May 28 – 30, 2015, Montréal, Québec A Canadian Approach to Lung Cancer Screening: What every radiologist should know.

May 28 – 30, 2015, Montréal, Québec Disclosure Statement: I have/had an affiliation, financial or otherwise, with a pharmaceutical company, medical device or communications organization, which could include: Speakers bureau: HIT Global, Intermune Subinvestigator on research sponsored by: Boehringer Ingelheim, CSL Behring, Grifols

Lung cancer kills more Canadians than breast, colon and prostate cancers combined. 1% of cancer donations. 7% of cancer research funding. Canadian Cancer Society’s Advisory Committee on Cancer Statistics. Canadian Cancer Statistics Toronto, ON: Canadian Cancer Society; Howlader N, et al. SEER Cancer Statistics Review, , based on November 2013 SEER data submission, posted to the SEER web site, April

Faster and safer Comparative average dose in mSv

randomized to CXR vs low dose CT 3 annual screens Age 55 to 74, > 30 pack years

Daria Manos 20% reduction in lung cancer specific mortality. Screen 320 high risk smokers to prevent one death from lung cancer.

US Preventative Services Task Force American Thoracic Society American College of Chest Physicians American Society of Clinical Oncology Cancer Care Ontario “YES! WE SHOULD SCREEN HIGH RISK PATIENTS!” Canadian Preventative Services Task Force – release date Fall 2015

Lung nodules are very common NLST data Positive screen False positive True positive

Majority “positive CT” need nothing more than one additional surveillance CT. Problems with existing definition of positive screen Follow up

Myth: Size is the most important predictor of malignancy. Change is more important than size. Nodules ≥ 10 mm: multiple important variables. Not all nodules ≥ 10mm need immediate work up. Problems with existing definition of positive screen Radiologist is more than a well paid measuring tape.

13 months CT too sophisticated a test to reduce to positive or negative results Problems with existing definition of positive screen

Lu-RADS 1No nodule Lu-RADS 2Benign nodule Lu-RADS 3Indeterminate (requires surveillance CT) Lu-RADS 44A – low risk 4B – likely low aggressive adenocarcinoma 4C – likely malignant Lu-RADS 5Malignant by CT Lu-RADS 6Tissue malignant NEGATIVE INDETERMINATE POSITIVE

LU-RADS Communicates level of concern. Groups nodules based on the best management. Recognizes not all worrisome nodules need same work up. Maintain safety but control work up costs. Reassurance that work up plan is appropriate. Identifies nodules for which negative PET/CT, bronchoscopy or biopsy would be discordant. Provides a roadmap for general radiologists. Provides a framework for comparable data.

LU-RADS 1 – return to screening No nodule Direct participant to smoking cessation support. Explain limitations of screening. Describe and instruct re: concerning symptoms.

LU-RADS 2 – return to screening Small nodules < 5mm

LU-RADS 2 – return to screening Small nodules < 5mm Stable nodules Solid stable for 2 years Subsolid stable for 5 years Benign nodules PFO Round atelectasis Benign calcification Hamartoma Specific benign tissue

LU-RADS 2 – return to screening No benefit follow up before next annual screen. Risk of lung cancer in next 2 years lower than prior to CT. Small nodules < 5mm Stable nodules Solid stable for 2 years Subsolid stable for 5 years Benign nodules PFO Round atelectasis Benign calcification Hamartoma Specific benign tissue

69 year old smoker One yearTwo yearsThree years Some of these nodules will be early cancer but overall no benefit for early follow up CT.

Lu-RADS 1No nodule Lu-RADS 2Benign nodule Lu-RADS 3 Indeterminate (requires surveillance CT) Lu-RADS 44A – low risk 4B – likely low aggressive adenocarcinoma 4C – likely malignant Lu-RADS 5Malignant by CT Lu-RADS 6Tissue malignant

LU-RADS 3 – Indeterminate recall for surveillance low dose CT 3 SMALL 3 LARGE

3 SMALL 5-9 mm Not stable long enough to call benign Too small for PET, biopsy, bronch Risk of cancer not high enough to justify work up. LU-RADS 3 – Indeterminate recall for surveillance low dose CT

Patients assume all nodules are cancer. (Wiener. Chest 2013).

Myth: 30-50% of lung nodules are malignant Journal of Nuclear Medicine 1999, Chest 2003, JTO 2011

For small solid nodules: Size is important but change is more important.

After 2 years of stability classify as LU-RADS 2 (benign). Serial growth upstages. LU-RADS 3 small (nodules 5-9 mm)

≥ 10 mm but CT or clinical features suggest inflammatory Follow in 4 to 12 weeks. 3 LARGE LU-RADS 3 – Indeterminate recall for surveillance low dose CT

Asymptomatic patients LU-RADS 3 – requires surveillance CT Follow up CTs

ED last month Pneumonia 3 mos ago LU-RADS 3 – requires surveillance CT Follow up CTs

3 large: Requires surveillance Nodules ≥ 10 mm with clinical or CT features suggesting transient process possible even if patient asymptomatic.

73 year old 50+ pack year current smoker One year earlier6 months later

3 months later Up to 50% of ground glass opacities in asymptomatic patients resolve on follow up.

LU-RADS 3L: Possibly transient: Baseline Subsolid Ill-defined gg halo air bronchograms Clinical features New large nodules What CT features suggest “possibly transient?”

Lu-RADS 44A – low risk 4B – likely low aggressive adenocarcinoma 4C – likely malignant POSITIVE CT Lu-RADS 4 4A – low risk 4B – likely low aggressive adenocarcinoma 4C – likely malignant

4A LOW RISK Nodule ≥ 10mm with benign but not definitive CT features. Hamartoma without fat Non-calcified granuloma ? round atelectasis, not definitive POSITIVE – but low risk

Any relevant priors? PET –good NPV here Core biopsy Serial CT Discussion POSITIVE – but low risk 4A LOW RISK Nodule ≥ 10mm with benign but not definitive CT features. Hamartoma without fat Non-calcified granuloma ? round atelectasis, not definitive

POSITIVE – but low risk

Lu-RADS 44A – low risk 4B – likely low aggressive adenocarcinoma 4C – likely malignant POSITIVE CT Lu-RADS 44A – low risk 4B – likely low aggressive adenocarcinoma 4C – likely malignant

4B LIKELY AIS or MIA Consider risks of surgery, wishes of patient Surgical biopsy vs monitor with CT Limitations of PET, bronch, perc biopsy LU-RADS 4: worrisome Non transient Subsolid ≥ 10 mm No solid or ≤ 5mm solid portion

1 year 2 years 4 years 5 years 6 years 7 years GG neoplasm may grow very slowly. Will the competing cause of death be more important?

5 years

Focal ground glass opacity can progress to invasive adenocarcinoma. 11 years

Beware of growth: Persistent + growth = near 100% neoplastic* * Chang. Chest. 2013

Growth can be missed 8 years

Beware increase in density 8 years 9.5 years10 years

Was the NLST long enough to evaluate these lesions? How to manage? Biopsy? To faciltate non surgical treatment

New GGO: Marked FDG uptake in GGO more likely to be inflammatory AIS by definition does not metastasize PET? Mild FDG uptake in persistent GGO strongly predictive of neoplasm Useful to plan surgery when multiple lesions present

Treatment for subsolid neoplasm Screening studies criticized for overtreatment of indolent disease. Was the NLST long enough to determine this? Consider competing causes of death. In situ disease in lung is difficult to resect Compared to breast, cervix, colon. No uniform approach

Resect all persistent GGO? Resect when solid portion develops vs.

Approach to GG neoplasm GG neoplasm common incidental finding Persistent GG - high likelihood of in situ neoplasm. GGO neoplasm unlikely invasive or metastatic but can develop into invasive disease with mets. Treatment decisions: Need to reflect size and change of nodule Comorbidity and competing causes of death Wishes of patient

Lu-RADS 44A – low risk 4B – likely low aggressive adenocarcinoma 4C – likely malignant POSITIVE CT Lu-RADS 44A – low risk 4B – likely low aggressive adenocarcinoma 4C – likely malignant

CT: Likely malignant 21 months Worrisome change

CT: Likely malignant Malignant rate depends on local rate of granulomatous infection. Worrisome baseline

CT: Likely malignant Negative PET bronch perc biopsy is discordant and should prompt team discussion.

Do we need a new paradigm? CT shows SPN Biopsy, bronchoscopy, PET Treat

Serial CT Clinical assessent +/-Biopsy +/-Bronch +/-PET Cancer likely Work up Biopsy/PET treat Cancer unlikely surveillance

New approach Not every worrisome nodule detected by CT requires the same work up. For some nodules negative work up will be reassuring, for other nodules it will not be. In addition to distinguishing benign from malignant nodules, CT can also help predict nodule aggression.

Screening CT for lung cancer has arrived in Canada. Will grow exponentially in next 10 years. Screening CT presents challenges to radiologists, including legal concerns. Subtle slow growth in subsolid neoplasm. Overcalling new or inflammatory nodules. Use serial CT, clinical evaluation, PET, biopsy and brochoscopy as team players not a hierarchy. Last words

Our behaviour as radiologists in these initial stages has the power to make or break screening. Last words

THANK YOU!