The Staging of Lung Cancer Using PET/CT - Admission/Application Essay Example

 I. Lung Cancer A. Population Lung cancer, the third most common type of cancer in the United States (US) subsequent to prostate and breast cancers, is predominant in the elderly. It is the leading cause of cancer – related death secondary to cancer in men and women alike with approximately 3 million new cases per year worldwide (Saunders et al. 1999; von Haag et al. 2002; de Wever et al. 2007; Stoppler, 2008). The American Lung Association (2008) reported that the average chance that a man develops lung cancer in a lifetime is about one in every thirteen, and in a woman, is one in every sixteen. B. Types of Lung Cancer There are two major types of lung cancer identified (von Haag et al. 2002; American Lung Association, 2008). These are: (1) Small cell lung cancer (SCLC) - Small cell lung cancer is the less common type of lung cancer and accounts to approximately 13 – 20 percent of all lung cancer cases. This type of lung cancer grows more quickly and is more likely to spread to other organs in the body (von Haag et al. 2002; de Wever et al. 2007; Eldridge, 2009). (2) Non-small cell lung cancer (NSCLC) - Non-small cell lung cancer accounts to approximately 80 - 87 percent of lung cancer cases. It generally grows and spreads more slowly than small cell lung cancer (American Lung Association, 2008). There are 3 sub-types of NSCLC, these are (von Haag et al. 2002; de Wever et al. 2007; American Lung Association, 2008; Stoppler, 2009; Eldridge, 2009): (a) Squamous cell carcinoma: About 25% to 30% of all lung cancers are this kind. They are linked to smoking and tend to be found in the middle of the lungs, near a bronchus. (b) Adenocarcinoma: This type accounts for about 40% of lung cancers. It is usually found in the outer part of the lung. (c) Large-cell (undifferentiated) carcinoma: About 10% to 15% of lung cancers are this type. It can start in any part of the lung. It tends to grow and spread quickly, which makes it harder to treat. The cells in these sub-types differ in size, shape, and chemical make-up (von Haag et al. 2002; de Wever et al. 2007; American Lung Association, 2008; Stoppler, 2009; Eldridge, 2009). C. Causes of Lung Cancer The predominant causes of lung cancer are: Smoking, passive smoking, Asbestos fibers, Radon gas, genetics, lung diseases, air pollution (Ko et al. 1997; Stoppler, 2008; EMedicine Health, 2009; Eldridge, 2009). Regardless of cause, the earlier the diagnosis, the greater the chances are of eliminating the continuation of the condition. D. Frequency In 2008 there will be about 215,020 new cases of lung cancer (both small cell and non-small cell) in the United States: 114,690 among men and 100,330 among women. About 161,840 people will die of this disease in 2008: 90,810 men and 71,030 women. Leading cause of death in women, rates are increasing for women but declining in men (American Lung Association, 2008). 589 people diagnosed everyday and 444 people die everyday (Caring Ambassadors, 2008). Accounts for 29% of cancer deaths more than the next three most common combined colon, prostate, and breast (American Lung Association, 2008). 84% diagnosed in advanced stages (Caring Ambassadors, 2008). These are imposing numbers, and a means had to be found to provide high quality diagnosis well prior to the patients reaching an advanced stage of the condition. E. Survival Rate The 15% five year survival rate (Caring Ambassadors, 2008) of non-Small Cell Lung Cancer Survival by Stage* (American Lung Association, 2008) are the following: Stage 5-year Relative Survival Rate I 47% II 26% III 8% IV 2% II. Staging Cancer A. Definition TNM classification system is a system that uses characteristics of the tumor (T), regional lymph node involvement (N), and the presence or absence of distant metastasis (M) to divide NSCLC into clinical stages (Silvestri, 2003; Caring Ambassadors, 2008). NSCLC are assigned a stage from I to IV in order of severity (Silvestri, 2003; Stoppler, 2008): Stage I: The cancer is confined to the lung. During this stage, the disease is still potentially curable with 50% 5 – year survival rate post surgery. Stages II and III: The cancer is confined to the chest (with larger and more invasive tumors classified as stage III). During stage II, 5 – year survival rate post surgery is only 30%; however, for clinical stage IIIA patients, 5 –year survival rate goes down to 17% and only 5% in clinical stage IIIB patients. Stage IV: The cancer has spread from the chest to other parts of the body and 5- year survival rate is almost negligible. According to Stoppler (2008), SCLC is staged using a two-tiered system, namely: Limited-stage SCLC, which refers to a cancer confined to its area of origin (i.e. in the chest). On the other hand, in extensive-stage SCLC, the cancer has already spread beyond the chest to other parts of the body. B. Purpose Fisher and Mortensen (2006) noted that in managing patients with lung cancer, the cardinal importance of managing disease extension is early diagnosis and accurate disease determination. American Lung Association (2008) viewed staging as the process of finding out how far the cancer has spread. This is very important because the treatment and the outlook for recovery of the patient will depend on the stage of the cancer (American Lung Association, 2008). Silvestri (2003) noted that TNM system is the basis for staging NSCLC. Silvestri (2003) added that staging can be used in predicting the survival rate of the patient and to guide the most appropriate treatment regimen or clinical trial that can be used for the patient. Staging is important in determining how a particular cancer should be treated, since lung-cancer therapies are geared toward specific stages (Stopper, 2008). Staging of a cancer is also critical in estimating the prognosis of a patient, with higher-stage cancers generally having a worse prognosis than lower-stage cancers (Stoppler, 2008). Necessity is the mother of invention, and the necessity for PET/CT was the fact that too many NSCLC patients were not being diagnosed until they could only be assisted by surgery. At the time, adjuvant chemotherapy and radiotherapy results had been “dismal” with most applications not prolonging survival rate. What the doctors needed was a methodology that identifies the cancer, much sooner than CT alone was capable on (Townsend et al. 2004; Blodgett et al. 2007; De Wever et al. 2007). III. Positron Emission Tomography (PET) A. History PET, positron emission tomography, is an analytical imaging technology developed to use compounds that are labeled with positron emitting radioisotopes as molecular probes to view and measure the biochemical process of mammalian biology in vivo (Phelps, 2000). PET scan is a powerful technique in imaging that holds greater hope especially in cancer diagnosis and treatment (PETNET Solutions, 2009). Brownell (1999) noted that positron imaging development covered several decades with the contributions made by various individuals. The unique challenges encountered in the detection to eradicate radiation and processing of data into an image format best suitable to detect a disease as well as to study physiological processes had drawn the attention of various outstanding physicists, chemists, biologists and physicians (Brownell, 1999). Brownell described that early development in this field dated back to early 1950’s. Having ascertained the problem, a device had to be created to detect these cancers. Gordon Brownell of Massachusetts General championed the project called Positron Emission Tomography (PET). The project had its birth in 1950 and it was introduced in a hospital setting in 1952 (Brownell, 1999). In 10 years the equipment had proved itself, and in 1962, the multiple detector positron imaging device that was primarily designed for brain timaging came on line (Brownell, 1999). In the period of 1968 to 1971, the tomographic imaging and the computed tomographic imaging devices were brought together and remained as the only device for a period of ten years (Brownell, 1999). Brownell stated that this was eventually succeeded by the PC-II and other commercial devices. In 1998, the first PET/CT prototype scanner became operational. In summary, Brownell (1999) recalled that in 1952, the First Clinical Positron Imaging Device was made; in 1962, the First Multiple Detector Positron Imaging Device came in; and in the period of 1968 – 1971, Tomographic Imaging Device and the First Computed Tomographic Imaging Device was made. Figure 1: This was the first clinical positron imaging device. In the picture are Drs. Brownell (left) and Aronow shown with scanner, 1953. (Source: Brownell, 1999). B. Purpose PET Imaging is an imaging device that is sensitive to the biological processes of a disease (Phelps, 2000). Disease as a biological process can be provided by molecular imaging a sensitive and informative means to identify, study, and diagnose the biological nature early in and throughout its evolution, as well as to provide biological information for development and assessment of therapies (Phelps, 2000). Phelps (2000) noted that a PET scan can differentiate a benign from malignant lesions as well as identify the biological cancer of cancer during its course. Phelps (2000) added the PET scan can also provide imagery to all organ systems of the body to detect the primary tumor and to determine its progress to metastasis as well as to determine the extent of the metastasis of malignancy throughout the body. However, Phelps (2000) pointed out that the value of PET in the diagnosing distant metastasis has become problematic because it cannot easily determine the correct number of false – negative PET lesions. C. Patient Preparation Radiology Info (2008) stated that prior to the procedure, women will be asked by physicians or technologist for possibilities of pregnancy or breastfeeding. Patients are also asked by physicians or technologists for any current medications, any allergies, and recent medical conditions (Radiology Info, 2008; PETNET Solutions, 2009). Metals objects may affect the CT images and must be left prior to the examination (Radiology Info, 2008; PETNET Solutions, 2009). Generally, patients will be asked not to eat or drink anything for several hours before a whole body PET/CT scan since eating may alter the distribution of the PET tracer in the body and can lead to a suboptimal scan (Radiology Info, 2008; PETNET Solutions, 2009). C. Image Formation Blodgett et al (2007) stated that an increasingly important role in diagnosing and staging malignancy is played by functional imaging with positron emission tomography (PET). PET with the use of labeled 18 F-fluoro-2-deoxy-glucose (FDG) is a recent addition to the medical technology for cancer imaging and may overcome the limitations of conventional lung cancer staging (Saunders, et al., 1999; von Haag, et al, 2002). FDG PET complements the more conventional computed tomography (CT) anatomic imaging modalities and magnetic resonance imaging (MRI) (Saunders et al. 1999; Blodgett et al. 2007). The use of 18 F-fluoro-2-deoxy-glucose (FDG)-PET in respiratory oncology is based on its ability to visualize the difference between the glucose metabolism of tissues (Saunders et al. 1999; Townsend et al. 2004; Bloggett, et al., 2007). Neoplastic cells have a much higher rate of glycolysis than non-neoplastic cells. Bloggett, et al. added that an increased cellular glucose uptake is most likely due to an increased expression of glucose transport proteins. FDG, a glucose analogue in which the oxygen molecule in position 2 is replaced by a positron-emitting 18fluorine, undergoes the same uptake as glucose, but is trapped metabolically and accumulated in the neoplastic cell after phosphorylation by hexokinase (Saunders et al. 1999; Vansteenkiste, 2001; Bloggett et al. 2007). Positron-emitting isotopes, such as 18fluorine, have an excess of protons and are therefore unstable. E. Image reconstruction A positron emitted from a neutron-rich, unstable radionuclide travels a short distance in tissue (path length varies depending on the particular radionuclide -- for F-18, up to a few mm) (Shulkin, 2005). The positron electron pair is annihilated, and its mass is converted to energy. Two oppositely directed 511 keV photons are produced. When these are simultaneously detected by 2 small detectors, the location of the event is presumed to have occurred somewhere along a line between the 2 detectors (Shulkin, 2005). The line formed by the paths of the photons is the line of response (Fahey, 2002; Shulkin, 2005). Rings of detectors are placed back to back to image several planes simultaneously. At least 2 factors limit the practical resolution of PET: the positron travels in tissue and thus the line of response represents the location of the annihilation rather than the location of the radionuclide that generated the positron, and the 511-keV photons may be directed slightly off 180 degrees due to kinetic energy of the traveling positron (Fahey, 2002; Shulkin, 2005). The theoretical resolution for current human scanners is 2-3 mm and for animal scanners 1 mm. Resolution is also affected by the size of the detector; in most scanners, the detector size is 4 mm or more. The PET scanner contains arrays of detectors in coincidence with each other to detect direct coincidences (line of response in the same ring) and cross coincidences (line of response crosses rings) (Fahey, 2002; Shulkin, 2005). IV. PET/CT A. History The first PET/CT prototype scanner became operational in 1998 (1). The design incorporated a spiral CT scanner with PET detectors mounted on the rear of the rotating CT assembly (Blodgett, Meltzer, and Townsend, 2004). The first commercial PET/CT scanners appeared in the clinical arena in 2001 (Blodgett et al. 2007). Thousands of cancer patients have been scanned on the combined PET/CT devices since the introduction of the first prototype of PET/CT in more than 5 years and during the initial experience, increased level of accuracy and confidence was noted compared to the separate readings, particularly in its ability to distinguish the pathology from the normal physiologic uptake (Townsend, et al, 2004; Blodgett et al. 2007). B. Purpose The PET/CT scanner, by combining two established modalities such as CT and PET, is an evolution in imaging technology, integrating two existing technologies that have historically progressed along separate but parallel paths. The two modalities are complementary, with CT images lacking the functional specificity of PET and PET images lacking the anatomic detail seen on CT (Townsend, Carney, Hall, and Yap, 2004). To date, more than 800 combined PET/CT scanners are installed in medical institutions all over the world (Blodgett, et al, 2007). PET/CT scanners are used for diagnosing and staging of malignant diseases as well as for monitoring the patient’s response to therapy (Blodgett, et al, 2007; Townsend, et al., 2004). In addition, Townsend, et al (2004) noted that CT images can be used to produce noiseless attenuation correction for the emission data of PET. Townsend et al. added that the combined PET/CT scanners help in bringing molecular imaging to the forefront of diagnosing, staging, therapy monitoring. V. Comparison of PET/CT to PET While the acquisition of accurately coregistered anatomic and functional images is a major strength of the combined PET/CT scanner, an additional advantage of the hardware fusion approach is the use of CT images for attenuation correction of the PET emission data, eliminating the need for a separate, lengthy PET transmission scan (Blodgett, Meltzer, and Townsend, 2004; de Wever et al. 2007). The use of the CT scan to generate PET attenuation correction factors (ACFs) not only reduces whole-body scan times by up to 40% but also provides essentially noiseless ACFs compared with those from standard PET transmission measurements, even with singles sources (Townsend et al. 2004; de Wever et al. 2007). There are also several morphologic changes of a lesion at the same time (de Wever et al. 2007). Third, one of the major tumor treatment modalities, radiation therapy (RT), uses CT data for treatment planning. Here, the use of PET/CT is again synergistic, as CT data can be used not only for anatomic reference and attenuation map, but also for planning of radiation (Townsend et al. 2004; de Wever et al. 2007; Blodgett et al. 2007). Finally, PET/CT is a “one-stop-shop” oncology examination, providing a single all- encompassing imaging study for the patient (Von Schulthess, 2004). Attenuation - corrected images are needed in order to gain more information on FDG uptake (Saunders et al. 1999; Vansteenkiste, 2001). VII. Conclusion From this review, one can bring to a close that in comparison to the two separate imaging methods of PET and CT, the integration of PET/CT provides more accurate information in diagnosing, staging, and monitoring the disease (Townsend et al. 2004). With PET/CT, significant improvements were statistically found in terms of staging a tumor (Hany, Kamel, Korom, Lardinois, Seifert, Von Schulthess, and Weder, 2003). For this reason, results suggest that combination of PET/CT is superior compared to PET or CT alone. Visual correlation of PET with CT is more effective in determining the stage of non small cell lung carcinoma (NSCLC) compared to PET or CT alone. Additionally, significant improvements in staging of tumor were found when integrated PET – CT was used. The anatomical correlation of the radionuclide uptake made possible a more precise delineation of the location of the primary tumor. Integrated PET–CT improved the diagnosis of chest-wall infiltration and mediastinal invasion by the tumor (Hany et al.). In the future, these advances will continue with new designs, faster electronics, increased computing power and scintillators with physical characteristics of PET that is far better than even LSO (Townsend et al. 2004) VIII. Literature Search Strategy The information was obtained from two different resources. The first came from the Galileo database. Different journals were found using MEDLINE, Academic Search Complete, and Research Library which were subcategories under the Galileo Database. The second source came from the internet resource. The search engine www.google.com was used to help further the research. The search terms used included positron emission tomography, computed tomography, lung cancer, and staging of lung cancer. IX. References American Lung Association. (2008). Trends in Lung Cancer Morbidity and Mortality 2008. Retrieved October 3, 2008, from http://www.lungusa.org/site/pp.asp?c=dvLUK9O0E&b=33347 Barker, J., Detterbeck, F., Margois, M.L., Silvestri, G.A., & Tanoue, L.T. (2003). The noninvasive staging of non-small cell lung cancer [Electronic version]. Chest, 123, 147s- 156s. Blodgett, T.M., Meltzer, C.C., & Townsend, D.W. (2007). PET/CT: Form and function [Electronic Version]. Radiology, 242(2), 360-385. 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