Screening and consequences
Ground glass lesions: How to deal with them Masahiro Tsuboi, MD, Ph.D Associate-professor, School of Medicine, Yokohama City University Chief, Division of Thoracic Surgery, Respiratory Disease Center Chair of Comprehensive Cancer Center, Yokohama City University Medical Center Group Chair, Lung Cancer Surgical Study Group in Japan Clinical Oncology Group (JCOG) 3rd European Lung Cancer Conference 2012
Terminology: GGO •
• • •
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Incidentally found on CT screening, or on investigating other lesions Recognized on highresolution CT; Thinsection / 1-3mm Localized or focal lesion Mild (moderate) increase of CT density, which does not obscure lung structures
BAC
(bronchioloalveolar carcinoma)
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Prognosis of GGO tumors:
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Sakurai H et al. Am J Surg Pathol 2004; 28: 198-206
Is the GGO lesion growing up?
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Yes, Growing Up!
Feb 7/ 2001 3rd European Lung Cancer Conference 2012
July 7/ 2003 Courtesy by Asamura H.
Yes, Growing Up!
Jan 21/ 2001 3rd European Lung Cancer Conference 2012
Jan 15/ 2003 Courtesy by Asamura H.
Peripheral lung adenocarcinoma Hypothesis; Natural history Malignant potential; low
Pure GGO GGA
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high
GGO GGAwith consolidation
GGO GGAwith larger consolidation and retraction Courtesy by Asamura H.
Is the GGO lesion always growing up?
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Not always !!
Feb 5/ 1998 3rd European Lung Cancer Conference 2012
Aug 4/ 2006 Courtesy by Asamura H.
Thoracic CT Screening for Lung Cancer • The Japanese Society of CT Screening has published the management method for detected shadows. http://www.jscts.org/pdf/guideline/NoduleManagement-v2.pdf • Screening site; In the screening CT, shadows >= 5mm should be examined • Hospital site; 1M after screening, thin-section CT should be performed. The reconstructed slice thickness; 1-3mm • According to the TS-CT findings, shadows are classified into 3 groups; Pure GGO, Mixed GGO, Solid Nodule 3rd European Lung Cancer Conference 2012
GG lesion should be evaluated by thin-slice CT
Screening CT 3rd European Lung Cancer Conference 2012
Thin-slice CT
Pure GGO 100% ground glass opacity Bronchiolo-alveolar carcinoma (BAC, Noguchi’s A/B) AAH, Focal pneumonia Decrease
5-9mm
TS-CT after 3M
Not change Increase
10-14mm >=15mm
? ?
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Biopsy or VATS
Back to screening CT TS-CT every 3M-6M for 2Y
Management of Pure GGO • If the size of a GGO is ≥ 5 mm but < 10 mm, follow-up CTs at 3, 12, and 24 months are recommended. • If the GGO increases in size or in density during followup, a diagnostic work-up recommended. • If the size of the GGO is ≥ 10 mm but < 15 mm, followup CT or resection depend on the hospital’s criteria. • If the GGO increases in size or density during follow-up, a diagnostic work-up is recommended. • If the size of a GGO is ≥ 15 mm, a diagnostic work-up is recommended.
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Guideline of the Japanese Society of CT Screening
Mixed GGO Ground glass opacity with solid part Adenocarcinoma (Noguchi’s Type C) Focal pneumonia Decrease Mixed GGO
TS-CT after 3M
Not change Increase
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Back to screening CT Biopsy or VATS / Surgical intervention
Managements for mixed GGO • Mixed GGO is sometimes seen on CT scans showing evidence of pneumonia, and in such cases a 3-month follow-up examination is recommended to determine whether the mixed GGO is persistent or not. • If the size of a mixed GGO is < 10 mm, followup CT is an option instead of resection.
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Guideline of the Japanese Society of CT Screening
What is the best surgical mode for GG lesions with adenocarcinoma ?
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Key decisions for Surgical intervention • Actually, there is no definite criteria regarding the surgical intervention. The comprehensive decision will be needed.
Key points are as follows; • TS-CT findings – Soild vs. Mixed GGO/Part-solid vs. Pure GGO
• Size – 5mm vs. 10mm vs. 15mm or more
• The follow-up TS-CT findings – Increasing in size, especially solid part – Changing the shape of solid part • Indentation, notching, and so on 3rd European Lung Cancer Conference 2012
Courtesy by Suzuki K.
3rd European Lung Cancer Conference 2012
Courtesy by Suzuki K.
3rd European Lung Cancer Conference 2012
JCOG0201 data: Prospective cohort study for stage IA lung adenocarcinoma All patients underwent the lobectomy with mediastinal LN dissection. The definition of the pathological non-invasive adeno.: pN0, V(-), Ly(-) Primary endpoint; Specificity Suzuki K, J Thorac Oncol. 2011 ;6:751-6
Five year survival data for radiological noninvasive peripheral adenocarcinoma; presented at the 14th WCLC 3rd European Lung Cancer Conference 2012
Definition of radiological non-invasive lung adenocarcinoma by C/T ratio Maximum consolidation diameter (C)
consolidation ground glass opacity Maximum tumor diameter (T)
Radiological non-invasive lung adenocarcinoma 3rd European Lung Cancer Conference 2012
T=17
C=6
C/T ratio = 6/17 = 0.35
For cT1a
C/T ratio ≤ 0.5 C/T ratio ≤ 0.25* *Exploratory analysis
Survival of radiological non-invasive lung adenocarcinoma (cT1a with C/T ≤ 0.25; N = 35)
vs. radiological invasive cT1a (C/T > 0.25; N =254) Overall survival Proportion of survival
5yr-OS: 97% 92.4% Radiological non-invasive adeno invasive cT1a (cT1a, C/T ≤ 0.25) Radiological invasive cT1a (C/T > 0.25)
Relapse free survival 5yr-RFS: 97% 87.7% invasive cT1a
p = 0.058 p = 0.171 lung adenocarcinoma Radiological non-invasive One death due to unknown cause but no relapse Years after enrollment Years after enrollment during 7.5yr follow-up
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JCOG0201 sub-analysis Summary and clinical study cT1a with C/T ratio ≤ 25% on TSCT
Predicted non-invasive lung adenocarcinoma with a specificity of 98.7%* *exploratory analysis
5-yr OS: 97% No relapse (phase II) CuredOne-arm by limited resection? Wide wedge resection* study (JCOG0804/WJOG4507L) is ongoing *Segmentectomy without lymph node dissection allowed, Because of the tumor location. 3rd European Lung Cancer Conference 2012
JCOG0804/WJOG4507L; Phase II Trial of Limited Resection (Wide wedge resection) for Possible Early Adenocarcinomas (GGO – Part-solid GGO) ; (Singlearm study) • Subject ---- Non-solid GGO or part-solid GGO Solid part < 25% • Why one arm? ----- Very few event (cancer-related death) to perform comparative study • Intervention ----- Wide Wedge resection • Endpoint ------ Recurrence-free survival rate at any site • Sample size----330 patients • Trial has started since June in 2009 PI; Tsuboi M (JCOG) & Yoshino I (WJOG) 3rd European Lung Cancer Conference 2012
JCOG0802/WJOG4607L; Phase III Randomized Trial between Lobectomy and Limited Resection for Partsolid GGO – Solid T1a disease Non-inferiority design
Randomize
Peripheral carcinoma, 0.5; N = 424)
Proportion of survival
Overall survival
1
Relapse free survival
5yr-OS: 96.7%
5yr-RFS: 95.8%
88.8%
81.5% Outcome
Pre-op C/T p-stage Relapse Predetermined radiological adeno size non-invasive ratio invasive cT1a
invasive cT1a (med LN, lung) 1.5Y (death) p