Cisplatin No Better than Standard Therapy for Anal Canal Cancer

Replacing mitomycin with cisplatin in chemoradiotherapy for cancer of the anal canal failed to improve either disease-free or overall survival and resulted in more patients needing colostomies, according to a study in the April 23 issue of the Journal of the American Medical Association.

Current standard therapy for anal canal cancer consists of fluorouracil plus mitomycin and radiotherapy. Previous studies have established that chemoradiation is more effective for smaller tumors. Researchers wondered whether initial chemotherapy with fluorouracil and cisplatin could improve outcomes by shrinking tumors before they were treated with the same agents and radiotherapy.

In this randomized phase III clinical trial, 644 patients with anal canal cancer received standard treatment with fluorouracil plus mitomycin and concurrent radiotherapy or induction chemotherapy with fluorouracil plus cisplatin, followed by concurrent treatment with fluorouracil, cisplatin, and radiation.

After a median follow-up of 2.5 years, the estimated 5-year disease-free survival rate was 60 percent for patients in the mitomycin group, compared with 54 percent in the cisplatin group. Estimated rates of overall survival, local recurrence, and distant metastasis were all worse for patients in the cisplatin group. In addition, at 5 years an estimated 19 percent of patients who received cisplatin needed colostomies, compared with 10 percent of patients who received mitomycin.

"These findings do not support the use of cisplatin in place of mitomycin in combination with fluorouracil and radiotherapy in the treatment of anal canal carcinoma," conclude principal investigator Dr. Jaffer A. Ajani of the University of Texas M.D. Anderson Cancer Center and his colleagues.

Ovarian Epithelial Tumors Traced to Fallopian Tubes

Researchers at Dana-Farber Cancer Institute have found that the source of disease in many cases of the most aggressive form of ovarian cancer, serous carcinoma, may not be the ovary at all, but rather the fimbria of the fallopian tube. Dr. Keren Levanon reported these findings at the American Association for Cancer Research annual meeting on April 14.

"Until now, there was no understanding of the basic pathogenesis or carcinogenesis of [ovarian] serous carcinoma," said Dr. Levanon at the meeting. Noting that the majority of ovarian cancers are diagnosed at an advanced stage, she continued: "We didn't really know what the early cancer lesion or precursor lesion looks like, so we couldn't analyze what went wrong."

Her team, which included collaborators at Brigham and Women's Hospital, searched for these early lesions by identifying cells with a "p53 signature" - mutations in the p53 gene and buildup of p53 protein in cells - in the tissues of women who, due to a high risk for developing ovarian and other cancers, volunteered to have their ovaries and fallopian tubes removed.

The team found a p53 signature most often in the secretory cells lining the finger-like appendages, called fimbria, at the ends of fallopian tubes. Dr. Levanon's team then developed an ex vivo model that they are using to continue studying these cells and the molecular events that lead to cancer. They hope this research will lead to targeted therapies and biomarkers for early detection.

Though they were surprised by their findings, explained Dr. Levanon, they were not surprised that ovarian cancer could begin in the fallopian tubes. "When we look at patients who are diagnosed with later-stage ovarian cancer," she said, "we find that they have these lesions in their fallopian tubes in close to 100 percent of cases." She also noted that patients who have prophylactic surgery to remove their ovaries sometimes develop tumors in other parts of their abdomen, which could result from shed cancer cells when the fallopian tubes are left intact.

Prognostic Test for Breast Cancer Profiles the Tumor Environment

Researchers have developed an experimental prognostic test for breast cancer based on the activity of 26 genes in the stroma of breast tumors - the connective tissue surrounding the tumors. The test provides information that is independent of other prognostic indicators, such as clinical tests and tumor gene signatures, Dr. Morag Park of McGill University and her colleagues reported online April 27 in Nature Medicine.

The role of the local tumor environment in promoting cancer is of great interest, but few studies have addressed how changes occurring in tumor stroma affect disease outcome.

The researchers developed and tested the 26-gene signature using tissue samples and clinical data from three large breast cancer databases. The results suggest that changes in breast tumor stroma play a crucial role in the progression and outcome of the disease.

In one analysis, the researchers detected an increase in the activity of certain immune-related genes in stroma samples from patients who were classified as having "good outcomes." These individuals may benefit from treatments that target tumors via the immune response, such as vaccine therapies in the adjuvant setting, the researchers say.

Combining the 26-gene stroma signature with other gene signatures improved the prediction of clinical outcomes beyond that achieved by using individual molecular signatures. These findings highlight the need to integrate all aspects of the tumor microenvironment into prognostic prediction, the authors conclude.

Pesticide Linked to Testicular Cancer Risk

Males exposed to a byproduct of the pesticide DDT may have an increased risk of testicular cancer, according to research published online in the Journal of the National Cancer Institute April 29. Blood levels of DDE, the main persistent metabolic product of DDT, were higher in a sample of American men with testicular germ cell tumors (TGCT) than in other men. This relatively rare cancer is often treatable, especially when detected early.

The U.S. banned DDT in 1973, but the pesticide continues to be used elsewhere. The chemical and its metabolites are stored in fat tissue and can accumulate, for instance, in humans and in fish. "While levels have declined in the population since the 1970s, DDE remains detectable in the majority of Americans," said lead investigator Dr. Katherine A. McGlynn of NCI's Division of Cancer Epidemiology and Genetics. "This study suggests that chemicals that persist in the environment may have effects years after their usage ceases."

A link between pesticides and testicular cancer was proposed decades ago, but testing the hypothesis has been a challenge because the disease is rare. The researchers studied 739 U.S. servicemen with TGCT and 915 healthy men who had provided blood samples to the Department of Defense, on average, 14 years before the current analysis.

The men in the group with the highest blood levels of DDE were 1.7 times more likely to develop TGCT than men with the lowest concentrations. If the risk estimates are correct, then DDT exposure could account for 15 percent of TGCT cases in the study.

DDT belongs to a family of organochlorine pesticides that may disrupt the body's endocrine system. "Because evidence suggests that TGCT is initiated in very early life, it is possible that exposure to these [pesticides] during fetal life or via breast feeding may increase the risk of TGCT in young men," the researchers write.