ANAL CANCER TREATMENT INFORMATION
What is Anal Cancer?
Epidermoid carcinoma of the anal region is most commonly diagnosed between the ages of 35 and 90 years, with the preponderance of cases in the literature between 58 and 64 years. The annual incidence rate steadily increases after the age of 30 years, reaching 4.7/100,000 after 85 years. An increased incidence has been observed in men younger than 45 years in the last decade. This increase was not seen in men over 45 years old or in women of any age.
VIRUSES AND OTHER INFECTIOUS AGENTS.
There is a relationship between papillomaviruses and the development of genital warts (condylomata acuminata), which can convert to squamous cell carcinomas after a long latent period of 5 to 40 years. Anal canal carcinoma has been associated with condylomata in the general population and in male homosexuals. In the case-control study reported by Daling and coworkers, squamous cell carcinoma (but not transitional cell carcinoma) was strongly associated with a history of genital warts (RR, 26.9 in males and 32.5 in females). In women without a history of genital warts, anal cancer was associated with seropositivity for herpes simplex virus type 1 (RR,4.1) and Chlamydia trachomatis (RR, 2.3). In men without a history of warts, there was an association with gonorrhea (RR, 17.2).
Although HIV has been questioned as a possible etiologic agent in homosexual men, Monfardini and coworkers showed that among 435 HIV-associated tumors in IV drug abusers in Italy, anal tumors were extremely rare. Among individuals with acquired immunodeficiency syndrome (AIDS), an increased risk of anal cancer has been found; the RR for homosexuals with AIDS was 84, and for heterosexuals with AIDS it was 38. Caussy and colleagues suggested that HIV-related immunodeficiency allows reactivation of latent HPV, which then leads to the epithelial abnormality.
Prior radiation therapy may play a role in the development of anal carcinoma, as may immunosuppression. Immunosuppressed renal transplant patients have a 100-fold increase in anogenital tumors compared with the rest of the population. In the case-control study reported by Daling and colleagues, current cigarette smoking was a major risk factor in both sexes (RR, 7.7 in women and 9.4 in men).
This substantiates the report by Daniell, who noted that 54% of 13 women with anal cancer were current smokers, compared with only 26% of 202 age-matched patients with anal cancer. In a matched controlled study of 56 women with anal carcinoma, there were strong associations with herpes simplex virus titer, cigarette smoking, and increasing numbers of sexual partners. In a multivariate analysis, cigarette smoking was an independent variable (P = .0126).
Many different histologic cell types may occur in the anal area. In addition to the more common types, other rare histologic entities can arise, such as small cell carcinomas similar to those in lung, and lymphoma. Melanomas constitute 1% to 2% of all anal cancers. The importance of anal melanoma lies in its poor prognosis, with a 5-year survival rate of only 8% to 12%.
Survival following lymph node dissection with positive nodes at presentation ranged from 0% to 20%. However, modern multimodality treatment has impacted greatly on this result. Patients who have lymph node dissection for metachronous lesions have a better long-term survival, with rates up to 83%. The majority of these recurrences occur by 2 years but may take up to 8 years to present.
How and Where Anal cancer Start?
It usually starts from a polyp, which is a protrusion of gut tissue which starts as being non- cancerous. These polyps are often screened for, and may be removed before becoming cancerous. If a polyp is less than 1 cm. across, it has only a 1% chance of being cancerous, but if it is larger than 2 cm. across, the chance of cancer rises to almost 50% . Polpys become much more common as we grow older, over 80% of people over 70 years old have at least one polyp.
The risk for developing Anal cancer is increased with:
1) A high fat, low fiber diet. (The NCI noted 40 studies making this association). This is thought due these foods taking longer to pass through the colon, thus allowing more contact with cancer-inducing chemicals ("carcinogens") in these foods. In contrast, high fiber foods stimulate the colon to move food through quickly, and lessen the chance for polyps to form. Colo-rectal cancer is rare in societies that eat mostly fruits and vegetables, and the vitamins in these (especially vitamins A and E ) may be protective. This is a reason that colon cancer is rarer in the Far East where less dietary fat is consumed.
2) Family Predisposition Certain cancers, namely colo-rectal, breast, uterine and ovarian, tend to occur with alteration of the same genes, known as the "family cancer syndrome" genes. While not all people with these inherited genes get cancer, many do. Around 15% of new patients with colo-rectal cancer have close family members with disease.
3) Hereditary syndromes causing multiple polyps in the digestive tract. For example, 100% of Familial Polyposis patients will get colon cancer if the colon isn't removed. In this condition, there are thousands of polyps in the colon, and the more polyps, the greater the chances for a cancerous one to arise. Other rarer syndromes include "Turcot's," where there are associated brain tumors, and "Gardner's," with tumors in other glandular areas. The Peutz- Jeghers syndrome has lots of polyps throughout the intestinal tract, but they are the more benign type ("hamartomas") and the risk of cancer is low.
4) Age older than 40 years . Younger patients rarely develop this cancer, but if so it tends to be very aggressive. The average patient is 60 years old. This goes along with more polyp formation as we get older, and a greater risk that the polyps will be abnormal ("dysplastic") with age.
5) Inflammatory bowel disease, especially ulcerative colitis (less in Crohn's). The risk of developing colon cancer with ulcerative colitis is about 2% per year. In these conditions, there are many more new intestinal cells being produced to replace those lost through inflammation and infection. The more new cells formed, the greater chance that a cancerous one will arise.
6) Radiation Exposure to the abdomen or pelvis may trigger cancer, but usually not for 10 to 50 years after the exposure. The chance of developing cancer from medical X-rays is remote, estimated at about 6 cases per million X-ray procedures. Moreover, the type of cancer induced by radiation is more likely to be a muscle, bone or cartilage tumor ("sarcoma") than the much more common adenocarcinoma of the colo-rectum.
7) Chemical Exposure ("carcinogens") from foods or even from substances produced within our own bodies. It is thought that eating burnt foods, nitrites, and various artificial additives and preservatives may increase cancer risk, but it is hard to prove. The more fats a person eats, the more bile salts their gall bladder releases, and these have been shown to promote polyp growth. It is very hard to eat a pure, clean diet in America.
8) Possible link to depression, with decreased immune system response. Generally, digestive diseases have been considered by psychiatry to result from "anger turned inward." It is now known that normal people's immune systems are able to recognize and destroy tiny cancer cells before they can spread. In the diseased or depressed person, the immune system does not function efficiently and may allow cancer to start. The flip side is that a good positive attitude helps cancer patients live longer and better. Over 50% of cancers are in the rectum or lowest portion of the colon, the sigmoid. In the colon, 25% of cancers are in the ascending portion, 15% in the transverse portion, and 10% in the descending portion. There has been a shift toward the right colon in the past 2 decades.
LOCAL SURGERY.
Epidermoid carcinoma of the anal margin, as in skin elsewhere, has a favorable prognosis and rarely requires radical surgery. Wide local excision of these lesions is an attractive approach because it can be performed with primary closure and infrequently requires a split-thickness skin graft. The use of a wide local excision implies that an adequate margin of normal tissue (1 cm) can be secured beyond the tumor without anal incontinence. If the tumor encompasses more than one half of the circumference of the anus, local excision should be abandoned due to poor anal control, and an APR is advocated.
Our review on Anal cancer contains information that is vital to anyone who has been diagnosed with this condition.
Q&A: Biologics in the Treatment of Metastatic Colorectal Cancer: Latest Data and Expert Insights.
Question:- Has one class of antihypertensive drugs shown greater benefit in treating bevacizumab-related hypertension than others?
Answer:- All classes of antihypertensives have been used and all have shown efficacy, with no indications that one has superior efficacy compared with the others. In an analysis of data from the BRiTE study (Kozloff M et al. 14th European Cancer Conference [ECCO 2007]. Abstract 3049.), 42.3% of the patients had hypertension at baseline and 18.7% developed increased hypertension during treatment; but baseline hypertension did not increase the risk of developing increased blood pressure with bevacizumab use. A number of different antihypertensive agents were used, and all of them were equally effective. Greater than 70% of the patients needed only one drug to manage the blood pressure, and 20% needed two classes of drugs to control it.
Question:- Where can one test for KRAS mutations if it indicates such a clear-cut distinction between responders and nonresponders to epidermal growth factor receptor (EGFR) inhibitor therapy?
Answer:- A test for KRAS mutations is not yet clinically available. However, I understand that this may change within the next 8 months. Based on clinical data reported to date (eg, Amado RG et al. ECCO 2007. Abstract 7LB; Amado et al. 2008 American Society of Clinical Oncology Gastrointestinal Cancers Symposium [ASCO-GI 2008]. Abstract 278; Hecht R et al. ASCO-GI 2008. Abstract 279.), I suspect that this test will be widely used once it does become available.
Question:- How can we best combine agents with oxaliplatin—for instance, when we encounter cumulative toxicities that force us to discontinue therapy early?
Answer:- The OPTIMOX2 study, a large phase 2 study conducted before the availability of bevacizumab, randomized patients between an OPTIMOX1 arm (6 cycles of FOLFOX7→LV5FU2 until progression→reintroduction of FOLFOX7) and the OPTIMOX2 arm (6 cycles of FOLFOX7→complete stop of chemotherapy and reintroduction of FOLFOX7 before the tumor progression reached baseline measures). Latest data reported from the OPTIMOX2 trial (Maindrault-Goebel F et al. 43rd Annual Meeting of the American Society of Clinical Oncology [ASCO 2007].
Abstract 4013) suggested that the stop-and-go strategy that includes complete chemotherapy-free intervals may be detrimental to overall survival and, therefore, is inferior to a stop-and-go strategy that includes a maintenance phase with 5-FU/LV. Based on OPTIMOX2 and other studies, it has become clear that we should treat patients to progressive disease and not stop all therapy before. However, the cumulative toxicities related to oxaliplatin often do not allow us to use this drug continuously until patients progress; consequently, modifications in oxaliplatin-based therapy are required. When using oxaliplatin in combination with other agents, the key is not to stop all therapy when neurotoxicity develops, but to only stop oxaliplatin for a necessary period of time, while continuing treatment with other agents. For example, if FOLFOX is used and oxaliplatin needs to be stopped, therapy with 5-FU/LV should continue. If therapy is started with FOLFOX + bevacizumab, oxaliplatin can be stopped if neutotoxicity develops, but bevacizumab and 5-FU/LV should be continued.
Question:- Have there been subgroup analyses in the PACCE or CAIRO2 studies to see which patients might be more likely to benefit and who might have increased risk of toxicities from the multidrug regimens?
Answer:- At this time, there are no published data available to answer this. It can be speculated that patients at increased risk of toxicities may include older patients and those with poor performance status, but this has not yet been confirmed.
You will learn about the causes, risk factors, common signs and symptoms, medical tests that are used to establish the diagnosis, and standard treatments. You will also learn about the latest clinical advances in the management of Anal cancer as well as about the newest treatment options that are available.
Our review on Anal cancer will also inform you about important new, exciting research in the area of Anal cancer. You will also learn about the doctors, hospitals, and medical centers that are at the leading edge in conducting clinical research about Anal cancer.
You won't find this combination of information anywhere else. It is easily accessible right here. We invite you to read our review on Anal cancer so that you will be armed with comprehensive, trustworthy information that may help you or someone you care about who has been diagnosed with Anal cancer.
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