NCCN Guidelines for Patients

Transcription

1 Non-Small Cell Lung Cancer NCCN Guidelines for Patients Version 2010 In honor and memory of Dana Reeve Also available at NCCN.com

2 Non-Small Cell Lung Cancer Table of Contents Map of the NCCN Member Institutions... 3 About the NCCN Guidelines for Patients... 4 About the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines )... 4 Non-Small Cell Lung Cancer Panel... 6 Introduction... 7 Making Decisions about Lung Cancer Treatment... 8 Lung Cancer Staging... 9 T Categories... 9 N Categories M Categories Treatment Pathways for Non-Small Cell Lung Cancer Initial Evaluation and Clinical Stage Stage I and II Pretreatment Evaluation Stage I and II and IIIA Treatment Stage IIB and IIIA Pretreatment Evaluation Stage IIB and IIIA Treatment Stage IIIA and Separate Nodule(s) Pretreatment Evaluation Stage IIIA (T1-3, N2) Treatment Separate Nodule(s) and Stage IV, IIIA (T4, N0-1) Treatment Stage IIIB (T1-3) Evaluation and Initial Treatment Stage IIIB and Stage IV Evaluation and Initial Treatment Stage IV Evaluation and Initial Treatment Follow-Up, Recurrence, and Widespread Disease Therapy For Recurrence and Widespread Disease General Principles of Pathologic Evaluation and Treatment Cancer Survivorship Care Lung Cancer Prevention and Screening Discussion Version Glossary NCCN Member Institutions

3 Map of NCCN Member Institutions The National Comprehensive Cancer Network (NCCN ), a not-for-profit alliance of 21 of the world s leading cancer centers, is dedicated to improving the quality and effectiveness of care provided to patients with cancer. Through the leadership and expertise of clinical professionals at NCCN Member Institutions, NCCN develops resources that present valuable information to the numerous stakeholders in the health care delivery system. As the arbiter of high-quality cancer care, NCCN promotes the importance of continuous quality improvement and recognizes the significance of creating clinical practice guidelines appropriate for use by patients, clinicians, and other health care decision-makers. The primary goal of all NCCN initiatives is to improve the quality, effectiveness, and efficiency of oncology practice so patients can live better lives. Fred Hutchinson Cancer Research Center/ Seattle Cancer Care Alliance UCSF Helen Diller Family Comprehensive Cancer Center Stanford Comprehensive Cancer Center Huntsman Cancer Institute at the U. of Utah City of Hope Comprehensive Cancer Center UNMC Eppley Cancer Center at The Nebraska Medical Center The University of Texas MD Anderson Cancer Center Robert H. Lurie Comprehensive Cancer Center of Northwestern U. Siteman Cancer Center at Barnes-Jewish Hospital and Washington U. School of Medicine St. Jude Children s Research Hospital/ U. of Tennessee Cancer Institute U. of Michigan Comprehensive Cancer Center U. of Alabama at Birmingham Comprehensive Cancer Center Roswell Park Cancer Institute The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute Vanderbilt-Ingram Cancer Center Dana-Farber/Brigham and Women s Cancer Center Massachusetts General Hospital Cancer Center Memorial Sloan-Kettering Cancer Center Fox Chase Cancer Center The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Duke Comprehensive Cancer Center H. Lee Moffitt Cancer Center & Research Institute 3

4 Non-Small Cell Lung Cancer About the NCCN Guidelines for Patients The National Comprehensive Cancer Network (NCCN ) aims to provide people with cancer and the general public state-of-the-art cancer treatment information in easy-to-understand language. The NCCN Guidelines for Patients, based on the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines ), are meant to help you when you talk with your doctor about treatment options that are best for you. These guidelines do not replace the expertise and clinical judgment of your doctor. About the NCCN Guidelines The NCCN Guidelines are the most comprehensive and most frequently updated clinical practice guidelines available in any area of medicine. These guidelines provide information that many doctors follow to make sure their decisions for people with cancer are well informed. The NCCN Guidelines are developed by 43 different NCCN Guidelines Panels composed of nearly 900 world-leading experts from each of the NCCN Member Institutions. Cancer is treated by teams of doctors and other health professionals who work together to diagnose and treat cancer. NCCN Guidelines Panels are multidisciplinary, which means they include experts in different fields reflecting the way cancer is treated. These fields include medical oncology, surgical oncology, radiation oncology, pathology, radiology, nursing, and social work. Recommendations in the NCCN Guidelines are based on evaluation of evidence from clinical trials that are published in the medical literature. Most of the panel members who develop the NCCN Guidelines perform both clinical research and treat people with cancer. The members of each NCCN Guideline Panel specialize in the specific tumors and diseases discussed in that NCCN Guideline. Some NCCN Guidelines Panels also have patient advocates to bring the patient s perspective to the panel discussions. NCCN Guidelines Panel Members volunteer more than 15,000 hours each year to revising and updating the NCCN Guidelines to reflect new data and clinical information. The NCCN Guidelines are used by doctors in academic centers and community practices to inform their decisions when diagnosing and treating people with cancer. The NCCN Guidelines encompass 97 percent of the tumors encountered in oncology practices, and these guidelines are continually updated as new information becomes available. With the NCCN Guidelines, doctors and patients have access to the same treatment regimens used by NCCN Guidelines Panel Members when they treat their patients. The decisions of the expert panel are based on scientific data coordinated with expert judgment. Community physicians may or may not perform research, but by using the NCCN Guidelines, they have information about the latest evidence from clinical trials and insights to the expertise found at leading cancer centers. 4

5 By showing the standard of care, guidelines can reduce variation in how patients are treated and help make sure everyone gets the best care for them. However, no one treatment is right for everyone. Clinical research shows that some treatments are better for a particular disease than others. Similarly, studies have demonstrated that different patients with the same cancer may need different treatments. In many cases, patient preference is important especially when selecting among several effective treatments each with different side effects. Recommendations included in the NCCN Guidelines are those that NCCN doctors feel are most useful based on the evidence published in medical journals and their own experience treating patients. Therefore, even if a treatment is part of the NCCN Guidelines, it may not be the right treatment for all people with cancer or all people with that particular cancer. This is because each patient has a specific medical history and individual circumstances. On the other hand, not including a particular treatment in the NCCN Guidelines only means that there is not strong enough evidence at this time to support using it as part of standard practice. In some cases, there may be ongoing clinical trials to determine whether the treatment is effective. Many new treatments are available because patients have participated in clinical trials. Additionally, new treatments that are not yet part of standard practice may only be available in clinical trials. You can discuss whether a clinical trial might be right for you with your doctor. The NCCN Guidelines for Patients translate the information that doctors use to help you and your family understand your treatment options. They empower you to discuss treatment choices with your health care team and make cancer care decisions that are right for you. For the most up-to-date versions of the NCCN Guidelines for Patients, visit NCCN.com. A diverse group of experts from NCCN Member Institutions developed the NCCN Guidelines for Non-Small Cell Lung Cancer. Listed on page 6 are the NCCN Guidelines Panel Members whose recommendations for treatment are featured in these NCCN Guidelines for Patients. 5

6 Non-Small Cell Lung Cancer Non-Small Cell Lung Cancer Panel David S. Ettinger, MD / Chair The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Wallace Akerley, MD Huntsman Cancer Institute at the University of Utah Hossein Borghaei, DO, MS Fox Chase Cancer Center Andrew Chang, MD University of Michigan Comprehensive Cancer Center Richard T. Cheney, MD Roswell Park Cancer Institute Lucian R. Chirieac, MD Dana-Farber/Brigham and Women s Cancer Center Thomas A. D Amico, MD Duke Comprehensive Cancer Center Todd L. Demmy, MD Roswell Park Cancer Institute Ramaswamy Govindan, MD Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine Frederic W. Grannis, Jr., MD City of Hope Comprehensive Cancer Center Leora Horn, MD, MSc, FRCPC Vanderbilt-Ingram Cancer Center Thierry Jahan, MD UCSF Helen Diller Family Comprehensive Cancer Center Anne Kessinger, MD UNMC Eppley Cancer Center at The Nebraska Medical Center Ritsuko Komaki, MD The University of Texas MD Anderson Cancer Center Feng-Ming Kong, MD, PhD, MPH University of Michigan Comprehensive Cancer Center Mark G. Kris, MD Memorial Sloan-Kettering Cancer Center Lee M. Krug, MD Memorial Sloan-Kettering Cancer Center Inga T. Lennes, MD Massachusetts General Hospital Cancer Center Billy W. Loo, Jr., MD, PhD Stanford Comprehensive Cancer Center Renato Martins, MD, MPH Seattle Cancer Care Alliance Janis O Malley, MD University of Alabama at Birmingham Comprehensive Cancer Center Raymond U. Osarogiagbon, MD, FACP University of Tennessee Cancer Institute 6 Gregory A. Otterson, MD The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute Jyoti D. Patel, MD Robert H. Lurie Comprehensive Cancer Center of Northwestern University Mary Pinder - Schenck, MD H. Lee Moffitt Cancer Center & Research Institute Katherine M. Pisters, MD The University of Texas MD Anderson Cancer Center Karen Reckamp, MD, MS City of Hope Comprehensive Cancer Center Gregory J. Riely, MD, PhD Memorial Sloan-Kettering Cancer Center Eric Rohren, MD, PhD The University of Texas MD Anderson Cancer Center Scott Swanson, MD Dana-Farber/Brigham and Women s Cancer Center Douglas E. Wood, MD Fred Hutchinson Cancer Research Center/ Seattle Cancer Care Alliance Stephen C. Yang, MD The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

7 Introduction These NCCN Guidelines for Patients TM : Non-Small Cell Lung Cancer are designed as a resource to assist patients with cancer when discussing treatment options with their doctors. These guidelines do not replace the expertise and clinical judgment of the doctor. There are several different subtypes of cancer that arise in the lung, which are categorized according to how the tumor cells appear under a microscope. These guidelines specifically address the non-small cell lung cancer subtype. It is also important to understand that cancers that start in other parts of the body, for example, the breast or intestines, can spread to the lung. While some people may still refer to this as lung cancer, it is treated differently than cancers that arise in the lung. Therefore, treatment of cancer that spreads to the lung is included in the individual NCCN Guidelines for Patients that corresponds to where the tumor first started (e.g., breast cancer). The NCCN Guidelines for Patients : Non-Small Cell Lung Cancer are designed to make cancer treatment more understandable. These guidelines apply to most but not all people with non-small cell lung cancer. Their relevance to you and your treatment will depend on your general health and personal circumstances. The guidelines include several important parts: An overview of important questions and issues to discuss with your doctor. Staging tables that drive the decisions about the best treatments. Your doctor can tell you which stage applies to your cancer. The pathways which outline the step-by-step treatment decisions from diagnosis through all phases of treatment and survivorship. Once you know the stage of your cancer, simply follow the arrows corresponding to that stage to view the treatment recommendations as set forth by the NCCN Guidelines Panel for Non-Small Cell Lung Cancer. These pathways are simplified versions of the pathways that doctors use in thinking about how to treat non-small cell lung cancer; however the content is still quite technical. Background information is provided in the Discussion section to help you understand this complicated information about non-small cell lung cancer. It includes the tests used in your medical evaluation, factors that lead doctors to recommend one treatment plan over others for a particular patients, description of the treatments themselves and how combinations of treatments are used together to provide the best possible outcomes, and the types of follow up needed after treatment is completed. A discussion of each of the pathways is provided, and Inevitably, you will encounter unfamiliar words and concepts, either in these guidelines or when talking with your doctor, so a glossary of cancer terms is included. These terms are shown in italics on the first mention in text. These guidelines are complicated because non-small cell lung cancer is a complex disease. Many users will find that it is convenient to move from one part of the guidelines to another and back again rather than reading from beginning to end. The table of contents can help you navigate from one area to another easily. 7

8 Non-Small Cell Lung Cancer Making Decisions about Lung Cancer Treatment A diagnosis of lung cancer is overwhelming for both patients and their families. A variety of tests will be recommended, followed by a discussion of treatment options, all of which will certainly lead to questions that patients will want to ask their cancer care team. However, it can be hard to know where to start to ask questions, and some patients and families may feel intimidated when talking to physicians. Therefore, it can be helpful to consider some general issues as you read through this guideline to help create a question list. Below are common issues associated with treatment of non-small cell lung cancer. Make sure you know the type of lung cancer you have, as this guideline only discusses non-small cell lung cancer. When making decisions about treatment, it is helpful to ask about the benefits, risks, and side effects of each treatment and how these can be managed. You may want to consider getting a second opinion from another lung cancer specialist before deciding on treatment. Ask the doctor about the best way to prepare for treatment and how to stay healthy while receiving it in order to speed recovery. - Ask about available support services, such as specially trained social workers and psychologists who understand the special needs of patients with cancer and their families. - Cancer support groups are very helpful and groups are available for both patients and loved ones; you may want to consider joining one. - Ask how you can help yourself remain fit and healthy: diet, exercise, acupuncture, vitamins, imagery, massage, etc. Feel free to ask the doctor whether he or she uses treatment guidelines, such as the NCCN Guidelines or other recognized clinical practice guidelines. Ask the doctor specific questions about treatment options, such as: - How long it will take to complete all of the treatments? - Will I be able to work or perform other normal activities during treatment? - Will the side effects of treatment be temporary or permanent? - What is the chance that the cancer will come back? - How much will the treatment cost and how can I find out how much my insurance will cover? You may want to ask the doctor whether participating in a clinical trial would be helpful (see page 39). If you smoke, it is important to stop now. Talk to your doctor or call QUIT NOW ( ) to find a Quitline in your area. You might want to discuss living wills or advanced directives with your cancer care team. Treatment options for lung cancer consist of surgery, radiation therapy, chemotherapy, and targeted therapy, which can be given in different orders, or combinations, according to the tumor stage. You will probably want to know which treatments you will receive and in what order they will be given. Your treatment will depend on how large your tumor is and whether it involves other parts of the lung or lymph nodes or has spread beyond the lungs. This is called the stage of your lung cancer (see Lung Cancer Staging, page 9). The cancer stage is important to know because treatment will be based on it. For this reason, the treatment pathways in this guideline are also organized by stage. To be sure you have the most up-to-date version of these NCCN Guidelines for Patients, visit the NCCN patient website (NCCN.com). 8

9 Lung Cancer Staging There are four general categories of treatment for non-small cell lung cancer: surgery, radiation therapy, chemotherapy, and targeted therapy. These therapies can be used in different orders and combinations. A key factor in determining how to best combine these options is the stage of the cancer. The stages of lung cancer can be broadly subdivided into stages I, II, III, and IV. Each of these stages (I IV) defines tumors that have similar prognoses and can be treated in the same general way. Each tumor stage contains tumors with specific combinations of tumor size (T), lymph node involvement (N), and metastases (M). Different imaging tests (see page 12) are initially used to stage the cancer, often followed by biopsy techniques to confirm the imaging results. After this workup has been completed, the cancer can be categorized according to its stage and specific TNM status. To follow the treatment pathways, it is important to know both the cancer stage and TNM classification. Below is more detailed information on the definitions of the T, N, and M categories and cancer staging. T Categories T categories are based on the size of the lung cancer, its location within the lungs, and its spread to nearby tissues. Tis: Cancer is found only in the layer of cells lining the air passages and has not spread into other lung tissues. This stage is also known as carcinoma in situ. T1: The cancer is 3 cm or smaller in size, surrounded by lung or visceral pleura (membranes that surround the lungs), and does not affect the main branches of the airways. T1 is further subdivided into: T1a cancer is 2 cm or smaller T1b cancer is larger than 2 cm and smaller or equal to 3 cm T2: The cancer is larger than 3 cm but no larger than 7 cm in greatest dimension with any of the following features: It involves a main bronchus but is not closer than 2 cm to the point where the trachea (windpipe) branches into the left and right main bronchi. It has spread to the membranes that surround the lungs. The cancer may partially block the airways, but this has not caused the entire lung to collapse or pneumonia to develop. T2 is further subdivided into: T2a cancer is larger than 3 cm but smaller or equal to 5 cm T2b cancer is larger than 5 cm but smaller or equal to 7 cm 9

10 Non-Small Cell Lung Cancer T3: The cancer is larger than 7 cm in greatest dimension, with any of the following features: It has spread to the chest wall, the diaphragm (breathing muscle that separates the chest from the abdomen), the mediastinal pleura (membranes surrounding the space between the lungs), or parietal pericardium (membranes of the sac surrounding the heart). It involves a main airway, and it is closer than 2 cm to the point where the trachea (windpipe) branches into the left and right main airway but does not involve this area. It has grown into the airways enough to cause one lung to entirely collapse or to cause pneumonia of the entire lung. There is a separate tumor nodule in the same lobe. T4: The cancer has one or more of the following features: It has spread to the mediastinum (space behind the chest bone and in front of the heart), heart, blood vessels near the heart, trachea (windpipe), nerve near the trachea, esophagus (tube connecting the throat to the stomach), backbone, or point where the windpipe branches into the left and right main airway. Two or more separate tumor nodules are present in a different lobe of the same lung. N Categories N categories depend on which, if any, of the lymph nodes near the lungs are affected by the cancer. N0: The cancer has not spread to lymph nodes. N1: The cancer has spread to the lymph nodes either in the lung or located around the area where the bronchus enters the lung. Affected lymph nodes are present only on the same side as the cancerous lung. N2: The cancer has spread to subcarinal lymph nodes (around the point where the windpipe branches into the left and right bronchi) or to lymph nodes in the mediastinum. Affected lymph nodes are on the same side of the cancerous lung. N3: The cancer has spread to lymph nodes near the collarbone on either side, and/or to hilar or mediastinal lymph nodes on the side opposite the lung with the tumor. 10

11 M Categories M categories depend on whether the cancer has spread to any distant tissues and organs. M0: No distant cancer spread. M1: Cancer has spread to one or more distant sites. Sites considered distant include other lobes of the lungs, lymph nodes further than those mentioned in N stages, and other organs or tissues such as the liver, bones, or brain. M1 is further subdivided into the following categories: M1a: Include any of the following: - Separate tumor nodules in a contralateral lobe - Tumor nodules on the lining of the lung surface (i.e., pleura) - Fluid around the lungs or heart that contains cancer cells (i.e., pleural or pericardial effusion) M1b: Distant spread This explanation of staging will help to determine what path you should follow throughout the next several pages of treatment pathways. Be sure to refer to the discussion section if you need clarification on any of the information within the pathways. Used with the permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois. The original source for this material is the AJCC Cancer Staging Manual, Seventh Edition (2010) published by Springer Science and Business Media LLC, 11

12 Initial Evaluation and Clinical Stage (For more detailed information, see page 43) TESTS AND EXAMS FOR THE DIAGNOSIS OF NON-SMALL CELL LUNG CANCER CLINICAL STAGE (ASSESSMENT) ADDITIONAL PRETREATMENT EVALUATION Patient has been diagnosed with nonsmall cell lung cancer based on test results Pathology review or description of cells and tissues made by a pathologist based on microscopic features Medical history (i.e., cough, chest pain, weight loss) and physical exam to assess general health and cancer symptoms Series of images known as a CT scan of the chest, upper abdomen, and adrenal glands Complete blood count, also called CBC. A test to check the number of red blood cells, white blood cells, and platelets in a sample of blood. Blood chemistry tests, a procedure in which a sample of blood is examined to measure the amounts of certain substances made within the body Counseling on stopping smoking Staging is usually based on the size of the tumor (T), whether lymph nodes contain cancer (N), and whether the cancer has spread from the original site to other parts of the body (M). Additional testing may be required prior to receiving treatment based upon the stage of your cancer. Review the staging tables with your doctor to determine your clinical stage. Follow the appropriate treatment pathway for your specific clinical stage See Staging Table (p. 13) 12

13 The first step is to determine the clinical stage of your lung cancer with the help of your doctor. Lung cancer staging definitions are provided on pages Next, follow the page listed for the pretreatment evaluation that corresponds with your stage. Clinical Stage T category N category M category Pretreatment Evaluation Stage IA T1ab N0 M0 See page 14 Stage IB T2a N0 M0 See page 14 Stage I T1ab T2a N0 M0 See page 14 Stage II T1ab 2a N1 M0 See page 14 Stage II T2b N0 M0 See page 14 Stage IIB T2b N1 M0 See page 14 Stage IIB T3 N0 M0 See page 14 Stage IIB T3 N0 M0 See page 16 Stage IIIA T3 N1 M0 See page 16 T4 N0-N1 Stage IIIA T1 3 N2 M0 See page 18 Separate nodule T1 3 M0 See page 18 Stage IIIB T1 3 N3 M0 See page 21 Stage IIIB T4 extension N2 3 See page 22 Stage IV Any T Any N M1a See page 22 Stage IV Any T Any N M1b - single See page 23 Stage IV Any T Any N M1b - multiple See page 23 13

14 Stage I and II Pretreatment Evaluation (For more detailed information, see page 44) CLINICAL STAGE (ASSESSMENT) Stage IA (peripheral T1ab, N0) a PRETREATMENT EVALUATION Lung function test (if not previously done) A test used to measure how well the lungs work, also known as pulmonary function test or PFT Bronchoscopy to examine the inside of the trachea, bronchi (air passages that lead to the lungs), and lungs Mediastinoscopy to examine the organs in the area between the lungs and nearby lymph nodes Endobronchial ultrasound (EBUS) if appropriate c PET/CT scan No cancer found in mediastinal nodes Operable Inoperable because of health status See Initial Treatment and Adjuvant Treatment (p. 15) Potentially curative radiation therapy Stage IB (peripheral T2a, N0) Stage I (central T1ab T2a, N0) b Stage II (T1ab 2a, N1; T2b, N0) Stage IIB (T2b, N1; T3, N0) Lung function test (if not previously done) A test used to measure how well the lungs work, also known as pulmonary function test or PFT Bronchoscopy to examine the inside of the trachea, bronchi (air passages that lead to the lungs), and lungs Mediastinoscopy to examine the organs in the area between the lungs and nearby lymph nodes Endobronchial ultrasound (EBUS) if appropriate PET/CT scan c Brain MRI (stage ll, and possibly stage IB) Mediastinal nodes contain cancer See Stage IIIA (p. 19) or Stage IIIB (p. 21) a Based on the CT scan of the chest: Peripheral refers to the outer third of the lung. b Based on the CT scan of the chest: Central refers to the inner two thirds of the lung. c Positive PET/CT scans findings need confirmation (e.g., MRI of the bone). If the PET/CT scan is positive in the mediastinum (area between the lungs), the lymph node needs to be tested. 14

15 Stage I and II and IIIA Treatment (For more detailed information, see page 44) INITIAL TREATMENT CLINICAL STAGE SURGICAL MARGINS ADJUVANT (ADDITIONAL) TREATMENT Stage IA (T1ab, N0) Tumor removed, no cancer at edges of specimen Tumor removed, but cancer at edges of specimen Observe Surgery to remove remaining cancer (preferred) or Radiation therapy Surgery to remove tumor and search for spread in nearby lymph nodes Stage IB (T2a, N0); Stage IIA (T2b, N0) Stage IIA (T1ab-T2a, N1) Stage IIB (T3, N0; T2b, N1) Stage IIIA (T1-3, N2) Tumor removed, no cancer at edges of specimen Tumor removed, but cancer at edges of specimen Tumor removed, no cancer at edges of specimen Tumor removed, but cancer at edges of specimen Tumor removed, no cancer at edges of specimen Tumor removed, but cancer at edges of specimen Observe or Chemotherapy if high-risk of recurrence e Surgery to remove remaining cancer followed by chemotherapy or Radiation with additional chemotherapy Chemotherapy with or without radiation therapy Surgery to remove remaining cancer followed by chemotherapy or Chemoradiation d with additional chemotherapy Chemotherapy and radiation therapy d Chemoradiation with additional chemotherapy dchemoradiation refers to treatment that combines chemotherapy and radiation therapy. If the tumor cannot initially be removed by surgery, chemotherapy and radiation therapy are given concurrently (at the same time) to attempt to make it surgically removable. If the tumor was removed and there is no residual cancer at the edges of the specimen, most NCCN institutions give chemotherapy and radiation one after the other, if the tumor was removed but residual cancer is at the edges of the specimen chemotherapy would be given together with radiation concurrently. e Patients who may be at a higher risk for recurrence are those whose cancer characteristics include: poorly differentiated tumor, these are tumors that lack the structure and function of normal cells and tend to grow at a faster rate, or large tumor size, or cancer has spread. 15

16 Stage IIB and IIIA Pretreatment Evaluation (For more detailed information, see page 46) CLINICAL STAGE (ASSESSMENT) PRETREATMENT EVALUATION Stage IIB (T3, N0) Stage IIIA (T3, N1; T4, N0-N1) Lung function test (if not previously done). A test used to measure how well the lungs work, also known as pulmonary function test or PFT Bronchoscopy to examine the inside of the trachea, bronchi (air passages that lead to the lungs), and lungs Endobronchial ultrasound (EBUS) Mediastinoscopy to examine the organs in the area between the lungs and nearby lymph nodes MRI of the brain, spine, and uppermost section of the chest PET/CT scan c Cancer is in the uppermost section of the chest (superior sulcus) and has not spread outside the chest Cancer is growing into the chest wall and has not spread outside the chest Cancer is growing into the main breathing tubes or into the mediastinum (area between the lungs) and has not spread outside the chest Cancer has spread to distant sites outside the chest See Treatment (p. 17) See Treatment (p. 17) See Treatment (p. 17) See Treatment for Widespread Disease Metastasis (p. 23) c Positive PET/CT scans findings need confirmation (e.g., MRI of the bone). If the PET/CT scan is positive in the mediastinum (area between the lungs), the lymph node needs to be tested. 16

17 Stage IIB and IIIA Treatment (For more detailed information, see page 46) PRETREATMENT EVALUATION INITIAL TREATMENT ADJUVANT (ADDITIONAL) TREATMENT Cancer is in the uppermost section of the chest (superior sulcus) and has not spread outside the chest Cancer is in the uppermost section of the chest (superior sulcus) and has not spread outside the chest Tumor can be completely removed with surgery Tumor may not be completely removed with surgery Tumor cannot be completely removed with surgery Preoperative concurrent chemoradiation d Preoperative concurrent chemoradiation d Concurrent chemoradiation as primary treatment d Surgery followed by chemotherapy Surgical reevaluation See Follow Up (p. 24) See Follow Up (p. 24) Tumor can be completely removed with surgery Tumor cannot be completely removed with surgery Surgery with chemotherapy Complete definitive (full dose) RT and chemotherapy See Follow Up (p. 24) Cancer is growing into the main breathing tubes or into the mediastinum (area between the lungs) and has not spread outside the chest Surgery (preferred) or Concurrent chemoradiation d or Chemotherapy Surgery Tumor removed, no cancer at edges of specimen Tumor removed, but cancer at edges of specimen Chemotherapy if not given as initial treatment Surgery to remove remaining cancer and chemotherapy if not given as initial treatment or Chemoradiation g with additional chemotherapy if not given as initial treatment See Follow Up (p. 24) d Chemoradiation refers to treatment that combines chemotherapy and radiation therapy. If the tumor cannot initially be removed by surgery, chemotherapy and radiation therapy are given concurrently (at the same time) to attempt to make it surgically removable. If the tumor was removed and there is no residual cancer at the edges of the specimen, most NCCN institutions give chemotherapy and radiation one after the other, if the tumor was removed but residual cancer is at the edges of the specimen chemotherapy would be given together with radiation concurrently. 17

18 Stage IIIA and Separate Nodule(s) Pretreatment Evaluation (For more detailed information, see page 46) CLINICAL STAGE (ASSESSMENT) PRETREATMENT EVALUATION MEDIASTINAL BIOPSY FINDINGS AND RESECTABILITY Stage IIIA (T1 3, N2) Lung function test (if not previously done). A test used to measure how well the lungs work, also known as pulmonary function test or PFT Bronchoscopy to examine the inside of the trachea, bronchi (air passages that lead to the lungs), and lungs Mediastinoscopy or biopsy of lymph nodes with fine needle through trachea or esophagus MRI of the brain PET/CT scan c No cancer found in lymph nodes Cancer found in lymph nodes on the same side of chest as the tumor Cancer found in lymph nodes on the other side of the chest from the tumor Cancer has spread outside the chest (metastatic disease) See Treatment (p. 19) See Treatment (p. 19) See Stage IIIB (p. 21) See Treatment for Widespread Disease Metastasis (p. 23) Separate lung nodule(s) (secondary tumor) (Stage IIB, IIIA, IV) Lung function test (if not previously done). A test used to measure how well the lungs work, also known as pulmonary function test or PFT Bronchoscopy to examine the inside of the trachea, bronchi (air passages that lead to the lungs), and lungs Mediastinoscopy or biopsy of lymph nodes with fine needle through trachea or esophagus MRI of the brain PET/CT scan c Main tumor and separate tumor(s) in the same lung Main tumor and separate tumor(s) in other lung Cancer cannot be completely removed with surgery Cancer has spread to distant sites outside the chest (metastatic disease) See Treatment (p. 20) See Treatment (p. 20) See Treatment (p. 20) See Treatment for Widespread Disease Metastasis (p.23) c Positive PET/CT scans findings need confirmation (e.g., MRI of the bone). If the PET/CT scan is positive in the mediastinum (area between the lungs), the lymph node needs to be tested. 18

19 Stage IIIA (T1-3, N2) Treatment (For more detailed information, see page 47) MEDIASTINAL BIOPSY FINDINGS AND RESECTABILITY INITIAL TREATMENT ADJUVANT (ADDITIONAL) TREATMENT T1-3, N0 No cancer found in lymph nodes T1-2, T3 Cancer found in lymph nodes on the same side of chest as tumor without invasion Surgery Tumor can be completely removed with surgery Tumor cannot be completely removed with surgery Brain MRI, if not previously done PET/CT scan, c if not previously done Surgery to remove tumors and mediastinal lymph nodes N0 1 N2 See Appropriate Guideline According to Stage (p.15) No evidence of distant spread of disease Cancer has spread to distant sites See Appropriate Guideline p. 15 or p. 16 Tumor removed, no cancer at edges of specimen Tumor removed, but cancer at edges of specimen Chemotherapy together with full dose radiation therapy or Short course of chemotherapy with or without radiation therapy See Treatment for Widespread Disease Metastasis (p. 23) Chemotherapy and radiation therapy Cancer stops growing Cancer grows d Chemoradiation with additional chemotherapy Cancer has spread to distant sites See Follow Up (p. 24) Surgery with or without chemotherapy and radiation therapy Radiation therapy (if not given) with or without chemotherapy T3 Cancer found in lymph nodes on the same side of chest as tumor with invasion Brain MRI, if not previously done PET/CT scan, c if not previously done No evidence of distant spread of disease Cancer has spread to distant sites Chemotherapy together with full dose radiation therapy See Treatment for Widespread Disease Metastasis (p. 23) See Follow Up (p.24) c Positive PET/CT scans findings need confirmation (e.g., MRI of the bone). If the PET/CT scan is positive in the mediastinum (area between the lungs), the lymph node needs to be tested. d Chemoradiation refers to treatment that combines chemotherapy and radiation therapy. If the tumor cannot initially be removed by surgery, chemotherapy and radiation therapy are given concurrently (at the same time) to attempt to make it surgically removable. If the tumor was removed and there is no residual cancer at the edges of the specimen, most NCCN institutions give chemotherapy and radiation one after the other, if the tumor was removed but residual cancer is at the edges of the specimen chemotherapy would be given together with radiation concurrently. 19

20 Separate Nodule(s) and Stage IV, IIIA (T4, N0-1) Treatment (For more detailed information, see page 47) CLINICAL STAGE (ASSESSMENT) INITIAL TREATMENT ADJUVANT (ADDITIONAL) TREATMENT Separate lung tumor, in same lung Surgery Tumor removed, no cancer at edges of specimen Tumor removed, but cancer at edges of specimen Chemotherapy Chemoradiation (if possible) Stage IV, M1a: Separate tumor in Treat as two primary lung opposite lung tumors if both curable See Evaluation (p. 12) Stage IIIA (T4, N0-1) Not removable by surgery, no pleural effusion (fluid in the tissue between wall of the lung and chest) d Concurrent chemoradiation Chemotherapy See Follow Up (p. 24) dchemoradiation refers to treatment that combines chemotherapy and radiation therapy. If the tumor cannot initially be removed by surgery, chemotherapy and radiation therapy are given concurrently (at the same time) to attempt to make it surgically removable. If the tumor was removed and there is no residual cancer at the edges of the specimen, most NCCN institutions give chemotherapy and radiation one after the other, if the tumor was removed but residual cancer is at the edges of the specimen chemotherapy would be given together with radiation concurrently. 20

21 Stage IIIB (T1-3) Evaluation and Initial Treatment (For more detailed information, see page 47) CLINICAL STAGE (ASSESSMENT) PRETREATMENT EVALUATION INITIAL TREATMENT Stage IIIB (T1 3, N3) Lung function test (if not previously done). A test used to measure how well the lungs work, also known as pulmonary function test or PFT Biopsy of any suspicious lymph node(s) to check for cancer in the mediastinum or other side of the chest, supraclaicular (above the collarbone), or in the neck or elsewhere MRI of the brain PET/CT scanc Tests and biopsies find no additional cancer in suspicious areas The suspicious lymph node on the other side of the chest from the tumor or chest wall contains cancer Cancer has spread to distant sites outside the chest (metastatic disease) See Appropriate Guideline for Initial treatment for stage I IIIA (p. 13) Concurrent chemoradiation d See Treatment for Widespread Disease Metastasis (p. 23) Chemotherapy c Positive PET/CT scans findings need confirmation (e.g., MRI of the bone). If the PET/CT scan is positive in the mediastinum (area between the lungs), the lymph node needs to be tested. d Chemoradiation refers to treatment that combines chemotherapy and radiation therapy. If the tumor cannot initially be removed by surgery, chemotherapy and radiation therapy are given concurrently (at the same time) to attempt to make it surgically removable. If the tumor was removed and there is no residual cancer at the edges of the specimen, most NCCN institutions give chemotherapy and radiation one after the other, if the tumor was removed but residual cancer is at the edges of the specimen chemotherapy would be given together with radiation concurrently. 21

22 Stage IIIB and Stage IV Evaluation and Initial Treatment (For more detailed information, see page 48) CLINICAL STAGE (ASSESSMENT) PRETREATMENT EVALUATION INITIAL TREATMENT Stage IIIB (T4 extension, N2 3) Biopsy of any suspicious lymph node to check for cancer in the mediastinum (space between the lungs) or other side of the chest, supraclaicular (above the collarbone), or in the neck or elsewhere MRI of the brain PET/CT scan c No cancer detected in suspicious lymph node(s) on the opposite side of chest Cancer found in suspicious lymph node(s) on the opposite side of chest Cancer has spread to distant sites outside the chest (metastatic disease) No cancer found in lymph nodes on same side of chest Cancer found in lymph nodes on same side of chest See Treatment of Stage IIIA (p. 18) Concurrent chemoradiation d Concurrent chemoradiation d See Treatment for Widespread Disease Metastasis (p. 23) Chemotherapy Chemotherapy Stage IV, M1a: pleural or pericardial effusion (fluid in the tissue of the chest or around the heart) Remove chest fluid and possibly remove fluid around heart. Thorcoscopy may be needed to check for spread of cancer in the lining of the chest cavity No cancer cells detected in fluid Cancer cells found in fluid See Appropriate Guideline for Initial Treatment (p. 13) See Treatment for Widespread Disease Metastasis (p. 23) c Positive PET/CT scans findings need confirmation (e.g., MRI of the bone). If the PET/CT scan is positive in the mediastinum (area between the lungs), the lymph node needs to be tested. d Chemoradiation refers to treatment that combines chemotherapy and radiation therapy. If the tumor cannot initially be removed by surgery, chemotherapy and radiation therapy are given concurrently (at the same time) to attempt to make it surgically removable. If the tumor was removed and there is no residual cancer at the edges of the specimen, most NCCN institutions give chemotherapy and radiation one after the other, if the tumor was removed but residual cancer is at the edges of the specimen chemotherapy would be given together with radiation concurrently. 22

23 Stage IV Evaluation and Initial Treatment (For more detailed information, see page 48) CLINICAL STAGE (ASSESSMENT) Stage IV, M1b: with a single tumor in a distant site PRETREATMENT EVALUATION Bronchoscopy to examine the inside of the trachea, bronchi (air passages that lead to the lungs), and lungs Mediastinoscopy to examine the organs in the area between the lungs and nearby lymph nodes MRI of the brain PET/CT scan c A tumor is found in the brain Cancer has spread to one adrenal gland (confirm findings with needle biopsy or resection) INITIAL TREATMENT Surgery to remove brain lesion followed by whole-brain radiation therapy with or without stereotactic radiosurgery (A type of external radiation therapy that uses special equipment to position the patient and precisely give a single large dose of radiation to a tumor. It is used to treat brain tumors and other brain disorders that cannot be treated by regular surgery) or Stereotactic radiosurgery (SRS) with or without whole-brain radiation therapy Localized therapy (surgery or radiation therapy) to treat adrenal lesion if lung lesion appears curable or See Systemic Therapy (p. 25) T1-2, N0-1; T3, N0 T1-2, N2; T3, N1-2; Any T, N3; T4, Any N Surgery to remove the lung lesion followed by chemotherapy or Stereotactic radiosurgery to the lung tumor or Chemotherapy followed by surgery to remove lung lesion See Systemic Therapy (p. 25) Stage IV, M1b: disseminated Treat as indicated by symptoms See Systemic Therapy (p. 25) c Positive PET/CT scans findings need confirmation (e.g., MRI of the bone). If the PET/CT scan is positive in the mediastinum (area between the lungs), the lymph node needs to be tested. 23

24 Follow Up, Recurrence, and Widespread Disease (For more detailed information, see page 49) FOLLOW UP THERAPY FOR RECURRENCE AND METASTASIS Cancer returned inside air passages causing partial or complete blockage Laser/stent/other surgery Brachytherapy (internal radiation) External-beam radiation therapy Photodynamic therapy (light therapy) No evidence of disease, stages I-IV: Medical history and physical exam to assess general health and cancer symptoms with a contrastenhanced chest CT every 4-6 mo for 2 y, then history and physical exam and a non-contrast-enhanced chest CT annually Counseling on stopping smoking PET or brain MRI is not indicated for routine follow up Cancer returned in or near the lungs Cancer returned outside the chest in a distant site Recurrent cancer can be completely removed by surgery Cancer returned in mediastinal lymph node Cancer returned in the superior vena cava (large vein in the chest) Cancer is causing severe bleeding into the air passages Spread to distant organs causing localized symptoms Cancer spread to many areas of the brain Spread to bones causing pain and/or fractures Only one tumor in a distant organ Cancer is widespread Surgery to remove the tumor External-beam radiation therapy Concurrent chemoradiation (if radiation not previously given) External-beam radiation therapy Placement of a stent (supportive tube inside vein to keep it open) External-beam radiation therapy Brachytherapy (internal radiation) Laser or surgery to remove the tumor Photodynamic therapy (light therapy) Embolization (block the flow of blood to the tumor) External-beam radiation therapy to relieve symptoms External-beam radiation therapy to relieve symptoms External-beam radiation therapy to relieve symptoms and surgery to prevent/repair fractures if needed Consider bisphosphonate therapy (drug therapy to strengthen bones) See Stage IV, M1b: Cancer has not spread with a single tumor in a distant site (p. 23) See Systemic Therapy and Best Supportive Care (p. 25) Cancer spread outside the chest to distant site(s) No treatment or Chemotherapy See Systemic Therapy and Best Supportive Care (p. 25) 24

25 Therapy For Recurrence and Widespread Disease (For more detailed information, see page 50) THERAPY FOR RECURRENCE AND WIDESPREAD DISEASE Systemic therapy and best supportive care Good general health (performance status 0-1) Intermediate general health (performance status 2) Poor general health (performance status 3-4) FIRST-LINE THERAPY Chemotherapy e or Bevacizumab with chemotherapy (if criteria met f or Cisplatin/pemetrexed g (if criteria met) or Cetuximab/vinorelbine/cisplatin or Erlotinib for EGFR h (epidermal growth factor receptor) mutation-positive tumors Cetuximab/vinorelbine/cisplatin or Chemotherapy e or Erlotinib for EGFR h (epidermal growth factor receptor) mutation-positive tumors Erlotinib for EGFR h (epidermal growth factor receptor) mutation-positive tumors or Best supportive care TUMOR RESPONSE Cancer shrinks or does not spread (cycle 1, cycle 2 ) Therapy continued for total of 4-6 cycles (total) Cancer shrinks or does not spread Cancer continues to grow and spread See Progressive Disease (p. 26) Continuation of current regimen until disease progression or Continuation maintenance i bevacizumab or cetuximab j or pemetrexed or Switch maintenance i g pemetrexed or erlotinib or docetaxel j or Observation e Cisplatin or carboplatin have been proven effective in combination with any of the following agents: paclitaxel, docetaxel, gemcitabine, vinorelbine, irinotecan, etoposide, vinblastine, pemetrexed. f Bevacizumab with chemotherapy is used only for patients with non-squamous NSCLC. Bevacizumab should not be given by itself unless as maintenance if initially used with chemotherapy. Bevacizumab should be given until progression. g Pemetrexed is not recommended for squamous histology. h Non-small cell lung cancer is tested for specific tumor markers for example EGFR. Results are used to guide selection of drugs. i Maintenance therapy may be given after 4-6 cycles of chemotherapy for patients with tumor response (cancer shrinks or does not spread) who have not progressed. Continuation maintenance refers to the use of at least one of the agents given in the first line. Switch maintenance refers to the initiation of a different agent, not included as part of the first-line regimen j Non-small cell lung cancer can be one or more different types of cells in the lung. These are adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. The cell type can guide selection of drug therapy 25

26 Therapy For Recurrence and Widespread Disease (For more detailed information, see pages 50-51) PROGRESSIVE DISEASE SECOND-LINE THERAPY THIRD-LINE THERAPY Good to intermediate general health (performance status 0-2) Different therapy: Docetaxel or Pemetrexed or Erlotinib k or Platinum-based drug with one other chemotherapy drug (if erlotinib given as first-line) Cancer continues to grow and spread Good to intermediate general health (performance status 0-2) Poor general health (performance status 3-4) Erlotinib k Cancer continues to grow and spread General health worsens Best supportive care General health remains good Best supportive care or Clinical trial Poor general health (performance status 3-4) Best supportive care k Patients with a performance status of 3 were included in the National Cancer Institute of Canada-Clinical Trials Group (NCIC-CTG) trial BR.21. Erlotinib may be considered for PS 3 and 4 patients with EGFR mutation. See Performance Status explanation (page 32). 26

27 General Principles of Pathologic Evaluation and Treatment Treatment recommendations should be made after joint consultation and/or discussion by a multidisciplinary team including surgical oncologists, radiation oncologists, medical oncologists, pulmonologists, and diagnostic radiologists. General Principles of Pathologic Evaluation The purpose of examining the tissue removed during a biopsy or surgery is to classify the type of lung cancer, determine the extent of invasion, assess the edges of the specimen are free of cancer or if any cancer cells remain in the surgical margins, and determine the molecular abnormalities of lung cancer that may be able to predict for sensitivity and resistance to epidermal growth factor receptor-tyrosinekinase inhibitors (EGFR-TKI). The World Health Organization (WHO) tumor classification system provides the foundation for tumor diagnosis, patient therapy, and clinical studies. The surgical pathology report should include the histologic classification published by the WHO for lung cancer. General Principles of Surgical Therapy Determination of whether a tumor can be removed by surgery should be performed by board-certified thoracic surgeons who perform lung cancer surgery as their main duty in their practice. Complete surgical removal is preferred over ablation (destruction of a body part or tissue or its function). It is important that the overall treatment plan be discussed and decided, along with all necessary imaging tests prior to any non-emergency treatment. General Principles of Radiation Therapy Radiation therapy can be offered as additional therapy for operable patients whose cancer can be completely removed with surgery. Radiation therapy may be offered as the primary local treatment for patients in order to shrink the tumor so they can have surgery. Radiation therapy is an important component of palliative treatment for patients with incurable disease. It can be given locally in the chest area as well as to distant sites outside the chest as palliative care for stage IV patients with widespread disease. General Principles of Chemotherapy or Chemoradiation Chemotherapy is also referred to as systemic therapy. In patients with early stage lung cancer, chemotherapy/chemoradiation is recommended as additional therapy for patients high-risk features or if there is cancer in the edges of the surgical specimen. Chemotherapy/chemoradiation may be given to shrink a tumor prior to surgery this is referred to as induction or neoadjuvant therapy. For advanced or widespread disease, chemotherapy prolongs survival, improves symptom control, and improves over all quality of life. May be given as first-line therapy, maintenance therapy, second-line therapy and even third-line therapy. Chemotherapy may be used as maintenance therapy. Continuation maintenance refers to the use of at least one of the agents given in first line therapy to patients who have received 4-6 cycles and have not had disease progression. Switch maintenance refers to using a different chemotherapy agent, not included as part of the first-line combination to patients who have received 4-6 cycles and have not had disease progression. Second- or third-line therapy is for patients who have experienced disease progression during or after first-line therapy. Best supportive care should be provided to patients with poor performance status and progressive disease during any stage of the treatment. 27