This is the current release of the guideline.

This guideline updates a previous version Socinski MA, Morris DE, Masters GA, Lilenbaum R. Chemotherapeutic management of stage IV non-small cell lung cancer. Chest 2003 Jan;123(1 Suppl):226S-43S.

Stage IV non-small cell lung cancer

Management
Treatment

Family Practice
Oncology
Pulmonary Medicine
Radiation Oncology
Thoracic Surgery

Advanced Practice Nurses
Allied Health Personnel
Health Care Providers
Nurses
Patients
Physicians
Psychologists/Non-physician Behavioral Health Clinicians
Social Workers

To provide updated, evidence-based, clinically relevant treatment guidelines for stage IV non-small cell lung cancer

Patients with stage IV non-small cell lung carcinoma (NSCLC)

Treatment/Management

1. Two-drug combination chemotherapy
2. Bevacizumab in addition to carboplatin and paclitaxel for some patients
3. Single-agent chemotherapy
4. Assessment of quality of life be measured using the Functional Assessment of Cancer Therapy-Lung (FACT-L) or European Organization for Research and Cancer Treatment Quality of Life Questionnaire (EORTC QLQ-C30)
5. Patient education about the risks and benefits of chemotherapy

• Response rate
• Survival (median, 1-year, and progression-free)
• Palliation of symptoms
• Quality of life
• Toxicity of treatment

Hand-searches of Published Literature (Primary Sources)
Searches of Electronic Databases

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 Stage IV Non-small Cell Lung Carcinoma (NSCLC)

In light of the recommendations made in 2003, additional questions that were believed to be pertinent to patients with advanced stage IIIB/IV NSCLC were asked. A systematic review of the literature was undertaken by the multidisciplinary writing committee to identify published materials, including both original articles and guidelines, that address lung cancer diagnosis, management, and treatment. Materials that are appropriate to this topic were obtained by literature search of a computerized database (MEDLINE) to identify relevant articles for review. Recommendations were developed by the writing committee and graded by a standardized method (see the "Availability of Companion Documents" field in this summary for "Methodology for Lung Cancer Evidence Review and Guidelines Development").

Not stated

Expert Consensus
Weighting According to a Rating Scheme (Scheme Given)

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.

Review of Published Meta-Analyses
Systematic Review

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.

Expert Consensus
Informal Consensus

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.

Grade of Recommendations Scale

Relationship of Strength of the Supporting Evidence to the Balance of Benefits to Risks and Burdens

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

Peer Review

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.

Definitions for the strength of evidence and recommendation grades (1A-2C) follow the recommendations.

1. In patients with stage IV non-small cell lung carcinoma (NSCLC) and a good performance status (PS), two-drug combination chemotherapy is recommended. The addition of a third cytotoxic chemotherapeutic agent is not recommended because it provides no survival benefit and may be harmful. Grade of recommendation, 1A
2. Bevacizumab improves survival combined with carboplatin and paclitaxel in a clinically selected subset of patients with stage IV NSCLC and good PS (nonsquamous histology, lack of brain metastases, and no hemoptysis). In these patients, addition of bevacizumab to carboplatin and paclitaxel should be considered a therapeutic option. Grade of recommendation, 1A
3. In patients who have stage IV NSCLC and are elderly (> 70 years old), single-agent chemotherapy is recommended for most. Grade of recommendation, 1A
4. However, in patients who have stage IV NSCLC, are elderly (≥70 years old), have a good PS, and lack significant comorbidities, two-drug combination chemotherapy is recommended as an option. Grade of recommendation, 1B
5. In patients who have stage IV NSCLC and are ≥80 years old, the benefit of chemotherapy is unclear and should be decided on the basis of individual circumstances. Grade of recommendation, 2C
6. In patients with stage IV NSCLC and a PS of 2, chemotherapy is recommended on the basis of defined response rates and symptom palliation. Grade of recommendation, 1B
7. In patients with stage IV NSCLC and a PS of 2, no specific recommendation can be given with regard to the optimal chemotherapeutic strategy. A single phase III trial showed a survival benefit to a carboplatin-based doublet compared with a single agent in a prospectively planned subset analysis. Grade of recommendation, 2C
8. It is recommended that patient-reported health-related quality of life be measured using the Functional Assessment of Cancer Therapy-Lung (FACT-L) or European Organization for Research and Cancer Treatment Quality of Life Questionnaire (EORTC QLQ-C30) questionnaire because it is a significant prognostic factor for survival. Grade of recommendation, 1A
9. It is recommended that patients with stage IV NSCLC receive adequate education about the risks and benefits of chemotherapy to enable active participation in the decision-making process regarding treatment selection. 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

Relationship of Strength of the Supporting Evidence to the Balance of Benefits to Risks and Burdens

None provided

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

Appropriate treatment and management of patients with stage IV non-small cell lung carcinoma (NSCLC)

Not stated

End of Life Care
Living with Illness

Effectiveness
Patient-centeredness

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

2003 Jan (revised 2007 Sep)

American College of Chest Physicians - Medical Specialty Society

American College of Chest Physicians

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

Primary Authors: Mark A. Socinski, MD, FCCP; Richard Crowell, MD, FCCP; Thomas E. Hensing, MD; Corey J. Langer, MD; Rogerio Lilenbaum, MD; Alan B. Sandler, MD; David Morris, MD

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
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

This is the current release of the guideline.

This guideline updates a previous version Socinski MA, Morris DE, Masters GA, Lilenbaum R. Chemotherapeutic management of stage IV non-small cell lung cancer. Chest 2003 Jan;123(1 Suppl):226S-43S.

This NGC summary was completed by ECRI on September 3, 2003. The information was verified by the guideline developer on October 1, 2003. This NGC summary was updated by ECRI Institute on November 27, 2007. The updated information was verified by the guideline developer on December 21, 2007.

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