Mr. B born 1942tg,sutedja@vumc.nl

History (1)History (1)

54-yrs old >40 pack years - slight hemoptysis

Feb. 2000: Severe dysplasia with brush cytology suspicious for cancer cells left upper lobe region

Referral for bronchoscopic evaluation

Please vote: Please vote: dysplasia dysplasia →→ cancer cancer

1. Progression of all lesions

2. Only high grade dysplasia progressive

3. Unpredicatable non-stepwise histological changes

4. Not an important finding

 

90,000 cells’limit <0.6 mm ???????????!Bota et al. 6.1% high grade CIS SCC 87%Moro Sibolot et al. SD/CIS persistent/CIS 63%/2 yrs Kennedy et al. SD sputum SD-malignancy 15.6%Breuer et al. SD CIS = 32% & Venmans et al CIS SCC 100%

Clonal Darwinism of carcinogenesisClonal Darwinism of carcinogenesis• Field of heterogeneous clones, “some”potentially

malignant with, each has its own time clock

• Non-stepwise histological changes (metaplasia may also become squamous cell cancer!)

• No accurate prediction for malignant development based on the initial WHO histological classification

Natural course of preneoplastic lesionsClinical Cancer Research 2005; 11: 537

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History (2)History (2) Autofluorescence bronchoscopy: upper

division bronchus (UDB between LB2-3) abnormal

Histology: severe dysplasia

Cytology revision by a panel: not suspicious!

July 2000: Repeat AFB squamous metaplasia

History (3)History (3)

May 2001 repeat AFB normal respiratory epithelium UDB

June 2002 repeat AFB squamous metaplasia, RB7 mild dysplasia

July 2002: HRCT no abnormalities

History (4)History (4)

Feb 2003: Repeat AFB squamous metaplasia; RB7 normal

Jan 2004: Repeat AFB squamous metaplasia HRCT: no abnormalities

Aug 2004: repeat AFB UDB suspicious; distal margin invisible at least severe dysplasia; brush cytology suspicious for malignant cells

Left upper division bronchusLeft upper division bronchus

VOTEVOTE:What to do:What to do

1. Follow up AFB and HRCT

2. Intraluminal treatment e.g. PDT, electrocautery, cryotherapy

3. Surgical resection

4. Stereotactic body radiotherapy

Occult cancer: HRCT + AFB + FDG-PETOccult cancer: HRCT + AFB + FDG-PET

Acc(ss)essible superficial intraluminal N0 with visible borders

Clinical decision and treatmentClinical decision and treatment

Distal microinvasion cannot be ruled out → Surgery. Pre-treated with argon plasma

Radical lobectomy and SND left upper lobe

Resected specimen: squamous metaplastic field and mild dysplasia, no residual CIS or microinvasive squamous cancer, N0 stage!

Follow-up: feb 2007Follow-up: feb 2007

AFB stump suspicious + RB3 RB7 abnormal

AFB “false negatives” (Helfritszh et al genetic abnormalities – impact?)

VOTEVOTE: CIS and AAH: CIS and AAH

1. Always surgical treatment

2. Treat bronchoscopically & SBRT

3. Wait and see until microinvasive SCC or GGO become partially solid

Early squamous: not a threat?Early squamous: not a threat? 38 patients primarily resectable,

intraluminally treated first having HRCT & FDG-PET scan occult cancer lesions

16 dead and 22 alive; med surv 20 months; Lung cancer death 5/16 = 31%; 4 metachronous occult cases due to previous tumor

Remaining 11 deaths: COPD, AMI, pancreatic ca, esoph.ca. CFA, sepsis etc

Early intervention: Early intervention: concon vs. vs. propro?? They will die from co-morbidities no

significant benefit from early intervention

Succesful early intervention allow more to suffer/die from co-morbidities

Clonal aggressive lesions incurable = CT screening interval cancer!

Cost-effective Cost-effective “tailored”“tailored” therapy therapy

Intraluminal

“Occult” Bulky

Coagulation &Recanalization

Accurate targetingof N0 tumor

Tailored i.e. local → surgery + minimal/non invasive (?)