Expert Insight Into: New Guidelines in the Treatment of Non

Projects In Knowledge is committed to protecting the privacy and confidentiality of visitors to our Web site. While Projects In Knowledge does not require that you provide us with personally identifiable information in order to visit our Web site, please note that in order to participate in the continuing medical education activities that we provide, it will be necessary for you to register with us and provide this information.

About this Privacy Policy
www.projectsinknowledge.com is our Web site for physicians and allied health care professionals, although it is open to non-professionals as well. The purpose of projectsinknowledge.com is to provide continuing medical education for healthcare professionals, and is intended for use only by a licensed healthcare professional.

Projects In Knowledge is the name we use to refer to our entire company, even though our formal corporate name is Projects In Knowledge, Inc. When we refer to ourselves as "we" or "Projects In Knowledge," we mean our company, Projects In Knowledge, Inc., including any subsidiary that we control (for example, a subsidiary that we own). We may share information among our subsidiaries that we own or control, but it is always protected under the terms of this privacy policy.

This privacy policy applies only to the Projects In Knowledge Web site. You should read the privacy policy at each Web site that you visit after you leave our site. We are not responsible for how other Web sites treat your privacy, once you leave the Projects In Knowledge site.

Privacy Policy Changes
If we change our privacy policy, we will post those changes on this page. Users should check this policy to keep abreast of any changes.

Information We Collect
In this section of our privacy policy, we discuss the different types of information we may collect about you, and the ways in which we collect them.

Information We Collect from Unregistered Visitors
Visitors to our Web site can access the Web site's home page and browse the site without disclosing any personally identifiable information. We do track information provided to us by your browser, including the Web site you came from (known as the "referring URL"), the type of browser you use, the time and date of access, and other information that does not personally identify you.

Information We Collect When You Register
Customers registering on our Web site for continuing medical education activities we provide are asked to provide us with identifying information, such as name, contact information, and other identifying information. On our registration screens, we clearly label which information is required for registration, and which information is optional and may be given at your discretion.

On our registration screens you will also find a “Burning Question” field. Submission of a “Burning Question” is completely voluntary. By submitting a “Burning Question,” you grant Projects In Knowledge the right to share it with faculty to consider as they prepare their continuing medical education presentations.

Listserves
When you are using a listserve—or member-only discussion board— on our Web site, you are posting a message and your user name, which is available for all registered members to see. You should not post any information to our listserves you want to keep private. It is a condition of our Web site that when participating in a listserve, you do not:

Restrict or inhibit any other user from using the listserve

Post or transmit any unlawful, threatening, abusive, libelous, defamatory, obscene, vulgar, pornographic, profane or indecent information of any kind, including, without limitation, any transmission constituting or encouraging conduct that would constitute a criminal offense, give rise to civil liability or otherwise violate any local, state, national or foreign law

Post or transmit any information, software or other material which violates or infringes upon the rights of others, including material which constitutes an invasion of privacy or infringement of publicity rights or which is protected by copyright, trademark or other proprietary right, or derivative works thereof, without first obtaining permission from the owner or right holder

Post or transmit any information, software or other material which contains a virus or other harmful component

Post, or transmit, or in any way exploit any information, software or other material for commercial purposes which contains advertising, promotions or marketing

By sending a message through the listserve, you grant Projects In Knowledge the non-exclusive right and license to display, copy, publish, distribute, transmit, print, and use such information. Projects In Knowledge reserves the right to terminate your access to, and use of, the listserve if you do not abide by these conditions.

Use of Cookies
Cookies are a technology used by the Projects In Knowledge Web site to identify a user as the user moves through the Web site. Your browser allows us to place some information on your computer's hard drive that identifies the computer you are using. We use cookies to track your usage throughout our Web site.

Your Web browser can be set to allow you to control whether you will accept cookies, reject cookies, or to notify you each time a cookie is sent to you. If your browser is set to reject cookies, Web sites that are cookie-enabled will not recognize you when you return to the Web site, and some Web site functionality may be lost. The Help section of your browser will tell you how to prevent your browser from accepting cookies.

Although cookies do not normally contain personally identifiable information, if you are a registered user we may associate your registration information with cookies our Web site places on your computer's hard drive. Associating a cookie with your registration data allows us to offer increased personalization and functionality. For example, you can elect to have our Web site "remember" you and bypass the registration process each time you register for one of our educational activities. Without cookies, this functionality would not be possible. Projects In Knowledge does not currently employ cookies for this use, but is considering it to make our registration processes more efficient for you.

Children's Privacy
Projects In Knowledge's Web site is designed and intended for use by adults, and is not intended for, nor designed to be used by children under the age of 18, or any other unlicensed, untrained individuals. We do not collect personally identifiable information from any person we know is a child under the age of 18.

Uses We Make of Information
In this section of our privacy policy, we identify the ways we may use information about you that we have collected.

Aggregate Data
We create aggregate data about visitors to our Web site for activity development and improvement. We also use it for market analysis. We may provide information from our Web site in aggregate form, with identifying information removed, to third parties. For example, we may tell a third party what percentage of our registered users reside in a particular geographical area. When aggregated information is provided, we pool it from many individual records and strip it of any data that could be used to identify an individual before it is used. Any third party that receives aggregated data must agree not to attempt to re-identify the people it belongs to. Projects In Knowledge does not sell any user data to any third party for commercial purposes.

Third Parties
In addition to aggregate information (discussed previously), we may share some kinds of information with third parties as described below.

Business Transfers: If we transfer a business unit (such as a subsidiary) or an asset (such as a Web site) to another company, we will require them to honor the applicable terms of this privacy policy.

Protection of Information
In this section of our privacy policy, we discuss the security measures we take to protect information that we have collected about you.

General Policies
We have implemented technology and security policies, rules and other measures to protect the personal data that we have under our control from unauthorized access, improper use, alteration, unlawful or accidental destruction, and accidental loss. We also protect your information by requiring that all our employees and others who have access to or are associated with the processing of your data respect your confidentiality. In addition, we have appropriate security measures in place in our physical facilities to protect against the loss or misuse of information at our site that we have collected from you.

Projects In Knowledge Employees
Projects In Knowledge employees are required to keep customer information private, as a condition of their employment with the company. Only selected, authorized Projects In Knowledge employees are permitted to access your registration information.
Employees are required to sign a confidentiality agreement. All employees and contractors must abide by our privacy policy, and those who violate that policy are subject to disciplinary action, up to and including termination of their employment and legal action.

Privacy Questions or Concerns about Our Web Site
For privacy questions or concerns about the Projects In Knowledge Web site, please contact privacy@projectsinknowledge.com.

Revision date: This policy was last updated on September 30, 2003.

Clinical Insights

The National Comprehensive Cancer Network (NCCN) recently revised its clinical practice guidelines for the diagnosis and treatment of non–small-cell lung cancer (NSCLC), including changes recommending potentially curative radiotherapy (RT) in patients with inoperable stages I and II disease and an increased frequency of surveillance following initial therapy (surgery or RT).
The NCCN also revised its chemotherapy recommendations, suggesting several new regimens for patients with advanced or metastatic disease, including cetuximab plus vinorelbine plus cisplatin and cisplatin plus pemetrexed, and the deletion of several adjuvant chemotherapy regimens previously recommended for patients with comorbidities or not able to tolerate cisplatin.
Although some investigators regard these guidelines as confusing and therefore not helpful in the screening and treatment of patients with NSCLC, others find them useful.

As the results of clinical trials become known, and as physicians implement these results in their practices, clinical practice guidelines in the diagnosis and treatment of cancer are revised. The National Comprehensive Cancer Network (NCCN) recently revised its clinical practice guidelines for the diagnosis and treatment of non–small-cell lung cancer (NSCLC), which accounts for 80% to 85% of lung cancer cases. This paper will review the highlights of those changes.

Several changes in guidelines are associated with screening and diagnosis. The guidelines now recommend that each tumor be pathologically evaluated to determine the extent of invasion, to establish the tumor involvement status of surgical margins, and to determine the molecular abnormalities that predict sensitivity or resistance to epidermal growth factor-tyrosine kinase inhibitors. Previous guidelines concerning the use of positron emission tomography (PET) scans in screening for NSCLC were changed to PET/computerized tomography (CT) scans. The NCCN recommends that positive PET/CT findings require pathologic or other radiologic confirmation, and that positive PET/CT findings in the mediastinum require pathologic confirmation of lymph node status.

Other changes in NCCN guidelines for staging include the addition of mediastinoscopy and CT-guided fine needle aspiration to the pretreatment pathologic mediastinal lymph node evaluation of patients with stage IIIA NSCLC; the addition of endobronchial ultrasound (EBUS) biopsy in the pretreatment evaluation of patients with stage IIIB NSCLC.

Other changes in guidelines are associated with treatment of primary NSCLC. Lung cancer is staged using the American Joint Committee on Cancer (AJCC) TNM staging system. Factors evaluated include the primary tumor (T), regional lymph nodes (N) and distant metastasis (M), with tumor grouped into four stages. Of patients who are staged, 25% will be stage I, 7% will be stage II, 32% will be stage III, and 36% will be stage IV; the 5-year survival rates for these patients are 47%, 26%, 8.4%, and 1.6%, respectively. The three modalities commonly used to treat patients with NSCLC are surgery, radiation therapy (RT), and chemotherapy. Depending on tumor stage, these modalities may be used alone or in various combinations, and chemotherapy regimens may vary.

Although surgical resection provides the best chance of cure for patients with stage I and stage II tumors and is recommended by the NCCN, patients with medically inoperable tumors should undergo curative RT. For patients with stage IA and stage IB disease, the recommended treatment is observation. For patients with stage IIA, IIB, and IIIA disease, the recommended treatment is adjuvant chemotherapy, although sequential chemotherapy/RT, or concurrent chemotherapy/RT, with or without chemotherapy, are also suggested.The new NCCN guidelines include a revision/update on the section entitled “Principles of Radiation Therapy” and a new table on dose volume constraints for the thorax (Table 1).

Table 1. Recommended Dose Volume Constraints for the Thorax

	Radiation Therapy (RT) alone	Chemotherapy/RT	Chemotherapy/RT/ Operation
Cord	50 Gy	45 Gy	45 Gy
Lung	20 Gy (<40%)	20 Gy (<35%)	20 Gy (<20%) 15 Gy (<30%) 10 Gy (<40%)
Heart	40 Gy (<100%) 50 Gy (<50%)	40 Gy (<50%)	40 Gy (<50%)
Esophagus	60 Gy (<50%)	55 Gy (<50%)
Liver	30 Gy (<40%)
Kidney	20 Gy (<50% of combined to both kidneys or <25% of one side is the other kidney is not functional

Surveillance recommendations have been updated for patients with NSCLC. These now include a history and physical, and a contrast-enhanced chest CT scan every 4 to 6 months for the first 2 years after initial treatment (surgery or RT), followed by a history and physical, and a non–contrast-enhanced chest CT scan every year thereafter. All patients should be referred for smoking cessation counseling. In addition, all patients should receive annual influenza vaccinations, as well as pneumococcal vaccination, with revaccination as appropriate.

Other NCCN guideline changes were made for treatment of tumor recurrence and metastasis. Generally, platinum-based chemotherapy regimens have been found to prolong survival, improve symptom control, and result in a superior quality of life compared with best supportive care. Although no platinum-based cytotoxic combination has been found clearly superior, new platinum combinations have been found relatively effective. The new NCCN guidelines now include albumin-bound paclitaxel and cetuximab for systemic therapy of patients with advanced or metastatic disease.

Locoregional recurrences may be treated by resection, external beam RT or concurrent chemoradiation. As first-line therapy in recurrent and metastatic NSCLC, bevacizumab plus chemotherapy is used in patients with performance status (PS) 0-1, nonsquamous histology, no history of hemoptysis, no metastases to the central nervous system, and no ongoing therapeutic anticoagulation. Bevacizumab is not given as single agent, unless it is as maintenance therapy in patients initially treated with bevacizumab plus chemotherapy. Patients who do not meet the above criteria for bevacizumab should be treated with chemotherapy alone.

The new guidelines have added two new treatment options for these patients (Table 2). The first, cetuximab plus vinorelbine plus cisplatin, was added as an option for patients with PS 0-2 and who meet the criteria for cetuximab, which include tumor expression of EGFR, no known brain metastases and no prior chemotherapy or anti-EGFR therapy. The second treatment option, for patients with PS 0-1 and nonsquamous histology, consists of cisplatin plus pemetrexed; to be followed, where warranted, by pemetrexed maintenance treatment.

Table 2. Recommended Regimens for Treatment of Patients with Recurrent or Metastatic NSCLC

First-line

PS 0-1	Chemotherapy, or Chemotherapy + bevacizumab, or Cisplatin + pemetrexed followed by pemetrexed maintenance, or Cetuximab + vinorelbine + cisplatin, or Chemotherapy* + erlotinib, or Erlotinib
PS 2	Cetuximab + vinorelbine + cisplatin, or Chemotherapy*
PS 3-4	Best supportive care

Second line

PS 0-2	Docetaxel, or Pemetrexed, or Erlotinib
PS 3	Erlotinib, or Best supportive care
PS 4	Best supportive care

Third line

PS 0-2	Erlotinib
PS 3	Erlotinib, or Best supportive care
PS 4	Best supportive care

*Recommended chemotherapy agents include cisplatin, carboplatin, paclitaxel, docetaxel, vinorelbine, gemcitabine, etoposide, irinotecan, vinblastine, mitomycin, ifosfamide, pemetrexed, and albumin-bound paclitaxel
† For patients with non-squamous histology

Chemotherapy regimens for adjuvant therapy have also been revised. In addition to the standard cisplatin-containing regimens (with vinorelbine, etoposide, or vinblastine), recent NCCN guidelines added two additional cisplatin-based regimens, with gemcitabine or docetaxel. Former guidelines included several chemotherapy regimens for patients with comorbidities or not able to tolerate cisplatin. The new guidelines include only one regimen, paclitaxel 200 mg/m2 on day 1 and carboplatin AUC 6 on day 1 of every 21-day cycle. The remaining regimens, gemcitabine plus carboplatin, docetaxel plus carboplatin, and gemcitabine plus docetaxel, were removed.

As first-line therapy for patients with advanced/metastatic disease, the NCCN now includes the following statement: Two drug regimens are preferred; a third cytotoxic drug does not increase survival, with the exception of bevacizumab or cetixumab in treatment-naïve PS0-1 NSCLC. For patients who never smoked or with activating EGFR mutation or gene amplification, the NCCN has recommended that physicians consider the use of erlotinib with/without chemotherapy; in its new guidelines, the NCCN recommends that, if a patient has a known KRAS mutation, therapy other than erlotinib should be considered.

As outlined above, the treatment of patients with NSCLC can be quite complex, including surgery, RT, and chemotherapy, with the latter two modalities given concurrently or sequentially, and with many possible chemotherapy regimens. The use of these modalities is dependent on many factors, including tumor stage at diagnosis, tumor resectability, the presence of positive or negative margins after resection, and responses to previous regimens. Flow charts included in the NCCN guidelines provide methods to evaluate and treat patients with NSCLC.

Reference

National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Non-Small Cell Lung Cancer. V.1.2009. Accessible at: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp

Privacy Policy

Expert Insight Into:
New Guidelines in the Treatment of Non–Small-Cell Lung Cancer (NSCLC)

Medical Writer: Richard J. Alexander, PhD
Expert Faculty: Roy S. Herbst, MD, PhD

Available for CME/CE:

Physicians

Nurses

Pharmacists

Estimated time for completion of this activity:

Target Audience

Activity Goal

Learning Objective (s)

CME Information: Physicians

Statement of Accreditation

Credit Designation

CE Information: Nurses

CE Information: Pharmacists

CME/CE Instructions

Available for CME/CE:

Physicians

Nurses

Pharmacists

Estimated time for completion of this activity:

Target Audience

Activity Goal

Learning Objective (s)

CME Information: Physicians

Statement of Accreditation

Credit Designation

CE Information: Nurses

CE Information: Pharmacists

CME/CE Instructions

Privacy Policy

Expert Insight Into: New Guidelines in the Treatment of Non–Small-Cell Lung Cancer (NSCLC)

Medical Writer: Richard J. Alexander, PhD Expert Faculty: Roy S. Herbst, MD, PhD

Available for CME/CE:

Physicians

Nurses

Pharmacists

Estimated time for completion of this activity:

Target Audience

Activity Goal

Learning Objective (s)

CME Information: Physicians

Statement of Accreditation

Credit Designation

CE Information: Nurses

CE Information: Pharmacists

CME/CE Instructions

Available for CME/CE:

Physicians

Nurses

Pharmacists

Estimated time for completion of this activity:

Target Audience

Activity Goal

Learning Objective (s)

CME Information: Physicians

Statement of Accreditation

Credit Designation

CE Information: Nurses

CE Information: Pharmacists

CME/CE Instructions

Expert Insight Into:
New Guidelines in the Treatment of Non–Small-Cell Lung Cancer (NSCLC)

Medical Writer: Richard J. Alexander, PhD
Expert Faculty: Roy S. Herbst, MD, PhD