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PET & COLORECTAL CANCER TABLE OF CONTENTS

A. INTRODUCTION – WHAT IS A PET SCAN?

Positron Emission Tomography (PET) is rapidly becoming a major diagnostic imaging modality used predominantly in determining the presence and severity of cancers. In the U.S. and in some provinces in Canada, it is currently the most effective way to check for cancer recurrences. Studies demonstrate that PET offers significant advantages over other forms of imaging such as CT or MRI scans in diagnosing disease.

PET images demonstrate the chemistry of organs and other tissues such as tumors. A radiopharmaceutical, such as F-18 FDG (fluorodeoxyglucose), which includes both sugar (glucose) and a radionuclide (a radioactive element) that gives off signals, is injected into the patient and its emissions are measured by a PET scanner. All cells use glucose (sugar) as an energy source. However, cancer cells grow faster than normal healthy cells and they use glucose at much higher rates than normal cells. This is the basis of imaging with F-18 FDG for cancer detection in PET scanning.

A PET scanner consists of an array of detectors that surround the patient. Using the gamma ray signals given off by the injected radionuclide, PET measures the amount of metabolic activity at a site in the body and a computer reassembles the signals into images. Cancer cells have higher metabolic rates than normal cells, and show up as denser areas on a PET scan that are nicely lit up. PET is useful in diagnosing certain cancers because it highlights areas with increased, diminished or no metabolic activity.

In addition to identifying many forms of cancer, PET can also identify damaged heart tissue, and brain disorders such as Alzheimer's, Parkinson's, and epilepsy. Technically, PET is a medical imaging technology that images the biology of disorders at the molecular level before anatomical changes are visible in other types of scans such as CT or MRI.

A PET scan is very different from an ultrasound, X-ray, MRI, or CT, which detect changes in the body structure or anatomy, such as a lesion (for example, a sizeable tumor) or musculoskeletal injury. A PET scan can distinguish between benign and malignant disorders (or between alive and dead tissue), unlike other imaging technologies which merely confirm the presence of a mass. A PET scan can detect abnormalities in cellular activity generally before there is any anatomical change. A PET scan can, in many cases, identify diseases earlier and more specifically than ultrasound, X-rays, CT, or MRI.

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Source: http://www.med.nyu.edu/di/petCt/faqs.html

Clinical trials have now demonstrated the utility of this modality, moving it from the research environment to the clinic over the last decade. The unique, functional information that PET provides is becoming essential to physicians in making decisions regarding future patient care and treatment.
As previously stated, a PET scan provides information about the body’s chemistry and cell function (metabolism) rather than pictures of the body’s anatomy or structure as shown by x-ray, ultrasound, CT scans or MRI. As a result, pet scans may reveal abnormalities of tumours that would otherwise go undetected.

A PET scan is performed by injecting a small amount of radioactive chemical into a vein (sugar labeled with radiotracer such as F-18 FDG). As the chemical travels through the body, it is absorbed by the organs and tissues. Since cancerous tissues feed abnormally on sugar, the affected cells and organs process more of the labeled sugar. During the test, a scanner records the energy produced by the patient’s cells. The scanner’s camera detects the gamma rays emitted from the patient and turns those into electrical signals, which are processed by a computer to generate the medical images. The computer converts the recording into three dimensional pictures of an area of the body and any cells that are changing show up at a brighter contrast to any surrounding, normal cells. There is very little preparation involved prior to a PET scan and patients are simply asked not to eat or drink for at least six hours prior to the scan. The test takes approximately 30 minutes to one hour to complete, though the patient is injected with the FDG radiotracer approximately one hour before the scan so it is important to plan for a visit of at least two hours. More information on patient preparation is available in Section D and F of this document.

B. WHAT IS A PET/CT?

Since PET measures cellular metabolism (rate at which injected sugar is absorbed), as opposed to MRI or CT, which “see” structure, it can be superior to these modalities, particularly in separating tumour from benign lesions, and in differentiating malignant from non-malignant masses such as scar tissue formed from treatments like radiation therapy. PET is often used in conjunction with CT scan through “fusion” to give a full three three-dimensional view of an organ and the location of cancer within that organ. Newer scanners are being made that are a combination of PET/CT devices.

A CT scan, or Computerized Tomography scan, emits x-rays which go through the patient to detectors. The computer uses this information to generate cross-sectional images of anatomical structures. The body does not come in contact with the scanner itself. Each cross-sectional picture or slice gives detailed anatomic location and changes in the anatomy. The use of oral and IV contrast agents can enhance the details by highlighting the gastrointestinal tract and other organs and blood vessels.

The PET/CT combination, as the name implies, combines two scanners, - the PET which shows metabolism and the function of cells, and the CT which shows detailed anatomy - is manly used for diagnosis, staging or restaging malignant disease and metastases and evaluation of treatment response. The two procedures together provide information about the location, nature of and the extent of the lesion. Hence, the combination scans can answer questions such as: Where is the tumour, how big is it, is it malignant, benign or due to inflammatory change, and has the cancer spread?

C. CANCER & PET

Normal body cells grow, divide and die in an orderly fashion replacing worn-out or dying cells and repairing injuries - a process called apoptosis. Sometimes these normal cells begin to grow uncontrollably. These abnormal cells outlive the body’s normal cells and continue to grow and divide forming new abnormal cells. The mass of extra cells forms a growth or tumour, which can be benign or malignant. Benign tumours are not cancerous. Benign tumours can be removed with low probability of recurrence and are usually not life threatening. But if the tumour is malignant, it is cancerous. In a process called metastasis, cells from a malignant tumour can break off and travel to other parts of the body via the bloodstream or lymphatic system where they begin to grow and replace normal tissue. Cells from a malignant colon tumour can spread to another organ, for example the liver. Although these cells are in the liver, they are indeed still colon cancer cells.

PET is considered particularly effective in identifying whether cancer is present or not, if it has spread, if it is responding to treatment, and if a person is cancer free after treatment. Cancers for which PET is considered particularly effective include lung, head and neck, colorectal, esophageal, lymphoma, melanoma, breast, thyroid, cervical, pancreatic, and brain as well as other less-frequently-occurring cancers.


D. COLORECTAL CANCER AND PET

As with all types of cancer, early diagnosis of colorectal cancer is key to its cure. Colorectal cancers probably develop slowly over a period of several years. Before a true cancer develops, there are often earlier changes in the lining of the colon or rectum. If found early, before it has metastasized, the disease is considered curable. However, as the tumor spreads to lymph nodes, a patient's chance of living at least five years drops to 40 - 60%. If the cancer has already spread to distant organs, the long-term survival may be lower.
As it relates to the diagnosis of early colorectal cancer, a study (Sakamoto, K et al., Inter J of Gastro Cancer, June 2007) found that PET was capable of noninvasively detecting an early colon cancer as small as 16mm as well as other cancers in the whole body and considered it to be a suitable screening examination.
Before PET, it was extremely difficult to monitor patients for suspected recurrence of colorectal cancer. The other techniques available for staging and assessment of potential recurrences may lack sensitivity and precision and frequently result in diagnostic and therapeutic delays. One study found that the sensitivity and specificity of PET/CT to colon cancer recurrence in patients after resection were 96.5% and 82.1% respectively (Kang S, et al., J Nucl Med 2008, 49: 257P).

In many colorectal cancer patients, pelvic CT could demonstrate a suspicious mass, but cannot distinguish mass tumor recurrence from postoperative or post radiation scar or is a recurrent cancer that must be treated. Further evaluation usually involves a biopsy. A positive biopsy is highly predictive of recurrence but because it is impossible to sample the entire mass, a negative biopsy cannot exclude recurrence.

Imaging with PET is critical in looking for the return of the cancer. In many patients with colorectal cancer, a mass may develop in the pelvis. A PET scan can identify whether the mass is suspicious of being cancerous because it will pick up the radioactive glucose and be seen on the scan results. If, however, the mass is scarring caused by the radiation treatments, no glucose uptake will be seen in the area of the mass. Reports in the scientific literature find that, in some tumours, PET correctly identifies detected lesions up to 95% of the time; however, the final word will of course rest with the pathology if a biopsy is performed.

PET can be used to image tumor response to therapy and to detect recurrence in successfully treated lesions. After surgery and other treatments, PET is an extremely important tool in monitoring whether any cancer cells have returned and if treatment should be re-started. For example, chemotherapy leads to changes in cellular activity and that is observable by PET long before structural changes can be measured by ultrasound, X-rays, CT, or MRI. A PET scan gives physicians another tool to evaluate treatments, perhaps even leading to a modification in treatment, before an evaluation could be made using other imaging technologies.

Belgian researchers reported that PET can find with near 100% certainty after a single course of chemotherapy if a patient with metastatic colorectal cancer is not responding positively to treatment as presented at the 2009 ASCO meeting. (Hendlisz, Alain, et al., ASCO 2009, Abstract #2533). The results of the study showed that if tumour metabolism does not respond after 14 days, the patient is unlikely to experience tumour shrinkage two or three months later on. Discovering this early on in treatment can help avoid unnecessary side effects and also allows physicians to attempt another type of therapy sooner to optimize results for patients.

The study, which consisted of folfox and folfiri administration, hypothesized that metabolic changes seen by comparing SUVs (see Section E) acquired before and two weeks after the first dose of chemotherapy would be predictive of standard morphological response for patients with advanced colorectal cancer. An early metabolic response was defined as a 15% or greater decrease of the SUV on day 14 after the first chemotherapy dose. A patient was deemed to have overall metabolic responsive disease if most or all of the lesions observed on the baseline PET showed a metabolic response, without any progressive lesion (new or > 25% increase of SUVmax).

In another rather large, multi-institutional study (Scott et al., J of Nucl Med, 2008, doi: 10.2967/jnumed.108.051615), authors confirmed the important role PET plays in the decision-making process of patients with colorectal cancer and the impact of PET on both the management and outcome of the disease. Based on the extent and progression of disease revealed by the scans, treatment physicians changed the planned management in more than 65% of patients assigned to the first group (suspected of recurrent disease) and nearly 50% in the second group (surgical candidates – liver or lung). The researchers also found additional disease sites in 48% of the first group and 44% in the second group.

PET is capable of showing the extent of the disease (called staging) of colorectal cancer. For patients whose cancer is newly diagnosed, it is important to determine if the cancer has spread to other parts of the body so that appropriate treatment can be commenced, while avoiding unnecessary therapies at the same time.

Colorectal cancer is less likely to recur after 5 years of there being no evidence of the disease; thus most patients who live 5 years without recurrence are considered cured. In the interim, however, ensuring that PET is a part of regular follow-up testing is important according to researchers.

In colorectal cancer, if the lymph nodes near the tumour or if a distant organ such as the liver has become involved by the cancer, they will take up more of the radioactive glucose. Whether or not distant organs are involved is a critical factor in deciding what the surgical and medical treatment will be. Some studies have shown that even if the cancer has spread in a limited fashion outside the colon, surgery combined with chemotherapy can be done to remove these other tumours and reduce the chance of recurrence.

The benefits of PET include
:


The concerns and risks associated with PET/CT include:


E. WHAT IS SUV (STANDARDIZED UPTAKE VALUE)?

Cancers show up as foci/areas of intense activity since cancer cells are more active and take up a lot of FDG. There can be other causes of intense activity such as inflammation, infection, or muscle activity. Measuring the SUV (standardized uptake value) is a semi-quantitative way to assess the activity in a given focus or area.

SUV represents the amount of activity in the focus relative to the activity in the other (normal) areas of the body. Typically, the SUV value of a metastatic lesion is above 2.5. The pattern of activity (the distribution of lesions in the different parts of the body) is also very important as different cancers have different preferential sites of metastasis. Also, patient’s history and findings on other anatomic imaging like CT scans and MRI are taken into consideration while reading the PET scans. Ultimately, all the SUV truly represents is a way for radiologists to identify the intensity of the brightness of the tissues the scan is measuring.

Lesions with uptake higher than that of blood pool often are malignant, while those with less intense uptake are most typically benign. To assign a quantitative value to FDG distribution, the amount of FDG uptake in a particular lesion is compared with the total body administered dose. A standardized uptake value (which is the ratio of FDG concentration in the lesion to the average FDG concentration in the body of > 2.5) has, according to the literature, been shown to be very sensitive and reasonably specific for malignant lesions. Benign lesions typically show FDG uptake in the 0.4 to 2 SUV range.

Other factors are taken into consideration when assigning SUVs. The location in the body identified to have increased metabolic activity (or hyper metabolic activity) may not necessarily contain any cancerous tissue because certain areas such as the brain (whose cells are fueled solely by glucose) and heart have a tendency to absorb more glucose (sugar) as part of their normal activities. Patient’s bowels will also absorb more glucose because the cells found in the bowels are typically more active and inclined to, therefore, absorb more of the sugar.
At times, there may also be benign causes of activity in the bowels as well. Diverticulitis and ulcerative colitis are both associated with some inflammation in the colon, and as such, are apt to collect more sugar than normal tissue would, but not an indicator of cancer. Hence, a false positive result is possible, as is the case with infection and inflammation sites, cardiac muscle, polyps, postoperative changes at a stoma site and thymic hyperplasia (enlargement of the thymus gland). On the other hand, false negatives may occur with small volume disease and small peritoneal metastases (though these may be picked up on CT).

Therefore, while the SUV may be a good indicator of malignant presence, it is not the only factor that is taken into consideration when reporting. Instead, along with the SUV, the location of the abnormality, the shape of the abnormality and the configuration with clinical history are all examined when reporting the findings of a PET/CT scan.

F. HOW TO PREAPRE FOR A PET SCAN AND WHAT TO EXPECT DURING A SCAN

A PET scan is usually performed on an outpatient basis and patients are told to wear comfortable clothes to their appointment. Patients undergoing a PET will be instructed to fast from midnight on the night before the scan and then abstain from breakfast the morning of so that the patient can avoid any intake of carbohydrates or sugar which could potentially compete with the tracer (F-18FDG) being administered for the scan. Hence, patients are requested they come in on an empty stomach to ensure that most tissues in the body are using free fatty acids as their energy source.

Patients are also instructed not to perform any vigorous exercise for a couple of days before the PET scan. Any vigorous exercise would stimulate the muscles to soak up the sugar or carbohydrates that are already in the body. Patients are advised to lie down and relax for approximately 45 minutes after injection to allow time for the radiotracer to accumulate in metabolically active cells. Any unnecessary patient movement during this period may result in uptake by muscle. Patients who are tense or shiver during this time often have FDG uptake in their neck muscles.

G. ACCESSING PET/CT – CCAC & KMH PARTNERSHIP

The use of PET/CT in the management of colorectal cancer is a powerful tool not only for the diagnosis of colorectal cancer, but as a go-to modality for assessing post chemotherapy response and the determination of recurrence in a setting where CEA levels are rising but CT results are negative.
To improve patient outcomes through early and accurate detection, the Colorectal Cancer Association of Canada has partnered with southern Ontario’s KMH Cardiology & Diagnostic Centres, which offer state-of-the-art PET/CT diagnostic services.

With multiple locations across the province, and a staff of highly qualified specialists, KMH offers PET/CT with attenuation correction using an advanced PET scanner that can transform the way doctors diagnose and treat cancer – including colorectal cancer. Their state of the art PET scanner helps doctors precisely identify the nature of the disease in pictures taken in an exam that generally lasts less than half an hour. The scanner features the highest image sensitivity in the industry, potentially lowering dose requirements, allowing faster patient exams, and enabling early stage disease detection. Information from the exam helps doctors diagnose disease early and accurately, and avoid putting patients through painful, invasive procedures.

KMH provides a consistently high level of service to patients and their physicians and is recognized as a leader in the healthcare industry. PET/CT services are available to colorectal cancer patients wishing to seek access through a physician referral (family physician, medical/surgical oncologist, or other healthcare provider) for which a requisition form is provided at the end of this document.

KMH is offering this valuable service at a substantially reduced cost to those patients referred by the CCAC. Should patients wish to obtain more information, they may do so by contacting the CCAC at:

1 877 50 COLON (26566) or KMH directly at 1-877-KMH-LABS (564-5227) or by visiting their website at www.kmhlabs.com

Download KMH Pet scan form

Sources:

Chen, LB et al., 18FDG PET/CT in detection of recurrence and metastasis of crc. World J Gastroenterology, 2007; 13(37): pp. 5025-5029 (PET/CT Use With Respect to detection, recurrence and metastatic disease)
Sobhani, E, et al., Early detection of recurrence by FDG-PET in the follow up of patients with colorectal cnacer. Vol. 98; Feb. 2008, pp. 875-880
Scott, et al., PET Changes management and improves prognostic stratification in patients with recurrent colorectal cancer: results of a multicentre prospective study. J of Nuclear Medicine. 2008; Vol. 49, No. 9: pp. 1451-1457
Zhang, C. et al., Diagnostic value of fdg-pet in recurrent colorectal carcinoma: a meta analysis. International J of Cancer. Vol. 124, Issue 1: pp. 167-173
Ruers, TJM, et al., Improved selection of patients for hepatic surgery of colorectal liver metastases with 18F-FDG PET: a randomized study. The J of Nuclear Medicine, published online on June 12, 2009 as doi:10.2967/jnumed.109.063040
Oyen, Wim, JG, et al., Improved selection of patients for hepatic surgery of colorectal liver metastases with 18F-FDG PET: a randomized study. J Nuclear Med. 2009; 50: pp. 1036-1041
Sakamoto, Kazuhiro, et al., Colon Cancer Detected by F-FDG PET. International J of Gastrointestinal Cancer; Vol. 36, No. 2: pp. 95-98
Kang, S, et al., Detection of colon cancer recurrence with F-18 FDG PET/CT in colorectal cancer patients after curative surgical resection: Value in patients with normal serum CEA level before surgery. J Nucl Med 2008; 49 (Suppl 1): 257 P
Strobel K, et al., Accuracy of FDG PET/CT with added CT morphologic information for detection of metastases. Radiology 2007; 244(2): 566-574
Hendlisz, Alain, et al., Is positron emission tomography (PET) with FDG an early predictor of the RECIST morphological response to chemotherapy in metastatic colorectal cancer patients (mCRC)? 2009 ASCO Annual Meeting. Abstract 2533. J Clin Oncology 27: 15s, 2009 (suppl abstract 2533)
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