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© Oxford University Press 2008.
IN THIS ISSUE
Hepatitis B Virus Genotypes and Mutants and Risk of HCCThe risk of hepatocellular carcinoma (HCC) increases with increasing serum level of hepatitis B virus (HBV). However, it is unclear whether HBV genotype and/or common variants in the precore and basal core promoter (BCP) regions of the HBV genome also contribute to the risk of HCC. Yang et al. (p. 1134) estimated the incidence of HCC in association with HBV genotype and precore and BCP mutants for 2762 Taiwanese men and women participated in a community-based cohort study with long-term follow-up. The participants were seropositive for HBV surface antigen but had not been diagnosed with HCC. HBV genotype C and the BCP A1762T/G1764A double mutant were independent risk factors for HCC, and the precore G1896A mutant was associated with a decreased risk of HCC. The authors suggest that knowledge of an individual's HBV genotype and precore and BCP mutation status, in addition to other factors, including age, sex, and serum HBV level, may help identify those who are at an increased risk for liver disease progression.
In an editorial, Llovet and Lok (p. 1121) discuss improvements over the last two decades in the prevention and treatment of HCC as well as in the early detection of HCC in the West due to the wide implementation of surveillance programs. They suggest that large randomized controlled trials of antiviral agents for the treatment of chronic HBV infection should stratify patients by the main risk factors for HCC tumor development, including HBV genotype and relevant mutations.
Prostatectomy vs Watchful Waiting: Extended Trial Follow-up
Only one randomized trial (the Scandinavian Prostate Cancer Group-4 [SPCG-4]) has compared the effect of prostatectomy with that of watchful waiting among men with early prostate cancer. In 2005, after a median follow-up of 8.2 years, men who underwent prostatectomy had lower prostate cancer mortality. Now, Bill-Axelson et al. (p. 1144) report data from the SPCG-4 after a median follow-up of 10.8 years. The percentages of men who had died from any cause in each group (137 of 347 [39.5%] in the prostatectomy group and 156 of 348 [44.8%] in the watchful waiting group) were not statistically significantly different, but prostate cancer–specific mortality (13.5% vs 19.5%) and diagnosis of distant metastases (19.3% vs 27.6%) were statistically significantly lower in the prostatectomy group. The differences in cumulative incidence of death from any cause, prostate cancer death, and distant metastases did not increase after 10 years. At 12 years, the cumulative incidence of overall mortality was 32.7% in the prostatectomy group and 39.8% in the watchful waiting group, that of prostate cancer mortality was 12.5% vs 17.9%, and that of distant metastasis was 19.3% vs 26%.
In an editorial, Wilt (p. 1123) summarizes the controversy and questions surrounding treatment options for localized prostate cancer. He discusses how the SPCG-4 data answer some of the questions and expresses hope that these data and data from other currently ongoing trials will direct evidence-based care in the future.
Breast Cancer Recurrence after Adjuvant Therapy
Adjuvant systemic therapy improves the survival of breast cancer patients, but many are still at risk of disease recurrence. Extended adjuvant hormone-targeted therapy improves disease-free survival of women with hormone receptor–positive breast cancers, but more data are needed to identify which women are at high risk of recurrence and should receive extended therapy and which women are not. To identify prognostic information to distinguish which breast cancer patients are at high risk of relapse after adjuvant therapy, Brewster et al. (p. 1179) evaluated data from more than 2800 patients with stage I–III breast cancer who were treated with adjuvant systemic therapy from January 1995 to November 2001 and were cancer-free 5 years after treatment began (the landmark). A total of 216 of the women had disease recurrence 10 years after the landmark time. The risk of recurrence 5 years after the landmark time among patients with stage I tumors was 7%, for stage II it was 11%, and for stage III it was 13%. Grade, hormone receptor status, and adjuvant hormone–targeted therapy were also associated with recurrence risk.
Treatment of Cancer-Related Fatigue
Cancer-related fatigue is an important clinical problem, but the role for drug treatment of cancer-related fatigue is not well defined. Minton et al. (p. 1155) conducted a systematic review and meta-analysis of the available evidence and have made recommendations for clinical practice and research. They identified 27 eligible trials of drug treatments for cancer-related fatigue (with a total of 6746 participants). Although the overall effect size for all drug classes was small, the authors found some evidence that methylphenidate, a stimulant, and hematopoietic agents relieved cancer-related fatigue. Progestational steroids and paroxetine were no better than placebo, however. The authors conclude that further research is required to investigate the ability of methylphenidate and hematopoietic agents to treat cancer-related fatigue.
Antitumor Effects of Doxorubicin Followed by Zoledronic Acid
The bisphosphonate zoledronic acid (Zol) is a potent inhibitor of osteoclastic bone resorption that has also been found to enhance the antitumor effects of chemotherapy agents, both in vitro and in in vivo cancer models with a high degree of tumor-induced bone disease. Using a mouse model, Ottewell et al. (p. 1167) investigated the effects of clinically achievable doses of doxorubicin (Dox) and Zol given alone, in sequence, and in combination, on the growth of subcutaneous tumors derived from a human breast cancer cell line. Mice treated simultaneously with Zol and Dox had smaller final tumor volumes than those treated with Dox alone, with Zol alone, or with Zol followed 24 hours later by Dox. Treatment with Dox followed 24 hours later by Zol almost completely abolished tumor growth. No evidence of bone disease was detected in any of the treatment groups. The authors suggest that patients with early-stage breast cancer may benefit from treatment that combines zoledronic acid with cytotoxic agents.
Incidence of Adenocarcinoma of the Esophagus Among Whites
Rapid increases in the incidence of adenocarcinoma of the esophagus have been reported among white men. Brown et al. (p. 1184) used data from the Surveillance, Epidemiology, and End Results program from January 1, 1975, through December 31, 2004, to explore the temporal patterns of this disease among white individuals by sex, stage, and age. A total of 22,759 patients with esophageal cancer were identified, of whom 9526 were diagnosed with adenocarcinoma of the esophagus. Adenocarcinoma incidence rates rose over the study period among white men and women regardless of stage and age. The authors conclude that the stage and age independence of the rates indicates that the increases are likely to be real and not an artifact of surveillance.
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J Natl Cancer Inst 2008 100: 1184-1187.
J Natl Cancer Inst 2008 100: 1179-1183.
J Natl Cancer Inst 2008 100: 1167-1178.
J Natl Cancer Inst 2008 100: 1134-1143.
J Natl Cancer Inst 2008 100: 1155-1166.
J Natl Cancer Inst 2008 100: 1144-1154.
J Natl Cancer Inst 2008 100: 1123-1125.
J Natl Cancer Inst 2008 100: 1121-1123.
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