Imaging Features of Lung ca and�LDCT Screening

Dr Hanna Damtew

Cardiothoracic imaging fellow

Assistant professor of radiology AAU

May 2024

CONTENT

INTRODUCTION

• Lung cancer refers to malignancy originating in the airways or pulmonary parenchyma.
• presenting symptoms include cough, hemoptysis, dyspnea and chest pain.
• Systemic symptoms may also be present such as weight loss, fatigue and clubbing.
• A locally advanced tumor may cause wheeze and stridor on respiratory examination.
• A pancoast tumor results in Horner's syndrome, atrophy of hand muscles and shoulder pain.

Epidemiology

• is the most common cancer worldwide
• second most frequent cause of cancer (after prostate cancer in men and breast cancer in women) and the most frequent cause of cancer death in the United States for both men and women
• An estimated 1.5% of all Ethiopian cancers involved the lung

• Risk factors

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• Tobacco smoking accounts for 80% to 90% of lung cancers(increases 20-30x)
• Increasing age ( <30yrs rare)
• Occupational exposures- 10% of lung cancer
• Asbestos exposure( particularly when causing Lung fibrosis)
• Diffuse pulmonary fibrosis - increases 10x.
• Chronic obstructive lung disease (chronic bronchitis and emphysema)
• Genetic predisposition - relatives of subjects with lung cancer have a higher risk
• Radiation therapy
• Indoor air pollution
• oncogenic viruses?? HIV 2.5x. ---- HPV vs squamous cell carcinoma of the lung

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Imaging modalities

Plain radiograph

first investigation performed during the workup of suspected lung cancer

easily accessible and low-risk imaging method

• Features on chest x ray include
• new or enlarged focal lesion,
• widened mediastinum suggestive of lymph node involvement,
• pleural effusion
• atelectasis and consolidation

CT�

• Provides detailed information about tumor location, size, and extensions
• CT with contrast should be performed for complete staging.
• assess the enhancement of tumors to distinguish benign from malignant lesions
• invasion of the mediastinal structures encasement of great vessels, esophagus, and main bronchi
• used to monitor the response to treatment and to plan the radiation therapy
• screening tool in carefully selected populations of patients.

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CT assessment of chest wall invasion is unreliable

• Rib destruction or extension of pulmonary mass into the chest wall remain the definite signs.
• Apart from bony invasion, MRI is better than CT in assessment of chest wall invasion and Pancoast tumor

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MRI

• is also useful in the assessment of mediastinal and chest wall invasion by virtue of its ability to determine fat-stripe invasion and involvement of the diaphragm and spinal canal.
• In addition, it has been shown to aid in differentiating lymph nodes from hila vessels due to the “flow void” phenomenon

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• MRI has disadvantages compared to CT, being slower and more expensive with poorer spatial resolution and providing limited lung parenchyma information.
• MRI can overestimate lymph node size because of respiratory movement, causing the blurring together of discrete nodes into a larger, conglomerate mass
• MRI is also poorly tolerated by claustrophobic patients and is contra-indicated in patients with indwelling electromagnetic devices and some prosthetic heart valves.

PET

• its advantage over other modalities lies in its sensitivity in detecting malignancy and its ability to image the entire body in one examination.
• PET is more accurate than CT in the detection or exclusion of mediastinal nodal metastases: sensitivities are 67–100% and 50–63% respectively whilst specificities are 81–100% and 59–94%
• PET is more accurate than conventional studies in detecting recurrent lung cancer and appears to be superior in distinguishing persistent or recurrent tumor from fibrotic scars
• PET/CT using the radiotracer 18F-FDG is a reliable noninvasive imaging modality to differentiate benign from malignant lesions

Lung CA Classifications

• Location vs histologic

Location

central

• Sqaumaous cell carcinoma,
• small cell carcinoma

peripheral

• Adenocarcinoma
• Large cell carcinoma

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Histologically

NSLC(80%-85%):

• Sqaumaous cell carcinoma,
• Adenocarcinoma,
• Large cell carcinoma

SCLC(15%-20%):

• small cell carcinoma

Neuroendocrine cell

• carcinoids

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�RADIOLOGICAL CHARACTERISTICS BY CELL TYPE�

• Adenocarcinoma
• 31% of all lung cancers
• peripherally located and measure <4 cm in diameter
• only 4% show cavitation
• Hila or hila and mediastinal involvement is seen in 51% of cases

Imaging

• either a localized ground glass opacity which grows slowly (doubling time>1 yr)
• or a solid mass which grows more rapidly (doubling time <1 yr) .

• In 2011 the International Association for the Study of Lung Cancer (IASLC) and several other societies jointly revised the classification for adenocarcinoma of lung

Adenocarcinoma in situ

• purely lepidic (growth along alveolar walls) and noninvasive tumor of 3 cm or smaller.
• If the lesion is resected, patients have 100% disease-free survival
• Atypical adenomatous hyperplasia (AAH) under the category of pre invasive lesions for lung adenocarcinoma
• Minimally invasive adeno carcinoma
• represents 3 cm or smaller lepidic predominant adenocarcinoma with an invasive component of ≤ 5mm
• 5-year disease-specific survival is nearly 100%
• Invasive adeno carcinoma -->5 mm invasion​
• Mucinous and non mucinous subtype
• Depending on the growth type histologically
• Lepidic predominant --- 5-year survival of 81%
• Acinar papillary and micropapillary predominant adenocarcinomas -------5-year survival of 54%

AIS --2–10% of all primary lung

• most common is a single pulmonary nodule or mass in 41%;
• there may be multicentric or diffuse disease in 36%
• 22% there is a localized area of parenchymal consolidation
• Hilar and mediastinal lymphadenopathy is uncommon

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• Persistent peripheral consolidation with associated nodules

in the same lobe or in other lobes should raise

the possibility of AIS

Squamous cell carcinoma

• 30% of all lung cancers
• These tumors are more often centrally located within the lung and may grow much larger than 4 cm in diameter
• Cavitation is seen in up to 82%
• They commonly cause segmental or lobar lung collapse due to their

central location and relative frequency

• the most common type accounting for Pancoast tumors

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Small cell lung cancer

18% of all lung cancers

• often present with bulky hila and mediastinal lymph node masses
• A mass in or adjacent to the hilum is characteristic of SCLC and

the tumor may well show mediastinal invasion

Large cell carcinoma

9% of all lung cancers

• poorly differentiated non small cell carcinoma (NSCLC)
• diagnosed histologically after exclusion of

adenocarcinomatous or squamous differentiation

• Large cell lung cancer is typically seen as a

large peripheral mass of solid attenuation and irregular margin.

Focal necrosis can be present.

Other characteristics include rapid growth and early metastasis.

Carcinoid tumor

1% of all lung cancers

• subgroup of neuroendocrine tumors of the lung,
• Carcinoids tend to be centrally (75% )rather than peripherally located (16-40%)
• calcification is seen in 26–33%
• typical carcinoid tumors of the lung
• considered much more common (~90%)
• low grade/well-differentiated
• 5‐yr survival is 95%
• Atypical carcinoid tumors of the lung
• less well-differentiated
• more aggressive
• 5‐yr survival is 57–66%

suspicious findings�

• Lesions larger than 3 cm that are new
• Measurable growth in any nodule or mass
• Pleural nodularity
• Asymmetric or significantly enlarged hilar or paratracheal nodes
• An endobronchial lesion
• An area of consolidation thought to be pneumonia that fails to resolve with medical management

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• Pleural effusions
• Non-dependent or substantial atelectasis
• Pleural plaques may indicate significant asbestos exposure

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• Concerning but less specific findings

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• A radiologist role is not only putting a diagnosis as benign or malignant but also helps in guiding the management option
• follow up vs image guided biopsy vs surgical vs chemo/radio therapy
• Follow up ---how frequent ?

FLESHIER SOCIETY 2017

• The Fleischer Society guidelines are the most referenced guidelines for management of pulmonary nodules detected incidentally on CT images

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• Most of the high-quality evidence for nodule management comes from screening studies that only included patients at high risk of lung cancer, and
• there is an acknowledged paucity of evidence for guiding nodule management in patients with a lower background risk of cancer

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• There is agreement about the need to minimize radiation dose for CT surveillance for nodules, and an acknowledgement of the low likelihood of malignancy in small nodules detected through any route

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LDCT SCREENING �

• In the 1970s and 1980s, two randomized controlled trials, the Mayo Lung Project and a Czechoslovakian trial , investigated whether early detection of lung cancer using chest radiography could reduce lung cancer mortality

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• mid and late 1990s, investigators in Japan and the United States demonstrated the potential benefits of low-dose CT screening for lung cancer.

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Lung cancer was found in 0.9%–2.7% at initial (prevalence) screening three to four times more than with chest radiography

Importantly, over 50% and up to 93% of the detected lung cancers were stage I

• In 2011, the National Lung Screening Trial (NLST) showed that participants who received low-dose computed tomography (LDCT) scans had a 20% lower risk of dying of lung cancer compared to participants who were screened with chest radiography

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• 2013 Two years later, the US Preventive Services Task Force recommended lung cancer screening (LCS) with LDCT in smokers with a 30-pack-year smoking history who currently smoke or have quit within the past 15 years .

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• In 2015, LDCT was reimbursed by Medicare and Medicaid Services, with implementation of LCS throughout the US . Final data of the randomized Dutch-Belgian NELSON trial (Nederlands-Leuvens Longkanker Screenings Onderzoek) showed a lung cancer-specific mortality reduction of 24% in men and 33% in women at 10-year follow-up .

The original classification was updated in 2019 and 2022 in the�

SMOKING CESSATION

• purpose of screening is to reduce the risk of lung cancer death, the importance of smoking cessation cannot be overemphasized.
• Smoking cessation gradually lowers the risk of lung cancer compared with continued smoking, though risk does not return to the level of the never smoker and continues to increase with age in all

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ELIGIBILITY

• age 50 – 77yrs previously (65-80yrs)
• asymptomatic
• smoking hx 20pack /yr (previously 30 packs/yr)
• smoking cessation ≤ 15 yrs

INDIVIDUAL RISK PREDICTION

• age , smoking hx (previously)
• race, socioeconomic status, body mass index, history of chronic obstructive pulmonary disease and family history of lung cancer

SHARED DECISION MAKING

• disclosure of the risks and benefits of a course of action by the provider

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• expression of personal preferences and values by the patient

Risk of screening

• Diagnostic testing
• CT scan to monitor indeterminate pulmonary nodules, resulting in additional radiation exposure ----both imaging and invasive procedures
• used a computer software program to measure nodule volume and classified screens as
• negative (largest nodule < 50 mm3 volume, or 4.6-mm diameter if spherical),
• positive (largest nodule > 500 mm3, or 9.8-mm diameter if spherical) with referral to clinician for workup, or
• indeterminate (largest nodule 50–500 mm3, or 4.8–9.8-mm diameter) with recommendation for a 3-month follow-up CT

• reduce the median reading times of lung cancer CT scans by almost half with the support of CAD systems and
• significant improvement in the interobserver agreement during follow-up management among radiologists
• dedicated CT lung screening viewer led to a higher proportion of positive screening results (Lung-RADS categories 3, 4A, or 4B) than did use of the standard viewer (67% vs 54%)

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Risk of screening Conti…..

Radiation exposure

• At the highest recommended volumetric CT dose index (CTDIvol) of 3.0 mGy in a standard-size patient, a 25-cm standard scan length, and 1.4 mSv
• According to the U.S. Food and Drug Administration, a CT with effective dose of 10 mSv may increase the possibility of developing a fatal cancer by 0.05%
• which scales linearly to a risk of 0.005% for a 1-mSv lung cancer screening CT.

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Risk of screening Conti…..

• Overdiagnosis.
• NLST data found that 18% of the screen-detected cancers in the CT arm may have been over diagnosed, primarily adenocarcinomas classified at the time as bronchioloalveolar cell type
• Statistical modeling studies that simulated longer follow-up estimated that 10% would be overdiagnosed
• Missed lung cancer.
• Retrospective review revealed abnormal findings of a positive screen in 40 of these,

22 likely missed, 14 misinterpreted as clinically significant but not suspicious for lung cancer, and

4 with nodules originally considered to be less than 4 mm or stable for more than 2 years, and

4 patients with no or minor abnormalities not suspicious for lung cancer

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• other presentations of lung cancer, such as cystic or bubbly lucencies with thickened walls or nodules and consolidation simulating pneumonia, is important in screening CT interpretation.

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• enlarged hilar lymph nodes,
• endobronchial nodules, and
• enlarged mediastinal lymph nodes

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(significant /potentially significant modifiers)

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Risk of screening Conti…..

• Incidental findings
• pulmonary abnormalities of emphysema, bronchitis, and interstitial lung disease and cardiovascular disease including coronary artery calcification and thoracic aortic aneurysm
• NLST were cardiovascular (8.5%), renal (2.4%), hepatobiliary (2.1%), adrenal (1.2%), and thyroid (0.6%)
• detection of incidental findings may reduce morbidity and mortality in some persons, but false-positive findings and overdiagnosis with unnecessary testing and treatment

Reporting technique

• Lung RADS criteria ----Lung Imaging Reporting and Data System
• The system is similar to the Fleischner criteria but designed for the subset of patients intended for low-dose screening studies.

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• The radiologists’ role in LCS goes beyond reading chest CTs and evaluating pulmonary nodules.
• Being part of a multidisciplinary team, radiologists are key players in numerous aspects of implementation of a high quality LCS program

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Category 0 (Incomplete)�

• Risk of malignancy --none
• Findings
• prior CT studies were performed but are not available
• lungs incompletely imaged
• more than 6 new nodules, rapid appearance of an 8mm or larger nodule and
• segmental or lobar consolidation findings suggest inflammation or infection

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• Recommendation-- comparison with prior studies before assignment of Lung-RADS classification

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Category 1 - negative

• Risk of malignancy <1% chance

Findings

• no lung nodules
• lung nodule(s) with specific findings favoring benign nodule(s)
• complete calcification
• central calcification
• popcorn calcification
• calcification in concentric rings
• fat-containing nodules
• Recommandation continue annual screening with LDCT

Category 2 -benign

• Risk of malignancy-- <1%

Findings

• juxta pleural nodule (within 15 mm of pleural space )
• <10mm mean diameter at baseline
• new and smooth, solid, oval, lentiform, or triangular

solid nodule(s)

• <6 mm at baseline
• new nodule <4 mm

part-solid nodule < 6 mm total mean diameter at baseline

ground glass nodule(s)

• <30 mm (version 1.1 -previously 20 mm)
• ≥30 mm and unchanged or slowly growing (version 1.1 change previously 20 mm)
• subsegmental airway nodule at baseline or stable(2.0 version )
• category 3 nodules that are stable or decreased at 6 months
• category 4B lesion that has a benign diagnosis on work up
• Recommendation continue annual screening with LDCT

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Category-3 probably benign

• Risk of malignancy 1-2%

Findings

solid nodule(s)

• between 6 and 8 mm at baseline
• new nodule between 4 mm and 6 mm

subsolid nodule(s)

• ≥6 mm total diameter with solid component <6 mm
• new <6 mm total diameter

ground glass nodule(s)

• ≥30 mm on baseline CT or new (version 1.1 change previously 20 mm)
• atypical thick-walled lung cyst with enlarging cystic component (mean diameter)
• category 4A lesion, stable or decreased in size at 3-month follow-up (excluding airway nodules)
• Recommendation screening with LDCT in 6 month

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Category-4A suspicious

Risk of malignancy 5-15%

FINDINGS

solid nodule(s)

• ≥8 mm to <15 mm at baseline
• growing nodule(s) <8 mm
• new nodule 6 mm to <8 mm

part solid nodule(s)

• ≥6 mm total diameter with solid component ≥6 mm to <8 mm
• new or growing <4 mm solid component
• segmental or more proximal airway nodule at baseline
• thick-walled cyst OR multilocular cyst at baseline OR thin- or thick-walled cyst that becomes multilocular
• Recommendation 3-month follow-up with LDCT/ PET-CT may be used if there is a ≥8 mm solid component

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Category-4B very suspicious

• Risk of malignancy >15%

FINDINGS

solid nodule(s)

• ≥ 15 mm at baseline
• new or growing, and ≥8 mm

part-solid nodule(s)

• solid component ≥8 mm
• new or growing ≥4 mm solid component
• atypical pulmonary cyst: thick-walled cyst with increasing wall thickness/nodularity OR growing multilocular cyst (mean diameter) OR
• multilocular cyst with increased loculation or new/increased opacity (nodular, ground glass, or consolidation)
• solid or part solid nodule growing slowly over multiple screening exam
• Recommendation chest CT with or without contrast, as appropriate
• PET-CT and/or tissue sampling depending on the probability of malignancy and comorbidities (PET-CT if solid component ≥8 mm)

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Category-4X very suspicious

• Risk of malignancy >15%
• FINDINGS
• category 3 or 4 nodules with additional features or imaging findings that increase the suspicion of malignancy

includes:

• spiculation
• ground glass nodule(s) that double in size in 1 year
• enlarged regional lymph nodes
• Recommendation chest CT with or without contrast, as appropriate
• PET-CT and/or tissue sampling depending on the probability of malignancy and comorbidities (PET-CT if solid component ≥8 mm)

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Practical points�

• nodule measurement should be in lung windows
• to calculate nodule mean diameter, measure both the long and short axis to one decimal point, and report mean nodule diameter to one decimal point. [previously recommended rounding to nearest whole number version 1.0.]
• only a single measurement is necessary for round nodules
• "growth" is an increase in size of ≥1.5 mm
• assignment of a Lung-RADS status is based on the most suspicious nodule
• category 4B management is based on multiple factors including overall patient status and patient preference
• solid nodules with smooth margins, an oval, lentiform or triangular shape, and maximum diameter less than 10 mm (perifissural nodules) should be classified as category 2. (version 1.1 addition)

References

• American College of Radiology ACR Lung-RADS® v2022
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206195/
• https://www.who.int/news/item/01-02-2024-global-cancer-burden-growing--amidst-mounting-need-for-services
• Thoracic imaging W –Richard -Webb
• State of the Art: Lung Cancer Staging Using Updated Imaging Modalities ,Nihal M. Batouty
• Differential diagnosis of localized pneumonic-type lung adenocarcinoma and pulmonary inflammatory lesion. Insights Imaging 13, 49 (2022).

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