new optimizing biomarker testing in lung carcinoma · 2019. 1. 19. · 3,101 724 202 76 decision...

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Optimizing Biomarker Testing in Lung Carcinoma

The CAP Guideline on Collection and Handling of Thoracic Small Biopsy and Cytology Specimens for Ancillary Studies

Sinchita Roy-Chowdhuri, MD PhDThe University of Texas MD Anderson Cancer Center

[email protected]@Sinchita_Roy

Objectives

• Challenges associated with specimen collection and resource allocation in pulmonary pathology

• Background and guideline development process

• Draft recommendations

• Conclusions and Q&A

Current Landscape of Lung Biomarker Testing in Small Specimens

Specimen Acquisition

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• CT guided transthoracic:

Biopsy

FNA

• Transbronchial/endobronchial:

FNA (EBUS TBNA)

Bronchial brushing, bronchial washing, BAL

Biopsy

• Body cavity fluids/effusions

• Metastasis of superficial lesions:

Ultrasound guided biopsy and/or FNA

Palpation-guided FNA


Establishing a Diagnosis

Travis WD et al. J Thorac Oncol. 2015 Sep;10(9):1243-1260.


Biomarkers to test

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Advanced NSCLC is Frequently Diagnosed by Cytology

Most NSCLC patients are diagnosed at an advanced stage and cytology samples may be the only tissue available for diagnosis and ancillary studies

Cytology Specimen Source:

• Aspiration

• Exfoliative (Effusions)


Cytology specimens

Several Variables Impact Testing Outcomes

Moore, H.M. Biotech Histochem. 2012 Jan;87(1):18-23. doi: 10.3109/10520295.2011.591833.

Can We Optimize Testing Outcomes?

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Defining the Problem

During the collection, triage and processing/handling of minimally invasive pathology specimens from patients with suspected or undiagnosed thoracic abnormalities, what procedural or methodological variables have been shown to optimize testing outcomes so that pathologists’ can provide an evaluation and accurate diagnosis?

Collaborating Societies

PAPANICOLAOU

SOCIETY OF

CYTOPATHOLOGY

Find Gullible the Best People Who Think it will be Fun

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Expert Panel Members

• Sinchita Roy-Chowdhuri, MD, PhD, Co-chair, CAP

• Christopher R. Gilbert, DO, Co-chair, ATS

• Sanja Dacic, MD, PhD, AMP

• Mohiedean Ghofrani, MD, MBA, CAP

• Peter Illei, MD, ASC

• Lester Layfield, MD, PSC

• Christopher Lee, MD, STR

• Claire Michael, MD, PSC

• Ross A. Miller, MD, PPS

• Jason W. Mitchell, MD, MPH, MBA, SIR

• Boris Nikolic, MD, MBA, SIR

• Jan Nowak, MD, PhD, AMP

• Nicholas J. Pastis, Jr., MD, CHEST

• Carol Ann Rauch, MD, PhD, CAP

• Amita Sharma, MD, STR

• Lesley Souter, PhD, methodology consultant

• Paul VanderLaan, MD, PhD, ASC

• Jesse Voss, CT(ASCP), ASC

• Brooke Billman

• Nicole Thomas, CAP Guideline Manager

Key Questions

1) With regard to each of the specimen types of interest, what evidence is available to determine the most effective protocols for sample collection, including:

• immediate handling of the specimen (e.g. how the needle biopsy is expelled from needle; selection of the appropriate media)

• the number of passes needed to ensure that the laboratory can obtain adequate materials for diagnostic testing

• the impact of ROSE on adequacy, quality, and triage of specimens

Key Questions (contd)

2) With regard to each of the specimen types, the preparations, and the tests to be performed, what evidence is available to determine the most effective methods for the handling and processing of specimens, including:

• the selection of appropriate media

• the optimal ischemic time?

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Key Questions (contd)

3) With regard to the various pathologic testing methods, what evidence is available to support an algorithm(s) for selection of specimens and sequence of testing, under defined circumstances?

Systematic Literature Review

Literature SearchTitle abstract

screening Full Text Review

screeningData Extraction

Quality Assessment for each study by methodologist

Grading

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Decision Making During Evaluation of Lung CancerThoughts from the Clinical Side

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Lung Cancer Diagnosis

Method of diagnosis depends on:• Size of tumor

• Location of tumor

• Presence of metastatic disease

• Overall clinical status of patient

CHEST 2013; 143(5)(Suppl):e142S–e165S

Diagnosis Alone is not Good Enough

CHEST 2013; 143(5)(Suppl):e142S–e165S

Tissue Acquisition Methods

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What is the Best Method

The “best” test does the following:

• Allows diagnosis and staging simultaneously

• Obtains adequate tissue for ancillary testing as will most likely be needed

• Maximizes yield

• Minimizes risk

• Suitable for your institution and your patient

Primum non nocere (Do No Harm)

Draft Guideline Statements

1. Recommendation – Endobronchial ultrasound guided transbronchial needle aspiration (EBUS TBNA) should be used, if available, for initial evaluation (diagnosis, staging, identification of recurrent/metastatic) of mediastinal and hilarlymph nodes, as well as centrally located parenchymal lesions visible with endobronchialultrasound.

21 written comments


2. Recommendation – When performing EBUS TBNAs, 21 or 22 gauge needles may be used.

20 written comments

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Case Presentation 1

• 72 y/o smoker presents with cough and intermittent hemoptysis

• Exam unremarkable

• CXR and CT imaging concerning for left upper lobe/hilarmass

• EBUS-TBNA of multiple lymph nodes

• ROSE POSITIVE for malignant cells

ROSE for diagnosis? ROSE for molecular markers?

Is it important?

ROSE Can Ensure Adequate Sampling and Appropriate Triage

• ROSE can ensure adequate sampling and triage

• Performing additional pass in anticipation of ancillary studies

• If molecular lab prioritizes cell blocks, maximize the needle rinse material for cell block

• If molecular lab prioritizes smears, minimize cell block material

Case Presentation 1:Final Diagnosis

A: Lymph node, 4R, FNA smears and cell block: Adenocarcinoma

B: Lymph node, Station 7, FNA smears and cell block: Adenocarcinoma

C: Lymph node, 4L, FNA smears and cell block: Adenocarcinoma

• IHC (specimen A cell block): TTF1 positive; p40 negative

Biomarker request:

• PD-L1 IHC; Mutation analysis (EGFR); FISH (ALK,ROS1)

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3. Recommendation - When performing EBUS TBNA, rapid onsite evaluation (ROSE) should be utilized, if available.

35 written comments


4. Recommendation – When performing EBUS TBNA:

• Without ROSE, the bronchoscopist should perform at minimum 3 and up to 5 passes.

• With ROSE, clinical judgment should be used to assess the number of passes needed.

Note: Additional passes may be required for ancillary studies.

24 written comments

Case Presentation 2

• 64 y/o female nonsmoker fell while walking on some ice and had horrible chest pain

• Went to ER to be evaluated

• No pertinent prior medical history

• Noted to have abnormality on same side as rib

• EBUS-TBNA, small hilar lymph node identified

• 11L: ROSE, lymphocytes, no definitive malignant cells

• Bronchoscopy with Navigation – unable to find lesion

• Converted to transthoracic approach• FNA and core needle bx of LUL lesion

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A: Lymph node, 11L, FNA smears and cell block: No metastatic carcinoma; lymphocytes present

B: Lung, LUL, FNA smears and cell block: Adenocarcinoma

C: Lung, LUL, core biopsy: Adenocarcinoma

• IHC (specimen C): TTF1 positive; p40 negative

Biomarker request:• PD-L1 IHC; Mutation analysis (EGFR); FISH (ALK,ROS1)


5. Strong Recommendation - For transthoracic needle procedures, ROSE should be utilized, if available. If performing CNB only, touch preparations may be used for ROSE.

44 written comments


6. Recommendation - For transthoracic fine needle aspirations (FNAs) ≥25 gauge needles may be used. For core needle biopsies (CNBs) ≥20 gauge needles may be used.

23 written comments

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7. Recommendation - For transthoracic FNA samples without CNB, the proceduralist should obtain multiple passes, if possible and should attempt to collect sufficient material for a tissue block (i.e., cell block, tissue clot).

28 written comments


8. Recommendation - For transthoracic CNB samples, the proceduralist should obtain a minimum of three core samples.

Note: Additional passes may be required for ancillary studies

39 written comments


9. Recommendation – When performing bronchoscopy for the investigation of peripheral nodules/abnormalities, additional image-guidance adjuncts (endobronchial ultrasound, navigational bronchoscopy techniques) should be used, if available.

10. Recommendation – For transbronchialsamples, ROSE should be used, if available.

11 written comments

23 written comments

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Case Presentation 3

• 42 year old female from Kenya with no past history presents with right sided shoulder pain to her PCP

• Physical normal, exam for decreased breath sounds

• In light of exam findings, PCP suggests CXR

• Thoracentesis1500cc bloody appearing effusion removed

Fluid triage: How much to send

and where?

Thoracentesis

Micro

Thoracentesis

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Thoracentesis

ADC

• IHC for subtyping

• Biomarker testing

TTF1


• Collected 15cc for biochemical and microbiological lab,

remainder sent to cytology

Left pleural fluid, thoracentesis:

Metastatic adenocarcinoma

• IHC performed (cell block): TTF-1 positive; Calretinin negative

Biomarker request:

• PD-L1 IHC; Mutation analysis (EGFR); FISH (ALK,ROS1)


11. Expert Consensus Opinion – The proceduralistshould send as much fluid volume as possibly attainable for cytologic evaluation.

41 written comments

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Advanced NSCLC is Frequently Diagnosed by Cytology

Most NSCLC patients are diagnosed at an advanced stage and cytology samples may be the only tissue available for diagnosis and ancillary studies

Cytology Specimen Source:

• Aspiration

• Exfoliative (Effusions)


12. Expert Consensus Opinion – When evaluating the adequacy of cytology FNA specimens for molecular analysis, ROSE should be used, if available.

26 written comments


13. Recommendation – CNB samples collected for mutational analysis, fluorescence in situ hybridization (FISH), and immunohistochemistry (IHC), should be fixed in 10% neutral buffered formalin.

26 written comments

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14. Recommendation – Cytology specimens (smears, cell blocks, liquid based cytology), may be used for mutational analysis, FISH, and IHC studies.

35 written comments

Case Presentation 4

• 18 y/o female from Ethiopia

• Cough, fevers, dysphagia, hemoptysis

• CT Chest done

• Bronchoscopy • BAL

• EBUS-TBNA


A: Lymph node, station 7, FNA smears and cell block:

No malignant cells identified

Inflammatory cells and necrotic debris

Comment: AFB and GMS stains are negative

B: Lung, left upper lobe, bronchoalveolar lavage, ThinPrep

cytology and cell block:

No malignant cells identified

Lymph node: mycobacterium complex confirmed via DNA probe

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15. Recommendation – When performing bronchoscopy for the investigation of tuberculosis, the use of EBUS TBNA, should be performed in addition to bronchoalveolarlavage and transbronchial biopsy, if available.

16. Recommendation – When performing EBUS TBNA for the evaluation of intrathoracic granulomatous lymphadenopathy with the suspicion of tuberculosis, specimens should be collected for cytology, microbiology (mycobacterial smear and culture), and TB-PCR evaluation, if available.

17. Recommendation – When collecting pleural fluid for diagnosis of extrapulmonary tuberculosis, specimens should be submitted for microbiology culture studies for mycobacteria using liquid media protocol.

18/9/6 written comments

No Recommendations

• The use of one collection media (i.e., formalin, CytoLyt, Hanks, or CytoRich), one fixative (i.e., alcohol or formalin), or one stain (DiffQuik or Papanicolaou) over another for ancillary studies in cytology specimens.

Cytology Collection/Handling

J Thorac Oncol. 2011;6: 203–206

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No Recommendations

• The use of a stylet for EBUS TBNAs

• The optimal ischemic time

• The sequence of testing for an algorithm

Conclusions

• The forthcoming CAP guideline offers 17 draft recommendations to help clinicians and laboratories collect, handle, and process small biopsy specimens to maximize the capability of appropriate downstream testing.

• Manuscript release ~ Q2 2019.

Acknowledgements

• The collaborating societies and their staff, the expert and advisory panel members for their time and commitment to the guideline

• Nicole Thomas & Sophia Dimoulis

@Sinchita_Roy

[email protected]

new optimizing biomarker testing in lung carcinoma · 2019. 1. 19. · 3,101 724 202 76 decision...

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