A free NCI-sponsored teleconference will highlight the new clinical research center at the National Institutes of Health. Focused on the needs and interests of cancer survivors, family members, and advocates, the teleconference will feature Dr. John Gallin, Director of the NCI Clincal Center. Callers will have an opportunity to ask questions.

+ **Clinical Trials at NCI: The New Clinical Research Center at NIH – Patients are Our Partners and
Our Heroes**
+ *Featuring Dr. John Gallin, Director, NIH Clinical Center*
+ Friday, December 16, 2005
+ 1:00 p.m. (EST)
+ USA Toll-Free: 1-800-857-6584
+ Passcode: 4683#

Toll-Free Playback: 1-800-216-4418 until Jan. 16, 2006 at 11:30 p.m. (EST)

Toll-free playback of the current teleconference — *Why Advocates Should Care About Animal Models in Cancer Research: Mouse Models of Human
Cancers Consortium (MMHCC)* is now available until Dec. 9, 2005 at 11:30 p.m. (EST). Call 1-800-677-8851 to hear it.

The teleconferences are sponsored by the NCI Office of Liaison Activities. Download a [flyer](http://la.cancer.gov/generalflyer.pdf) describing the series.

Radiotherapy before surgery can reduce the size of some rectal cancers making it possible to remove the tumor without harming the sphincter muscle that closes the rectum and controls bowel movements. When surgeons are able to preserve the sphincter, rectal cancer patients can avoid permanent colostomies. Being able to predict which patients will respond to radiation therapy would help doctors to select those who would benefit most from presurgical treatment.

Researchers at McGill University have found that [levels of VEGF expression](http://www3.interscience.wiley.com/cgi-bin/abstract/112102167/ABSTRACT) are a useful way of predicting whether or not radiotherapy before surgery will reduce rectal tumors. VEGF — vascular endothelial growth factor — is a protein produced by cells, including cancer cells, that encourages the development of nearby blood vessels.

They measured levels of VEGF expression in 59 rectal tumor biopsies taken before radiation treatment. The studied samples were either from tumors that had completely responded to radiation therapy and where cancer was no longer evident to either surgeons or pathologists (CR — complete response) or from tumors that did not shrink during radiation treatment (NR — nonresponsive).

The average VEGF expression in nonresponsive tumors was significantly higher than that of tumors that responded completely to presurgical radiation. Over half of nonresponsive tumors had VEGF levels of 80% of greater. On the other hand, half of complete responders had VEGF levels of less than 10%. Eleven tumors had no reactivity to VEGF at all (0%) and all had responded completely to radiotherapy.

Inti Zlobec, M.Sc. and colleagues in the Department of Pathology at McGill University in Montreal reported the results of their research in the [early online edition of Cancer](http://www3.interscience.wiley.com/cgi-bin/abstract/112102167/ABSTRACT) on October 12, 2005. They wrote,

The results of this study indicate that VEGF assessed immunohistochemically from preirradiation tumor biopsies may be a useful marker of rectal tumor response to preoperative radiotherapy.

Hyperplastic polyps found in the lower part of the colon (*distal colon*) during sigmoidoscopy or colonoscopy do not predict more serious *neoplastic* polyps in the upper part of the colon (*proximal colon*) according to a study reported in the October 2005 [American Journal of Medicine](http://www.amjmed.com/article/PIIS0002934305001737/abstract)

Hyperplastic polyps are benign and do not have the potential to become colorectal cancers. However, adenomas or neoplastic polyps do. Removing adenomatous polyps before they become malignant is one important way to prevent colorectal cancer. Some doctors have thought that finding a hyperplastic polyp in the lower or distal colon might signal the presence of more dangerous neoplastic polyps in the upper or proximal colon. If they found one during a screening sigmoidoscopy, they scheduled the patient for a colonoscopy to look at the entire colon.

During screening colonoscopies, researchers at Virginia Mason Medical Center in Seattle classified patients into three groups: 1) those with hyperplastic polyps only in their distal colons, 2) those with distal adenomas with or without hyperplastic polyps, and 3) those with no distal polyps of either kind.

Of the nearly 2,400 people without symptoms of colorectal cancer who were screened during the study, 18% had at least one neoplastic polyp, 4% had advanced neoplasia where the polyp was larger than 1 centimeter or had other signs that it was approaching malignancy.

However, the percentage of those with neoplastic polyps in their proximal colons was not significantly different whether or not patients had hyperplastic polyps in their distal colons or not. 9% of those without distal hyperplastic polyps had neoplastia in their proximal colons compared to 12% of those who did not have such distal polyps. Two percent of both groups had advanced neoplasia in their proximal colons.

Adenomas in the distal colon *did* signal additional neoplastic adenomas in the proximal colon in about 1/3 of cases.

Otto Lin and his colleagues concluded:

Patients with distal hyperplastic polyps, unlike those with distal adenomas, do not exhibit an increased risk for proximal neoplasia or proximal advanced neoplasia compared to those with no distal polyps. The discovery of hyperplastic polyps on screening sigmoidoscopy should not prompt colonoscopy.

They further emphasize the need to biopsy hyperplastic polyps during sigmoidoscopy to ensure that they were not adenomas.

It will be important for practitioners who perform screening sigmoidoscopies to biopsy distal polyps (as opposed to automatically referring all patients with distal polyps for colonoscopy).

More information about the study is available on [*Medscape*](http://www.medscape.com/viewarticle/516564)

There is general agreement that the benefits of beginning screening at age 50 for people of average risk of colorectal cancer outweigh its potential risks. However, it isn’t clear at what age risks no longer are balanced by benefits.

Whether or not screening will make a difference for an individual depends on age, other existing illnesses, and potential life expectancy. In addition, some older people may experience more complications during screening tests increasing their risk.

Researchers at the University of Washington in Seattle report an analysis of screening benefits in the elderly in the October 2005 issue of [*Gastroenterology*](http://www.gastrojournal.org/article/PIIS0016508505013910/abstract). Cynthia Ko and her team looked at men and women, aged 70 to 94 years of age with various health conditions and life expectancies. They determined the number of people it would be necessary to screen to prevent one colon cancer-related death and also the numbers necessary to encounter a complication for three different approaches to screening — annual fecal occult blood tests, flexible sigmoidoscopy every 5 years, or colonoscopy every 10 years.

For instance, one cancer-related death would be prevented by screening 42 healthy men aged 70–74 years with colonoscopy, 178 healthy women aged 70–74 years with fecal occult blood tests, 431 women aged 75–79 years in poor health with colonoscopy, or 945 men aged 80–84 years in average health with fecal occult blood tests. While colonoscopy had the greatest benefit, it also had the greatest risk of complications. However, at all ages and life expectancies, the potential reduction in mortality from screening outweighed the risk of colonoscopy-related death.

The study identified four groups of elderly people for whom screening with colonoscopy was likely to have more risk than benefit:

+ Women aged 70 to 79 years in poor health
+ Women aged 85 to 89 years in average health
+ Men aged 70 to 74 years in poor health
+ Men aged 90 to 94 years in good health

Dr. Cynthia Ko told [*Reuters Health*](http://today.reuters.com/news/newsArticle.aspx?type=healthNews&storyID=2005-11-15T183409Z_01_FLE566824_RTRUKOC_0_US-COLON-CANCER-SCREENING.xml&archived=False)

The decision to pursue screening should be individualized and should take into account a patient’s life expectancy, comorbidity, and preferences.

In an [accompanying editorial](http://www.gastrojournal.org/article/PIIS0016508505017506/fulltext) Carmen Lewis reminds readers that the study assumes information about life expectancy that may not be true for an individual and urges that information from the research be used to guide discussions between patients and their doctors in making screening decisions:

Ko and Sonneberg have provided important estimations helpful for individualized decision making for colorectal cancer screening in patients ages 70 and older. However, their findings are estimations based on average life expectancies of the US population. Physicians’ abilities to accurately estimate life expectancy for individual patients is poor and, at present, even calculated estimations are of questionable validity. Furthermore, patients may vary significantly in how they value the potential benefits from screening compared with the potential harms Therefore, this information should be used as an aid to help inform patients about the risks and benefits of colon cancer screening, and then with their physicians, patients can explore their personal values and make the decision that is right for them.

Mt. Sinai School of Medicine has begun [Phase I human immunology trials](http://www.cancer.gov/search/ViewClinicalTrials.aspx?cdrid=335463&version=Patient&protocolsearchid=1942444) of a special gene designed to enter cancer cells and make them visible to the human immune system. Patients with liver metastases from colorectal cancer are sought for the trial.

In laboratory animal studies, the treatment extended life for all animals with breast or colorectal cancers and completely destroyed all tumors in 20 to 30 percent of them.

During tumor immunization researchers are able to insert a gene into the cancer cell that tells the cell to produce Interleukin-12, a protein that is a powerful signal to particular white cells in the body’s immune system to destroy the cancer cell. Ordinarily, cancer cells are ignored by the immune system and are able to continue to grow unchecked.

In a [news release](http://fusion.mssm.edu/media/content.cfm?storynum=266) from Mt. Sinai,Savio Woo, Ph.D., Professor and Chairman of the Department of Gene and Cell Medicine at Mount Sinai School of Medicine, explained,

“Cancer cells are able to grow unimpeded by the body’s defenses because they look very similar to healthy cells, with only very subtle differences that pass under the radar screen of the body’s immune cells. We use gene transfer technology to insert an immune enhancing gene into the cancer cells that makes them visible to the body’s natural immune defenses.”

Max W. Sung, M.D is leading the clinical trial. He explains the procedure that will be used to inject the gene into a liver tumor,

“The procedure does not require surgery and is done with just local anesthesia to the skin, Using one to three needles, the disarmed virus harboring the IL12 gene is injected through the skin into a metastatic tumor in the liver. We perform an ultrasound exam at the same time to track the needles so that we can deliver the virus to the correct location. The entire procedure can be completed within half an hour.”

For more information on the clinical trial patients or their doctors should contact Vivian Mitropoulou at (212) 241-6046.

An article in [Science Daily](http://www.sciencedaily.com/releases/2005/11/051107083122.htm) has more information about immunology research at Mt. Sinai.