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Tunnell Cancer Center Annual Report 2009-2010
Tunnell Cancer Center Annual Report 2009-2010
Michele D. Thomas, M.D., FACS, FASCRS, Medical Oncologist
Colorectal cancer is the most preventable visceral cancer, and its incidence makes it one of the most important. It affects nearly one million people worldwide annually, thereby constituting a major worldwide burden on healthcare. Colorectal cancer (CRC) is the fourth most frequently diagnosed cancer in males and females in the United States with approximately 147,000 new cases and 57,000 deaths annually. It accounts for 11 percent of cancers and is the second most common cause of cancer death. The lifetime probability of an individual developing CRC is 5–6 percent. In the U.S. nearly 90 percent of cases are diagnosed in patients over age 50, with risk increasing with age. The risk of developing CRC in 80–84 year-olds is seven times that of 50–54 year-old patients. Over the last decade there appears to be a reduced incidence of colorectal cancer. Mortality is also decreasing, which suggests greater awareness and improved detection with screening. There should be an obvious reduction in mortality due to early detection and removal of polyps. When the disease is at an early stage or localized, the five-year survival approaches 90 percent. The overall five-year survival for CRC is 63 percent, making it a “survivable cancer.” Nevertheless, 65 percent of cancers are diagnosed at an advanced stage.
Race, Ethnicity and Geography
Ashkenazi Jews—increased risk due to gene mutation African-Americans—higher risk in U.S. Hispanic-Americans—lower risk Higher rates in North America, Western Europe, Australia Lower rates in Africa and Asia
Environmental factors (mostly dietary) are considered to play a major role in the disease. The role of diet in the pathogenesis of CRC has long been speculated; however, the risk is unclear. It is difficult to determine whether certain dietary components (high in fruits, vegetables, and fiber and low in fats and red meat) may be responsible for decreasing risk. Ingestion of saturated animal fat has been implicated in carcinogenesis. There has been no compelling evidence in the medical literature to implicate total dietary fat intake in the development of CRC; however, there has been more compelling evidence that there may be some link of regular dietary intake of red meat associated with CRC. The potential carcinogenic mechanisms in red meat appear to be unrelated to fat content. Red meat contains iron which is a “pro-oxidant” (increases free radical production), it stimulates production of N-nitroso compounds (known carcinogens), and cooking it over an open flame may cause formation of carcinogenic hydrocarbons. Epidemiologically based studies have suggested that a diet containing 3.5 ounces or more of red meat daily may be responsible for a 12–17 percent increased risk in CRC in some populations. Fruits and vegetables have been extensively evaluated as a source of anti-oxidants, carotenoids, ascorbate, and other bioactive compounds that may protect against carcinogens. Overall, the medical evidence for the role of intake of fruits and vegetables in the prevention of CRC has been inconsistent. Fiber was one of the first dietary factors thought to have a protective effect against CRC. Possible mechanisms include increase in transit time through the gut and absorption of potential carcinogens; however, there has been no consistent evidence that a diet high in fiber has a protective effect for CRC. Calcium supplementation has undergone substantial experimental testing, and epidemiological evidence exists to support the fact that there are beneficial effects of calcium on the development of CR neoplasia. One study demonstrated that calcium supplementation of 1200mg daily for four years or 2000mg daily for three years yielded a reduction on development of colorectal adenomas. Folate deficiency may lead to cancer through disruption of DNA synthesis and repair. There has been shown to be a significant relationship between higher folate intake and decreased risk of CRC or adenoma formation. Folate consumption in the U.S. is increasing as the FDA mandated folate fortification in all flour and grain products in the U.S. since 1998. Alcohol consumption holds a possible role in CRC carcinogenesis by altering folate absorption. Evidence indicates that two or more drinks per day are associated with increased risk of CRC.
Aspirin and “NSAID” use has a protective effect in “observational studies” but is not considered a cost-effective means of prophylaxis for colonic neoplasm. Hormone replacement therapy use suggests reduction in incidence and mortality in observational studies; however, given potential adverse effects, it is not to be used as a preventative means for CRC. Obesity seems to increase the risk of CRC in men and premenopausal women. Greater physical activity is associated with a small reduced risk of CRC. Smoking, especially cigarette smoking, in more recent evidence has a two-fold to three-fold increase in adenoma risk compared to nonsmoking. Inflammatory bowel disease (IBD) patients are known to be at increased risk for CRC; however, the magnitude of increased risk is still being studied. Family history has long been identified with increased risk.
Through the Patient’s Eyes
“My life is not about me, but what I can do to help.”
As a department manager in a local supermarket, Reber Whitner was wrapped up in the daily grind of making money and focusing on the material world. Then, in 2006, he was diagnosed with Stage 3 colon cancer. He faced a long, slow road to recovery. “My faith blossomed,” he says. “I learned that life is not my plan; it is God's plan.”
Reber found his peace in yoga. “The breath work…it helps you cope and deal with situations…it gets you in touch with your inner self.”
Two years ago Reber started Stiff Man's Yoga: a free yoga class at the Delaware Wellness Community in Rehoboth. It's available weekly to cancer survivors and their partners, spouses, and caregivers.
“Cancer was a gift. It made me realize what is important.”
Screening for CRC
Average-risk individuals include those with no symptoms associated with CRC, no personal history of CRC or adenomatous polyps, no family history of CR neoplasia, no IBD, and no unexplained anemia. The choice of a screening strategy for average-risk individuals is made largely due to influence from the patient’s PCP, the patients themselves, and third-party payers. In 2001, Medicare began authorization for reimbursement for screening colonoscopy for average-risk patients. A sample screening strategy is shown in the chart that follows for average, moderate, and high-risk individuals.
Colonoscopy remains the only screening test that allows detection and removal of pre-malignant lesions. It has become the screening test of choice by most physicians due to its sensitivity for detection of lesions and ability to remove lesions. The accessibility of the test has also been reasonably good. Patient acceptance has also improved over the last decade due to greater awareness of the benefits of the test, improved anesthetic regimens, and selection of alternative preparation regimens.
CT colography (virtual colonoscopy) was developed in an attempt to increase compliance with CRC screening. It utilizes CT scanning with thin sections and 3-D reconstruction to examine the colon. This technique has not gained great favor as the accuracy for detection of polyps has not been shown to be as good as colonoscopy; it still requires a thorough preparation, and biopsy or polypectomy cannot be performed as part of the procedure.
Surveillance for CRC and Polyps
A personal history of adenomatous polyps or colorectal adenocarcinoma places a person at higher risk for developing a metachronous or new lesion. Surveillance colonoscopy is recommended for these individuals. A rational surveillance strategy should take into account the patient’s risk, age, co-morbid conditions, life expectancy, pattern of neoplastic growth, completeness of prior exams, and histologic features of prior neoplasms. For example, after simple single polypectomy, colonoscopy should follow in three to five years; for multiple large or dysplastic appearing polyps, six to 12 months; post-resection surveillance colonoscopy for those undergoing prior curative resection, one year followed by three-year intervals. The elderly or those with substantial co-morbidities and limited life expectancy may have no benefit from surveillance.
Screening and Surveillance Estimates
Only 10–30 percent of adults in the U.S. undergo regular screening for CR cancer despite a high rate of screening for breast cancer by mammography (75 percent) and cervical cancer by PAP smear testing (66 percent). It remains troubling that so much energy and expense are placed on the treatment of advanced or recurrent CR cancer while more emphasis must be placed on detection of early-stage cancers and removal of premalignant lesions.
The clinical presentation of patients with colon cancer varies from those who are asymptomatic to those who have symptoms associated with anemia, abdominal pain, change in bowel habits, rectal bleeding, or occult blood in the stool. Evaluation by colonoscopy will provide the surgeon with important information including location, size, and other physical characteristics that may be relevant to the patient’s management. Tissue biopsy is also important for diagnosis. Other pre-operative tests that may be obtained include blood work (CBC, metabolic panel, liver function, CEA), CT scan and PET/CT scan. The patient may require additional testing of cardiac and pulmonary systems to ensure a favorable state of health prior to surgical intervention.
The primary treatment of cancer of the colon is surgical resection. The standard “open” surgical technique has long been the mainstay of therapy; however, over the last decade a number of techniques have been examined for efficacy in their use toward the surgical extirpation of CRC, the most popular of which is laparoscopic or minimally invasive surgery. This particular technique involves the use of a video laparoscope and highly specialized instruments for dissection and resection of the colon. The minimally invasive technique allows the use of much smaller incisions and may give the patient advantages in terms of post-operative pain and recovery time. Laparoscopy has been used successfully for treating polyps that are unresectable using the colonoscope as well as for treating other benign diseases of the colon. The most challenging aspect in applying this technique is the learning curve for this type of advanced laparoscopic work. Some surgeons have utilized a “hybrid“ of this approach called the “hand-assisted” technique, whereby a special port is fashioned to allow the use of the surgeon’s hand as an adjunctive tool to the laparoscopic dissection. The utilization of the laparoscopic technique for cancer surgery remained in question for a number of years due to the nature of the disease process and the necessity of adhering to specific techniques during dissection. It has only been since 2004 that this has been an accepted technique in the surgical treatment of CRC. The Clinical Outcomes of Surgical Therapy Study Group (COST trial) showed that laparoscopic colectomy for curable cancer results in equivalent cancer-related survival to open colectomy when performed by experienced surgeons (pre-requisite of 20 benign disease cases). Adherence to standard cancer resection techniques including, but not limited to, complete exploration of the abdomen, adequate proximal and distal margins, ligation of the major vessels at their respective origins, containment and careful tissue handling, and en bloc resection with negative tumor margins using the laparoscopic approach will result in acceptable outcomes.
Other surgical methods that have gained some popularity over the last decade include transanal endoscopic microsurgery (TEMS) and natural orifice translumenal endoscopic surgery (NOTES). These, as well as other advanced techniques, are reserved for use in major centers specializing in such an approach.
Staging and Prognostic Factors
The “TNM” classification is used to designate tumor stage (I–IV) through combinations of different descriptors T (depth of tumor involvement in the colon), N (lymph node involvement), and M (metastases). The importance of staging is for treatment planning and prognosis and is performed both by clinical and pathological methods.
Stage I T1 or T2 N0 M0 Stage II T3 or T4 N0 M0 Stage III Any T N1 or N2 M0 Stage IV Any T Any N M1
Lymph node involvement is the most important prognostic factor in patients with CRC. The accuracy of colon cancer staging improves with increasing number of LN evaluated microscopically. Fifteen lymph nodes per specimen is the minimum number accepted in the “harvest” in order to ensure accurate staging.
Advanced patient age, obstruction, perforation, blood transfusion, and inability to achieve a curable resection with advanced stage lesions are all clinical prognostic factors associated with poorer outcome. Histologic, biochemical, and genetic factors that are associated with a worse prognosis include poorly differentiated lesions (higher grade), mucin-producing tumors, presence of microsatellite instability (loss of ability to repair errors in DNA replication), signet cell histology, venous invasion, perineural invasion, and DNA ploidy associated with aneuploid cells. A CEA (carcinoembryonic antigen) level greater than 15 suggests increased risk of metastases. This is not a definite predictor but is often used to follow patients to detect occult metastases or recurrence after resection.
The sentinel node mapping is less important in CRC than breast and melanoma malignancy. Utility of this technique may be marginal as resection of the primary lymphovascular pedicle is of paramount importance in performing proper oncologic resection and, unlike breast lymph node harvesting, adds little to no morbidity to the procedure.
Patterns of spread of CRC include intramural spread (within the wall of the bowel), transmural spread (through the wall of the bowel), implantation or carcinomatosis (adherence of cancer to structures or surfaces within the abdominal cavity), lymphatic spread (most common route for metastatic disease to liver), and hematogenous spread (less common cause of metastases to lung and other sites). Adequate margins of resection above and below the area of tumor growth (usually at least 5 cm, but the full extent of resection is usually defined by division of the primary lymphovascular pedicle and the supplied tissues) and around the tumor (radially or invading into adjacent structures) control against local recurrence.
The presence of distant metastases are evaluated by using US, CT, MRI, CXR, and PET and are almost always in liver or lung, with bone and brain being less likely.
Adjuvant chemotherapy is post-resection treatment. The purpose is to destroy microscopic residual disease, thereby preventing later development of metastatic disease. Therapy for known macroscopic metastatic cancer is not considered adjuvant therapy. Most new chemotherapeutic agents are tested in randomized trials with patients with known metastatic disease. If they are beneficial in this patient population with acceptable side effects, they are then used in clinical trials in patients with nonmetastatic disease. Patients with Stage III colon cancer (any T, N1 or N2, Dukes’ C) are at high risk for recurrence, and administration of post-operative chemotherapy with a 5-FU based regimen has a proven benefit in decreasing recurrence and improving survival. Stage II (T3 or T4, N0, Dukes’ B2) patients are often offered adjuvant therapy, as it may be beneficial in certain high-risk patients. Patients with Stage II colon cancer who are considered at higher risk for recurrence include those with tumor perforation, adherence or invasion of adjacent organs; nonploidy on flow cytometry; poor differentiation tumor histology; venous, lymphatic, or perineural invasion; and possibly the presence of molecular markers suspicious for micrometastatic disease. The most common sites of failure of treatment include the liver, peritoneal cavity, or other distant sites. Examples of chemotherapeutic agents and combinations include 5-FU and Leucovorin, 5FU/Oxaloplatin/Leucovorin (FOLFOX), 5-FU/CPT-11/Leucovorin, Capecitabine (Xeloda), and Irinotecan (CPT-11).
Beebe Medical Center Data
As with the general population, there is a greater proportion of males to females with colon cancer. The majority of cases were detected between the ages of 60 and 84 years. In comparing the proportion of left- to right-sided colon cancers, Beebe Medical Center recorded a pattern of distribution similar to that of the Delaware State Cancer Registry. A nearly equal distribution of patients underwent surgery alone and surgery plus chemotherapy as the modality of treatment at Beebe Medical Center. A higher proportion of patients were treated with chemotherapy in addition to surgery at the state level. The number of cases diagnosed at Beebe Medical Center seems to have declined, which matches the national trend. At Beebe Medical Center those patients with Stage I cancer had a five-year survival of 76 percent, Stage II was 62.6 percent, Stage III was 44.6 percent, and those with metastatic disease 5.8 percent. These rates are in alignment with state and national averages.