Four Cancer Genomics Papers Retracted From Top Journals

Roxanne Nelson

March 04, 2011

March 4, 2011 — Four cancer genomics papers from researcher Anil Potti, MD, and colleagues have been retracted from prestigious medical journals.

The latest retraction is of a paper on lung cancer genomics published in the New England Journal of Medicine in 2006. In a letter to the journal, Dr. Potti and his coauthors ask that their paper be retracted, and say they "deeply regret" the effect that this action has on the work of other researchers.

This is the fourth retraction by Dr. Potti, who resigned from his positions at the Duke University School of Medicine and the Duke Institute for Genome Science & Policy, both in Durham, North Carolina, last November. He had been suspended by Duke amid concerns about his research and whether or not he had lied on a grant application.

The much cited and now retracted 2006 study, entitled A Genomic Strategy to Refine Prognosis in Early-Stage Non–Small-Cell Lung Cancer (N Engl J Med. 2006;355:570-580), reported on novel gene-expression profiles that predicted the risk for recurrence of nonsmall-cell lung cancer. At that time, Dr. Potti told Medscape Medical News that this was a "huge deal."

"We are moving away from treating cancer patients as a population and are beginning to focus instead on single patients with individual characteristics," he said.

In their retraction published online March 2, the authors write: "Using a sample set from a study by the American College of Surgeons Oncology Group (ACOSOG) and a collection of samples from a study by the Cancer and Leukemia Group B (CALGB), we have tried and failed to reproduce results supporting the validation of the lung metagene model described in the article."

The study has been cited 290 times, according to Thomson Scientific's Web of Knowledge, and a correction to the article was issued in 2007 (N Engl J Med. 2007;356:201-202).

Continuing Saga

The saga of Dr. Potti has been long and tumultuous, involving not only concerns about the validity of his research, but allegations of misconduct. In July 2010, Dr. Potti was suspended by Duke after the publication of an article in The Cancer Letter, which reported that he overstated his academic achievements by claiming to be a Rhodes scholar.

As reported by the New York Times last year, a spokesperson from the Rhodes House at Oxford University in the United Kingdom confirmed that Dr. Potti had never been the recipient of a Rhodes scholarship.

When questions about Dr. Potti's credentials became public, the American Cancer Society (ACS) suspended payment of a $729,000 grant that it had awarded to him to study lung cancer genetics. The grant was given to him on the basis of his resume, which included mention of the Rhodes scholarship, Otis W. Brawley, MD, the chief medical officer of ACS, told the New York Times.

In addition to his suspension, patient enrolment was halted in 3 ongoing trials funded by the National Cancer Institute after a number of biostatisticians and cancer researchers at academic institutions, including Harvard, Princeton, and Johns Hopkins, began questioning the methodology behind the 3 clinical trials in question (2 in lung cancer and 1 in breast cancer).

In a letter sent to the director of the National Cancer Institute, a group of 31 scientists called for the suspension of ongoing trials because of concerns about the prediction models that were being used. The models were developed on the basis of research reported by Dr. Potti and Joseph Nevins, PhD, also from Duke University, but the validity of those models was called into question after peer-reviewed reanalyses of their work.

About the same time, the Lancet Oncology issued an expression of concern over a paper published in the journal in 2007, which described the validation of gene signatures to predict the response of breast cancer to neoadjuvant chemotherapy (Lancet Oncol. 2007;8:1071-1078). This was issued after the journal was contacted by senior author Richard Iggo, PhD, from the Swiss Institute for Experimental Cancer Research in Epalinges, Switzerland, and first author Hervé Bonnefoi, MD, from the Institut Bergonié, University of Bordeaux, France, who "expressed grave concerns about the validity of their report in light of evolving events."

They said that they had repeatedly tried to contact their coauthors at Duke University (including Dr. Potti) who had been responsible for the statistical analyses in the report, but were ignored.

The Lancet Oncology recently issued a retraction of that study (2011;12:116).

In January 2011, Nature Medicine published a retraction of a 2006 article that had been corrected on 4 separate occasions (Nat Med. 2006;12:1294-1300). First author Dr. Potti and his coauthors wrote that they had "been unable to reproduce certain crucial experiments showing validation of signatures for predicting response to chemotherapies, including docetaxel and topotecan." Even though they believed that their underlying approach to developing predictive signatures is valid, "a corruption of several validation datasets precludes conclusions regarding these signatures" (Nat Med. 2011;17:135).

Last November, the Journal of Clinical Oncology retracted a 2007 paper that was coauthored by Dr. Potti (J Clin Oncol. 2007;25:4350-4357). The retraction was reportedly initiated by Dr. Nevins, and stated that the authors "have been unable to reproduce the experiments demonstrating a capacity of a cisplatin response signature to validate in either a collection of ovarian cancer cell lines or ovarian tumor samples" (J Clin Oncol. 2010;28:5229).

N Engl J Med. Published online March 2, 2011. Abstract

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