lung%20cancer
LUNG CANCER
Lung cancer is having a malignant tumor in the lungs especially in the cells lining air passages.
Primary tumor-related signs and symptoms are cough, dyspnea, hemoptysis, and chest discomfort.
Signs and symptoms due to intrathoracic spread may involve the nerves (hoarseness, dyspnea, muscle wasting of upper limb, Horner's syndrome), chest wall and pleura (chest pain, dyspnea) and vascular structures (facial swelling, dilated neck veins, cardiac tamponade) & viscera (dsyphagia).
The signs and symptoms due to metastatic spread are bone pain with or without pleuritic pain, neurologic symptoms, limb weakness, unsteady gait, cervical lymphadenopathy, and skin nodules.

Staging

Staging of Non-Small Cell Lung Cancer (NSCLC)
  • Clinical staging is established initially from history, physical exam, pathologic findings, chest, upper abdomen, and adrenal computed tomography (CT) scan, complete blood count with platelet count, and chemistry profile of the patient
    • Pathologic mediastinal lymph node evaluation may be done through mediastinoscopy, mediastinotomy, endobronchial ultrasound (EBUS), endoscopic ultrasound (EUS), endobronchial ultrasound-guided fine needle aspiration (EBUS-FNA), endoscopic ultrasound-guided-fine needle aspiration (EUS-FNA), or CT-guided biopsy
    • Supraclavicular lymph node metastasis in NSCLC may be staged using CT, PET-CT scan, or neck ultrasound fine needle aspiration (FNA)
    • Fluoro-D-glucose-positron emission tomography computed tomography (FDG PET-CT) scanning is recommended for detection of distant metastases in NSCLC

Revised Tumor, Nodes and Metastases (TNM) System (7th Edition)

  • Proposed by the International Association for the Study of Lung Cancer (IASLC) and adopted by the American Joint Committee on Cancer (AJCC) and Union Internationale Contre le Cancer
  • Determines if the patient would benefit from surgical resection and may predict patient’s survival
  • Currently recommended to classify both NSCLC and small cell lung cancer (SCLC)

Tumor Evaluation

  • Evaluates the degree of spread of the primary tumor

TX

  • Primary tumor cannot be assessed, or tumor is present in malignant cells in sputum or bronchial washings but not seen in imaging or bronchoscopy

T0

  • No evidence of primary tumor

Tis

  • Carcinoma in situ; squamous cell carcinoma in situ; adenocarcinoma in situ (adenocarcinoma with pure lepidic pattern, ≤3 cm greatest dimension)

T1

  • Tumor size ≤3 cm in greatest dimension, surrounded by lung or visceral pleura, without invasion that is more proximal than the lobar bronchus in bronchoscopy

T1mi

  • Minimally invasive adenocarcinoma (adenocarcinoma ≤3 cm greatest dimension with predominantly lepidic pattern and ≤5 mm invasion in greatest diameter)

T1a

  • Tumor size is ≤1 cm in greatest dimension; superficial spreading tumor with invasion limited to the bronchial wall and with possible proximal extension to the main bronchus

T1b

  • Tumor size >1 cm but ≤2 cm in greatest dimension

T1c

  • Tumor size >2 cm but ≤3 cm in greatest dimension

T2

  • Tumor size >3 cm but ≤5 cm or tumor with any of the following features: Involves main bronchus without involvement of the carina; with atelectasis or obstructive pneumonitis extending to the hilar region; Invades the visceral pleura

T2a

  • Tumor size >3 cm but ≤4 cm in greatest dimension

T2b

  • Tumor size >4 cm but ≤5 cm in greatest dimension

T3

  • Tumor size is >5 cm but ≤7 cm in greatest dimension or tumor directly involving any of the following: chest wall, pericardium, phrenic nerve or separate nodules in the same lobe

T4

  • Tumor size is >7 cm in greatest dimension with invasion of these relevant structures: mediastinum, heart, great vessels, trachea, diaphragm, recurrent laryngeal nerve, esophagus, vertebral body and carina, or separate tumor nodules in different ipsilateral lobe

Regional Lymph Node (LN) Evaluation

  • Evaluation of extent of nodal involvement
    • Mediastinal lymph node involvement usually makes surgical resection inappropriate

NX

  • Regional LN cannot be assessed

N0

  • No regional LN metastasis

N1

  • Metastases in ipsilateral peribronchial and/or hilar LN and intrapulmonary nodes, including involvement by direct extension

N1a

  • Involvement of single-station N1

N1b

  • Involvement of multiple-station N1

N2

  • Metastases in ipsilateral mediastinal and/or subcarinal lymph node

N2a1

  • Single-station N2 without involvement of N1

N2a2

  • Single-station N2 with involvement of N1

N2b

  • Involvement of multiple-station N2

N3

  • Metastasis in contralateral mediastinal or hilar or ipsilateral or contralateral scalene, or supraclavicular LN

Evaluation of Distant Metastasis

M0

  • No distant metastasis
M1
  • Distant metastasis

M1a

  • Malignant pleural or pericardial effusion or tumor with pleural or pericardial nodules or presence of separate nodules in the contralateral lobe

M1b

  • Single extrathoracic metastasis in a single organ

M1c

  • Multiple extrathoracic metastasis in ≥1 organ

Staging

Occult carcinoma

  • TX N0 M0

Stage 0

  • Tis N0 M0

Stage IA1

  • T1mi N0 M0; T1a N0 M0

Stage IA2

  • T1b N0 M0

Stage IA3

  • T1c N0 M0

Stage IB

  • T2a N0 M0

Stage IIA

  • T2b N0 M0

Stage IIB

  • T1a N1 M0
  • T1b N1 M0
  • T1c N1 M0
  • T2a N1 M0
  • T2b N1 M0
  • T3 N0 M0

Stage IIIA

  • T1a N2 M0
  • T1b N2 M0
  • T1c N2 M0
  • T2a N2 M0
  • T2b N2 M0
  • T3 N1 M0
  • T4 N0 M0
  • T4 N1 M0

Stage IIIB

  • T1a N3 M0
  • T1b N3 M0
  • T1c N3 M0
  • T2a N3 M0
  • T2b N3 M0
  • T3 N2 M0
  • T4 N2 M0

Stage IIIC

  • T3 N3 M0; T4 N3 M0

Stage IVA

  • Any T Any N M1a; Any T Any N M1b

Stage IVB

  • Any T Any N M1c

Residual Tumor After Treatment

R0

  • No identifiable tumor remaining, surgical margins are negative

R1

  • Microscopically positive margins but without visible tumor remaining

R2

  • Remaining tumor is grossly visible or palpable

Staging of Small Cell Lung Cancer (SCLC)
  • Full staging of SCLC should include history, physical exam, computed tomography (CT) scan of the chest and/or abdomen,, magnetic resonance imaging (MRI) or CT scan of the head and a bone scan from the base of skull to mid-thigh if positron emission tomography (PET) scan is not obtained and limited stage is suspected
    • Bone marrow aspirate for biopsy is advised in patients with nucleated red blood cells on peripheral blood smear, neutropenia, thrombocytopenia and no evidence of other metastasis
    • Chest X-ray and PET scan may be optional part of initial evaluation
  • The updated TNM system (8th ed) by International Association for the Study of Lung Cancer (IASLC) may be used for staging SCLC
  • Staging should not delay the start of treatment for >1 week because SCLC is a very aggressive disease, with faster doubling time, higher growth fraction, and earlier development of metastasis

Limited Disease (LD)

  • Confined to the primarily affected hemithorax, mediastinum or supraclavicular nodes
  • Equivalent to stages I to III of the TNM system except T3-4 with multiple lung nodules that do not fit or are too extensive in a tolerable radiation field
  • Pulmonary function tests, bone imaging, and mediastinal staging via mediastinoscopy, mediastinotomy, endobronchial/esophageal ultrasound-guided biopsy and video-assisted thoracoscopy may be performed prior to initial treatment
    • Mediastinal staging may not be performed if patient decides against surgical resection

Extensive Disease (ED)

  • Metastases found beyond the supraclavicular areas, in contralateral chest or at distant sites
  • Same as stage IV of the TNM system or T3-4 with multiple lung nodules that do not fit in a tolerable radiation field

  • No distant metastasis

Assessment

  • Identify comorbidities (ie heart, kidney, liver problems)
  • Assess performance status (PS)
    • Usually utilizes the grading system developed by the Eastern Cooperative Oncology Group (ECOG) to determine disease progression, effect of disease to the patient, prognosis and suitability of the treatment employed
      • Grade 0 - Fully active; no restriction
      • Grade 1 - With restrictions to strenuous activity but can do light work
      • Grade 2 - Capable of self-care but not other activity
      • Grade 3 - Performs limited self-care and stays in bed or chair for >50% of waking hrs
      • Grade 4 - Disabled; restricted to bed or chair
      • Grade 5 - Dead
  • Evaluate pulmonary function
    • Spirometry is recommended to patients being considered for lung surgery
    • May indicate increased risk of perioperative death and cardiopulmonary complication with standard lung surgery (ie FEV1 <40%, carbon monoxide diffusion capacity <40%, max O2 uptake <10 mL/kg/min, arterial O2 sat <90%)
  • Identify histologic subtype and genetic alterations/mutations
    • Immunohistochemical staining is used to identify gene rearrangements and mutations and fusions, and to differentiate primary pulmonary adenocarcinoma from the following: Squamous cell carcinoma, large cell carcinoma, metastatic carcinoma, and malignant mesothelioma
      • It is also used to determine if there is neuroendocrine differentiation
  • Other assays being used include next-generation sequencing (NGS), real-time polymerase chain reaction (PCR), Sanger sequencing and fluorescence in situ (FISH) analysis     
  • Predictive biomarkers (eg EGFR, ALK, ROS1, BRAF V600E, KRAS, NTRK, PD-L1) are molecules that is indicative of mutations and rearrangements that are used as therapeutic targets
    • Targeted agents with activity against a specific genetic alteration include include Crizotinib, Cabozantinib,Vandetanib, Ado-trastuzumab emtansine, Nivolumab + Ipilimumab and Nivolumab
    • T790M testing should be done in patients with EGFR mutation with possible resistance to initial treatment
Risk Categories

High Risk
  • Patients 55-77 years old with smoking history of ≥30 pack years or have already stopped smoking for <15 years or
  • Patients ≥50 years old with smoking history of ≥20 pack years and with other risk factors aside from second hand smoking
Moderate Risk 
  • Patients ≥50 years old with smoking history of ≥20 pack years or exposure to second hand smoking but without additional risk factors
Low Risk
  • Patients <50 years old and/or with smoking history of <20 pack years

History

Patients should be asked for the presence or absence of:

  • Dizziness or headache - to rule out brain metastasis
  • Bone or joint pain - to rule out bone metastasis
  • Other head or neck symptoms - to rule out other tumors

Laboratory Tests

Confirmatory Tests

Sputum Cytology
  • Due to poorly controlled sample collection, diagnostic yield tends to be low
  • Should be reserved for patients in whom bronchoscopy or fine needle aspiration biopsy (FNAB) is contraindicated

Histologic Diagnosis

  • Cell size is the major distinguishing factor of NSCLC and SCLC
  • The 2 most common types of lung cancer are:
    • Non-small cell lung cancer (NSCLC)
      • A slow-growing type of epithelial lung cancer that accounts for approximately 85% of all lung cancers (most common)
      • Classic features such as keratin pearls and gland formation differentiates NSCLC from SCLC
    • Small cell lung cancer (SCLC) 
      • A fast-growing cancer that forms in the tissues of the lungs that easily spreads to other parts of the body (aggressive and rare type)
      • Accounts for about 15% of all reported cases of lung cancer
      • Cell size is twice the size of the lymphocytes
      • Other features that distinguishes SCLC from NSCLC are hyperchromatic appearance, high nuclear to cytoplasmic ratio, cohesive sheets of small blue cells with rosette formation, cell fragility and crush artifact with necrosis 
  • Three main subtypes of NSCLC: 
    • Adenocarcinoma
      • Cancer that begins in the glandular or secretory cells
      • Comprises 40% of the NSCLC
      • May develop in patients who do not smoke
    • Squamous cell carcinoma
      • Cancer that forms in the squamous cells showing keratinization and/or intercellular bridges
      • Centrally located and can be found in larger bronchi
      • Comprises 25-30% of the NSCLC
    • Poorly differentiated or large cell carcinoma
      • Comprises 10-15% of the NSCLC

Immunohistochemistry (IHC)

  • Aids in the determination of the specific subtype of NSCLC
  • IHC stains used include: Thyroid transcription factor 1 (TTF1), napsin A, p40, p63
    • Adenocarcinoma: TTF1, napsin A
    • Squamous cell carcinoma: p40, p63
    • NSCLC-NOS: If neither TTF1 nor p40 are positive
World Health Organization (WHO)/International Association for the Study of Lung Cancer (IASLC) Classification
  • Epithelial tumors
    • Squamous cell carcinoma
      • Papillary
      • Clear cell 
      • Small cell
      • Basiloid
    • Adenocarcinoma
      • Lepidic, acinar, papillary, micropapillary, invasive mucinous (mixed invasive mucinous, nonmucinous), colloid, fetal, enteric, solid adenocarcinoma, minimally invasive (nonmucinous, mucinous), preinvasive lesions [atypical adenomatous hyperplasia, adenocarcinoma in situ (mucinous, nonmucinous)]
    • Pulmonary neuroendocrine tumors
      • Carcinoid tumors (typical carcinoid, atypical carcinoid)
      • Small cell lung carcinoma (combined small cell neuroendocrine carcinoma)
      • Large cell neuroendocrine carcinoma (LCNEC) (combined LCNEC)
    • Large cell carcinoma
    • Adenosquamous carcinoma
    • Sarcomatoid carcinomas (pleomorphic, spindle cell, giant cell, carcinosarcoma, pulmonary blastoma)
    • Other and unclassified carcinomas (lymphoepithelioma-like, NUT carcinoma)
    • Preinvasive lesion (diffuse idiopathic pulmonary neuroendocrine cell hyperplasia)
    • Salivary gland-type tumors (mucoepidermoid, adenoid cystic, epithelial-myoepithelial, pleomorphic)
    • Papillomas [squamous cell (exophytic, inverted), glandular, mixed squamous and glandular]
    • Adenomas (sclerosing pneumocytoma, alveolar, papillary, mucinous cystadenoma, mucous gland)
  • Mesenchymal tumors
    • Pulmonary hamartoma, chondroma, PEComatous (lymphangioleiomyomatosis, PEComa benign - clear cell tumor, PEComa malignant), congenital peribronchial myofibroblastic tumor, diffuse pulmonary lymphangiomatosis, inflammatory myofibroblastic tumor, epithelioid hemangioendothelioma, pleuropulmonary blastoma, synovial sarcoma, pulmonary artery intimal sarcoma, pulmonary myxoid sarcoma with EWSR1–CREB1 translocation, myoepithelial (myoepithelioma, myoepithelial carcinoma)
  • Lymphohistiocytic tumors
    • Extranodal marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT lymphoma), diffuse large cell lymphoma, lymphomatoid granulomatosis, intravascular large B cell lymphoma, pulmonary Langerhans cell histiocytosis, Erdheim-Chester disease)
  • Tumors of ectopic origin
    • Germ cell tumors (teratoma mature/immature), intrapulmonary thymoma, melanoma, meningioma, NOS
  • Metastatic tumors

 

Imaging

Noninvasive Imaging Procedures

Chest X-ray

  • Should be performed in all patients in whom lung cancer is suspected but should not be used alone as a screening tool
  • Not enough sensitivity to determine lymph node involvement
  • Usual findings in lung cancer include solitary pulmonary nodule, pulmonary or hilar mass, poorly resolving pneumonia, and pleural effusion

Chest Computed Tomography (CT) Scan

  • Defines size, location and characteristics of pulmonary mass
  • Determines presence of lymphadenopathy
  • Allows evaluation of surrounding structures
  • May be used to evaluate presence of pleural effusion
  • Standard imaging procedure for determining metastasis
  • Low-dose computed tomography (LDCT) is the recommended screening tool to detect lung cancer among defined high-risk population
    • May lower lung cancer-specific mortality by 20%
  • Multidetector CT may be considered for very small benign or malignant lung nodules

Positron Emission Tomography (PET) Scan

  • Determines normal from neoplastic tissues even as small as 1 cm
  • May be performed in patients with solitary lung lesions
  • Can increase accuracy of staging patients
  • Positive results are due to: 
    • Infection or inflammation
    • Absence of lung cancer with localized infection
    • Presence of lung cancer with post-obstructive infection 
    • Presence of lung cancer with inflammation in the node, parenchyma and pleura
  • False-negative results are due to:
    • Small nodule 
    • Non-solid nodule or ground-glass opacity (GGO)
    • Adenocarcinoma in situ 
    • Carcinoid tumor
  • Better than computed tomography scan for mediastinal staging in non-small cell lung cancer; however, it is not reliable in identifying brain and urinary tract metastases

PET/CT Scan

  • May be done to assess distant metastases (eg bone metastasis) and guide mediastinal evaluation
    • Superior to positron emission tomography scan alone and to other standard imaging but inferior in detecting metastases to the brain
  • Improves target accuracy of radiation therapy in patients with significant atelectasis and in patients with contraindication to IV CT contrast
  • If PET/CT scan is not available then bone scan may be used as an alternative in identifying bone metastasis
  • Fluorodeoxyglucose (FDG)-PET-CT scan is useful for the evaluation of solitary lung nodules, intra-thoracic pathological LN and distant metastases

Brain Magnetic Resonance Imaging (MRI) Scan

  • More preferred than CT scan in identifying brain metastasis 
Invasive Imaging Procedures

Bronchoscopy
  • Used for diagnosing and staging central and peripheral lung lesions
    • May be used as a confirmatory test for suspected central lesions
    • A required procedure prior to surgical resection
  • Electromagnetic guidance for bronchoscopy increases bronchoscopy sensitivity (60%), specificity (91%), and accuracy (67%) for peripheral lesions.

Fine Needle Aspiration Biopsy (FNAB)

  • Recommended confirmatory test for solitary extrathoracic site suspected to be a metastatic lesion
  • May be done blindly but preferably guided by computed tomography (CT), magnetic resonance imaging (MRI), fluoroscopy or ultrasound
    • Computed tomography-guided fine needle aspiration/percutaneous core biopsy - 86-94% sensitive, 41-100% specific, 83-93% accurate for peripheral pulmonary lesions

Endobronchial or Esophageal Ultrasound-guided Biopsy [transesophageal endoscopic ultrasound-guided FNA (EUS-FNA) or endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA)]

  • Minimally invasive technique used for mediastinal staging, as compared to mediastinoscopy
    • Studies have shown that endobronchial ultrasound-guided transbronchial needle aspiration achieved similar results for the mediastinal staging of lung cancer hence may possibly replace mediastinoscopy in patients with potentially resectable non-small cell lung cancer
      • Diagnostic yield of 80% for peripheral lesions; 82-94% sensitive for central lesions
      • Has low rates of nondiagnostic and false-negative biopsy findings, may be done in small subcentimeter nodes, and can confirm radiographically positive mediastinum
      • Allows access to the hilar and interlobar lymph nodes which can not be reached by mediastinoscopy
    • Video-assisted thoracoscopy is another minimally invasive technique used in mediastinal staging
  • Endobronchial ultrasound or endoscopic ultrasound are done as part of pretreatment evaluation in patients with stage I-IIIA (T4 extension, N0-1; T3, N1)
    • May be preferred over mediastinoscopy in sampling mediastinal lymph nodes, reserving mediastinoscopy and mediastinal lymph node dissection until the planned surgical resection

Mediastinoscopy

  • Gold standard preoperative procedure for evaluating mediastinal nodes
    • Recommended in patients with peripheral T2a, central T1ab, or T2 lesions with negative PET/CT scan
  • A preoperative mediastinoscopy should be considered in patients found negative for malignancy in endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) but clinically positive in PET-CT scan

Screening

  • Several recommendations have emerged for screening of lung cancer, including those by the American Association for Thoracic Surgery, the National Comprehensive Cancer Network (NCCN), the United States Preventive Services Task Force (USPSTF), the European Society of Radiology (ESR) and the European Respiratory Society (ERS)
  • ESR and ERS recommend that lung cancer screening be conducted within clinical trials or routine clinical practice with multidisciplinary medical centers, to include individuals 55-80 years old, with smoking history of ≥30 pack years, current smoker, or those who have quit smoking within the last 15 years
  • Individuals with comorbidities precluding curative therapy and without consent to undergo curative therapy
  • It is recommended that all screening and follow-up CT scans should be performed at a dose of 100-120 kVp and 40-60 mAs or less 
Screening Trials
  • National Lung Screening trial (NLST): 1st US-based randomized controlled lung screening trial for current smokers or who used to consume >30 pack-years with ages of 55-74 years
  • European NEderlands-Leuvens Screening ONderzoek (NELSON) trial: 2nd largest screening trial and the largest European randomized controlled trial in Europe used to assess patient risk based on age and smoking history 
Recommendations for Patients with Lung Nodules on Initial Screening Using Low-Dose Computed Tomography (LDCT)
  • Solid nodule
    • For solid nodule ≤5 mm, annual LDCT is recommended until patient has been excluded for definitive treatment
    • For single solid nodule 6-7 mm, LDCT should be fulfilled at 6 months
    • For an 8-14 mm solid nodule, LDCT should be considered at 3 months; may also consider PET/CT
    • Patients with ≥15 mm solid tumor, chest CT with contrast and/or PET/CT is recommended
      • LDCT after 3 months should be considered in patients with low risk for lung cancer
      • Biopsy or surgical excision is recommended for patients at high risk for lung cancer
    • For patients with solid endobronchial nodule, LDCT ≤1 month is recommended, followed by bronchoscopy if without resolution
  • Part-solid nodule
    • For part-solid nodule ≤5 mm, annual LDCT is recommended until patient has been excluded for definitive treatment
    • LDCT after 6 months is recommended for patients with ≥6 mm part-solid nodule with solid component ≤5 mm
      • If with 6-7 mm solid component, LDCT is recommended 3 months after initial screening or may also consider PET/CT
    • Patients with part-solid nodule with solid component of ≥8 mm, chest CT with contrast and/or PET/CT is recommended
      • If highly suspicious for lung cancer, biopsy or surgical resection should be considered
      • LDCT after 3 months is recommended for patients at low risk for lung cancer
  • Non-solid nodule
    • Annual LDCT is recommended for non-solid nodules ≤19 mm until patient has been excluded for definitive treatment
    • LDCT 6 months after initial screening is recommended for patients with ≥20 mm non-solid nodule
Recommendations for Follow-up or Annual Screening Using Low-Dose Computed Tomography (LDCT)
  • New nodules
    • For suspected infection or inflammation, LDCT should be done in 1-3 months
    • For suspected infection or inflammation that is resolving, LDCT should be repeated in 3-6 months until it reaches resolution or stability
    • For patients with suspected infection or inflammation that has been resolved, annual LDCT is recommended
    • For patients with suspected infection or inflammation that is persistent or the nodule is enlarging and those without suspected inflammation or infection, please see recommendations on solid/part-solid/non-solid nodules on follow-up below
  • Solid nodules
    • For ≤7 mm solid nodule that is unchanged on follow-up, an annual LDCT is recommended  
    • For 8-14 mm solid nodule that is unchanged on follow-up, LDCT should be done in 6 months, if still unchanged after 6 months then, an annual low-dose computed tomography (LDCT) is recommended 
    • For ≥15 mm solid unchanged on follow-up, a LDCT in 6 months or PET/CT scan is recommended
    • For unchanged findings in a year or for ≤3 mm new solid nodule on follow-up, an annual LDCT is still recommended
    • For ≤3 mm new solid nodule on follow-up, annual LDCT is recommended 
    • For 4-5 mm new solid nodule on follow-up, LDCT should be done in 6 months
    • For 6-7 mm new solid nodule on follow-up, LDCT should be done in 3 months
    • For ≥8 mm new solid nodule on follow-up, chest CT scan with or without contrast and/or PET/CT scan is recommended 
    • For ≤7 mm growing nodule on follow-up, LDCT should be done in 3 months
    • For ≥8 mm growing nodule on follow-up, chest CT scan with or without contrast and/or PET/CT scan is recommended
    • Based on patient risk: 
      • If with low risk for lung cancer, LDCT after 6 months is recommended
      • LDCT in 3 months for ≥6 mm solid nodule on chest CT with contrast and/or PET/CT
      • Biopsy or surgical resection is recommended for patients at high risk for lung cancer
  • Part-solid nodules
    • For ≤5 mm part-solid nodule that is unchanged on follow-up, and ≥6 mm part-solid nodule and with 6-7 mm solid component, annual LDCT is also recommended
    • For ≥6 mm part-solid nodule and with ≥8 mm solid component, LDCT in 6 months or PET/CT scan is recommended
    • If the part-solid nodule is unchanged, then an annual LDCT is recommended
    • For new part-solid nodule that is ≤5 mm on follow-up, LDCT should be done in 6 months
    • For new or growing part-solid nodule that is ≥6 mm in size with a growing ≤3 mm solid component on follow-up, LDCT should be done in 3 months
    • For new or growing part-solid nodule with ≥4 mm solid component, chest CT scan with contrast and/or PET/CT scan is recommended
  • Non-solid (NS) nodules
    • For ≤19 mm new and stable NS nodule, annual LDCT is recommended 
    • For ≥20 mm new and stable NS nodule, LDCT should be done in 6 months, then annually once stable
    • For ≥20 mm stable NS nodule, LDCT should be done in 6 months 
    • For ≤19 mm growing NS nodule, LDCT should be done in 6 months
    • For ≥20 mm growing NS nodule, LDCT should be done in 6 months or biopsy or surgical excision
  • Multiple NS nodules
    • For pure NS nodules, measure the largest nodule and manage based on size as a NS nodule
    • For dominant nodules with part-solid component, measure the largest nodule and manage based on size as a part-solid nodule
  • For patients without lung nodules on LDCT, an annual screening with LDCT is recommended
    • Should be done until the patient is no longer a candidate for definitive treatment 
  • A follow-up LDCT in 1-3 months is recommended for patients with multiple nodules or other findings suggestive of possible occult infection or inflammation
  • Bronchoscopy should be done in patients with solid endobronchial nodule on LDCT screening
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