nicole bouchard md frcpc pulmonologist april 29 2011 l.
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Nicole Bouchard MD FRCPC Pulmonologist April 29, 2011. Lung cancer staging in 2011: use of pet Scan and other modalities. Disclosure. I cannot identify any potential conflict of interest. Objectives. 1) Select the appropriate diagnostic tests to accurately stage lung cancer

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disclosure
Disclosure
  • I cannot identify any potential conflict of interest.
objectives
Objectives
  • 1) Select the appropriate diagnostic tests to accurately stage lung cancer
  • 2) Understand the strengths and weaknesses of PET Scan for lung cancer staging
  • 3) Propose a rational approach to optimally stage mediastinal lymph nodes
slide4
TNM

Lababede O, Chest 2011; 139: 183-189

diagnostic tests
Diagnostic tests
  • CT scan:
    • chest and upper abdomen
  • PET-CT:
    • if a radical treatment is considered
  • Pulmonary function testing
  • Imaging of the head (MRI):
    • if symptoms
    • for small cell lung cancer
    • maybe in stage 3 disease NSCLC

Lim E, Thorax 2010; 65 (Suppl III); iii1-iii27

Alberts WM, Chest 2007; 132; 1S-19S

diagnostic tests6
Diagnostic tests
  • Bone scintigraphy? PET is more sensitive
    • to avoid an unnecessary PET-CT
    • PET: from base of skull to upper thighs
diagnostic tests7
Diagnostic tests
  • Least invasive approach that provides both the diagnostic and the stage
    • bronchoscopy, transthoracic CT guided needle biopsy, radial probe EBUS
    • EBUS, EUS, mediastinoscopy, VATS
    • US guided needle aspiration: thoracentesis, cervical lymph node, liver
    • EUS: left adrenal metastasis
diagnostic tests8
Diagnostic tests
  • → Adequate sample
  • IASLC/ATS/ERS International Multidisciplinary Classification of Lung Adenocarcinoma

NSCLC are to be classified into adenocarcinoma or squamous cell carcinoma

    • gefitinib, pemetrexed, bevacizumab

Travis WD, Journal of Thoracic Oncology 2011; 6: 244-285

diagnostic tests9
Diagnostic tests
  • Wait times and costs
    • 2852 patients
    • provincial cancer registry: Manitoba
    • ≥ 25% of patients waited more than 55 days

Cheung WY, Lung Cancer 2010 Sep [ Epub ahead of print ]

diagnostic tests10
Diagnostic tests
  • Multidisciplinary team
    • 1222 patients with NSCLC, 2001-2007
    • survival?

Freeman RK, Eur J Cardiothoracic Surg 2010; 38: 1-5

pet ct scan
PET-CT Scan
  • Preoperative PET-CT
    • prospective, randomized

study

    • 189 patients, NSCLC
    • conventional staging (CT of the abdomen, bronchoscopy) or conventional staging plus PET-CT
    • PET-CT: reduced the number of futile thoracotomies, had no effect on survival

Fischer B, NEJM 2009; 361: 32-39

pet ct scan12
PET-CT Scan
  • Preoperative PET-CT
    • prospective, randomized trial
    • 337 patients, stage 1-3A

NSCLC

    • PET-CT or conventional

(abdominal CT & bone scan)

    • cranial imaging
    • PET-CT: spares more patients from inappropriate surgery, but also incorrectly upstaged disease

Maziak DE, Ann Intern Med 2009; 151: 221-228

pet ct scan13
PET-CT Scan
  • T stage (SUVmax 2,5)
    • false positive: infectious and inflammatory lesions
    • false negative: carcinoid, certain adenocarcinomas, uncontrolled diabetes, cavity with necrotic center, lesion < 8 mm

Lim E, Thorax 2010; 65 (Suppl III); iii1-iii27

pet ct scan14
PET-CT Scan
  • Solitary pulmonary nodule (8 - 30 mm) and an initial SUVmax 2.6
    • retrospective study, CHUS, PET-CT
    • 20 / 65 (31%) patients: diagnosis of cancer; mostly adenocarcinomas
    • risk factors for malignancy: higher 18F-FDG uptake, spiculated nodule
    • SUVmax 1: new threshold?

Houle MA, Can Respir J 2010; 17, suppl B: 6B

pet ct scan15
PET-CT Scan
  • N stage
    • CT

> 10 mm in short axis diameter

sensitivity 57-61%, specificity 79-82%

    • PET

sensitivity 84%, specificity 89%

false negative: small volume, low metabolic activity

false positive: inflammation → sampling

size of the lymph node is important

Lim E, Thorax 2010; 65 (Suppl III); iii1-iii27

Alberts WM, Chest 2007; 132; 1S-19S

pet ct scan16
PET-CT Scan
  • M stage
    • sensitivity 93%, specificity 96%
    • detect metastases:

15%, more with advanced stage

Lim E, Thorax 2010; 65 (Suppl III); iii1-iii27

pet ct scan17
PET-CT Scan
  • Sample of any isolated distant lesion
    • 350 patients
    • 21% had a solitary lesion: 46% had a benign lesion or another cancer (second cancer or recurrence)

Lardinois D, J Clin Oncol 2005; 23: 6846-6853

mediastinal lymph nodes ln
Mediastinal lymph nodes (LN)
  • No lymph node sampling if uptake is within normal limits on PET-CT and < 1 cm
    • false negative rate: 5-7% for a peripheral tumor
    • if central tumor, N1 enlargement?
    • N2 or N3 ≥ 1 cm but PET negative?
  • Lymph node sampling if PET uptake is positive, to avoid false positive results
    • EBUS/EUS; +/- mediastinoscopy if negative
mediastinal lymph nodes ln19
Mediastinal lymph nodes (LN)
  • EBUS: 2, 4, 7, 10, 11
  • EUS: 2L, 4L, 7, 8, 9
  • mediastinoscopy: 2R, 4R, anterior part of 7

Goldstraw P, IASLC Staging Manual in Thoracic Oncology, 2009

ebus meta analysis 1
EBUS: meta-analysis (1)
  • Study caracteristics

Adams K, Thorax 2009; 64: 757-762

ebus meta analysis 122
EBUS: meta-analysis (1)
  • Sensitivity 88%
  • Specificity 100%
ebus meta analysis 2
EBUS: meta-analysis (2)
  • Sensitivity 93%
  • Specificity 100%
  • Only 2 complications
    • 2 / 1299 patients (0,15%)
    • pneumothorax
    • patient with COPD: hypoxemia during the procedure

Gu P, European Journal of Cancer 2009; 45: 1389-1396

ebus false negative rate
EBUS: false negative rate
  • False negative rates
    • 20-25%
  • External validity
    • other studies have been published
ebus learning curve
EBUS: learning curve
  • Learning curves
    • 500 patients
    • 5 EBUS operators
    • no learning from

prior experience

    • operators 3 & 5: still

in the learning phase

after 100 procedures

Kemp SV, Thorax 2010; 65: 534-538

ebus cost effectiveness
EBUS: cost effectiveness
  • Cost effectiveness
    • cost-beneficial in comparison with surgical mediastinoscopy, for a prevalence as low as 30%
    • negative results confirmed by mediastinoscopy: cost-beneficial according to the prevalence of LN metastases (>79%)

Steinfort D, J Thorac Oncol 2010; 5: 1564-1570

ebus how many aspirations
EBUS: how many aspirations?
  • 650 aspirations (163 MLN stations) in 102 patients, ROSE not available
    • best diagnostic value: 3 aspirations

(sensitivity: 69.8%, 83.7%, 95.3%, 95.3%)

    • 2 aspirations: when at least one tissue core

Lee H, Chest 2008; 134: 368-374

ebus which needle
EBUS: which needle?
  • 21-gauge versus 22-gauge aspiration needle
  • 45 lesions
    • same diagnostic yield
    • 21G: better histological preservation but more blood contamination

Nakajima T, Respirology 2010 Sep [ Epub ahead of print ]

ebus mutations and sclc
EBUS: mutations and SCLC
  • Mutation analysis
    • EGFR and KRAS mutations can be performed in cytologic specimens (EUS/EBUS)
    • also EML4-ALK fusion gene
  • SCLC: high diagnostic yield

Schuurbiers OC, J Thorac Oncol 2010: 5: 1664-1667

Nakajima T, J Thorac Oncol 2011; 6: 203-206

Wada H, Ann Thorac Surg 2010; 90: 229-234

eus meta analysis
EUS: meta-analysis
  • 18 studies
  • No major complications; minor complications: 10 cases (0.8%),

Micames CG, Chest 2007; 131: 539-548

tbna ebus eus
TBNA, EBUS, EUS
  • 138 consecutive patients
  • known or suspected lung cancer on CT

Wallace MB, JAMA 2008; 299: 540-546

ebus eus single scope
EBUS & EUS: single scope
  • 139 consecutive patients, enlarged LN (CT)
  • EBUS & EUS: single linear US bronchoscope by one operator

Herth FJ, Chest 2010: 138: 790-794

ebus eus single scope33
EBUS & EUS: single scope
  • 150 potentially operable patients, prospective study
  • EBUS +/- EUS used for MLN inaccessible or difficult to access by EBUS
  • 2 false negative (by mediastinoscopy)

Hwangbo B, Chest 2010; 138: 795-802

ebus versus mediastinoscopy
EBUS versus mediastinoscopy
  • 66 patients, prospective crossover trial
  • Prevalence of malignancy: 89%
  • Diagnostic yield
    • EBUS: 91% versus mediastinoscopy: 78% (p=0.007)
    • disagreement: subcarinal lymph nodes (24%; p=0.011)
    • no difference: true pathologic N stage (per patient)
  • Ernst A, Journal of Thoracic Oncology 2008; 3; 577-582
aster study
ASTER study
  • Randomized controlled multicenter trial
  • 241 patients
  • Lung or mediastinal abnormality on CT, no extrathoracic metastases
  • EUS & EBUS (systematic sampling) and surgical staging if negative or surgical staging (mediastinoscopy): N2 & N3

Annema JT, JAMA 2010; 304: 2245-2252

aster study36
ASTER study
  • Nodal metastases
    • 62 patients by combined staging (p=0.02)
    • 41 patients by surgical staging
    • mediastinoscopy: 11 patients to identify 1 with nodal metastasis
  • Thoracotomy unnecessary
    • 21patients in the mediastinoscopy group
    • 9 patients in the combined group (p = 0.02)
  • No increase rate of complications
conclusion
Conclusion
  • PET-CT: before surgery and radiotherapy
  • When N2 or N3 is suspected on PET: EBUS; mediastinoscopy if negative
  • Complete mediastinal staging: EBUS +/- EUS; role of mediastinoscopy?
  • Further studies are ongoing
    • preoperative EBUS, EBUS vs mediastinoscopy, surgical staging vs endosonography