NSCLC Diagnosis and Treatment

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Updated August 2013
Contents
This chapter outlines:
2. Current Detection & Diagnostic Methods for NSCLC
3. Physicians Who Diagnose and Treat NSCLC
4. Staging NSCLC
5. Treatment Options for NSCLC
1. Introduction
7. References
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6. Personalized Medicine in Practice
Introduction
The diagnosis and treatment of lung cancer is complex and
varies from country to country. This section of the Toolkit
provides background on the diagnosis and treatment of the
disease, outlining the clinical process for managing the disease
and providing useful links for further information.
Once a diagnosis of non-small cell lung cancer (NSCLC) has
been confirmed and the stage of the disease and specific
pathology of the tumor have been determined, there are
multiple treatment pathways available
1,2
click here for further
information on these pathways.
Treatment of NSCLC is guided by the disease stage at
diagnosis and the general health of the patient
1
click here for
further information on disease stage.
Many early-stage lung cancers are found accidentally when a
patient has a chest x-ray or CT scan for another reason.
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Continued on the next page
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Introduction Continued
However, more than three-quarters of all cases of NSCLC are
diagnosed late, at Stage III or IV, when prognosis is poor.
3
Late diagnosis and limited effectiveness of current treatment
modalities help make NSCLC a particularly lethal form of
cancer; as a result, only 15 percent of all lung cancer patients
are alive five years or more after diagnosis
13
click here for
further information on disease prognosis.
There are three traditional forms of treatment for lung cancer,
including NSCLC, which can be used in different orders and
combinations: surgery, radiation therapy, chemotherapy (also
known as cytotoxic chemotherapy).
1,2,13
For some tumors, including NSCLC, cancer treatment is
evolving from a one size fits all model to a personalized
approach which requires additional diagnosis.
4
Treatments
that target these molecular characteristics, or biomarkers, are
being developed with the goal of yielding better patient
outcomes than traditional types of treatment.
5,6,7
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Detection
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Lung cancer may be suspected based on specific
symptoms related to the lungs, including:
A persistent cough
Shortness of breath
Chest pain, often made worse by deep breathing
Bloody or rust-colored sputum
For further information on testing guidelines click here
and here
After a physical exam is performed and a medical history is
taken to assess the patients condition and risk factors for
lung cancer, a chest x-ray or CT scan is done to detect the
presence, location, size and extent of the tumor.
Current Detection & Diagnostic Methods for NSCLC
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Testing
The following elements may be involved in testing for NSCLC:
Biopsy
1
this is performed once the tumor has been located, to acquire a tissue sample to
confirm cell type, grading and assist in staging (also known as TNM staging)
Pathology testing
1
this is done on the tissue sample to determine:
Firstly, if it is lung cancer or a cancer that spread to the lungs from another part of the body
Other tests (including examination of tissue under a microscope) establish the type of lung
cancer, the grade of the tumor (the higher the grade, from 1 to 4, the more aggressive the
cancer is likely to be) and whether it has spread to lymph nodes or other parts of the body
click here for information on cancer staging
Molecular tissue testing
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(otherwise known as molecular genetic testing) these additional
tests may be done to determine the presence or absence of certain biomarkers (also known
as tumor markers) that can influence treatment decisions.
Blood tests
1
these are performed to assess the general health of the patient, including
the function of organs such as the liver and kidney and to indicate if the lung cancer has
spread to the liver or bones. These tests include a complete blood count (CBC; also known
as full blood count [FBC])
Sputum cytology
1
where a phlegm sample is examined for the presence of cancer cells;
bronchial brushing or lavage is often done in conjunction with sputum cytology
Current Detection & Diagnostic Methods for NSCLC
Continued
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Detection & Diagnostics
Patients can be diagnosed and treated via many different
methods, often beginning in primary care and then moving
through a range of different healthcare professionals,
including:
Primary care physicians may be the first to identify the symptoms
of lung cancer in their patients and refer them to a cancer center (if there is
one available) or specialist for accurate diagnosis (including staging) and
treatment
Radiologists help diagnose NSCLC with CT and X-ray technology
Radiation Oncologists treat disease with radiation therapy
Pathologists analyze tissue samples to determine the cell type and
grade of lung cancer in some instances they may also perform biopsies
Oncologists help diagnose NSCLC and usually manage the overall
care of NSCLC patients, defining and directing treatment regimens
Chest physicians/pulmonologists may perform a biopsy to
assist in diagnosis and staging; and also treat diseases of the chest
Thoracic surgeons perform biopsies, operate to resect NSCLC
lesions which is important for staging and managing the disease. In some
cases, thoracic surgeons can completely resect early disease, which can
lead to a cure in some patients.
Physicians Who Diagnose and Treat NSCLC
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Staging NSCLC
Treatment of NSCLC depends in large part on the clinical
stage of the cancer. Staging is based on three factors:
1
The size of the tumor (T)
Whether lymph nodes contain cancer (N)
Whether the cancer has spread from the lung to other parts of
the body (M)
The stages of NSCLC range from Stage IA to Stage IV,
with more than a dozen total stages, based on variations in
T, N and M.
1,2,8
For more information on lung cancer
staging, click here.
At diagnosis, NSCLC patients can be divided into three
groups that reflect both the extent of the disease and the
treatment approach:
9
Surgically resectable disease
Locally and/or regionally advanced disease
Distant metastatic disease
For more information on NSCLC treatment options go to the
next slide
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Treatment Options for NSCLC Overview
Overview
NSCLC is a complex disease with multiple options for
treatment depending on the stage of the disease, the
health of the patient and the histological and genetic
characteristics of the tumor
Results of standard treatment for NSCLC are generally
poor except for the most localized cancers
9
Newly diagnosed patients with NSCLC are potential
candidates for studies evaluating new targeted forms of
treatment
9
Click here for more information on targeted forms of
treatment
Understanding the biology of NSCLC patients tumors as
completely as possible (e.g., biomarkers) helps support
treatment planning;
10
however, performing molecular
testing upon initial diagnosis will require a fundamental
shift in treatment practice
11
Click here for more information on biomarkers
Continued on the next page
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Treatment Options
For NSCLC treatment guidelines in the United States, click here (note: registration is
required).
Treatment Options for NSCLC Overview, continued
Continued from the previous page
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Current Treatments
1,2
Type of Disease:
Potentially
Curable
Type of Disease:
Potentially Non-
Curable
Surgery is the most potentially curative therapeutic option for
NSCLC, depending on the stage of the disease and is often
combined with other treatments; however for many patients
their cancer has progressed too far for this to be an option
Radiation therapy combined with chemotherapy can produce
a cure in a small number of patients and can provide
palliation (also known as end of life care) in most patients
Adjuvant chemotherapy may provide additional incremental
benefits to patients with resectable (operable) NSCLC; in
patients with advanced-stage disease, chemotherapy offers
modest improvements in median survival, though overall
survival is poor
2
Targeted therapies that help to block or inhibit the growth of
cancer cells have been developed for the treatment of
advanced NSCLC;
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Tumor stage
9
Treatment may include one or a combination of the following
9
Occult NSCLC (cancer cells found in sputum
but no tumor present in imaging tests)
Surgery
Stage 0 (Carcinoma in Situ) Surgery
Photodynamic therapy using an endoscope
Electrocautery, cryosurgery or laser surgery via endoscope
Stage I NSCLC Surgery
Chemoprevention (often follows surgery)
Radiation therapy
Stage II NSCLC Surgery
Chemotherapy (often follows surgery)
Radiation therapy
Stage IIIA NSCLC Surgery
Chemotherapy (often follows surgery)
Radiation therapy (either on its own or in combination with either surgery or
chemotherapy)
Stage IIIB NSCLC Chemotherapy combined with radiation therapy
Radiation therapy as palliative therapy
Stage IV NSCLC Combination chemotherapy (sometimes in combination with targeted therapy)
Maintenance therapy (given after combination chemotherapy)
Laser therapy and/or radiation therapy
Radiation therapy as palliative therapy
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Click here to go directly to the US National Cancer Institute information on treating
different stages of NSCLC.
Treatment Options for NSCLC Overview, continued
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Personalized Medicine in Practice: a New Paradigm
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Personalized Paradigm
Metastatic disease (stage IIIB/ IV)
Biomarkers can direct treatment
towards targeted therapy or clinical
trials (where available)
EGFR
K-RAS ERCC1 ALK TS B-RAF HER-2
Non-Personalized Paradigm
Non-squamous
cell carcinoma
Metastatic disease (stage IIIB/ IV)
Squamous cell
carcinoma
Treatment decisions largely based on
histology
Treatment decisions based on knowledge of
disease driver (biomarker)
Some treatments that target biomarkers (e.g.,
ALK, EGFR) are available
Clinical trials are underway to investigate other
disease drivers (e.g., K-RAS)
NSCLC Treatment Paradigm
References
1. National Comprehensive Cancer Network NCCN Guidelines for patients. NonSmall Cell
Lung Cancer. V. 1.2012 http://www.nccn.org/patients/patient_guidelines/nscl/index.html.
Accessed March 6, 2013.
2. National Comprehensive Cancer Network NCCN Clinical practice Guidelines in
Oncology. NonSmall Cell Lung Cancer. V. 2.2012.2011 http://www.nccn.org.
Accessed March 6, 2013.
3. Hurria A, Kris MG. Management of Lung Cancer in Older Adults. CA Cancer J Clin .
2003;53:325341.
4. Diamandis M, White MA, Yousef GM. Personalized Medicine: Marking a New Epoch in
Cancer Patient Management. Mol Cancer Res.2010,8(9): 1175-1187.
5. Mok TS, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J
Med. 2009;361:947957.
6. Spigel et al. Randomized multicenter double-blind placebo controlled phase II study
evaluating MetMAb, an antibody to met receptor, in combination with erlotinib, in patients
with advanced non-small-cell lung cancer. Presented at European Society of Medical
Oncology; October 8-12, 2010; Milan Italy [Oral Presentation] LBA15.
7. Institute National du Cancer. Cancer Plan 2009-2013; 2009. Updated February 4, 2011.
http://www.plan-cancer.gouv.fr/images/stories/fichiers/plancancer20092013_english.pdf.
Accessed May 11, 2011.
8. DAddario G, Fru M, Reck M, et al. Metastatic nonsmallcell lung cancer: ESMO Clinical
Practice Guidelines for diagnosis, treatment and followup. Ann Oncol.
2010;21(S5):v103v115.
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References Continued
9. National Cancer Institute. Nonsmall cell lung cancer treatment (PDQ); 20102011.
http://www.cancer.gov/cancertopics/pdq/treatment/non-small-cell-
lung/healthprofessional/AllPages. Accessed March 1, 2011.
10. Welsh S, Powis G. Personalized medicine for cancer. In: Hayat MA, ed. General
Methods and Overviews, Lung Carcinoma and Prostate Carcinoma. Union, NJ:
Springer; 2008:93107. Methods of Cancer Diagnosis, Therapy, and Prognosis; vol 2.
11. Cheng H, Xu X, Costa DB et al. Molecular Testing in Lung Cancer: The Time Is Now
Curr Oncol Rep. 2010;12:335348.
12. Hallberg B, Palmer RH. Crizotinib latest champion in the cancer wars? N Engl J Med.
2010;363(18):17601762.
13. Reade CA, Ganti AK. EGFR targeted therapy in non-small cell lung cancer: potential
role of cetuximab. Biologics. 2009;3:215-24. Epub 2009 Jul 13.
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