professor, University of TorontoDivision of Thoracic Surgery, Toronto General Hospital

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Boston Marriott Copley Place, Boston, MA November 17th, 2012

Disclosure• Educational and research grants from Olympus Medical

Systems Corp.• Consultant for Olympus America Inc.• Consultant for Intuitive Surgical Inc.• Novadaq Corp.• Veran Medical Technologies

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Lung Cancer

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Tissue Diagnosis Staging

Treatment for Stage I NSCLC

• Anatomic resection is the gold standard• Local control ~90%• Overall Survival ~60-80%

• Medically inoperable stage I patients represent a big challenge• Up to 25% of all stage I patients• Untreated 5 year Overall Survival 5-10%

• Conventionally fractionated RT a poor second choice (~30 treatments over 6 weeks)

• 30-60% local control

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Survey of SBRT use in USA

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1600 American radiation oncologists Of 1373 contactable physicians, 551responses (40.1%) received

63.9% of physicians using SBRT of whom nearly half adopted it in 2008 or later

most common disease sites were lung (89.3%), spine (67.5%), and liver (54.5%) tumors

Cancer 2011;117:4566–72

Princess Margaret Hospital SBRT Criteria

• Ongoing phase II (2004 – present)• Pts deemed medically inoperable by a thoracic

surgeon• ECOG PS 0-3• NSCLC• T1 or T2 lesion, <5cm N0 M0 • PET –ve elsewhere• Previous thoracic RT acceptable provided no

significant overlap• No lower limit for lung function

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Surgery for Early Lung Cancer

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Lobectomy Limited Resection

CALGB 140503• Phase III Randomized Trial of Lobectomy vs Sublobar

Resection for Small (<2cm) Peripheral NSCLC

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Randomization

Surgery

Confirmation of NSCLC on PathN0 status on frozen section

(4R, 7, 10R on right)(5or6, 7, 10L on left)

Lobectomy Limited Resection

Options for high-risk pts with stage I NSCLC

• Sublobar resection (wedge or segmentectomy)• Surgery provides tumor histology• Lymph node sampling/dissection may provide identification of other

occult disease• Better pathological staging may inform decision of an adjuvant regimen• Better loco-regional control

• SBRT• May result in better QOL• Since better loco-regional control may not translate into better survival

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Diagnostic tools for peripheral lung nodules

• Clinical History• Old Films• Chest CT• FDG-PET

• CT guided TTNA• Bronchoscopy (EBUS, Navigational bronchoscopy, etc)• Surgery

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Is tissue Dx mandatory prior to SBRT?

• Stereotactic body radiotherapy (SBRT) SPN clinically diagnosed as lung cancer with no path confirmation: comparison with NSCLC

• Comparison of outcomes of Bx proven NSCLC (n=115) vs SPN clinically diagnosed as lung cancer (CDLC) (n=58) treated with SBRT (2005-2011)

• Treatment outcome of CDLC group was almost identical to that of NSCLC• SBRT can be legitimately applied to CDLC, provided that they are carefully diagnosed

by integrating various clinical findings

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Takeda et al, Lung Cancer. 2012 ;77(1):77-82

3y Local Control Regional-free Mets-free Cause-specific Survival

Overall Survival

NSCLC 80% 88% 70% 74% 54%

CDLC 87% 91% 74% 71% 57%

Mediastinal Staging• Clinical staging can markedly differ from pathologic staging

• 24% clinically overstaged• 20% clinically understaged• 190 cN2 patients: 38% pN0 / pN1, 6% pN3• 119 cN2 patients: 14% with pN2

• ATS/ERS/ESTS: obtain pathologic evaluation in patients thought to be a surgical candidate before thoracotomy

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Bülzebruck et al, Cancer 1992; 70: 1102Watanabe et al, Ann Thorac Surg 1991; 51: 253

Am J Respir Crit Care Med 1997; 156: 320Cerfolio et al Ann Thorac Surg 2005; 80: 1207

De Leyn et al, Eur J Cardiothorac Surg 2007; 32: 1

Surgical Staging (Cervical Mediastinoscopy)• Considered “Gold Standard”• Sensitivity 80%, Specificity 100% • FN rate 10%• Downside

• Invasive• Unable to reach posterior subcarinal LN, #5, #6• Non-operable candidates may have to undergo

surgical staging

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Endoscopic Staging (EBUS-TBNA)

• Access to all LN stations accessible by Med as well as N1 nodes

• A minimally invasive modality which can be performed under LA

• Performed in over 1800 centres

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Lung ca mediastinal staging• EBUS-TBNA Systematic Review and Meta-analysis

• 10 studies (n=817)• Sensitivity = 0.88 (95%CI, 0.79-0.94), Specificity = 1.00 (95%CI, 0.92-1.00)

• Results compare favorably with published results for PET and CT

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Adams et al. Thorax; 2009; 64: 757-62

Lung ca staging (EBUS vs PET)　 　 　 　 　 　 　 　

Sensitivity NPV

Study Year Number Criteria EBUS PET EBUS PET

Yasufuku et al 2006 102 Potentially operable pts 92.3 80 97.4 91.5

Hwangbo et al 2009 117 Potentially operable pts 90 70 96.7 85.2

Herth et al 2008 97 PET, CT negative 89 98.9

Bauwens et al 2008 106 PET positive 93 97

Rintoul et al 2009 109 PET positive 91 　 60 　

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• EBUS-TBNA compared to PET• Two studies in potentially operable patients show that EBUS is superior

to PET or CT for LN staging• EBUS spares invasive procedures• Tissue confirmation of PET-positive lesions is recommended to prove

that the lesions are truly malignant

EBUS-TBNA in non-operable pt with NSCLC pursuing radiotherapy as primary treatment

• 49 pts with NSCLC considered for Carbon Ion Radiotherapy (CIRT) with abnormal PET-CT accumulations in mediastinum and/or hilum

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Nakajima et al. J Thorac Oncol. 2010;5: 606–611

EBUS-TBNA in non-operable pt with NSCLC pursuing radiotherapy as primary treatment

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Nakajima et al. J Thorac Oncol. 2010;5: 606–611

43 pts had N0 diseaseDx accuracy 93.9%

81F, COPD, RUL SPN• Chest X-ray

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81F, COPD, RUL SPN• CT Mapping

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81F, COPD, RUL SPN• TBNA, TBBx, Brush, Wash – squamous cell ca

• EBUS-TBNA – N0 disease

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Summary• The need for SBRT is increasing in an aging population

• The success depends primarily on accurate staging prior to SBRT

• Accurate LN staging by EBUS-TBNA will allow opportunities for high-risk inoperable pts with NSCLC to undergo minimally invasive treatment

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Division of Thoracic SurgeryToronto General HospitalUniversity Health Network

Kazuhiro Yasufuku, MD, PhD, FCCPkazuhiro.yasufuku@uhn.ca

Thank you