I appreciate the courtesy of Kusumoto at NCC for this presentation. What is Early Lung Cancers. Early Lung Cancers. Early Lung Cancers 18/10/55

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1 I appreciate the courtesy of Kusumoto at NCC for this presentation. Dr. What is Early Lung Cancers DEATH Early period in its lifetime Curative period in its lifetime Early Lung Cancers Early Lung Cancers Considerable long-term survival is available by the appropriate treatments Japanese pulmonologists, thoracic surgeons, pathologists, radiation oncologists, and thoracic diagnostic radiologists manage the patients with lung cancer subject to this general rule. Definition of early hilar or central lung cancers (A) Clinical Criteria 1) There are no radiological abnormal findings including CT, tomography and chest radiographs. 2) There are no lymph nodes and distant metastases on conventional radiological modalities. (B) Endoscopical Criteria 1) Localized from trachea to sub-segmental bronchi 2) Distal margin of the lesion can be identified 3) The diameter in long axis is equal or less than 2.0 cm 4) Histopathologically squamous cell carcinoma General Rule for clinical and pathological record of lung cancer The 7 th edition Nov 2010 by The Japan Lung Cancer Society Definition of early hilar or central lung cancers (A) Clinical Criteria 1) There are no radiological abnormal findings including CT, tomography and chest radiographs. 2) There are no lymph nodes and distant metastases on conventional radiological modalities. (B) Endoscopical Criteria 1) Localized from trachea to sub-segmental bronchi 2) Distal margin of the lesion can be identified 3) The diameter in long axis is equal or less than 2.0 cm 4) Histopathologically squamous cell carcinoma General Rule for clinical and pathological record of lung cancer The 7 th edition Nov 2010 by The Japan Lung Cancer Society 1

2 Long-term survival of early hilar or central lung cancers Definition of early peripheral lung cancers The 5-year survival 100% n=27 Watanabe Y, et al. J Surg Oncol 48:875-80, % n=26 Terzi A, et al. Lung Cancer 27: The 10-year survival No definition 92% n=27 Watanabe Y, et al. J Surg Oncol 48:875-80, 1991 General Rule for clinical and pathological record of lung cancer The 7 th edition Nov 2010 by The Japan Lung Cancer Society HRCT findings of small peripheral lung cancers 100% ground glass attenuation (pure GGA): non-solid nodule pure ground glass nodule (pure GGN) ground glass attenuation and solid component (part-solid nodule or semi-solid nodule) subsolid nodule: pure GGA and part-solid nodule solid nodule Travis WD, et al: International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol 6: , The New Pathological classification of small adenocarcinomas Atypical adenomatous hyperplasia (AAH) Adenocarcimona in situ (AIS) Minimally invasive adenocarcinoma (MIA) Lepidic predominant adenocarcinoma (LPA) Acinar PA Papillary and micropapillary PA Solid PA Mucinous adenocarcinoma Colloid adenocacimona, etc. No BAC Bronchioloalveolar carcinoma Travis WD, et al: International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol 6: , The New Pathological classification of small adenocarcinomas Atypical adenomatous hyperplasia (AAH) Adenocarcimona in situ (AIS) Minimally invasive adenocarcinoma (MIA) Lepidic predominant adenocarcinoma (LPA) Acinar PA Papillary and micropapillary PA Solid PA Mucinous adenocarcinoma Colloid adenocacimona, etc. Travis WD, et al: International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol 6: , The New Pathological classification of small adenocarcinomas Pure GGN Part-solid nodule Atypical adenomatous hyperplasia (AAH) Adenocarcimona in situ (AIS) Minimally invasive adenocarcinoma (MIA) Lepidic predominant adenocarcinoma (LPA) Acinar PA Papillary and micropapillary PA Solid PA Mucinous adenocarcinoma Colloid adenocacimona, etc. Solid nodule Variants Travis WD, et al: International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol 6: ,

3 To Find Early Lung Cancers Earlier Detection might be Effective? Radiograph and Cytology? Fontana RS, et al. Chest 67: , 1991 Oken MM, et al. JAMA 306, , 2011 Low-Dose CT Screening Lung cancer low-dose CT Screening Bach PB, et al. JAMA 2007; 297: increased cases, no mortality change VS. Henschke CI, et al. NEJM 2006; 355: increased early stage %, extended 5-year survival NLST RT. NEJM 2011; 365: heavy smoker (at least 30 pack years) 20% reduction in mortality Dutch-Belgian NELSON Trial Italung-CT Trial ongoing Lung cancer low-dose CT Screening NLST RT. NEJM 2011; 365: heavy smoker (at least 30 pack years) 20% reduction in mortality Smoking rate has been decreasing Thailand 22.5% 18.1% Japan 33.7% 23.9% USA 16.1% France 26.2% F: 10% M: 36% My personal experience Between 1999 and 2007 At one screening institution 1500 examinees per year (with; 60% and without; 40% smoking) LDCT (7mm gapless) I interpreted all exams Many pure GGNs and part-solid nodules showing excellent prognosis My personal experience My outpatient service quickly filled to over flowing On 2007, the institution was closed by the reformation by prime minister Jun-ichiro Koizumi Even now I still have some?patients? (with no symptom, only GGN) at my outpatient division I never wish to start a new LDCT screening program again My personal experience First 2 years results 7/1320 (530/100,000) among smokers 2 Sq, 4 Ad and 1 unknown 2/830 (240/100,000) no smokers 2 Ad (pure GGN) Stage IA (78%), IB (11%), IV (11%) Normal 33%, Follow-up 30% 21% of all participants resulted in POSITIVE on CT (3 rd year 9%) 2 thymomas, 1 thyroid ca, 6 pneumonias, 4 IP, each 2 benign tumors, Tb and ectasis 3

4 Harms of LDCT screening A lot of cases with False Positive Cancer panic syndrome Long term follow up with CT resulting in high dose protocol low cost performance Time Swenson consuming SJ, et al. Lung cancer screening for with Pts CT: Mayo and clinic experience. MDs Radiology 226: , 2003 Benefit of early detection: mortality Lead-time bias with symptoms without symptoms Length bias low-grade malig. only Overdiagnosis bias not COD malig insignificant cancers HRCT findings of small peripheral lung cancers 49-year-old Man with a Pure GGN pure ground glass nodule (pure GGN) Mostly round localized GGN 75% AIS 6% AAH 19% Organizing P/Fibrosis Kim HY, et al. Radiology 245: , 2007 AIS: Noguchi type A 57-year-old Man with a Pure GGN 57-year-old Man with a Pure GGN T1WI T2WI CE-T1WI Atypical adenomatous hyperplasia (AAH) Rt. S2,10x8 mm GGA 100% dynamic MRI 4

5 57-year-old Man with a Pure GGN 46-year-old Woman with a Pure GGN FDG-PET coronal (MPR coronal) AIS, Noguchi type B (MPR sagittal) 46-y-o Woman Pure GGN Dynamic CE-MRI T2WI T1WI CE-T1WI MRI 46-year-old Woman with a Pure GGN FDG-PET MIA, Noguchi type C 0.4 5

6 Adenocarcinoma in situ: AIS Are these pure GGNs really the early lung cancer? CT: 18 mm in diameter, inhomogeneous GGN tiny high attenuation spots Pathological findings: non-invasive adenocarcinoma inhomogeneous collapse and fibrotic area Woman in her 60s Found on CT screening High attenuation Pure GGN Woman in her 50s Incidentaloma Irregular shaped Pure GGN A case with a Pure GGN: follow-up A case with pure GGN: follow-up, 69-year-old May 2001 (43-y-o) May 2007 (6-y later: 49-y-o) Nov 2001 May 2002 Mar

7 61-year-old Woman (never smoker) Pure GGN 72-year-old Man with a Pure GGN 4 years later HRCT 72-year-old Man with a Pure GGN 72-year-old Man with a Pure GGN T1WI MRI T2WI CE-T1WI late phase Dynamic CE MIA localized interstitial fibrosis Pure GGNs Mostly round localized GGN 75% AIS 6% AAH 19% OP/Fibrosis Kim HY, et al. Radiology 245: , 2007 Hara M, et al. Radiat Med 20:93-95, 2002 A round shape means AAH or AIS Most of cases will enlarge very slowly Surgical procedure might not be the first choice Pure GGNs might remain early status during a very long period There would be a few cases showing an interval enlargement 7

8 HRCT findings of small peripheral lung cancers 59-year-old Man with a Part-solid nodule ground glass attenuation and solid component (part-solid nodule or semi-solid nodule) solid component within GGN to some extent not always round shape relatively high attenuation GGN Travis WD, et al: International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol 6: , Minimally invasive adenocarcinoma (Noguchi type C) 62-year-old Man with a Part-solid nodule Minimally invasive adenocarcinoma: MIA Lepidic predominant adenocarcinoma (Noguchi type C) CT: 15 mm in long axis, part-solid nodule, 7 mm solid component Pathological findings: Lepidic proliferation 3 mm fibroblast proliferation Invasive adenocarcinoma lepidic pattern predominant: LPA Invasive adenocarcinoma lepidic pattern predominant: LPA CT: 14 mm in long axis, pure GGN Pathological findings: Lepidic proliferation, central papillary proliferation CT: 20 mm in long axis, part-solid nodule 7 mm solid component at the marginal region of the lesion Pathological findings: Lepidic proliferation, 10 x 10 mm central fibrotic area 8

9 65-year-old Woman with a Part-solid nodule (T2a) 65-year-old Woman with a Part-solid nodule (T2a) HRCT T1WI MRI T2WI CE-T1WI 65-year-old Woman with a Part-solid nodule (T2a) 65-year-old Woman with a Part-solid nodule (T2a) Dynamic CE MIA FDG-PET 65-year-old Woman with a Part-solid nodule (T2a) Minimally Invasive Adenocarcinoma(T1b) Macroscopic finding 9

10 54-year-old Man with a Part-solid nodule (T1a) 54-year-old Man with a Part-solid nodule (T1a) T1WI HRCT MRI T2WI CE-T1WI 54-year-old Man with a Part-solid nodule (T1a) Minimally Invasive Adenocarcinoma(T1b) Dynamic CE Woman in her 80s Left pleural effusion Incidentaloma Part-solid nodule Woman in her 70s with bladder ca. Incidentaloma Part-solid nodule 10

11 54-year-old man with a Part-solid nodule 2 months later 43-year-old Man with a Part-solid nodule HRCT findings of small peripheral lung cancers solid component alone (solid nodule) Tuberculosis On HRCT distinct border, irregular margin, spicula, and pleural indentation etc. lobulation round shape long and narrow along with bronchiole Travis WD, et al: International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol 6: , year-old Man with a tiny Solid nodule Correlation the CT finding with pathological one - 5-year survival and surgical technique - Adenocarcimona (2cm and less, n=175) pathological finding CT finding non-invasive invasive Pure GGN Part-solid nodule (GGA 50% or more) 100% Wedge resection 100% Wedge resection 93.4% Segmentectomy Acinar PA Noguchi type E Solid nodule 100% Wedge resection 79.1% Lobectomy NCC Thoracic Surgery, Suzuki K, et al. 11

12 56-year-old Man (smoker) with a Solid nodule How about Sq CCs and Sm CCs? severe emphysema 3 mm reconstruction thickness, NDCT (Oct 2004) A 12x8 mm Solid nodule in his upper lobe (S1+2a) Found on LDCT (20 months before: 10x8 mm) Interval enlargement was observed compared to the previous CT (6 months before) 56-year-old Man (smoker) with a Solid nodule 65-year-old Man (smoker) with a Solid nodule Oct 2004 FDG-PET Mar mm reconstruction thickness 10x8 mm on CT homogeneously enhanced FDG-PET 20 months before shows a faint uptake Moderately Differentiated Sq CC (T1aN0M0) 2009 follow-up was terminated without recurrences (still heavy smoker) 2010 a new oropharyngeal ca. (Sq CC) was found Screening CT 1 month later 3 months later Small Cell Lung Cancer 70-year-old Man with a tiny Solid nodule Small cell lung cancers show rapid progression and it would be hard to find them in early stage on screening CT The other aggressive cancers are as well Stage I small cell lung cancers are exceptionally experienced that can be resected by chance Tuberculoma Screening CT 6 months later 12

13 80-year-old Man (smoker) with a Solid nodule 69-year-old Woman (non-smoker) with a Solid nodule showing shaggy margin 1 year and 6 months later 3 months later HRCT findings of small peripheral lung cancers Multiple adenocarcinomas SUV 1.1 SUV 1.3 Rt. S1,GGA 80% 25x20 mm MIA, WD ad ca Rt. S2,GGA 20% 15x12 mm MIA, WD ad ca SUV year-old Man with triple cancers Rt. S6,GGA 75% 14x10 mm MIA, WD ad ca Rt. S2,GGA 50% 37x34 mm, LPA 61-year-old Woman with double cancers FDG-PET coronal Noguchi C type GGA 50% 64-y-o Woman double cancers PET spot SUV 0.6 Poorly D. Ad ca SUV 0.8 Rt. S9,pure GGN 15x11 mm, AIS 13

14 64-y-o Woman with double cancers SUV 4.3 P.D. ad ca LN metastasis SUV 3.8 TP LN metastasis SUV 3.9 TP The differential diagnosis for small solid nodules might sometimes become very difficult SUV 1.0 Noguchi C type, GGA 50% Definition of early peripheral lung cancers Adenocarcinoma Pure GGNs (AIS) Part-solid nodules (MIA and LPA) Keep being an early stage during pts life and require no treatments Keep being an early stage during long period and can be diagnosed on CT Solid nodules There might be some cases and may be checked on CT Squamous cell carcinoma Small cell carcinoma There might be some cases and may be checked on CT Early cases may be hard to be found on CT Smokers 14