Lung Cancer



Lung Cancer


Todd M. Blodgett, MD

Carl Fuhrman, MD

Sanjay Paidisetty, BS









One week after discharge status post right lower lobectomy for NSCLC, coronal PET (A) shows focal FDG activity image. PET/CT (C) localizes the lesion image to the pericardium, without obvious abnormality on the CECT (B). Autopsy confirmed a pericardial metastasis.






Coronal PET (A) and PET/CT (C) from the same PET/CT exam as the previous image show a hepatic lesion image not detected on axial CECT (B). Unsuspected additional lesions were also present image.


TERMINOLOGY


Abbreviations and Synonyms



  • Non-small cell lung cancer (NSCLC)


  • Adenocarcinoma


  • Bronchogenic carcinoma


  • Squamous cell carcinoma (SCCA)


  • Bronchoalveolar carcinoma (BAC)


  • Large cell carcinoma (LCCA)


Definitions



  • Glandular carcinomas of varying histology arising in lung parenchyma


IMAGING FINDINGS


General Features



  • Best diagnostic clue



    • Peripheral irregular spiculated pulmonary nodule in a smoker



      • Malignant in > 90% of patients


    • Hilar and mediastinal lymphadenopathy


    • Bronchial stenosis and associated atelectasis


  • Location



    • Adenocarcinoma: Periphery of upper lobe


    • SCCA: Central


  • Size



    • By time of detection



      • At screening: 8-15 mm


      • Symptomatic: 25 mm


    • Size is not a reliable indicator of nodal involvement



      • 21% of subcentimeter nodes = malignant


      • 40% of nodes > 1 cm = benign


    • LCCA: > 4 cm at diagnosis


  • Morphology



    • Spiculated irregular ill-defined nodule is specific for malignancy



      • Borders may also be lobulated or smooth


Imaging Recommendations



  • Best imaging tool



    • CT for delineating extent of disease


    • PET/CT for prognosis and staging


    • MR for diagnosing neural invasion



      • CNS, Pancoast invasion of brachial plexus


    • No imaging tool is specific enough to defer lymph node biopsy if required for treatment planning



    • Mediastinoscopy most common method for assessing mediastinal lymph nodes


  • Protocol advice



    • CT



      • To include adrenals, image caudally from thoracic inlet to inferior edge of liver


      • Pleural and diaphragmatic tumor spread best imaged with multiplanar reformatting


      • Screening CT studies should be performed without contrast and with the lowest possible mAs


    • FDG PET



      • Serum glucose < 150 mg/dL (reschedule hyperglycemic patients)


      • 90 minute uptake period


    • PET/CT



      • Modified breath-hold techniques employed to reduce misregistration artifact


      • Sensitivity in lower lobes may be minimized without maximal inspiration


CT Findings



  • General findings



    • Current CT does not provide adequate anatomic detail to separate invasion from simple contact between tumor and adjacent organ


    • NECT adequate for evaluation of primary tumor, but less sensitive for vascular invasion and liver metastases


    • CECT can reveal small endobronchial lesions and better elicit small mediastinal nodes



      • Particularly hilar nodes that may otherwise missed due to proximity to vessels


    • Bronchial obstruction with lobar collapse or post-obstructive pneumonitis


    • Peripheral lesions



      • SCCA more likely to demonstrate cavitation


      • Peripheral adenocarcinoma may be solid, mixed solid/ground-glass, or ground-glass


  • Staging



    • CT has not demonstrated improved staging accuracy with the advent of multislice detectors


    • Malignant potential and degree of contrast enhancement may be related due to increased vascularity of lung cancer lesions


  • Lymph nodes



    • Upper size limits for suspicion of malignancy



      • > 5 mm hilum and > 10 mm mediastinum


    • Size criteria are insensitive, as normal-sized nodes often harbor malignancy



      • Sensitivity 41-54%


      • Combined PET/CT may correct 81% of false negatives on CT


    • Measurement errors inherent with borderline node size of 5 mm


    • Mediastinal and hilar nodal metastasis is not predicted by characteristics of primary tumor



      • Size, margins, necrosis, bronchovascular thickening


    • Best predictor of mediastinal nodal metastasis is peak enhancement of malignant lung nodules



      • > 100 HU or > 60 HU of net enhancement in stage T1 NSCLC


      • Mediastinoscopic biopsy recommended in the setting of these findings whether FDG PET is positive or not


    • Supraclavicular nodal sensitivity of 67-85%



      • Area often obscured by beam-hardening artifacts


      • Delayed scans may improve detection


      • Transverse scan may not accurately depict short-axis measurement of nodes


    • Normal structures that mimic lymph nodes



      • External/internal jugular veins


      • Vertebral veins


      • Common carotids


      • Scalene and longus colli muscles


  • Metastatic disease



    • High resolution CT to detect lymphangitic carcinomatosis


    • Look for metastasis to non-tumor lobe


    • CECT can demonstrate pleural metastases in pleural effusion


    • Adrenal evaluation complicated by insensitivity of morphologic criteria for presence of malignancy




      • May be evaluated with NECT


      • 17% of normal-appearing adrenals may harbor malignancy


      • Overall, fewer than half of adrenal masses in patients with lung cancer will be due to metastasis


Nuclear Medicine Findings



  • PET/CT



    • Central to initial and post-treatment evaluation and management of NSCLC


    • Depicts response to treatment accurately and predicts prognosis


    • Influences management by demonstrating occult disease


    • Provides high contrast between tumor and adjacent structures like mediastinum, chest wall, atelectasis


    • Helps determine cause of pleural effusion


  • Normal uptake



    • Low level in thyroid, breast, and mediastinal blood pool


    • Talking can cause laryngeal uptake


    • Anxiety may be manifested as uptake in the SCM


    • Brown fat in neck, paravertebral, mediastinal, and axillary regions


    • Also seen in esophagus, spleen, liver, and bowel


  • Initial diagnosis


  • FDG PET criteria for malignancy (less specific than sensitive)



    • FDG uptake > background mediastinal uptake


    • Max SUV ≥ 2.5; however wide overlap of SUVs between benign and malignant processes


    • Any activity above background levels in lesion < 1-1.5 cm


  • For SPN larger than 1.0 cm, PET has sensitivity and specificity of 95-98% and 73-85% respectively



    • Same predictive value as observation of nodule growth on CT


  • Nodules < 2.5 cm may be misinterpreted as non-FDG-avid due to partial volume averaging on PET



    • Recovery coefficient helps correct SUV in smaller nodules for purposes of quantitative determinations


  • Tumor with low metabolic rate (low grade adenocarcinoma, BAC, carcinoid)


  • Subtypes may show low FDG uptake despite aggressiveness



    • BAC, carcinoid, low grade adenocarcinoma


  • Staging


  • Detection of disease



    • PET can identify metastases that would be occult on conventional workup (e.g., adrenal metastases)


    • Detects bone metastases with equal sensitivity to and greater specificity than bone scintigraphy


    • False positives with benign inflammatory disease > 1.0 cm


    • False negatives in subcentimeter lesion with limited cancer invasion


    • Low sensitivity of 47% for stage T1 NSCLC


    • 100% PPV and high NPV for mediastinal nodal metastasis


    • Brain metastases may be overlooked due to high background FDG avidity


    • Necrotic metastases may be negative (e.g., adrenal masses)


  • Influence on management



    • PET more sensitive than clinical exam for supraclavicular lymphadenopathy



      • Significant indicator of inoperable disease


      • Confirmation by histopathology is mandatory when positive PET/CT would deny patient chance for potentially curative treatment


    • High NPV of 93% helps avoid invasive procedures like fine needle aspiration (FNA) when there is no FDG uptake



      • Microscopic disease may be present, and mediastinal surgical staging may still be indicated


    • Thoracotomy



      • PET has greater than 90% NPV for nodal disease


      • Patients with negative mediastinal nodes may proceed directly to thoracotomy without need for mediastinoscopy


      • PET may also avoid non-therapeutic thoracotomy in 20% by detecting previously occult distant disease


    • PET/CT may alter 50% of radiotherapy gross tumor volume estimation compared to targeting with CT alone



      • Clinical impact yet to be determined


      • Gross tumor volume (GTV) shown to include all pathologically involved mediastinal lymph nodes


      • More positive lymph nodes are detected by PET/CT compared to CT alone


  • Prognosis



    • FDG PET may provide information on prognosis independent from standard staging algorithms


    • Primary tumor with SUV ≥ 5.0



      • Associated with significant increase in post-operative relapse in early stage lung cancer


    • Intense uptake in bone marrow also associated with poorer outcome


  • Response to treatment


  • Decrease in FDG avidity of malignant lesion by 60% following 2-3 cycles of chemotherapy



    • May indicate good response and be predictive of improved survival


  • Some tumors may show falsely decreased SUV post-therapy (“stunned”) but still represent threat of recurrence


  • False positives



    • Nonmalignant metabolically active conditions



      • Active inflammation, infection, granulomatous disease


    • Pattern of physiologic muscle uptake typically



      • Bilateral, symmetric, fusiform, or elongated; seldom confused with presence of malignancy


      • Asymmetric uptake can occur


    • Increased glycolysis in leukocytes, lymphocytes, macrophages



      • Produce uptake in areas of infection, inflammation


    • Examples of benign processes that may mimic malignancy



      • Atherosclerotic plaque


      • Reflux esophagitis



      • Tuberculous caseating granuloma


      • Sarcoidosis


      • Wegener granulomatosis


      • Amyloidosis


      • Pulmonary infarction


      • Pulmonary embolus


      • Pulmonary hamartomas


      • Needle biopsy site


      • Mediastinoscopy


      • Talc pleurodesis, which may remain FDG positive for several years


      • Empyema


      • Pneumonias usually produce low grade uptake but avid uptake can occur


      • Organizing pneumonia as a single focus of consolidation can mimic lung cancer


  • Patients with false positives on PET/CT often have comorbid pulmonary complications, such as



    • Obstructive pneumonia


    • Chronic bronchitis


    • Interstitial pneumonia


    • Bronchiectasis


    • Silicosis


    • Previous pulmonary tuberculosis


DIFFERENTIAL DIAGNOSIS


Metastases



  • Usually less spiculated than primary pulmonary malignancies


  • Variably FDG avid


Infection



  • Pneumonia may show intense focal uptake and is easily mistaken for malignancy


  • Repeat PET to rule out presence of underlying malignancy


Granulomatous Disease



  • Mediastinal and hilar adenopathy generally symmetrical and FDG avid


  • Predominantly in upper lobes


  • Calcification is common


Pulmonary Infarct



  • Early following infarct, may show intense FDG activity


  • Usually becomes less intense over time


  • Distribution of occluded artery


Hamartoma



  • Generally noninflammatory with little FDG uptake


  • “Popcorn” calcifications


PATHOLOGY


General Features



  • General path comments: Sputum analysis is insensitive, with false negative in 40% of cases


  • Genetics



    • NSCLC associated with amplification of oncogenes (e.g., ras family) in 30% of cases



      • Also inactivation of tumor suppression genes


      • Portends worse prognosis


    • Genetic predisposition plays role in vulnerability to risk factors (e.g., smoking)


  • Etiology



    • Tobacco is the cause of lung cancer in ˜ 90% of cases



      • Disease was practically unknown prior to the rise of cigarette smoking in the 1920s


      • 15% of lung cancer in patients who do not smoke is caused by passive smoke


    • Asbestos exposure in a patient who smokes confers 80-90x increased risk of lung cancer


    • Radon accounts for 2-3% of lung cancer and is a byproduct of uranium decay (miners)


  • Epidemiology



    • In USA: 170,000 new cases/year (90k in men and 80k in women); 150,000 deaths/year


    • Estimated 1 million new cases/year worldwide


    • NSCLC accounts for ˜ 80% of all lung cancers


  • Associated abnormalities: COPD


Gross Pathologic & Surgical Features



  • Cavitation is common in SCCA


Microscopic Features



  • Adenocarcinoma: Forms glands and produces mucin, which can be identified with mucicarmine or PAS staining


  • SCCA: Large irregular nuclei, coarse nuclear chromatin, large nucleoli



    • Presence of intercellular bridging among cells arranged in sheets is pathognomonic


  • LCCA: Large cells with prominent nucleoli in the absence of mucin production or intercellular bridging


Staging, Grading, or Classification Criteria



  • Primary lesion (T)



    • Tx: Tumor cannot be assessed, + sputum/washings


    • T0: No evidence of primary tumor


    • Tis: Carcinoma in situ


    • T1: < 3 cm, completely surrounded by lung; no main bronchi invasion


    • T2: > 3 cm, involving main bronchus > 2 cm from the carina, visceral pleura; atelectasis/pneumonitis extending to hila


    • T3: Invading chest wall, diaphragm, mediastinal pleura, parietal pericardium, main bronchus < 2 cm from the carina



      • Total atelectasis of whole lung


    • T4: Invading the mediastinal structures, vertebrae, carina; separate tumor nodules in same lobe; malignant pleural effusion


  • Mediastinal and hilar lymph nodes (N)



    • N1: Hilar lymph nodes at vessel branch point


    • N2: Ipsilateral to primary tumor (subcarinal lymph node is ipsilateral)


    • N3: Contralateral lymph node, supraclavicular fossa


  • Stages



    • 0 (TisN0M0)


    • 1A (T1N0M0)


    • IB (T2N0M0)


    • IIA (T1N1M0)


    • IIB [(T2N1M0), (T3N0M0)]


    • IIIA [(T1-3 N2M0), (T3N1M0)]



    • IIIB [(any T, N3M0), (T4, any N, M0)]


    • IV (any T, any N, M1)


CLINICAL ISSUES


Presentation



  • Most common signs/symptoms



    • Central primary tumor



      • Cough, dyspnea, wheezing, and hemoptysis


      • Atelectasis and post-obstructive pneumonia


    • Peripheral primary tumor may cause the above



      • ± Pleural effusion and pain related to pleural and chest wall invasion


    • Locoregional spread may cause SVC obstruction and nerve infiltration



      • Leads to hoarseness, diaphragm paralysis, and Horner syndrome, as well as brachial plexus neuropathy


    • Paraneoplastic symptoms may include hypercalcemia and PTHrP production


  • Other signs/symptoms



    • Recurrent pneumonia in same lobe


    • Metastasis to supraclavicular lymph node



      • Indicator of inoperable disease


      • Palpation of supraclavicular lymph nodes is unreliable for detection


Demographics



  • Age: > 50 years


  • Gender



    • M:F approaching 1:1 in USA


    • M > F worldwide


    • Mortality higher in males, increasing in females


  • Ethnicity: African-American:Caucasian:Native American = 1.5:1:0.2


Natural History & Prognosis



  • Most patients present with advanced disease


  • Adenocarcinoma has worse prognosis per stage than SCCA (except T1N0)


  • Staging criteria include



    • Histologic type


    • Tumor size


    • Regional lymph node involvement


    • Presence of metastatic disease


  • Mediastinal lymph node metastasis is found in 16-21% of patients with stage T1 NSCLC


  • Metastatic relapse occurs in up to 20% of patients who have undergone surgery


Treatment



  • Stages 1 & 2: Patients with no metastatic lymph nodes (N0 disease) or with only intrapulmonary or hilar lymph nodes (N1 disease)



    • Resection with adjuvant chemo in selected cases


  • Stage 3A: Neoadjuvant chemoradiation, then surgery in selected


  • Stage 3B: Chemoradiation, then surgery in selected T4N0


  • Stage 4: Chemotherapy, palliative radiation in selected



    • Solitary brain mets: Resection of brain met and primary if possible


  • Radiation or RFA: Symptomatic inoperable lesions



    • Some patients with inoperable NSCLC can be cured with radiotherapy


DIAGNOSTIC CHECKLIST


Consider



  • Suspicious CT morphology should be biopsied even with negative PET


  • Suspicious FDG PET findings should be biopsied/removed without following growth on CT


  • Consider PET/CT for ALL patients with newly diagnosed NSCLC



SELECTED REFERENCES

1. Bryant AS et al: Differences in outcomes between younger and older patients with non-small cell lung cancer. Ann Thorac Surg. 85(5):1735-9; discussion 1739, 2008

2. Cerfolio RJ et al: Survival of patients with unsuspected N2 (stage IIIA) nonsmall-cell lung cancer. Ann Thorac Surg. 86(2):362-6; discussion 366-7, 2008

3. Decker RH et al: Advances in radiotherapy for lung cancer. Semin Respir Crit Care Med. 29(3):285-90, 2008

4. Hampton T: New studies target lung cancer prevention, imaging, and treatment. JAMA. 300(3):267-8, 2008

5. Hanin FX et al: Prognostic value of FDG uptake in early stage non-small cell lung cancer. Eur J Cardiothorac Surg. 33(5):819-23, 2008

6. Hart JP et al: Radiation pneumonitis: correlation of toxicity with pulmonary metabolic radiation response. Int J Radiat Oncol Biol Phys. 71(4):967-71, 2008

7. Higaki F et al: Preliminary retrospective investigation of FDG-PET/CT timing in follow-up of ablated lung tumor. Ann Nucl Med. 22(3):157-63, 2008

8. Kased N et al: Prognostic value of posttreatment [18F] fluorodeoxyglucose uptake of primary non-small cell lung carcinoma treated with radiation therapy with or without chemotherapy: a brief review. J Thorac Oncol. 3(5):534-8, 2008

9. Lima CG Jr et al: Is there a definitive answer to the question of involved-field radiotherapy for inoperable non-small-cell lung cancer? J Clin Oncol. 26(13):2235; author reply 2235-6, 2008

10. Ohno Y et al: Non-small cell lung cancer: whole-body MR examination for M-stage assessment—utility for whole-body diffusion-weighted imaging compared with integrated FDG PET/CT. Radiology. 248(2):643-54, 2008

11. Yi CA et al: Non-small cell lung cancer staging: efficacy comparison of integrated PET/CT versus 3.0-T whole-body MR imaging. Radiology. 248(2):632-42, 2008

12. Poettgen C et al: Correlation of PET/CT findings and histopathology after neoadjuvant therapy in non-small cell lung cancer. Oncology. 73(5-6):316-23, 2007

13. Decoster L et al: Complete metabolic tumour response, assessed by 18-fluorodeoxyglucose positron emission tomography ((18)FDG-PET), after induction chemotherapy predicts a favourable outcome in patients with locally advanced non-small cell lung cancer (NSCLC). Lung Cancer. (In Press)

14. Wilson DO et al: The Pittsburgh Lung Screening Study (PLuSS): Outcomes within 3 years of a first CT Scan. Am J Respir Crit Care Med. (In Press)


Sep 22, 2016 | Posted by in MAGNETIC RESONANCE IMAGING | Comments Off on Lung Cancer
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