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Guideline Summary NGC-5927
Guideline Title
  Evaluation of patients with pulmonary nodules: when is it lung cancer?: ACCP evidence-based clinical practice
  guidelines. (2nd Edition)

Bibliographic Source(s)
   Gould MK, Fletcher J, Iannettoni MD, Lynch WR, Midthun DE, Naidich DP, Ost DE, American College of Chest Physicians.
   Evaluation of patients with pulmonary nodules: when is it lung cancer?: ACCP evidence-based clinical practice

   guidelines (2nd edition). Chest 2007 Sep;132(3 Suppl):108S-30S. [211 references] PubMed

Guideline Status
  This is the current release of the guideline.
  This guideline updates a previous version: Tan BB, Flaherty KR, Kazerooni EA, Iannettoni MD. The solitary pulmonary
  nodule. Chest 2003 Jan;123(1 Suppl):89S-96S.



Scope
Disease/Condition(s)
  Solitary pulmonary nodule (SPN)

Guideline Category
  Diagnosis

  Evaluation

  Management

Clinical Specialty
   Family Practice

  Oncology

  Pulmonary Medicine

  Thoracic Surgery

Intended Users
  Advanced Practice Nurses

  Allied Health Personnel

  Health Care Providers

  Nurses

  Patients

  Physicians

  Psychologists/Non-physician Behavioral Health Clinicians

  Social Workers

Guideline Objective(s)
  To provide clinically relevant, evidence-based guidelines for appropriate imaging modalities and diagnostic testing, and
  indications for obtaining preoperative tissue diagnosis for patients with a solitary pulmonary nodule

Target Population
  Patients with a solitary pulmonary nodule (SPN)

Interventions and Practices Considered
  Diagnostic Interventions
       1.  Chest x-ray (CXR)
       2.  Tissue Diagnosis 
       3.  Chest computed tomography (CT) 
       4.  Magnetic resonance imaging (MRI) (considered but not recommended routinely) 
       5.  Fluorodeoxyglucose (FDG)-positron emission tomography (PET)
       6.  Bronchoscopy 
       7.  Transthoracic needle biopsy
Diagnostic Interventions
        1.  Chest x-ray (CXR)
        2.  Tissue Diagnosis 
        3.  Chest computed tomography (CT) 
        4.  Magnetic resonance imaging (MRI) (considered but not recommended routinely) 
        5.  Fluorodeoxyglucose (FDG)-positron emission tomography (PET)
        6.  Bronchoscopy 
        7.  Transthoracic needle biopsy
  Management
  Therapeutic Surgical Procedures
        1.  Lobectomy 
        2.  Wedge resection/segmentectomy 
        3.  Systemic lymph node dissection for all pulmonary resections 
        4.  External beam radiation 
        5.  Experimental treatment such as stereotactic radiosurgery and radiofrequency ablation 
        6.  Pulmonary metastasectomy 
        7.  Follow-up

Major Outcomes Considered
   l   Sensitivity and specificity of diagnostic tests 

    l     Diagnostic yield



Methodology
Methods Used to Collect/Select the Evidence
  Hand-searches of Published Literature (Primary Sources)

  Searches of Electronic Databases

Description of Methods Used to Collect/Select the Evidence
  Overview
  The American College of Chest Physicians (ACCP) chose the Duke University Center for Clinical Health Policy Research
  to perform formal systematic reviews of the current evidence in the five new non-small cell lung cancer (NSCLC) topic
  areas, as well as to provide a search for the existing guidelines, systematic reviews, and meta-analyses in all of the
  topics areas. In addition, the Agency for Healthcare Quality and Research) AHRQ agreed to fund the BlueCross
  BlueShield Association Technology Evaluation Center to perform the formal systematic review of literature on small cell
  lung cancer (SCLC). The Health Outcomes Research Group of the Department of Epidemiology and Biostatistics at
  Memorial Sloan-Kettering Cancer Center conducted a full-scale review of the literature since the first set of guidelines
  in the area of screening for lung cancer to assist that particular writing group.
  The formal systematic reviews of the five new topic areas were guided by the appropriate chapter editors and their
  writing committees, in concert with the Executive Committee of the panel.
  The two EPC research teams conducted a variety of systematic computerized bibliographic database searches including
  the following: (1) a search for systematic reviews, guidelines, and meta-analyses published since the last ACCP lung
  cancer guideline (MEDLINE, The Cochrane Library, National Guidelines Clearinghouse); (2) targeted searches for reviews
  in each of five selected treatment sections (solitary pulmonary nodules, stage I and II, stage IIIA, stage IIIB, stage
  IV); these searches, run in OVID version of MEDLINE, were performed in July and August 2005 and were limited to
  publication years since 1995, English language, and human subjects; and (3) searches related to SCLC are described in
  the evidence chapter on SCLC.
  Search terms included the medical subject heading terms lung neoplasms (exploded) and bronchial neoplasms for the
  lung cancer concept. Each topic search utilized key words specific to the key questions of interest (complete search
  strategies are available on request from the authors).
  Strategy Specific for the Treatment of Patients with Pulmonary Nodules
  To update previous recommendations on the evaluation of patients with pulmonary nodules, guidelines on lung cancer
  diagnosis and management that were published between 2002 and May 2005 were identified by a systematic review of
  the literature (see the "Availability of Companion Documents" field in this summary for "Methodology for Lung Cancer
  Evidence Review and Guidelines Development"). Those guidelines, which include recommendations that are specific to
  the treatment of patients with pulmonary nodules, were identified for inclusion in this chapter. Supplemental material
  that is appropriate to this topic was obtained by literature search of a computerized database (MEDLINE), as described
  in the chapter of these guidelines by Wahidi et al. In addition, we identified articles by searching our own files and by
  reviewing reference lists provided by the Thoracic Oncology NetWork of the American College of Chest Physicians
  (ACCP). A multidisciplinary writing committee composed of three pulmonologists, two thoracic surgeons, and two
  radiologists developed the recommendations and graded the strength of the recommendations and the quality of the
  supporting evidence by using a standardized method (see "Methodology for Lung Cancer Evidence Review and Guideline
  Development").

Number of Source Documents
  Not stated

Methods Used to Assess the Quality and Strength of the Evidence
  Expert Consensus

  Weighting According to a Rating Scheme (Scheme Given)

Rating Scheme for the Strength of the Evidence
Number of Source Documents
  Not stated

Methods Used to Assess the Quality and Strength of the Evidence
  Expert Consensus

  Weighting According to a Rating Scheme (Scheme Given)

Rating Scheme for the Strength of the Evidence
  High Randomized controlled trials (RCTs) without important limitations or overwhelming evidence from observational
  studies*
  Moderate RCTs with important limitations (inconsistent results, methodologic flaws, indirect, or imprecise) or
  exceptionally strong evidence from observational studies*
  Low or very low Observational studies or case series
  *Although the determination of magnitude of the effect based on observational studies is often a matter of judgment, the guideline
  developers offer the following suggested rule to assist this decision: a large effect would be a relative risk >2 (risk ratio < 0.5) [which would
  justify moving from weak to moderate], and a very large effect is a relative risk > 5 (risk ratio < 0.2) [which would justify moving from weak
  to strong]. There is some theoretical justification in the statistical literature for these thresholds (the magnitude of effect that is unlikely or
  very unlikely to be due to residual confounding after adjusted analysis). However, once the decision is made, authors should be explicit in
  justifying their decisions.


Methods Used to Analyze the Evidence
  Review of Published Meta-Analyses

  Systematic Review

Description of the Methods Used to Analyze the Evidence
  Quality of evidence is scored in three categories with high-quality evidence obtained from randomized controlled trials
  (RCTs) without important methodologic limitations based on the study design, the consistency of the results, and the
  directness of the evidence. In extraordinary circumstances, significant and consistent evidence from observational
  studies could also be ranked as high quality. RCTs with important methodologic limitations or flaws, inconsistent
  results, or indirect or imprecise results would be scored as medium quality, as well as exceptionally strong evidence
  from observational studies. Other observational studies or case-series data would fall into the low quality of evidence
  category. It is the interface of the quality of the evidence and the balance of benefits to harms or burdens that
  determines the strength of the recommendation, with a 1A recommendation being the strongest and 2C the weakest.

Methods Used to Formulate the Recommendations
  Expert Consensus

  Informal Consensus

Description of Methods Used to Formulate the Recommendations
  Writing committees studied the evidence and summary tables or reviewed the literature for their assigned topics,
  developing their arguments for the recommendations and suggested grading of those recommendations that were put
  forth for early drafts. The Executive Committee of the panel, composed of the Chair, Vice-Chair, methodologist, and
  both project managers, reviewed drafts of each chapter of the manuscript during the writing process. Sections that
  were determined to be potentially overlapping were shared among the appropriate chapter editors, and conference calls
  were organized to coordinate the placement of these sections and to confirm that there would be no conflicting
  information or recommendations.
  A conference of the panel was convened in July 2006, prior to which time all panelists, including representatives from
  the invited organizations, were requested to review the complete manuscript and identify recommendations for which
  the proposal, wording, or grading were determined to be controversial or could be interpreted as controversial by
  others, incorrectly evolved from the evidence, disagreement existed with regard to the proposal or the grading, or
  required full panel discussion and further review for any reason. When the panelists who were present were not in
  unanimous agreement with the proposed recommendations or the grading of the recommendations, informal group
  consensus techniques were employed. After the meeting, a series of conference calls were convened to finish the
  discussions and finalize the recommendations. There were a few chapters for which there was insufficient time for full
  dialogue during the meeting; in the interest of ensuring that the recommendations followed the evidence, the
  conference calls were necessary. This process ensured the "buy-in" of the panelists and was deemed to be a worthwhile
  effort.

Rating Scheme for the Strength of the Recommendations
  Grade of Recommendations Scale
  Grade                        Recommendation
  1A                           Strong
  1B                           Strong
  1C                           Strong
  2A                           Weak
  2B                           Weak
  2C                           Weak

  Relationship of Strength of the Supporting Evidence to the Balance of Benefits to Risks and Burdens
                                                            Balance of Benefits to Risks and Burdens
         Quality of Evidence            Benefits Outweigh           Risks/Burdens Outweigh             Evenly Balanced            Uncertain
                                         Risks/Burdens                      Benefits
  High                                         1A                             1A                             2A                        
  Moderate                                     1B                             1B                             2B                        
  Low or very low                              1C                             1C                             2C                      2C

Cost Analysis
2C                           Weak

  Relationship of Strength of the Supporting Evidence to the Balance of Benefits to Risks and Burdens
                                                          Balance of Benefits to Risks and Burdens
         Quality of Evidence          Benefits Outweigh           Risks/Burdens Outweigh             Evenly Balanced   Uncertain
                                       Risks/Burdens                      Benefits
  High                                       1A                             1A                             2A               
  Moderate                                   1B                             1B                             2B               
  Low or very low                            1C                             1C                             2C             2C

Cost Analysis
  A formal cost analysis was not performed and published cost analyses were not reviewed.

Method of Guideline Validation
  Peer Review

Description of Method of Guideline Validation
  Following final chapter revisions and incorporation of these ultimate recommendations and grading, a concluding review
  was conducted by the guideline panel Executive Committee. The guidelines were then submitted for review and
  approval to the American College of Chest Physicians Health and Science Policy Committee (ACCP HSP) Committee, as
  well as the Thoracic Oncology Network of the college.



Recommendations
Major Recommendations
  Definitions for the strength of evidence and recommendation grades (1A-2C) follow the recommendations.
       1.  In every patient with a solitary pulmonary nodule (SPN), we recommend that clinicians estimate the pretest 
       probability of malignancy either qualitatively by using their clinical judgment or quantitatively by using a validated
       model. Grade of recommendation, 1C
       2.  In every patient with an SPN that is visible on chest radiography (CXR), we recommend that previous CXRs and 
       other relevant imaging tests be reviewed. Grade of recommendation, 1C
       3.  In patients who have an SPN that shows clear evidence of growth on imaging tests, we recommend that tissue 
       diagnosis should be obtained unless specifically contraindicated. Grade of recommendation, 1C
       4.  In a patient with an SPN that is stable on imaging tests for at least 2 years, we suggest that no additional 
       diagnostic evaluation be performed, except for patients with pure ground-glass opacities on CT, for whom a longer
       duration of annual follow-up should be considered. Grade of recommendation, 2C
       5.  In a patient with an SPN that is calcified in a clearly benign pattern, we recommend no additional diagnostic 
       evaluation. Grade of recommendation, 1C
       6.  In every patient with an indeterminate SPN that is visible on CXR, we recommend that CT of the chest should be
       performed, preferably with thin sections through the nodule. Grade of recommendation, 1C
       7.  In every patient with an indeterminate SPN that is visible on chest CT, we recommend that previous imaging 
       tests should be reviewed. Grade of recommendation, 1C
       8.  In a patient with normal renal function and an indeterminate SPN on CXR or chest CT, we recommend that CT 
       with dynamic contrast enhancement be considered in centers with experience performing this technique. Grade of
       recommendation, 1B
       9.  In patients with low-to-moderate pretest probability of malignancy (5 to 60%) and an indeterminate SPN that
       measures at least 8 to 10 mm in diameter, we recommend that F-18 fluorodeoxyglucose (FDG)-positron emission
       tomography (PET) imaging should be performed to characterize the nodule. Grade of recommendation, 1B
       10.
           In patients with an SPN that has a high pretest probability of malignancy (> 60%), or patients with a 
       subcentimeter nodule that measures < 8 to 10 mm in diameter, we suggest that FDG-PET not be performed to
       characterize the nodule. Grade of recommendation, 2C
       11.
           In every patient with a SPN, we recommend that clinicians discuss the risks and benefits of alternative 
       management strategies and elicit patient preferences. Grade of recommendation, 1C
       12.
           In patients with an indeterminate SPN that measures at least 8 to 10 mm in diameter and who are candidates 
       for curative treatment, observation with serial CT scans is an acceptable management strategy in the following
       circumstances:
          l     When the clinical probability of malignancy is very low (< 5%) 
          l   When clinical probability is low (< 30 to 40%) and the lesion is not hypermetabolic by FDG-PET or does not
          enhance > 15 Hounsfield units (HU) on dynamic contrast CT
          l     When needle biopsy is nondiagnostic and the lesion is not hypermetabolic by FDG-PET
          l     When a fully informed patient prefers this nonaggressive management approach
       Grade of recommendation, 2C
       13.
           In patients who have an indeterminate SPN that measures at least 8 to 10 mm in diameter and undergo 
       observation, we suggest that serial CT scans be repeated at least at 3, 6, 12, and 24 months. Grade of
       recommendation, 2C
       14.
           In patients who have an indeterminate SPN that measures at least 8 to 10 mm in diameter and are candidates 
       for curative treatment, it is appropriate to perform a transthoracic needle biopsy or bronchoscopy in the following
       circumstances:
          l   When clinical pretest probability and findings on imaging tests are discordant; for example, when the pretest 
          probability of malignancy is high and the lesion is not hypermetabolic by FDG-PET
          l     When a benign diagnosis requiring specific medical treatment is suspected 
          l   When a fully informed patient desires proof of a malignant diagnosis before surgery, especially when the risk 
          of surgical complications is high
       In general, we suggest that transthoracic needle biopsy be the first choice for patients with peripheral nodules
       unless the procedure is contraindicated or the nodule is inaccessible. We suggest that bronchoscopy be performed
14.
       In patients who have an indeterminate SPN that measures at least 8 to 10 mm in diameter and are candidates 
   for curative treatment, it is appropriate to perform a transthoracic needle biopsy or bronchoscopy in the following
   circumstances:
     l   When clinical pretest probability and findings on imaging tests are discordant; for example, when the pretest 
     probability of malignancy is high and the lesion is not hypermetabolic by FDG-PET
     l     When a benign diagnosis requiring specific medical treatment is suspected 
     l   When a fully informed patient desires proof of a malignant diagnosis before surgery, especially when the risk 
     of surgical complications is high
   In general, we suggest that transthoracic needle biopsy be the first choice for patients with peripheral nodules
   unless the procedure is contraindicated or the nodule is inaccessible. We suggest that bronchoscopy be performed
   when an air bronchogram is present or in centers with expertise in newer guided techniques.
   Grade of recommendation, 2C
   15.
       In surgical candidates with an indeterminate SPN that measures at least 8 to 10 mm in diameter, surgical 
   diagnosis is preferred in most circumstances, including:
     l     When the clinical probability of malignancy is moderate to high (> 60%) 
     l     When the nodule is hypermetabolic by FDG-PET imaging
     l     When a fully informed patient prefers undergoing a definitive diagnostic procedure
   Grade of recommendation, 1C
   16.
       In patients with an indeterminate SPN in the peripheral third of the lung and chose surgery, we recommend that 
   thoracoscopy be performed to obtain a diagnostic wedge resection. Grade of recommendation, 1C
   17.
       In a patient who chooses surgery with an indeterminate SPN that is not accessible by thoracoscopy, 
   bronchoscopy, or transthoracic needle aspiration (TTNA), we recommend that a diagnostic thoracotomy be
   performed. Grade of recommendation, 1C
   18.
       In patients who undergo thoracoscopic wedge resection for an SPN that is found to be cancer by frozen section, 
   we recommend that anatomic resection with systematic mediastinal lymph node sampling or dissection be
   performed during the same anesthetic. Grade of recommendation, 1C
   19.
       In patients who have an SPN who are judged to be marginal candidates for lobectomy, we recommend definitive 
   treatment by wedge resection/segmentectomy (with systematic lymph node sampling or dissection). Grade of
   recommendation, 1B
   20.
       For the patient who has an SPN and is not a surgical candidate and prefers treatment, we recommend that the 
   diagnosis of lung cancer be confirmed by biopsy, unless contraindicated. Grade of recommendation, 1C
   21.
       For the patient who has a malignant SPN and is not a surgical candidate and prefers treatment, we recommend 
   referral for external-beam radiation or to a clinical trial of an experimental treatment such as stereotactic
   radiosurgery or radiofrequency ablation. Grade of recommendation, 2C
   22.
       For surgical candidates who have subcentimeter nodules and no risk factors for lung cancer, the frequency and 
   duration of follow-up (preferably with low-dose CT) should depend on the size of the nodule. We suggest the
   following:
     l   Nodules that measure up to 4 mm in diameter not be followed up, but the patient must be fully informed of 
     the risks and benefits of this approach
     l     Nodules that measure > 4 to 6 mm be re-evaluated at 12 months without additional follow-up if unchanged
     l   Nodules that measure > 6 to 8 mm be followed up sometime between 6 and 12 months, and then again 
     between 18 and 24 months if unchanged
   Grade of recommendation, 2C
   23.
       For surgical candidates who have subcentimeter nodules and one or more risk factors for lung cancer, the 
   frequency and duration of follow-up (preferably with low-dose CT) should depend on the size of the nodule. We
   suggest the following:
     l   Nodules that measure up to 4 mm in diameter be re-evaluated at 12 months without additional follow-up if
     unchanged
     l   Nodules that measure > 4 to 6 mm should be followed up sometime between 6 and 12 months and then again
     between 18 and 24 months if unchanged
     l   Nodules that measure > 6 to 8 mm be followed up initially sometime between 3 months and 6 months, then 
     subsequently between 9 and 12 months, and again at 24 months if unchanged.
   Grade of recommendation, 2C
   24.
       For surgical candidates with subcentimeter nodules that display unequivocal evidence of growth during follow-
   up, we recommend that definitive tissue diagnosis be obtained by surgical resection, transthoracic needle biopsy, or
   bronchoscopy. Grade of recommendation, 1C
   25.
       For individuals who have subcentimeter nodules and are not candidates for curative treatment, we recommend 
   limited follow-up (in 12 months) or follow-up when symptoms develop. Grade of recommendation, 1C
   26.
       In patients who are candidates for curative treatment with a dominant SPN and one or more additional small 
   nodules, we recommend that each nodule be evaluated individually, as necessary and curative treatment should not
   be denied unless there is histopathologic confirmation of metastasis. Grade of recommendation, 1C
   27.
       In surgical candidates with a solitary pulmonary metastasis, we recommend that pulmonary metastasectomy be 
   performed if there is no evidence of extrapulmonary malignancy and there is no better available treatment. Grade
   of recommendation, 1C
   28.
       In surgical candidates with an SPN that has been diagnosed as small cell lung cancer (SCLC), we recommend 
   surgical resection with adjuvant chemotherapy, provided that noninvasive and invasive staging exclude the
   presence of regional or distant metastasis. Grade of recommendation, 1C
   29.  In patients who have an SPN and in whom SCLC is diagnosed intraoperatively, we recommend anatomic 
   resection (with systematic mediastinal lymph node sampling or dissection) under the same anesthesia when there
   is no evidence of nodal involvement and when the patient will tolerate resection. Surgery should be followed by
   adjuvant chemotherapy. Grade of recommendation, 1C
Definitions:
Quality of Evidence Scale
28.
            In surgical candidates with an SPN that has been diagnosed as small cell lung cancer (SCLC), we recommend 
        surgical resection with adjuvant chemotherapy, provided that noninvasive and invasive staging exclude the
        presence of regional or distant metastasis. Grade of recommendation, 1C
        29.  In patients who have an SPN and in whom SCLC is diagnosed intraoperatively, we recommend anatomic 
        resection (with systematic mediastinal lymph node sampling or dissection) under the same anesthesia when there
        is no evidence of nodal involvement and when the patient will tolerate resection. Surgery should be followed by
        adjuvant chemotherapy. Grade of recommendation, 1C
  Definitions:
  Quality of Evidence Scale
  High - Randomized controlled trials (RCTs) without important limitations or overwhelming evidence from observational
  studies*
  Moderate - RCTs with important limitations (inconsistent results, methodologic flaws, indirect, or imprecise) or
  exceptionally strong evidence from observational studies*
  Low or very low - Observational studies or case series
  *Although the determination of magnitude of the effect based on observational studies is often a matter of judgment, the guideline
  developers offer the following suggested rule to assist this decision: a large effect would be a relative risk > 2 (risk ratio < 0.5) [which would
  justify moving from weak to moderate], and a very large effect is a relative risk > 5 (risk ratio < 0.2) [which would justify moving from weak
  to strong]. There is some theoretical justification in the statistical literature for these thresholds (the magnitude of effect that is unlikely or
  very unlikely to be due to residual confounding after adjusted analysis). However, once the decision is made, authors should be explicit in
  justifying their decisions.

  Grade of Recommendations Scale
   Grade                        Recommendation
   1A                           Strong
   1B                           Strong
   1C                           Strong
   2A                           Weak
   2B                           Weak
   2C                           Weak

  Relationship of Strength of the Supporting Evidence to the Balance of Benefits to Risks and Burdens
                                                             Balance of Benefits to Risks and Burdens
          Quality of Evidence            Benefits Outweigh           Risks/Burdens Outweigh             Evenly Balanced          Uncertain
                                          Risks/Burdens                      Benefits
   High                                         1A                             1A                             2A                      
   Moderate                                     1B                             1B                             2B                      
   Low or very low                              1C                             1C                             2C                    2C

Clinical Algorithm(s)
  The following clinical algorithms are provided in the original guideline document:
    l     Recommended management algorithm for patients with SPNs that measure 8 to 30 mm in diameter 
    l   Recommended management algorithm for patients with subcentimeter pulmonary nodules that measure < 8 mm
    in diameter



Evidence Supporting the Recommendations
Type of Evidence Supporting the Recommendations
  The type of supporting evidence is identified and graded for each recommendation (see "Major Recommendations").



Benefits/Harms of Implementing the Guideline Recommendations
Potential Benefits
  Appropriate diagnosis and management of patients with pulmonary nodules

Potential Harms
  Diagnosis
  Risks for false-positive and false-negative test results
  Complications of Transthoracic Needle Aspiration
  Complications include minor pneumothorax in approximately 25% of procedures and major pneumothorax that requires
  chest tube drainage in approximately 5% of procedures. Identified risk factors for pneumothorax include smaller lesion
  size, deeper location, proximity to fissures, the presence of emphysema, lateral pleural puncture site, and a smaller
  angle of entry between the needle and the pleura. Risk factors for chest tube drainage include emphysema, proximity
  to fissures, and the need to traverse aerated lung.



Contraindications
Contraindications
  Transthoracic needle aspiration is contraindicated in the patient with a single lung. Relative contraindications to this
  procedure are the patient with pulmonary hypertension, coagulopathy or a bleeding diathesis, severe chronic
  obstructive pulmonary disease (COPD), or vascular malformations.
Contraindications
Contraindications
  Transthoracic needle aspiration is contraindicated in the patient with a single lung. Relative contraindications to this
  procedure are the patient with pulmonary hypertension, coagulopathy or a bleeding diathesis, severe chronic
  obstructive pulmonary disease (COPD), or vascular malformations.



Implementation of the Guideline
Description of Implementation Strategy
  The publication of the Diagnosis and Management of Lung Cancer: ACCP Evidence-Based Clinical Practice Guidelines;
  Second Edition in CHEST is the first of two dissemination vehicles. The circulation of the journal is 23,000 subscribers
  and libraries, including six translations and distribution to 107 countries. All subscribers received a copy of this full-text
  guideline. The American College of Chest Physicians (ACCP) Clinical Resource on Lung Cancer is composed of a printed
  publication and an accompanying CD-ROM, containing a quick reference guide for physicians and other health-care
  providers, patient-targeted educational materials, and a set of slides for use in educational or clinical contexts. In
  addition, the recommendations and grading are personal digital assistant downloadable from the clinical resource. This
  product is available for purchase from the ACCP. The patient education materials are accessible free of charge on

  www.chestnet.org           .
  The implementation and translation of evidence-based clinical practice guidelines facilitates knowledge uptake, critical
  for practice change, and should ultimately lead to better patient-focused care. The HSP Subcommittee on
  Implementation has proposed to collaborate with the Governors, Thoracic Oncology Network, and other groups within
  the ACCP to disseminate and implement the guidelines in their local communities. Residency and specialty training
  programs are encouraged to use the guidelines in journal clubs and grand rounds. Other organizations that were invited
  to send representatives to the final conference and review the proposed drafts were also requested to endorse the
  guidelines and market them to their membership through their own communication channels.

Implementation Tools
  Clinical Algorithm

  Patient Resources

  Resources
  For information about availability, see the Availability of Companion Documents and Patient Resources fields below.



Institute of Medicine (IOM) National Healthcare Quality Report Categories
IOM Care Need
  Getting Better

IOM Domain
  Effectiveness

  Patient-centeredness

  Timeliness


Identifying Information and Availability
Bibliographic Source(s)
   Gould MK, Fletcher J, Iannettoni MD, Lynch WR, Midthun DE, Naidich DP, Ost DE, American College of Chest Physicians.
   Evaluation of patients with pulmonary nodules: when is it lung cancer?: ACCP evidence-based clinical practice

  guidelines (2nd edition). Chest 2007 Sep;132(3 Suppl):108S-30S. [211 references] PubMed

Adaptation
  Not applicable: The guideline was not adapted from another source.

Date Released
  2003 Jan (revised 2007 Sep)

Guideline Developer(s)
  American College of Chest Physicians - Medical Specialty Society

Source(s) of Funding
  American College of Chest Physicians

Guideline Committee
  American College of Chest Physicians (ACCP) Expert Panel on Lung Cancer Guidelines

Composition of Group That Authored the Guideline
  Primary Authors: Michael K. Gould, MD, FCCP; James Fletcher, MD; Mark D. Iannettoni, MD, FCCP; William R. Lynch, MD;
  David E. Midthun, MD, FCCP; David P. Naidich, MD, FCCP; David E. Ost, MD, FCCP

Financial Disclosures/Conflicts of Interest
  Funding for both the evidence review and guideline development was supported by educational grants from
  AstraZeneca LP, Bristol-Myers Squibb Company, Eli Lilly and Company, Genentech, and Sanofi-Aventis. Representatives
American College of Chest Physicians (ACCP) Expert Panel on Lung Cancer Guidelines

Composition of Group That Authored the Guideline
  Primary Authors: Michael K. Gould, MD, FCCP; James Fletcher, MD; Mark D. Iannettoni, MD, FCCP; William R. Lynch, MD;
  David E. Midthun, MD, FCCP; David P. Naidich, MD, FCCP; David E. Ost, MD, FCCP

Financial Disclosures/Conflicts of Interest
  Funding for both the evidence review and guideline development was supported by educational grants from
  AstraZeneca LP, Bristol-Myers Squibb Company, Eli Lilly and Company, Genentech, and Sanofi-Aventis. Representatives
  from these companies were neither granted the right of review, nor were they allowed participation in any portion of
  the guideline development process. This precluded participation in either conference calls or conferences. No panel
  members or ACCP reviewers were paid any honoraria for their participation in the development and review of these
  guidelines.
  The ACCP approach to the issue of potential or perceived conflicts of interest established clear firewalls to ensure that
  the guideline development process was not influenced by industry sources. This policy is published on the ACCP Web

  site at www.chestnet.org      . All conflicts of interest within the preceding 5 years were required to be disclosed by all
  panelists, including those who did not have writing responsibilities, at all face -to-face meetings, the final conference,
  and prior to submission for publication. The most recent of these conflict of interests are documented in this guideline
  Supplement. Furthermore, the panel was instructed in this matter, verbally and in writing, prior to the deliberations of
  the final conference. Any disclosed memberships on speaker's bureaus, consultant fees, grants and other research
  monies, and any fiduciary responsibilities to industry were provided to the full panel in writing at the beginning of the
  conference and at submission for publication.

Guideline Endorser(s)
  American Association for Bronchology - Disease Specific Society

  American Association for Thoracic Surgery - Medical Specialty Society

  American College of Surgeons - Medical Specialty Society

  American Society for Therapeutic Radiology and Oncology - Not stated

  Asian Pacific Society of Respirology - Disease Specific Society

  Oncology Nursing Society - Professional Association

  Society of Thoracic Surgeons - Medical Specialty Society

  World Association of Bronchology - Disease Specific Society

Guideline Status
  This is the current release of the guideline.
  This guideline updates a previous version: Tan BB, Flaherty KR, Kazerooni EA, Iannettoni MD. The solitary pulmonary
  nodule. Chest 2003 Jan;123(1 Suppl):89S-96S.

Guideline Availability

  Electronic copies: Available to subscribers of Chest - The Cardiopulmonary and Critical Care Journal       .
  Print copies: Available from the American College of Chest Physicians, Products and Registration Division, 3300 Dundee
  Road, Northbrook IL 60062-2348.

Availability of Companion Documents
  The following are available:
  Executive Summary:
    l     Alberts MW. Diagnosis and management of lung cancer executive summary. Chest 2007 Sep;132(3 Suppl):1S-19.
  Background Articles:
    l     Alberts WM. Introduction: diagnosis and management of lung cancer. Chest 2007 Sep;132(3 Suppl):20S-22.
    l   McCrory DC, Lewis SZ, Heitzer J, Colice GL, Alberts WM. Methodology for lung cancer evidence review and 
    guideline development. Chest 2007 Sep;132(3 Suppl):23S-28.
    l     Alberg AJ, Ford JG, Samet JM. Epidemiology of lung cancer. Chest 2007 Sep;132(3 Suppl):29S-55.

  Electronic copies: Available to subscribers of Chest - The Cardiopulmonary and Critical Care Journal       .
  Print copies: Available from the American College of Chest Physicians, Products and Registration Division, 3300 Dundee
  Road, Northbrook IL 60062-2348.
  The following is also available:
    l   ACCP clinical resources: Diagnosis and management of lung cancer: ACCP evidence-based clinical practice
    guidelines (2nd edition).

  Available from the American College of Chest Physicians Web site        .

Patient Resources
  The following are available:
    l  Lung cancer guides: lung cancer...am I at risk? Patient education guide. Northbrook (IL): American College of 
    Chest Physicians, 2004. 12 p.
l   ACCP clinical resources: Diagnosis and management of lung cancer: ACCP evidence-based clinical practice
    guidelines (2nd edition).

  Available from the American College of Chest Physicians Web site                   .

Patient Resources
  The following are available:
    l  Lung cancer guides: lung cancer...am I at risk? Patient education guide. Northbrook (IL): American College of 
    Chest Physicians, 2004. 12 p.
    l   Lung cancer guides: What if I have a spot on my lung? Do I have cancer? Patient education guide. Northbrook 
    (IL): American College of Chest Physicians, 2004. 16 p.
    l   Lung cancer guides: living with lung cancer. Patient education guide. Northbrook (IL): American College of Chest 
    Physicians, 2004. 12 p.
    l  Lung cancer guides: advanced lung cancer: issues to consider. Patient education guide. Northbrook (IL): American 
    College of Chest Physicians, 2004. 12 p.
  Electronic copies: Available in Portable Document Format (PDF) from the American College of Chest Physicians (ACCP)

  Web site       .
  Please note: This patient information is intended to provide health professionals with information to share with their patients to help them
  better understand their health and their diagnosed disorders. By providing access to this patient information, it is not the intention of NGC
  to provide specific medical advice for particular patients. Rather we urge patients and their representatives to review this material and then
  to consult with a licensed health professional for evaluation of treatment options suitable for them as well as for diagnosis and answers to
  their personal medical questions. This patient information has been derived and prepared from a guideline for health care professionals
  included on NGC by the authors or publishers of that original guideline. The patient information is not reviewed by NGC to establish whether
  or not it accurately reflects the original guideline's content.


NGC Status
  This NGC summary was completed by ECRI on June 30, 2003. The information was verified by the guideline developer
  on July 25, 2003. This NGC summary was updated by ECRI Institute on November 7, 2007. The updated information
  was verified by the guideline developer on December 21, 2007.

Copyright Statement
  This NGC summary is based on the original guideline, which is subject to the guideline developer's copyright
  restrictions.



Disclaimer
NGC Disclaimer
  The National Guideline Clearinghouse™ (NGC) does not develop, produce, approve, or endorse the guidelines 
  represented on this site.
  All guidelines summarized by NGC and hosted on our site are produced under the auspices of medical specialty
  societies, relevant professional associations, public or private organizations, other government agencies, health care
  organizations or plans, and similar entities.
  Guidelines represented on the NGC Web site are submitted by guideline developers, and are screened solely to
  determine that they meet the NGC Inclusion Criteria which may be found at http://www.guideline.gov/about/inclusion-
  criteria.aspx.
  NGC, AHRQ, and its contractor ECRI Institute make no warranties concerning the content or clinical efficacy or
  effectiveness of the clinical practice guidelines and related materials represented on this site. Moreover, the views and
  opinions of developers or authors of guidelines represented on this site do not necessarily state or reflect those of
  NGC, AHRQ, or its contractor ECRI Institute, and inclusion or hosting of guidelines in NGC may not be used for
  advertising or commercial endorsement purposes.
  Readers with questions regarding guideline content are directed to contact the guideline developer.

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Spn chest 2003

  • 1. NGC banner Guideline Summary NGC-5927 Guideline Title Evaluation of patients with pulmonary nodules: when is it lung cancer?: ACCP evidence-based clinical practice guidelines. (2nd Edition) Bibliographic Source(s) Gould MK, Fletcher J, Iannettoni MD, Lynch WR, Midthun DE, Naidich DP, Ost DE, American College of Chest Physicians. Evaluation of patients with pulmonary nodules: when is it lung cancer?: ACCP evidence-based clinical practice guidelines (2nd edition). Chest 2007 Sep;132(3 Suppl):108S-30S. [211 references] PubMed Guideline Status This is the current release of the guideline. This guideline updates a previous version: Tan BB, Flaherty KR, Kazerooni EA, Iannettoni MD. The solitary pulmonary nodule. Chest 2003 Jan;123(1 Suppl):89S-96S. Scope Disease/Condition(s) Solitary pulmonary nodule (SPN) Guideline Category Diagnosis Evaluation Management Clinical Specialty Family Practice Oncology Pulmonary Medicine Thoracic Surgery Intended Users Advanced Practice Nurses Allied Health Personnel Health Care Providers Nurses Patients Physicians Psychologists/Non-physician Behavioral Health Clinicians Social Workers Guideline Objective(s) To provide clinically relevant, evidence-based guidelines for appropriate imaging modalities and diagnostic testing, and indications for obtaining preoperative tissue diagnosis for patients with a solitary pulmonary nodule Target Population Patients with a solitary pulmonary nodule (SPN) Interventions and Practices Considered Diagnostic Interventions 1.  Chest x-ray (CXR) 2.  Tissue Diagnosis  3.  Chest computed tomography (CT)  4.  Magnetic resonance imaging (MRI) (considered but not recommended routinely)  5.  Fluorodeoxyglucose (FDG)-positron emission tomography (PET) 6.  Bronchoscopy  7.  Transthoracic needle biopsy
  • 2. Diagnostic Interventions 1.  Chest x-ray (CXR) 2.  Tissue Diagnosis  3.  Chest computed tomography (CT)  4.  Magnetic resonance imaging (MRI) (considered but not recommended routinely)  5.  Fluorodeoxyglucose (FDG)-positron emission tomography (PET) 6.  Bronchoscopy  7.  Transthoracic needle biopsy Management Therapeutic Surgical Procedures 1.  Lobectomy  2.  Wedge resection/segmentectomy  3.  Systemic lymph node dissection for all pulmonary resections  4.  External beam radiation  5.  Experimental treatment such as stereotactic radiosurgery and radiofrequency ablation  6.  Pulmonary metastasectomy  7.  Follow-up Major Outcomes Considered l   Sensitivity and specificity of diagnostic tests  l   Diagnostic yield Methodology Methods Used to Collect/Select the Evidence Hand-searches of Published Literature (Primary Sources) Searches of Electronic Databases Description of Methods Used to Collect/Select the Evidence Overview The American College of Chest Physicians (ACCP) chose the Duke University Center for Clinical Health Policy Research to perform formal systematic reviews of the current evidence in the five new non-small cell lung cancer (NSCLC) topic areas, as well as to provide a search for the existing guidelines, systematic reviews, and meta-analyses in all of the topics areas. In addition, the Agency for Healthcare Quality and Research) AHRQ agreed to fund the BlueCross BlueShield Association Technology Evaluation Center to perform the formal systematic review of literature on small cell lung cancer (SCLC). The Health Outcomes Research Group of the Department of Epidemiology and Biostatistics at Memorial Sloan-Kettering Cancer Center conducted a full-scale review of the literature since the first set of guidelines in the area of screening for lung cancer to assist that particular writing group. The formal systematic reviews of the five new topic areas were guided by the appropriate chapter editors and their writing committees, in concert with the Executive Committee of the panel. The two EPC research teams conducted a variety of systematic computerized bibliographic database searches including the following: (1) a search for systematic reviews, guidelines, and meta-analyses published since the last ACCP lung cancer guideline (MEDLINE, The Cochrane Library, National Guidelines Clearinghouse); (2) targeted searches for reviews in each of five selected treatment sections (solitary pulmonary nodules, stage I and II, stage IIIA, stage IIIB, stage IV); these searches, run in OVID version of MEDLINE, were performed in July and August 2005 and were limited to publication years since 1995, English language, and human subjects; and (3) searches related to SCLC are described in the evidence chapter on SCLC. Search terms included the medical subject heading terms lung neoplasms (exploded) and bronchial neoplasms for the lung cancer concept. Each topic search utilized key words specific to the key questions of interest (complete search strategies are available on request from the authors). Strategy Specific for the Treatment of Patients with Pulmonary Nodules To update previous recommendations on the evaluation of patients with pulmonary nodules, guidelines on lung cancer diagnosis and management that were published between 2002 and May 2005 were identified by a systematic review of the literature (see the "Availability of Companion Documents" field in this summary for "Methodology for Lung Cancer Evidence Review and Guidelines Development"). Those guidelines, which include recommendations that are specific to the treatment of patients with pulmonary nodules, were identified for inclusion in this chapter. Supplemental material that is appropriate to this topic was obtained by literature search of a computerized database (MEDLINE), as described in the chapter of these guidelines by Wahidi et al. In addition, we identified articles by searching our own files and by reviewing reference lists provided by the Thoracic Oncology NetWork of the American College of Chest Physicians (ACCP). A multidisciplinary writing committee composed of three pulmonologists, two thoracic surgeons, and two radiologists developed the recommendations and graded the strength of the recommendations and the quality of the supporting evidence by using a standardized method (see "Methodology for Lung Cancer Evidence Review and Guideline Development"). Number of Source Documents Not stated Methods Used to Assess the Quality and Strength of the Evidence Expert Consensus Weighting According to a Rating Scheme (Scheme Given) Rating Scheme for the Strength of the Evidence
  • 3. Number of Source Documents Not stated Methods Used to Assess the Quality and Strength of the Evidence Expert Consensus Weighting According to a Rating Scheme (Scheme Given) Rating Scheme for the Strength of the Evidence High Randomized controlled trials (RCTs) without important limitations or overwhelming evidence from observational studies* Moderate RCTs with important limitations (inconsistent results, methodologic flaws, indirect, or imprecise) or exceptionally strong evidence from observational studies* Low or very low Observational studies or case series *Although the determination of magnitude of the effect based on observational studies is often a matter of judgment, the guideline developers offer the following suggested rule to assist this decision: a large effect would be a relative risk >2 (risk ratio < 0.5) [which would justify moving from weak to moderate], and a very large effect is a relative risk > 5 (risk ratio < 0.2) [which would justify moving from weak to strong]. There is some theoretical justification in the statistical literature for these thresholds (the magnitude of effect that is unlikely or very unlikely to be due to residual confounding after adjusted analysis). However, once the decision is made, authors should be explicit in justifying their decisions. Methods Used to Analyze the Evidence Review of Published Meta-Analyses Systematic Review Description of the Methods Used to Analyze the Evidence Quality of evidence is scored in three categories with high-quality evidence obtained from randomized controlled trials (RCTs) without important methodologic limitations based on the study design, the consistency of the results, and the directness of the evidence. In extraordinary circumstances, significant and consistent evidence from observational studies could also be ranked as high quality. RCTs with important methodologic limitations or flaws, inconsistent results, or indirect or imprecise results would be scored as medium quality, as well as exceptionally strong evidence from observational studies. Other observational studies or case-series data would fall into the low quality of evidence category. It is the interface of the quality of the evidence and the balance of benefits to harms or burdens that determines the strength of the recommendation, with a 1A recommendation being the strongest and 2C the weakest. Methods Used to Formulate the Recommendations Expert Consensus Informal Consensus Description of Methods Used to Formulate the Recommendations Writing committees studied the evidence and summary tables or reviewed the literature for their assigned topics, developing their arguments for the recommendations and suggested grading of those recommendations that were put forth for early drafts. The Executive Committee of the panel, composed of the Chair, Vice-Chair, methodologist, and both project managers, reviewed drafts of each chapter of the manuscript during the writing process. Sections that were determined to be potentially overlapping were shared among the appropriate chapter editors, and conference calls were organized to coordinate the placement of these sections and to confirm that there would be no conflicting information or recommendations. A conference of the panel was convened in July 2006, prior to which time all panelists, including representatives from the invited organizations, were requested to review the complete manuscript and identify recommendations for which the proposal, wording, or grading were determined to be controversial or could be interpreted as controversial by others, incorrectly evolved from the evidence, disagreement existed with regard to the proposal or the grading, or required full panel discussion and further review for any reason. When the panelists who were present were not in unanimous agreement with the proposed recommendations or the grading of the recommendations, informal group consensus techniques were employed. After the meeting, a series of conference calls were convened to finish the discussions and finalize the recommendations. There were a few chapters for which there was insufficient time for full dialogue during the meeting; in the interest of ensuring that the recommendations followed the evidence, the conference calls were necessary. This process ensured the "buy-in" of the panelists and was deemed to be a worthwhile effort. Rating Scheme for the Strength of the Recommendations Grade of Recommendations Scale Grade Recommendation 1A Strong 1B Strong 1C Strong 2A Weak 2B Weak 2C Weak Relationship of Strength of the Supporting Evidence to the Balance of Benefits to Risks and Burdens Balance of Benefits to Risks and Burdens Quality of Evidence Benefits Outweigh Risks/Burdens Outweigh Evenly Balanced Uncertain Risks/Burdens Benefits High 1A 1A 2A   Moderate 1B 1B 2B   Low or very low 1C 1C 2C 2C Cost Analysis
  • 4. 2C Weak Relationship of Strength of the Supporting Evidence to the Balance of Benefits to Risks and Burdens Balance of Benefits to Risks and Burdens Quality of Evidence Benefits Outweigh Risks/Burdens Outweigh Evenly Balanced Uncertain Risks/Burdens Benefits High 1A 1A 2A   Moderate 1B 1B 2B   Low or very low 1C 1C 2C 2C Cost Analysis A formal cost analysis was not performed and published cost analyses were not reviewed. Method of Guideline Validation Peer Review Description of Method of Guideline Validation Following final chapter revisions and incorporation of these ultimate recommendations and grading, a concluding review was conducted by the guideline panel Executive Committee. The guidelines were then submitted for review and approval to the American College of Chest Physicians Health and Science Policy Committee (ACCP HSP) Committee, as well as the Thoracic Oncology Network of the college. Recommendations Major Recommendations Definitions for the strength of evidence and recommendation grades (1A-2C) follow the recommendations. 1.  In every patient with a solitary pulmonary nodule (SPN), we recommend that clinicians estimate the pretest  probability of malignancy either qualitatively by using their clinical judgment or quantitatively by using a validated model. Grade of recommendation, 1C 2.  In every patient with an SPN that is visible on chest radiography (CXR), we recommend that previous CXRs and  other relevant imaging tests be reviewed. Grade of recommendation, 1C 3.  In patients who have an SPN that shows clear evidence of growth on imaging tests, we recommend that tissue  diagnosis should be obtained unless specifically contraindicated. Grade of recommendation, 1C 4.  In a patient with an SPN that is stable on imaging tests for at least 2 years, we suggest that no additional  diagnostic evaluation be performed, except for patients with pure ground-glass opacities on CT, for whom a longer duration of annual follow-up should be considered. Grade of recommendation, 2C 5.  In a patient with an SPN that is calcified in a clearly benign pattern, we recommend no additional diagnostic  evaluation. Grade of recommendation, 1C 6.  In every patient with an indeterminate SPN that is visible on CXR, we recommend that CT of the chest should be performed, preferably with thin sections through the nodule. Grade of recommendation, 1C 7.  In every patient with an indeterminate SPN that is visible on chest CT, we recommend that previous imaging  tests should be reviewed. Grade of recommendation, 1C 8.  In a patient with normal renal function and an indeterminate SPN on CXR or chest CT, we recommend that CT  with dynamic contrast enhancement be considered in centers with experience performing this technique. Grade of recommendation, 1B 9.  In patients with low-to-moderate pretest probability of malignancy (5 to 60%) and an indeterminate SPN that measures at least 8 to 10 mm in diameter, we recommend that F-18 fluorodeoxyglucose (FDG)-positron emission tomography (PET) imaging should be performed to characterize the nodule. Grade of recommendation, 1B 10.   In patients with an SPN that has a high pretest probability of malignancy (> 60%), or patients with a  subcentimeter nodule that measures < 8 to 10 mm in diameter, we suggest that FDG-PET not be performed to characterize the nodule. Grade of recommendation, 2C 11.   In every patient with a SPN, we recommend that clinicians discuss the risks and benefits of alternative  management strategies and elicit patient preferences. Grade of recommendation, 1C 12.   In patients with an indeterminate SPN that measures at least 8 to 10 mm in diameter and who are candidates  for curative treatment, observation with serial CT scans is an acceptable management strategy in the following circumstances: l   When the clinical probability of malignancy is very low (< 5%)  l   When clinical probability is low (< 30 to 40%) and the lesion is not hypermetabolic by FDG-PET or does not enhance > 15 Hounsfield units (HU) on dynamic contrast CT l   When needle biopsy is nondiagnostic and the lesion is not hypermetabolic by FDG-PET l   When a fully informed patient prefers this nonaggressive management approach Grade of recommendation, 2C 13.   In patients who have an indeterminate SPN that measures at least 8 to 10 mm in diameter and undergo  observation, we suggest that serial CT scans be repeated at least at 3, 6, 12, and 24 months. Grade of recommendation, 2C 14.   In patients who have an indeterminate SPN that measures at least 8 to 10 mm in diameter and are candidates  for curative treatment, it is appropriate to perform a transthoracic needle biopsy or bronchoscopy in the following circumstances: l   When clinical pretest probability and findings on imaging tests are discordant; for example, when the pretest  probability of malignancy is high and the lesion is not hypermetabolic by FDG-PET l   When a benign diagnosis requiring specific medical treatment is suspected  l   When a fully informed patient desires proof of a malignant diagnosis before surgery, especially when the risk  of surgical complications is high In general, we suggest that transthoracic needle biopsy be the first choice for patients with peripheral nodules unless the procedure is contraindicated or the nodule is inaccessible. We suggest that bronchoscopy be performed
  • 5. 14.   In patients who have an indeterminate SPN that measures at least 8 to 10 mm in diameter and are candidates  for curative treatment, it is appropriate to perform a transthoracic needle biopsy or bronchoscopy in the following circumstances: l   When clinical pretest probability and findings on imaging tests are discordant; for example, when the pretest  probability of malignancy is high and the lesion is not hypermetabolic by FDG-PET l   When a benign diagnosis requiring specific medical treatment is suspected  l   When a fully informed patient desires proof of a malignant diagnosis before surgery, especially when the risk  of surgical complications is high In general, we suggest that transthoracic needle biopsy be the first choice for patients with peripheral nodules unless the procedure is contraindicated or the nodule is inaccessible. We suggest that bronchoscopy be performed when an air bronchogram is present or in centers with expertise in newer guided techniques. Grade of recommendation, 2C 15.   In surgical candidates with an indeterminate SPN that measures at least 8 to 10 mm in diameter, surgical  diagnosis is preferred in most circumstances, including: l   When the clinical probability of malignancy is moderate to high (> 60%)  l   When the nodule is hypermetabolic by FDG-PET imaging l   When a fully informed patient prefers undergoing a definitive diagnostic procedure Grade of recommendation, 1C 16.   In patients with an indeterminate SPN in the peripheral third of the lung and chose surgery, we recommend that  thoracoscopy be performed to obtain a diagnostic wedge resection. Grade of recommendation, 1C 17.   In a patient who chooses surgery with an indeterminate SPN that is not accessible by thoracoscopy,  bronchoscopy, or transthoracic needle aspiration (TTNA), we recommend that a diagnostic thoracotomy be performed. Grade of recommendation, 1C 18.   In patients who undergo thoracoscopic wedge resection for an SPN that is found to be cancer by frozen section,  we recommend that anatomic resection with systematic mediastinal lymph node sampling or dissection be performed during the same anesthetic. Grade of recommendation, 1C 19.   In patients who have an SPN who are judged to be marginal candidates for lobectomy, we recommend definitive  treatment by wedge resection/segmentectomy (with systematic lymph node sampling or dissection). Grade of recommendation, 1B 20.   For the patient who has an SPN and is not a surgical candidate and prefers treatment, we recommend that the  diagnosis of lung cancer be confirmed by biopsy, unless contraindicated. Grade of recommendation, 1C 21.   For the patient who has a malignant SPN and is not a surgical candidate and prefers treatment, we recommend  referral for external-beam radiation or to a clinical trial of an experimental treatment such as stereotactic radiosurgery or radiofrequency ablation. Grade of recommendation, 2C 22.   For surgical candidates who have subcentimeter nodules and no risk factors for lung cancer, the frequency and  duration of follow-up (preferably with low-dose CT) should depend on the size of the nodule. We suggest the following: l   Nodules that measure up to 4 mm in diameter not be followed up, but the patient must be fully informed of  the risks and benefits of this approach l   Nodules that measure > 4 to 6 mm be re-evaluated at 12 months without additional follow-up if unchanged l   Nodules that measure > 6 to 8 mm be followed up sometime between 6 and 12 months, and then again  between 18 and 24 months if unchanged Grade of recommendation, 2C 23.   For surgical candidates who have subcentimeter nodules and one or more risk factors for lung cancer, the  frequency and duration of follow-up (preferably with low-dose CT) should depend on the size of the nodule. We suggest the following: l   Nodules that measure up to 4 mm in diameter be re-evaluated at 12 months without additional follow-up if unchanged l   Nodules that measure > 4 to 6 mm should be followed up sometime between 6 and 12 months and then again between 18 and 24 months if unchanged l   Nodules that measure > 6 to 8 mm be followed up initially sometime between 3 months and 6 months, then  subsequently between 9 and 12 months, and again at 24 months if unchanged. Grade of recommendation, 2C 24.   For surgical candidates with subcentimeter nodules that display unequivocal evidence of growth during follow- up, we recommend that definitive tissue diagnosis be obtained by surgical resection, transthoracic needle biopsy, or bronchoscopy. Grade of recommendation, 1C 25.   For individuals who have subcentimeter nodules and are not candidates for curative treatment, we recommend  limited follow-up (in 12 months) or follow-up when symptoms develop. Grade of recommendation, 1C 26.   In patients who are candidates for curative treatment with a dominant SPN and one or more additional small  nodules, we recommend that each nodule be evaluated individually, as necessary and curative treatment should not be denied unless there is histopathologic confirmation of metastasis. Grade of recommendation, 1C 27.   In surgical candidates with a solitary pulmonary metastasis, we recommend that pulmonary metastasectomy be  performed if there is no evidence of extrapulmonary malignancy and there is no better available treatment. Grade of recommendation, 1C 28.   In surgical candidates with an SPN that has been diagnosed as small cell lung cancer (SCLC), we recommend  surgical resection with adjuvant chemotherapy, provided that noninvasive and invasive staging exclude the presence of regional or distant metastasis. Grade of recommendation, 1C 29.  In patients who have an SPN and in whom SCLC is diagnosed intraoperatively, we recommend anatomic  resection (with systematic mediastinal lymph node sampling or dissection) under the same anesthesia when there is no evidence of nodal involvement and when the patient will tolerate resection. Surgery should be followed by adjuvant chemotherapy. Grade of recommendation, 1C Definitions: Quality of Evidence Scale
  • 6. 28.   In surgical candidates with an SPN that has been diagnosed as small cell lung cancer (SCLC), we recommend  surgical resection with adjuvant chemotherapy, provided that noninvasive and invasive staging exclude the presence of regional or distant metastasis. Grade of recommendation, 1C 29.  In patients who have an SPN and in whom SCLC is diagnosed intraoperatively, we recommend anatomic  resection (with systematic mediastinal lymph node sampling or dissection) under the same anesthesia when there is no evidence of nodal involvement and when the patient will tolerate resection. Surgery should be followed by adjuvant chemotherapy. Grade of recommendation, 1C Definitions: Quality of Evidence Scale High - Randomized controlled trials (RCTs) without important limitations or overwhelming evidence from observational studies* Moderate - RCTs with important limitations (inconsistent results, methodologic flaws, indirect, or imprecise) or exceptionally strong evidence from observational studies* Low or very low - Observational studies or case series *Although the determination of magnitude of the effect based on observational studies is often a matter of judgment, the guideline developers offer the following suggested rule to assist this decision: a large effect would be a relative risk > 2 (risk ratio < 0.5) [which would justify moving from weak to moderate], and a very large effect is a relative risk > 5 (risk ratio < 0.2) [which would justify moving from weak to strong]. There is some theoretical justification in the statistical literature for these thresholds (the magnitude of effect that is unlikely or very unlikely to be due to residual confounding after adjusted analysis). However, once the decision is made, authors should be explicit in justifying their decisions. Grade of Recommendations Scale Grade Recommendation 1A Strong 1B Strong 1C Strong 2A Weak 2B Weak 2C Weak Relationship of Strength of the Supporting Evidence to the Balance of Benefits to Risks and Burdens Balance of Benefits to Risks and Burdens Quality of Evidence Benefits Outweigh Risks/Burdens Outweigh Evenly Balanced Uncertain Risks/Burdens Benefits High 1A 1A 2A   Moderate 1B 1B 2B   Low or very low 1C 1C 2C 2C Clinical Algorithm(s) The following clinical algorithms are provided in the original guideline document: l   Recommended management algorithm for patients with SPNs that measure 8 to 30 mm in diameter  l   Recommended management algorithm for patients with subcentimeter pulmonary nodules that measure < 8 mm in diameter Evidence Supporting the Recommendations Type of Evidence Supporting the Recommendations The type of supporting evidence is identified and graded for each recommendation (see "Major Recommendations"). Benefits/Harms of Implementing the Guideline Recommendations Potential Benefits Appropriate diagnosis and management of patients with pulmonary nodules Potential Harms Diagnosis Risks for false-positive and false-negative test results Complications of Transthoracic Needle Aspiration Complications include minor pneumothorax in approximately 25% of procedures and major pneumothorax that requires chest tube drainage in approximately 5% of procedures. Identified risk factors for pneumothorax include smaller lesion size, deeper location, proximity to fissures, the presence of emphysema, lateral pleural puncture site, and a smaller angle of entry between the needle and the pleura. Risk factors for chest tube drainage include emphysema, proximity to fissures, and the need to traverse aerated lung. Contraindications Contraindications Transthoracic needle aspiration is contraindicated in the patient with a single lung. Relative contraindications to this procedure are the patient with pulmonary hypertension, coagulopathy or a bleeding diathesis, severe chronic obstructive pulmonary disease (COPD), or vascular malformations.
  • 7. Contraindications Contraindications Transthoracic needle aspiration is contraindicated in the patient with a single lung. Relative contraindications to this procedure are the patient with pulmonary hypertension, coagulopathy or a bleeding diathesis, severe chronic obstructive pulmonary disease (COPD), or vascular malformations. Implementation of the Guideline Description of Implementation Strategy The publication of the Diagnosis and Management of Lung Cancer: ACCP Evidence-Based Clinical Practice Guidelines; Second Edition in CHEST is the first of two dissemination vehicles. The circulation of the journal is 23,000 subscribers and libraries, including six translations and distribution to 107 countries. All subscribers received a copy of this full-text guideline. The American College of Chest Physicians (ACCP) Clinical Resource on Lung Cancer is composed of a printed publication and an accompanying CD-ROM, containing a quick reference guide for physicians and other health-care providers, patient-targeted educational materials, and a set of slides for use in educational or clinical contexts. In addition, the recommendations and grading are personal digital assistant downloadable from the clinical resource. This product is available for purchase from the ACCP. The patient education materials are accessible free of charge on www.chestnet.org  . The implementation and translation of evidence-based clinical practice guidelines facilitates knowledge uptake, critical for practice change, and should ultimately lead to better patient-focused care. The HSP Subcommittee on Implementation has proposed to collaborate with the Governors, Thoracic Oncology Network, and other groups within the ACCP to disseminate and implement the guidelines in their local communities. Residency and specialty training programs are encouraged to use the guidelines in journal clubs and grand rounds. Other organizations that were invited to send representatives to the final conference and review the proposed drafts were also requested to endorse the guidelines and market them to their membership through their own communication channels. Implementation Tools Clinical Algorithm Patient Resources Resources For information about availability, see the Availability of Companion Documents and Patient Resources fields below. Institute of Medicine (IOM) National Healthcare Quality Report Categories IOM Care Need Getting Better IOM Domain Effectiveness Patient-centeredness Timeliness Identifying Information and Availability Bibliographic Source(s) Gould MK, Fletcher J, Iannettoni MD, Lynch WR, Midthun DE, Naidich DP, Ost DE, American College of Chest Physicians. Evaluation of patients with pulmonary nodules: when is it lung cancer?: ACCP evidence-based clinical practice guidelines (2nd edition). Chest 2007 Sep;132(3 Suppl):108S-30S. [211 references] PubMed Adaptation Not applicable: The guideline was not adapted from another source. Date Released 2003 Jan (revised 2007 Sep) Guideline Developer(s) American College of Chest Physicians - Medical Specialty Society Source(s) of Funding American College of Chest Physicians Guideline Committee American College of Chest Physicians (ACCP) Expert Panel on Lung Cancer Guidelines Composition of Group That Authored the Guideline Primary Authors: Michael K. Gould, MD, FCCP; James Fletcher, MD; Mark D. Iannettoni, MD, FCCP; William R. Lynch, MD; David E. Midthun, MD, FCCP; David P. Naidich, MD, FCCP; David E. Ost, MD, FCCP Financial Disclosures/Conflicts of Interest Funding for both the evidence review and guideline development was supported by educational grants from AstraZeneca LP, Bristol-Myers Squibb Company, Eli Lilly and Company, Genentech, and Sanofi-Aventis. Representatives
  • 8. American College of Chest Physicians (ACCP) Expert Panel on Lung Cancer Guidelines Composition of Group That Authored the Guideline Primary Authors: Michael K. Gould, MD, FCCP; James Fletcher, MD; Mark D. Iannettoni, MD, FCCP; William R. Lynch, MD; David E. Midthun, MD, FCCP; David P. Naidich, MD, FCCP; David E. Ost, MD, FCCP Financial Disclosures/Conflicts of Interest Funding for both the evidence review and guideline development was supported by educational grants from AstraZeneca LP, Bristol-Myers Squibb Company, Eli Lilly and Company, Genentech, and Sanofi-Aventis. Representatives from these companies were neither granted the right of review, nor were they allowed participation in any portion of the guideline development process. This precluded participation in either conference calls or conferences. No panel members or ACCP reviewers were paid any honoraria for their participation in the development and review of these guidelines. The ACCP approach to the issue of potential or perceived conflicts of interest established clear firewalls to ensure that the guideline development process was not influenced by industry sources. This policy is published on the ACCP Web site at www.chestnet.org  . All conflicts of interest within the preceding 5 years were required to be disclosed by all panelists, including those who did not have writing responsibilities, at all face -to-face meetings, the final conference, and prior to submission for publication. The most recent of these conflict of interests are documented in this guideline Supplement. Furthermore, the panel was instructed in this matter, verbally and in writing, prior to the deliberations of the final conference. Any disclosed memberships on speaker's bureaus, consultant fees, grants and other research monies, and any fiduciary responsibilities to industry were provided to the full panel in writing at the beginning of the conference and at submission for publication. Guideline Endorser(s) American Association for Bronchology - Disease Specific Society American Association for Thoracic Surgery - Medical Specialty Society American College of Surgeons - Medical Specialty Society American Society for Therapeutic Radiology and Oncology - Not stated Asian Pacific Society of Respirology - Disease Specific Society Oncology Nursing Society - Professional Association Society of Thoracic Surgeons - Medical Specialty Society World Association of Bronchology - Disease Specific Society Guideline Status This is the current release of the guideline. This guideline updates a previous version: Tan BB, Flaherty KR, Kazerooni EA, Iannettoni MD. The solitary pulmonary nodule. Chest 2003 Jan;123(1 Suppl):89S-96S. Guideline Availability Electronic copies: Available to subscribers of Chest - The Cardiopulmonary and Critical Care Journal  . Print copies: Available from the American College of Chest Physicians, Products and Registration Division, 3300 Dundee Road, Northbrook IL 60062-2348. Availability of Companion Documents The following are available: Executive Summary: l   Alberts MW. Diagnosis and management of lung cancer executive summary. Chest 2007 Sep;132(3 Suppl):1S-19. Background Articles: l   Alberts WM. Introduction: diagnosis and management of lung cancer. Chest 2007 Sep;132(3 Suppl):20S-22. l   McCrory DC, Lewis SZ, Heitzer J, Colice GL, Alberts WM. Methodology for lung cancer evidence review and  guideline development. Chest 2007 Sep;132(3 Suppl):23S-28. l   Alberg AJ, Ford JG, Samet JM. Epidemiology of lung cancer. Chest 2007 Sep;132(3 Suppl):29S-55. Electronic copies: Available to subscribers of Chest - The Cardiopulmonary and Critical Care Journal  . Print copies: Available from the American College of Chest Physicians, Products and Registration Division, 3300 Dundee Road, Northbrook IL 60062-2348. The following is also available: l   ACCP clinical resources: Diagnosis and management of lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). Available from the American College of Chest Physicians Web site  . Patient Resources The following are available: l  Lung cancer guides: lung cancer...am I at risk? Patient education guide. Northbrook (IL): American College of  Chest Physicians, 2004. 12 p.
  • 9. l   ACCP clinical resources: Diagnosis and management of lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). Available from the American College of Chest Physicians Web site  . Patient Resources The following are available: l  Lung cancer guides: lung cancer...am I at risk? Patient education guide. Northbrook (IL): American College of  Chest Physicians, 2004. 12 p. l   Lung cancer guides: What if I have a spot on my lung? Do I have cancer? Patient education guide. Northbrook  (IL): American College of Chest Physicians, 2004. 16 p. l   Lung cancer guides: living with lung cancer. Patient education guide. Northbrook (IL): American College of Chest  Physicians, 2004. 12 p. l  Lung cancer guides: advanced lung cancer: issues to consider. Patient education guide. Northbrook (IL): American  College of Chest Physicians, 2004. 12 p. Electronic copies: Available in Portable Document Format (PDF) from the American College of Chest Physicians (ACCP) Web site  . Please note: This patient information is intended to provide health professionals with information to share with their patients to help them better understand their health and their diagnosed disorders. By providing access to this patient information, it is not the intention of NGC to provide specific medical advice for particular patients. Rather we urge patients and their representatives to review this material and then to consult with a licensed health professional for evaluation of treatment options suitable for them as well as for diagnosis and answers to their personal medical questions. This patient information has been derived and prepared from a guideline for health care professionals included on NGC by the authors or publishers of that original guideline. The patient information is not reviewed by NGC to establish whether or not it accurately reflects the original guideline's content. NGC Status This NGC summary was completed by ECRI on June 30, 2003. The information was verified by the guideline developer on July 25, 2003. This NGC summary was updated by ECRI Institute on November 7, 2007. The updated information was verified by the guideline developer on December 21, 2007. Copyright Statement This NGC summary is based on the original guideline, which is subject to the guideline developer's copyright restrictions. Disclaimer NGC Disclaimer The National Guideline Clearinghouse™ (NGC) does not develop, produce, approve, or endorse the guidelines  represented on this site. All guidelines summarized by NGC and hosted on our site are produced under the auspices of medical specialty societies, relevant professional associations, public or private organizations, other government agencies, health care organizations or plans, and similar entities. Guidelines represented on the NGC Web site are submitted by guideline developers, and are screened solely to determine that they meet the NGC Inclusion Criteria which may be found at http://www.guideline.gov/about/inclusion- criteria.aspx. NGC, AHRQ, and its contractor ECRI Institute make no warranties concerning the content or clinical efficacy or effectiveness of the clinical practice guidelines and related materials represented on this site. Moreover, the views and opinions of developers or authors of guidelines represented on this site do not necessarily state or reflect those of NGC, AHRQ, or its contractor ECRI Institute, and inclusion or hosting of guidelines in NGC may not be used for advertising or commercial endorsement purposes. Readers with questions regarding guideline content are directed to contact the guideline developer.