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Vol 102 Issue 2 Summary Transcript

Hi and welcome to the JNCI podcast, a production of the Journal of the National Cancer Institute. I’m Steve Graff, JNCI’s assistant news and media editor, and I’ll be taking you through issue 2.

Up first: When is cancer care cost-effective? In this issue’s review, researchers provide a systematic overview of cost utility analysis in oncology. Also, an article and accompanying editorial look at the prevalence of right-sided tumors vs. left-sided ones after colonoscopies. This issue also includes studies on the effects of gain-framed messages in smoking quitlines, the paracrine pathway and its role in pancreatic cancer cell invasion, and the risks of pancreatic cancer within families. And finally, in this issue’s brief communication, researchers found that knockdown of transcription factor E2F1 reduces the invasive potential of melanoma cells.

All that in more detail coming up next….

As the cost of cancer treatment has grown over time, so has the number of cost-effectiveness studies. Cost–utility analyses (CUAs) of cancer-related interventions have received increased attention in the medical literature and are being used to inform reimbursement decisions in many health-care systems.

In a review of the literature published online January 7, researchers compiled data from 242 cancer-related cost-utility analyses that were published over the last decades. Over half of these studies dealt with breast cancer, colorectal cancer, or hematological malignancies.

Most covered cancer treatments, but some covered cancer screening or cancer prevention, such as by vaccination. More than half of the examined interventions had an incremental cost-effectiveness ratio of less than $50,000 (in 2008 US $) per quality-adjusted life-years gained. The authors found only modest improvements in the technical quality of the cost-effectiveness literature since their last analysis in 2000.

The prevalence of left-sided advanced colorectal neoplasms, but not right-sided advanced neoplasms, was lower in participants in a community setting who had received a colonoscopy in the preceding 10 years, according to a new study published online December 30.

Effectiveness of colonoscopy in preventing colorectal cancer has been studied, but evidence from community settings is sparse, especially with respect to anatomical site.

To study this, Hermann Brenner, of the Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, in Heidelberg, Germany, and colleagues conducted a cross-sectional study among 3,287 participants of screening colonoscopy aged 55 years or older from the state of Saarland between May 2005 and December 2007. Previous colonoscopy history was obtained by standardized questionnaire, and its association with prevalence of advanced colorectal neoplasms was estimated.

Advanced colorectal neoplasms were detected in 308 of the 2,701 participants with no previous colonoscopy compared with 36 of the 586 participants who had undergone colonoscopy within the preceding 10 years. Prevalence of left-sided advanced colorectal neoplasms, but not right-sided advanced neoplasms, was substantially lower within a 10-year period after colonoscopy in this community setting.

In an accompanying editorial, Nancy N. Baxter, of the Division of General Surgery at St Michael’s Hospital, University of Toronto, and Linda Rabeneck, of the Depart

According to a new study published online January 7, smokers who received gain-framed messaging from quitline specialists (for instance, stressing the benefits of quitting) had slightly better cessation outcomes than those who received standard-care messaging (for instance, potential losses from smoking and benefits of quitting). Researchers also established that quitline specialists can be trained to provide gain-framed messaging with good fidelity.

Benjamin A. Toll, of the Department of Psychiatry, Yale University School of Medicine in New Haven, Conn., and colleagues randomly assigned 28 specialists working at the New York State Smokers’ Quitline to two groups: one group delivered standard-care messaging and one was trained to deliver gain-framed messages. The researchers assessed whether specialists could be trained to consistently deliver gain-framed messages to smokers and evaluated the cessation outcomes of clients exposed to both kinds of messages. A total of 813 people were exposed to gain-framed messaging and 1,222 were exposed to standard messaging.

Smokers who received gain-framed messaging reported statistically significantly more quit attempts and a higher rate of abstinence from smoking at the 2-week follow-up interview. However, at 3 months there was no difference between the groups. Researchers also found that quitlines can train staff to deliver gain-framed messages in a consistent fashion.

In an accompanying editorial, Robert T. Croyle, of

Pancreatic cancer cell invasion along nerves is regulated by a paracrine pathway that involves glial cell-derived neurotrophic factor, which may be a possible target for preventing the invasion, according to a new study published online January 12 .

To better understand how pancreatic cancer cells infiltrate nerve cells, Ziv Gil., of the department of otolaryngology, head and neck surgery, at Tel Aviv Sourasky Medical Center in Israel, and colleagues used an in vitro Matrigel dorsal root ganglion and pancreatic cancer cell coculture model to assess the interaction between nerves and cancer cell migration, as well as the role of glial cell-derived neurotrophic factor.

The researchers found that the migration of tumor cells along nerves was more rapid than that in the absence of nerves, and the secretion of glial cell-derived neurotrophic factor induced the migration. Mice treated with an inhibitor of the pathway regulating the factor’s expression had reduced nerve invasion. Also, tumors from patients with pancreatic cancer that had invaded nerves expressed more factor receptors than normal tissue.

According to another study published online January 12, a person who has multiple family members with pancreatic cancer is six times as likely to develop that cancer. This risk is even higher, nine times that of the general population, if one of their relatives developed their cancer under the age of 50.

Young-onset cancer is a hallmark of many familial cancer syndromes, but it was not clear whether family members of young-onset familial pancreatic cancer patients were at greater risk than family members of older-onset patients.

Alison P. Klein, at Sol Goldman Pancreatic Cancer Research Center at Johns Hopkins School of Medicine in Baltimore, and colleagues compared the observed incidence of pancreatic cancer in over 9,000 individuals from 1,718 families. Standardized incidence ratios for familial pancreatic cancer and for sporadic pancreatic cancer were calculated with data from the National Familial Pancreas Tumor Registry and compared with those from the SEER database.

Relatives of familial pancreatic cancer patients had a more than six-fold higher incidence of pancreatic cancer than the general population. Those with relatives diagnosed before the age of 50 years had a more than ninefold higher incidence. In contrast, individuals with just a single relative with pancreatic cancer were at twice the risk of pancreatic cancer whether or not the relative with pancreatic cancer was diagnosed before or after the age of 50.

In this issue’s brief communication published online December 23, researchers found that inhibition of transcription factor E2F1 reduced epidermal growth factor receptor (EGFR) expression and reduced the invasive potential but not proliferation of metastatic melanoma cells

To investigate E2F1’s role in cancer progression, Brigitte M. Pützer, of the department of vectorology and experimental gene therapy at the University Rostock in Germany, and colleagues used E2F1 gene silencing in melanoma cells and in mice to compare cell growth and invasive potential and tumor growth and formation of metastatic lesions. The authors also examined expression of EGFR, a protein previously found to be associated with cancer progression, and effects of its inhibition.

Melanoma cells with reduced E2F1 expression had lower invasive potential even though they grew at the same rate as control cells. Tumors in animals with reduced E2F1 expression grew at similar rates, but formed fewer metastatic lesions than control tumors. EGFR expression was decreased in E2F1-silenced cells, and its inhibition reduced the invasive potential of these cells.

That’s it for this edition of the JNCI podcast. Check out this month’s JNCI interview with Dr. Adriana Albini, who discusses her recent JNCI review on the field of ‘cardio-oncology.’

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I’m Steve Graff, and thanks for listening…