Clinical Abstracts From Overseas

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MULTIPLE SITES FROM AROUND THE WORLD

Effects of Preoperative Radiotherapy on Quality of Life

A randomized trial of 1350 patients with rectal cancer from Canada, New Zealand, South Africa, and the United Kingdom found that preoperative radiotherapy reduced the risk of recurrence but increased sexual dysfunction and bowel leakage.

Patients received either 1 week of radiation (25 Gy) prior to surgery or surgery followed by selective chemoradiation (45 Gy, 25 exposures over 5 wk) in patients with positive margins. The study noted a 4% reduction in the 3-year rate of recurrence for patients in the preoperative radiation arm compared with 11% for patients undergoing chemoradiation postoperatively. Additionally, the 5-year recurrence-free survival rate was higher in patients who underwent preoperative radiation.

Using questionnaires, researchers assessed patients’ quality of life over a 3-year period following completion of treatment. They obtained a baseline score at initiation of therapy and administered additional surveys every 3 months following treatment in the first year, then every 6 months for the remaining 2 years. Higher scores correlated to worse functioning.

At 3 months’ follow-up, both groups reported decreased physical functioning and male sexual function. At 6 months, men in the preoperative radiotherapy group reported poorer sexual function than men who underwent postoperative chemoradiation, and this trend persisted for the remainder of the study period. Although overall ratings of bowel function remained the same between both groups, patients who had preoperative radiotherapy reported a higher incidence of bowel incontinence, with 16.4% reporting that they had experienced “quite a bit” or “very much” unintentional release of stools, compared with 6.5% in the postoperative group (P = .003). Although the rate dropped at 24 months’ assessment, it remained higher for the preoperative therapy group.

Results may be affected by declining participation; 87% of patients participated at baseline, dropping to 43% by the end of the 3-year period. The study’s results indicate, however, that patients and their physicians must weigh the benefits of improved rate of recurrence- free survival associated with preoperative radiotherapy against the increased risks of diminished sexual and bowel function postoperatively.

Sebag-Montefiore D, et al. The impact of short course pre-operative radiotherapy on patients’ quality of life: data from the MRC CR07/NCIC CO16 randomised clinical trial in patients with rectal cancer. In: Proceedings from the 50th Annual Meeting of the American Society for Therapeutic Radiology and Oncology; September 22, 2008; Boston, MA; Abstract 61.

SWEDEN

How Countries in the European Union Rate on Uptake of New Oncology Agents

The speed at which member countries of the European Union approve marketing of the newest oncology agents—which are usually biologics—varies from country to country. Researchers from the Karolinska Institute, Stockholm, Sweden, used sales data from IMS Health Inc to track the uptake of newer agents across 27 countries over a 10-year period. The United Kingdom appeared to be the slowest in introducing new oncology drugs and consequently had the lowest use. The study suggests this is probably because of a provision that requires the National Institute for Cost Effectiveness to qualify the agent for coverage first.

Austria, Switzerland, and France demonstrated relatively quick access to the newest oncology products. The study observed the greatest use of new agents in France. At the start of the decade being evaluated, Spain appeared to introduce new products promptly, but over time, researchers report, this trend slowed somewhat. The study notes that although one might intuitively link the introduction of new products to improved clinical status and better cancer outcomes, a separate study that included detailed epidemiologic data would be needed to determine whether any correlation existed.

Wilking N. European disparities in access to cancer drugs. Paper presented at: 33rd European Society for Medical Oncology Congress; the annual meeting of the European Society for Medical Oncology; September 2008; Stockholm, Sweden.

CANADA

Undiagnosed Cancer in Patients with Unprovoked Thromboembolism

We know that patients with malignant tumors are at high risk for experiencing a venous thromboembolism (VTE). Is the reverse also true? Could an undiagnosed tumor be the cause of an unprovoked VTE? Researchers from the University of Ottawa conducted a retrospective review to quantify the risk of cancer in seemingly cancer-free patients who suffer a VTE. They also wanted to determine whether a VTE should be viewed as an indication that intensive cancer screening is warranted.

Researchers evaluated 36 studies concerning patients with a newly diagnosed unprovoked VTE and the prevalence of occult cancer diagnosed at baseline and at 6 and 12 months following VTE. The literature review also encompassed 14 articles and 1 abstract that met inclusion criteria for evaluating the benefit of limited cancer screening versus comprehensive testing in individuals with a VTE.

Across all 36 studies, 6.1% of patients who experienced an idiopathic VTE were found to have cancer at baseline. At 12 months post-VTE, the prevalence of diagnosed cancer increased to 10.0%. Investigators suggested that as many as 10% of patients with seemingly unprovoked VTE have undiagnosed cancer. They found that conducting extensive screening with abdominal and pelvic computed tomography scanning increased the rate of cancer detection by 41% compared with limited screening.

The study concluded that using an extensive cancer screening strategy identifies more cases of undetected cancer in patients with VTE than a regular, periodic screening strategy. Considering the relatively few cases of cancer found, the associated costs, and the impact of extensive cancer screening on cancer-free survival rates, however, the question remains as to whether it constitutes a cost-effective strategy for patients who suffer a VTE.

Carrier M, Le Gal G, Wells PS, et al. Systematic review: The Trousseau syndrome revisited: should we screen extensively for cancer in patients with venous thromboembolism?

2008;149(5):323-333.

Ann Intern Med.

ITALY

Patients with Cancer May Benefit from Mediterranean Diet

For purposes of this study, researchers considered the ‘Mediterranean diet’ to be one rich in olive oil, grains, fruits, nuts, fish, and vegetables, with moderate intake of red wine. Italian researchers have confirmed the benefits of this diet for people with chronic diseases and cancer.

Nutritional scientists and physicians from Florence conducted a meta-analysis of 12 studies on dietary habits and health, examining data for 1.6 million enrollees. The health of these individuals was tracked anywhere from 3 to 18 years. Greater adherence to a Mediterranean diet over the assessment period correlated to a 9% reduction in the overall mortality rate. The reduction in cancer rates was a more modest 6%, but this outcome was statistically significant (P <.001). The authors did not evaluate whether there were any discernible relationships between the diet and specific types of cancer.

The level of benefit derived from a Mediterranean diet seemed to correlate directly with the degree to which an individual adhered to the diet; the more closely individuals adhered to the key components of the diet, the lower their risk of mortality due to certain diseases. Ensuring sufficient population-wide adherence to the Mediterranean diet is a daunting obstacle. As the authors note, “Despite this worldwide promotion of the Mediterranean diet, a progressive shift to a non—Mediterranean dietary pattern, even in countries bordering the Mediterranean Sea, has progressively developed.”

Sofi F, Cesari F, Abbate R, et al. Adherence to Mediterranean diet and health status: metaanalysis.

2008;337:a1344.

BMJ.

NORWAY

Cholesterol Drug Combination’s Link to Cancer Unclear

At a recent cardiology conference held in Munich, Germany, researchers from Norway and the United Kingdom presented studies that attempted to clarify the apparent link between cancer and the use of combined simvastatin/ezetimibe to treat high cholesterol. Neither study offered clear results.

The Norwegian SEAS (Simvastatin and Ezetimibe in Aortic Stenosis) study¹ included 1873 patients who experienced coronary valve malfunction. Patients received the combination drug or placebo to lower their cholesterol in an effort to determine whether this would prevent future cardiac problems. In the drug cohort, 105 patients (11.1%) developed cancer compared with 70 (7.5%) in the placebo group (P = .01).

Following this, Dr Richard Peto, PhD, a biostatistician from Oxford University in the United Kingdom, and colleagues conducted a meta-analysis² of data from two UK trials: IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) and SHARP (Study of Heart and Renal Protection). IMPROVE-IT randomized patients to receive combination simvastatin/ezetimibe or simvastatin alone, and SHARP randomized patients to the combination drug or placebo. Peto et al found that fewer patients treated with the ezetimibe combination developed cancer (313 vs 326, respectively; P = .061), although the ezetimibe cohorts reported more deaths due to cancer (97 vs 72; P = .07), but this was not a significant excess.

When factoring in the data from SEAS, Peto and associates noted that the overall higher rate of cancer development in the ezetimibe arm did not meet statistical significance. Dr. Peto said, “The available results from these 3 trials do not provide credible evidence of any adverse effect of ezetimibe on rates of cancer.” Nor did any of the trials note significant excess at any particular tumor site. Despite a nominally significant increase in cancer deaths among patients taking ezetimibe, Peto et al found no evidence of a trend in the risk ratio for incidence of death from cancer with increasing duration of follow-up. The authors of both studies suggested that any increase in the incidence of cancer or the number of cancer deaths in the ezetimibe cohorts was likely due to chance.

¹Rossebo AB, Pederson TR, Boman K, et al. Intensive Lipid Lowering with Simvastatin and Ezetimibe in Aortic Stenosis.

2008;359(13):1343-1356.

²Peto R, Emberson J, Landry M, et al. Analyses of cancer data from three ezetimibe trials.

2008;359(13):1357-1366.

NEJM.

NEJM.

SWEDEN

Increased Cancer Risks Uncovered for Patients with Ulcerative ColitisMost gastroenterologists recognize that patients with ulcerative colitis (UC) have an increased risk for colorectal and liver cancers and leukemias. This has sparked recommendations that patients with UC undergo screenings for colorectal cancer more frequently. Swedish epidemiologists wondered whether patients with UC were also at greater risk for other malignancies and found that they were—but only if they had been hospitalized for UC.This long-term follow-up trial used the Swedish Hospital Discharge Registry and the Swedish Cancer Registry to track 27,606 patients hospitalized for UC over a 40-year span, from 1964-2004. A total 2058 patients developed cancer, indicating an overall increased risk for cancer of 46% and an excess risk 1 year after hospitalization of 29%. Compared to patients who were never hospitalized for UC, patients with the disorder demonstrated increased risk for tumors of the breast, pancreas, and prostate; nonthyroid endocrine gland tumors; non- Hodgkin lymphoma; multiple melanoma; and small intestinal carcinoids.

A patient’s degree of risk for a particular cancer type depended largely on age at first hospitalization for UC. Patients aged <25 years were more likely to develop colorectal, hepatobiliary, and pancreatic cancers than patients aged >25 years when first hospitalized for UC. Patients aged >64 years at the time of first hospitalization were at greater risk for endocrine tumors than for the other cancer types identified.Researchers emphasize that the increased risks apply only to patients hospitalized for UC. They also caution that the greater surveillance these particular patients with UC received may have contributed to an increased rate of diagnosis.

Hemminki K, Li X, Sundquist J, et al. Cancer risks in ulcerative colitis patients.

2008;123(6):1417-1421.

Int J Cancer.

AUSTRALIA

Room for Improvement in Lung Cancer Care

Lung cancer accounts for the greatest number of cancer deaths Down Under, but population-wide information on the treatment patients with lung cancer receive has been lacking. Using a national cancer registry, researchers from the University of New South Wales in Australia evaluated how care was managed for these patients and whether access to care was an issue.

They obtained details on care management for 1812 patients who received a lung cancer diagnosis in the 13-month period from November 2001-December 2002. The sample comprised 66% men and 33% women, with a median age of 71 years. In total, 71% had non— small cell lung cancer and 15% had small-cell tumors; pathology was unconfirmed for 13% of patients.

Post-diagnosis, only 10% of patients did not see a lung cancer specialist after diagnosis and one-third did not receive cancer-specific treatment. Women, older patients, those with advanced disease, or patients who failed to consult with a lung cancer specialist were among those who did not get treatment specific to a diagnosis of lung cancer.

In total, 39% of patients underwent radiotherapy, 30% used chemotherapy, and 17% had surgical excision; the remaining patients received multimode therapy. Median survival from the time of initial diagnosis was 172 days, and unadjusted median survival at 2 years was only 17%.

Researchers caution that because the data used was from 2001-2002, it may not reflect up-to-date approaches for treating lung cancer. The study concludes that many Australians with lung cancer have not been receiving cancer-specific therapy, although the treatment patterns observed generally followed national guidelines.

Vinod SK, O’Connell DL, Simonella L, et al; Collaboration for Cancer Outcomes, Research, and Evaluation (CCORE). Gaps in optimal care for lung cancer. J Thorac Oncology. 2008;3(8):871-879.

ITALY

New Cervical Cancer Test Outperforms Pap Smear

Testing for the biomarker protein p16-INK4A may be an efficient way to test for cervical cancer cells and may someday supplant the standard Papanicolaou test (Pap smear). Investigators from the New Technologies for Cervical Cancer Working Group in Italy found that testing for the biomarker protein p16-INK4A in conjunction with human papillomavirus (HPV) testing had 88% sensitivity and 61% specificity, overall. The combination test also returned a low false-positive rate, which has long been the Achilles heel of conventional cytology.

Researchers administered the biomarker test to 1137 women who tested positive for HPV in a 2004 study on the efficacy of HPV testing (N = 24,500). HPV testing has been found to have greater sensitivity than Pap smears in detecting cervical intraepithelial neoplasia but less specificity. Adding p16-INK4A testing improved specificity of HPV testing.

Researchers emphasize that using the tests together may translate to a 1.5-fold increase in the number of high-grade cervical intraepithelial neoplastic lesions detected when compared with the Pap smear and reduce the number of women referred unnecessarily for colposcopy.

Carozzi F, Confortini M, Palma PD, et al. Use of p16-INK4A overexpression to increase the specificity of human papillomavirus testing: a nested substudy of the NTCC randomised controlled trial.

2008; [E-pub ahead of print].

Lancet Oncology.