© 2001 by Oxford University Press
Journal of the National Cancer Institute, Vol. 93, No. 8, 571,
April 18, 2001
© 2001 Oxford University Press
IN THIS ISSUE |
The poor survival rates of patients with stage I non-small-cell lung cancer (NSCLC) following surgical treatment are primarily due to second primary tumors (SPTs) and recurrences. In a phase III randomized trial, Lippman et al. (p. 605) compared NSCLC patients who received the retinoid isotretinoin with those who received placebo to determine the efficacy of this chemopreventive agent in preventing SPTs and recurrences and reducing overall mortality. The authors found no statistically significant differences between the placebo and isotretinoin arms of the study with respect to any of these three end points. However, they unexpectedly found a statistically significant interaction between isotretinoin and smoking. The authors concluded that isotretinoin was ineffective in preventing SPTs in NSCLC and suggest that isotretinoin may be harmful in current smokers and beneficial in never smokers.
Optimizing Intravesical Therapy for Bladder Cancer
Patients at high risk for recurrence after surgical removal of superficial bladder cancer are often given intravesical chemotherapy with mitomycin C as adjuvant therapy. In this procedure, the drug is delivered directly into the bladder. In an attempt to improve on standard treatment, Au et al. (p. 597) developed a new protocol designed to enhance the drug’s concentration in urine and thereby increase delivery to tumor cells. The authors describe results from a randomized trial comparing their optimized treatment with the standard treatment. They report that patients in the optimized arm had a longer median time to recurrence and a greater recurrence-free fraction than patients in the standard arm. Moreover, improvements were found in all risk groups defined by tumor stage, grade, focality, and recurrence, and they were achieved without a clinically significant increase in toxicity.
In an accompanying editorial, Montie (p. 572) points out that Au et al.’s study population was heterogeneous with respect to stage and grade. He notes that, although delay in recurrence may be an important end point for patients with low-grade bladder cancer, the desired end point for patients with high-grade cancers is the elimination of the cancer. Thus, he suggests, Au et al.’s results may be most appropriately applied to patients with low-grade and noninvasive cancers.
Second Cancers in Childhood Cancer Survivors
More effective therapies for childhood cancers have resulted in a substantial increase in the number of childhood cancer survivors. Understanding the degree to which these survivors are at increased risk for second cancers later in life is important. Neglia et al. (p. 618) addressed this question by looking at a cohort of more than 13,500 childhood cancer patients, who survived at least 5 years after diagnosis. The estimated cumulative incidence of a second cancer 20 years after the childhood cancer diagnosis was 3.2%. After adjusting for exposure to radiotherapy used in the treatment of the childhood cancer, the authors found that the risk of second cancers of any type was associated with female sex, diagnosis of a childhood cancer at a younger age, or a diagnosis of Hodgkin’s disease. Although only 1.9 excess cancers occurred per 1000 years of patient follow-up, the authors conclude that patients and health care providers must be aware of the risk factors so surveillance and prevention strategies are appropriately implemented.
"The success in treating children with cancer should not be overshadowed by the incidence of second malignant neoplasms."
—Neglia et al.
Lymph Node Staging by Positron Emission Tomography
Removing axillary lymph nodes for histologic examination for metastases is used to determine whether adjuvant treatment is necessary for patients with breast cancer. However, at least 80% of patients with tumors of 20 mm or less have negative lymph nodes and might avoid lymph node removal if an alternative method to identify such patients were available. In this issue, Greco et al. (p. 630) evaluate whether positron emission tomography with 2-[18F]fluoro-2-deoxy-D-glucose (FDG-PET) could be used. They found that FDG-PET appears to be an accurate noninvasive technique to predict axillary status in patients with breast cancer and identify patients who could avoid having their axillary lymph nodes removed. The authors encourage multicenter studies to confirm their results.
COX2 and Colon Cancer
Colon cancer was one of the first cancers for which highly penetrant disorders resulting from mutations in single genes—including APC and DNA mismatch repair genes—were identified. More recently, cyclooxygenase 2 (COX2), which catalyzes a step in the synthesis of prostaglandins, has been shown to play a role in colon cancer development in mice and humans. Wiesner et al. (p. 635) hypothesized that the gene encoding COX2 might exhibit variability that could affect risk of colon cancer. The investigators used polymorphic markers flanking the COX2 locus to examine the likelihood that a common parental COX2 allele was shared among pairs of siblings in which both siblings had developed colon cancer or precancerous adenomas. By entering these data into a genetic model, the investigators conclude that the COX2 gene does not appear to be associated with colon cancer in either a dominant or recessive inheritance pattern.
Familial Risk of Pancreatic Cancer
Although pancreatic cancer is the fifth leading cause of cancer-related deaths in the United States, smoking and increasing age are its only known risk factors. Schenk et al. (p. 640) conducted in-person interviews in a case–control study to determine whether a family history of pancreatic cancer increased the risk for pancreatic cancer in first-degree relatives. The authors found that a positive family history of pancreatic cancer increased the risk of pancreatic cancer approximately twofold. For ever smokers with a family history of pancreatic cancer diagnosed before age 60 years, the authors found that the risk of pancreatic cancer was approximately eightfold. The authors conclude that routine questioning of patients about their family history of pancreatic cancer may help identify individuals at high risk for the disease.
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