Ground glass lesions: How to deal with them

Transcription

1 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)

2 Terminology: GGO 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

3 BAC (bronchioloalveolar carcinoma)

4 Prognosis of GGO tumors: Sakurai H et al. Am J Surg Pathol 2004; 28:

5 Is the GGO lesion growing up?

6 Yes, Growing Up! Feb 7/ 2001 July 7/ 2003 Courtesy by Asamura H.

7 Yes, Growing Up! Jan 21/ 2001 Jan 15/ 2003 Courtesy by Asamura H.

8 Peripheral lung adenocarcinoma Hypothesis; Natural history Malignant potential; low high Pure GGO GGA GGO GGA with consolidation GGO GGA with larger consolidation and retraction Courtesy by Asamura H.

9 Is the GGO lesion always growing up?

10 Not always!! Feb 5/ 1998 Aug 4/ 2006 Courtesy by Asamura H.

11 Thoracic CT Screening for Lung Cancer The Japanese Society of CT Screening has published the management method for detected shadows. 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

12 GG lesion should be evaluated by thin-slice CT Screening CT Thin-slice CT

13 Pure GGO 100% ground glass opacity Bronchiolo-alveolar carcinoma (BAC, Noguchi s A/B) AAH, Focal pneumonia 5-9mm 10-14mm >=15mm TS-CT after 3M?? Decrease Not change Increase Biopsy or VATS Back to screening CT TS-CT every 3M-6M for 2Y

14 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. Guideline of the Japanese Society of CT Screening

15 Mixed GGO Ground glass opacity with solid part Adenocarcinoma (Noguchi s Type C) Focal pneumonia Mixed GGO TS-CT after 3M Decrease Not change Increase Back to screening CT Biopsy or VATS / Surgical intervention

16 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. Guideline of the Japanese Society of CT Screening

17 What is the best surgical mode for GG lesions with adenocarcinoma?

18 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

19 Courtesy by Suzuki K.

20 Courtesy by Suzuki K.

21 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 ;6:751-6 Five year survival data for radiological noninvasive peripheral adenocarcinoma; presented at the 14 th WCLC

22 Definition of radiological non-invasive lung adenocarcinoma by C/T ratio Maximum consolidation diameter (C) consolidation ground glass opacity Maximum tumor diameter (T) T=17 C=6 C/T ratio = 6/17 = 0.35 Radiological non-invasive lung adenocarcinoma For ct1a C/T ratio 0.5 C/T ratio 0.25* *Exploratory analysis

23 Proportion of survival 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 5yr-OS: 97% Relapse free survival 5yr-RFS: 97% 92.4% Radiological non-invasive invasive adeno ct1a (ct1a, C/T 0.25) Radiological invasive ct1a (C/T > 0.25) 87.7% invasive ct1a Radiological non-invasive p = lung adenocarcinoma p = One death due to unknown cause but no relapse Years after enrollment during 7.5yr follow-up Years after enrollment

24 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%* 5-yr OS: 97% No relapse *exploratory analysis Cured One-arm by limited (phase resection? II) Wide wedge resection* study (JCOG0804/WJOG4507L) is ongoing *Segmentectomy without lymph node dissection allowed, Because of the tumor location.

25 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 patients Trial has started since June in 2009 PI; Tsuboi M (JCOG) & Yoshino I (WJOG)

26 JCOG0802/WJOG4607L; Phase III Randomized Trial between Lobectomy and Limited Resection for Partsolid GGO Solid T1a disease Non-inferiority design Peripheral carcinoma, <=2 cm Negative hilar node Randomize Lobectomy Since Aug Segmentectomy Stratified factors; Institute, Gender, Histology (Ad vs, Non-ad), Solid or non-solid Endpoints: Primary: OS Secondary: pulmonary function Sample size: 1,100/485 PI: Asamura H. (JCOG) & Okada M (WJOG)

27 Proportion of survival Survival of predefined radiological non-invasive lung adeno (ct1 with C/T 0.5; N = 121) vs. radiological invasive ct1 (C/T > 0.5; N = 424) Overall survival Relapse free survival 5yr-OS: 96.7% 5yr-RFS: 95.8% Pre-op size 1 2.5cm (ct1b) 2 2.1cm (ct1b) Years after enrollment 88.8% 81.5% C/T p-stage Relapse Outcome ratio invasive ct1a invasive ct1a 0.44 pt1an2 1.1Y (med LN, lung) 1.5Y (death) 0 pt1an0 p< Y (lung*) p< Y *second primary? (alive) Predetermined radiological non-invasive adeno (ct1, C/T 0.5) Predetermined radiological invasive ct1 (C/T > 0.5) Years after enrollment

28 Surgery: summary-2 There is no clear scientific evidence on the following issues. Follow-up Treatment intervention; timing, modality, procedures The speculations based on clinical experiences are as follows. Less than 15mm pure GGO; Followed up within 3-6 months 5-10mm mixed GGO; Re-examination within 3 month is recommended mm mixed GGO (C/T rate=50% or less) Re-examination within 3 month is recommended. More than 10mm mixed GGO (C/T rate=more 50%) ; Tissue confirmation is recommended Take home messages How to treat the small GG lesions?

29 Take home messages How to treat the small GG lesions? As for the surgical intervention; American and Japanese studies are ongoing. At the moment, More than 20mm mixed GG adenocarcinoma (C/T rate=50% more) ; lobectomy is prior. 20mm or less mixed GG adenocarcinoma (C/T rate=50% or less); sublobar resection may be considerable. Surgical procedures depend on location, size, CT findings (density, C/T rate) and/or frozen pathological findings.

30 Future consideration If the CT screening-detected lung cancer is proven as the non-invasive early stage lung cancer based on TS-CT, Is it necessary to do surgical intervention, especially pure GGO? Long natural history? One of opitions: follow-up (Ongoing trial in NCCH) How about the other modalities? SBRT?, RFA?, etc How to treat the multi-focal cancers? GG lesions & AAH have the possibility of multiple cancer of the lung.

31 July 13, 2012 September 30, 2012 October 31, 2012