Children Often Develop Fragile Bones from Cancer and its Treatment

Research suggests that children treated for cancer are at greater risk years later for bone problems such as osteoporosis and fractures. An article in the April 1 issue of Cancer marshals evidence from a variety of studies and sources, leading its authors to conclude that "loss of bone mineral is clearly a common consequence of the treatment of cancer in children and adolescents."

A number of factors appear to contribute, argue Drs. Alessandra Sala and Ronald D. Barr of McMaster University in Hamilton, Ontario. A major factor is multiagent chemotherapy with drugs such as methotrexate and ifosfamide that "have been labeled as especially toxic to bone," yet are commonly used to treat soft tissue and bone tumors. Cranial radiation therapy for children with brain tumors and some of the leukemias and lymphomas can sometimes trigger growth hormone disorders that compromise bone formation. Acute lymphoblastic leukemia is one of the most common childhood cancers, where the disease itself may compromise bone density, and where cumulative doses of glucocorticosteroid treatments most definitely do.

In all of these situations, the heightened physical activity that usually occurs in childhood is hindered, impeding patients' ability to accumulate the bone mineral density necessary to avoid osteoporosis in adulthood.

The authors conclude that reduced bone density in "children with cancer is of multifactorial origin, requiring comprehensive strategies for amelioration and prevention." Possible agents that warrant further study are the bisphosphonates and imatinib. Other strategies include more physical exercise, limiting the total cranial radiation dose, and overcoming calcium and vitamin D dietary deficiencies.

Strenuous Long-Term Physical Activity Lowers Risk of Breast Cancer

California researchers have found that strenuous long-term physical activity decreases a woman's risk of invasive and in situ breast cancer, according to study results published in the February 26 Archives of Internal Medicine.

Dr. Leslie Bernstein of the University of Southern California and colleagues evaluated 107,034 participants from the NCI-funded California Teachers Study, a prospective study of current and retired female California public school teachers and administrators established in 1995-1996. Researchers collected information on the participants' level of physical activity - moderate or strenuous - between high school and their current age (or age 54, if the participant was 55 or older), as well as activity in the past 3 years.

Women who annually participated in more than 5 hours per week of strenuous activity had a lower risk of invasive breast cancer compared with the least active women. Long-term moderate activity and strenuous and moderate activity in the past 3 years were not associated with invasive breast cancer. Researchers also found that women who participated in long-term strenuous or moderate physical activity had a decreased risk of ER-negative invasive breast cancer, but not of ER-positive invasive breast cancer.

Participants had also reported information on relevant breast cancer risk factors, including race/ethnicity, family history of breast cancer, age at menarche, reproductive history, menopausal status, use of hormone therapy and oral contraceptives, height, weight, diet, smoking history, alcohol consumption, mammography screening history, and breast biopsy history. However, these factors did not account for the relationship between exercise and breast cancer.

The authors noted, "In summary, these results provide additional evidence supporting a protective role for long-term strenuous recreational physical activity on risk of invasive and in situ breast cancer, whereas the beneficial effects of moderate activity are less clear."

Radiation and Chemo Before Esophageal Cancer Surgery Improves Survival

A significant survival benefit was evident for the preoperative (neoadjuvant) use of combination chemoradiotherapy and, to a lesser extent, for chemotherapy alone in patients with localized esophageal cancer in a meta-analysis of data from numerous clinical trials that was published online February 15 in Lancet Oncology.

Traditional management of patients with localized esophageal cancer has been by surgical resection alone; however, "survival is poor…and many patients develop metastatic disease or locoregional recurrence soon after surgery," noted the researchers, led by Dr. Val Gebski of the National Health and Medical Research Council Clinical Trials Centre at the University of Sydney in Australia. Because of the high rate of surgical complications, "focus has turned to neoadjuvant treatment" as a way to improve survival, they added.

The meta-analysis included 10 randomized comparisons of neoadjuvant chemoradiotherapy versus surgery alone (1,209 patients) and 8 studies of neoadjuvant chemotherapy versus surgery in 1,724 patients.

Results for chemoradiotherapy studies showed a 13-percent absolute improvement in survival at 2 years, with similar results for different tumor types: squamous cell carcinoma (SCC) and adenocarcinoma. Analysis of the neoadjuvant chemotherapy studies indicated a 2-year absolute survival benefit of 7 percent. Chemotherapy had no significant effect on all-cause mortality for patients with SCC, although there was a significant benefit for those with adenocarcinoma.

Most of the studies included in the meta-analysis were started before 1994. "[C]urrent trials have used higher doses of radiation (typically 50 Gy) that are likely to result in better downstaging of overt tumours as well as death of micrometastases," the researchers added.