PDQ (Physician Data Query)

News | 5 of 6 Heidi Rehm, M.D., an associate professor at Harvard Medical School and medical director of the Broad Institute's Clinical Research Sequencing Platform in Cambridge, Mass., said she's impressed with how labs reporting to ClinVar are working to identify and resolve differences in interpretation. Rehm was instrumental in creating ClinVar and said that discrepancies often occur simply because one interpretation in the database might be older than a newer one supported by more recent data. “I would encourage all commercial and independent labs to upload their variants into public databases so that we can reach consensus on our interpretations,” Balman~a said. “And our study is identifying variations that we think it's important to focus on first.” ClinVar now uses a star system to grade approved submitters. The ENIGMA Consortium, for instance, which works on breast cancer variants, and InSight, which works P National Cancer Institute's source DQ (Physician Data Query) is the of comprehensive cancer information. It contains peer-reviewed, evidencebased cancer information summaries on treatment, supportive care, screening, prevention, genetics, and complementary and alternative medicine. The summaries are regularly updated by six editorial boards. The following PDQ summaries were recently updated: Hamdy FC, Donovan JL, Lane JA, et al.: 10-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer. N Engl J Med 375 (15): 14151424, 2016. Donovan JL, Hamdy FC, Lane JA, et al.: Patient-Reported Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer. N Engl J Med 375 (15): 14251437, 2016. The PDQ Prostate Cancer Treatment summary was recently updated to include information on the ProtecT trial (NCT02044172 and ISRCTN20141297). The trial screened 82,429 men with PSA S W E N - on gastrointestinal tumors, both have a four-star rating because their interpretations are well supported and transparent. Conversely, labs that don’t provide transparent interpretations might get one or no star. Rehm said that older interpretations and zero-star contributors present ongoing challenges that she and those who administer ClinVar are trying to manage. Still, qualified lab directors might review the same evidence and reach different conclusions, she added. “And in these instances, there’s no right or wrong interpretation,” she said. “It’s like the practice of medicine—one doctor might look at your torn meniscus and say you need knee surgery, and the other one might recommend physical therapy. Genetics isn’t any different.” Potential legal implications for accountability can arise when gene test interpretations lead to harmful management decisions. The case of Williams v. Athena concerns a boy who died in 2008 testing and diagnosed 2,664 men with clinically localized prostate cancer, of whom 1,643 (median age 62 years, range 50–69 years) consented to a randomly assigned comparison of active monitoring, radical prostatectomy (nerve-sparing when possible), or external-beam 3-D conformal radiation therapy (74 Gy in 37 fractions). The primary endpoint was prostate cancer-specific mortality. With a median follow-up of 10 years, there were 17 deaths from prostate cancer, with no statistically significant differences among the three study arms. Likewise, all-cause mortality was nearly identical in all three study arms. There were statistically significant differences in progression to metastatic disease among the treatment arms that began to emerge after 4 years, but these differences had not translated into any difference in mortality at the 10-year follow-up. There were substantial differences in patient-reported outcomes among the three management approaches. after being tested for Dravet syndrome, a cause of severe epilepsy associated with mutations in the SCNIA gene. Since standard anticonvulsants exacerbate seizures in such patients, a positive result would have altered the boy’s treatment. But the testing laboratory, Athena, at first concluded that his specific SCNIA gene mutation was a VUS. The child died while being treated with standard therapy. Then several years later, Athena revised its assessment of the gene from VUS to pathogenic—without supplying any further information. The plaintiff alleges that Athena was negligent in interpreting the mutation, and lawyers are now debating, among other issues, whether the treating physician or the laboratory is legally responsible for variant interpretation. The case is under review by the U.S. District Court for the District of South Carolina. https://www.cancer.gov/types/pros tate/hp/prostate-treatment-pdq#link/_ 1988 The PDQ Pediatric Cancer Treatment Board recently completed a comprehensive review of the Childhood Astrocytomas Treatment summary. The Board conducted a review of the published literature and updated the citations. To review the summary, please use the following link: https://www.cancer.gov/types/brain/ hp/ (...truncated)