Immune Response in Colorectal Tumors Linked to Longer Survival

European researchers are reporting that increased levels of a specific family of immune cells in colorectal cancer tumors independently correlate with better progression-free and overall survival. Writing in the December 22 NEJM, the researchers also demonstrated that existence of any one of three pathologic signs of early metastatic disease - vascular emboli and lymphatic or perineural invasion, collectively known as VELIPI - inversely correlated with progression-free and overall survival.

The study, led by Dr. Jerome Galon from the French research institute INSERM, involved an analysis of tissue samples from 959 patients who had undergone surgery to treat their cancer.

In 415 samples analyzed using tissue microarray, a large volume of effector memory T cells, in particular CD45RO+ cells, was associated with a superior clinical outcome compared with those with low levels: a median disease-free survival of 36.5 months and overall survival of 53.2 months, compared with 11.1 months and 20.6 months, respectively.

"VELIPI-negative tumors contained high numbers of CD450RO+ cells as compared to VELIPI-positive tumors," the researchers wrote. "In addition, a high density of memory T cells was associated with tumors without lymph node involvement and metastases."

According to Dr. Mac Cheever, on special assignment in NCI's Division of Cancer Biology, it's no surprise that increased overall survival was correlated with VELIPI absence. "What is new and remarkable is the degree to which it was correlated with the presence of tumor-infiltrating memory T cells," he said.

The results confirm the importance of an immune response in patient outcomes, he continued. "The data strongly imply that many cancers now cured by surgery are curable - that is, VELIPI-negative - only because of an ongoing immune response discernable at the time of diagnosis," Dr. Cheever said. "These studies help to validate the substantial current investment in therapeutic vaccines and also should stimulate an even greater interest in preventive vaccines."

Letrozole Superior to Tamoxifen for Breast Cancer

Tamoxifen was the first widespread hormone treatment for breast cancer, and has been targeted toward postmenopausal women with estrogen receptor-positive tumors with great success for nearly 20 years. Aromatase inhibitors are now beginning to supplant tamoxifen as standard hormone therapy, and results from a large international trial (BIG 1-98) involving more than 8,000 postmenopausal women from 27 countries show that letrozole (Femara) is better at preventing breast cancer recurrence and metastasis. The trial results were published in the December 29 NEJM.

The study authors wrote that "particularly notable was our finding of a significant reduction in the risk of distant recurrence" - 27 percent in favor of letrozole patients. They were also 19 percent less likely to relapse.

In an accompanying editorial, Dr. Sandra Swain of NCI's Center for Cancer Research noted that 5 other large clinical trials had evaluated aromatase inhibitors in almost 30,000 women, with largely positive results. She also commented that aromatase inhibitors are "critically important for improving the outcome among postmenopausal women with breast cancer who have positive or negative lymph nodes and who are at substantial risk for recurrent disease."

Many patients may still continue to rely on tamoxifen because of cost and different side effects. Tamoxifen still produced an 81.4-percent rate of disease-free survival at 5 years. Letrozole increased arthritis, bone fractures, and cardiac events, while blood clots and endometrial cancer were more likely with tamoxifen.

Analyses of Lymphoma Incidence Trends by Subtype Suggest Priorities for Future Research

NCI researchers found striking differences in incidence patterns and time trends by lymphoma subtype, age, sex, and race/ethnic group in a large U.S. population-based assessment published in the January 1 issue of Blood.

Although lymphoma is the fifth most common category of neoplasms in the United States, the causes of this group of diseases are largely unknown, noted scientists from NCI's Division of Cancer Epidemiology and Genetics (DCEG). The researchers analyzed almost 115,000 lymphoma cases diagnosed between 1992 and 2001 in 12 Surveillance, Epidemiology, and End Results (SEER) registries. The researchers used the 2001 World Health Organization lymphoma classification system in their analysis.

"Analyses of the incidence patterns and trends of the lymphoma subtypes in the general population can provide us with clues regarding etiology and suggest promising areas for future research," said Dr. Lindsay Morton, DCEG research fellow and lead author on the study.

For example, during the 10-year period, rates of diffuse large B-cell lymphoma and follicular lymphoma in the elderly increased 1.4 percent and 1.8 percent per year, respectively, whereas rates for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) declined 2.1 percent per year, suggesting that exposures to the still unknown causes of these lymphoma subtypes may have changed. The investigators also noted variation in the incidence of lymphoma subtypes by age. "These age differences suggest that the timing of key exposures may differ by subtype," Dr. Morton noted.

The study also included the first comprehensive analysis of lymphoma incidence patterns among Asian Americans, showing considerably lower rates for CLL/SLL and Hodgkin lymphoma. In contrast, whites had the highest burden for most subtypes, especially hairy cell leukemia and follicular lymphoma, whereas African Americans had the highest rates for plasma cell and T-cell lymphomas.

Cervical Cancer Cells Can Cause Trouble Years Later

Years after treatment for cervical cancer, some women experience cancerous or precancerous lesions of the vulva and vagina. These lesions can be caused by cervical cancer cells that migrate and lay dormant in the lower genital tract, according to research published in the December 21 Journal of the National Cancer Institute.

Researchers from the University of Heidelberg in Germany canvassed 1,500 women with a history of cervical cancer and found 21 who developed vaginal or vulvar cancer or precancerous lesions from 3 to 12 years after treatment - usually hysterectomy. The researchers compared tissue samples from seven of the women with tissue taken from the new lower genital tract lesions.

In six of the cases, the cells of both samples contained identical signatures of human papillomavirus (HPV) infection. HPV causes cervical and genital lesions when the virus integrates into the genome of epithelial cells. But because it invades the genome at a random location, the researchers could say with certainty that cells showing HPV at the same location in the genome sprang from the same population of early cancer cells.

They conclude that the late-onset vaginal and vulvar lesions arose after a population of cells broke from the original cervical lesion early, migrated, and lay dormant.