Schwaederle Maria, Parker Barbara A, Schwab Richard B, Fanta Paul T, Boles Sarah G, Daniels Gregory A, Bazhenova Lyudmila A, Subramanian Rupa, Coutinho Alice C, Ojeda-Fournier Haydee, Datnow Brian, Webster Nicholas J, Lippman Scott M, Kurzrock Razelle
Center for Personalized Cancer Therapy, Moores Cancer Center, Division of Hematology-Oncology, Department of Medicine, Department of Radiology, School of Medicine, Department of Pathology, School of Medicine, and Division of Endocrinology & Metabolism, Department of Medicine, University of California San Diego, La Jolla, California, USA.
Center for Personalized Cancer Therapy, Moores Cancer Center, Division of Hematology-Oncology, Department of Medicine, Department of Radiology, School of Medicine, Department of Pathology, School of Medicine, and Division of Endocrinology & Metabolism, Department of Medicine, University of California San Diego, La Jolla, California, USA
Oncologist. 2014 Jun;19(6):631-6. doi: 10.1634/theoncologist.2013-0405. Epub 2014 May 5.
DNA sequencing tests are enabling physicians to interrogate the molecular profiles of patients' tumors, but most oncologists have not been trained in advanced genomics. We initiated a molecular tumor board to provide expert multidisciplinary input for these patients.
A team that included clinicians, basic scientists, geneticists, and bioinformatics/pathway scientists with expertise in various cancer types attended. Molecular tests were performed in a Clinical Laboratory Improvement Amendments environment.
Patients (n = 34, since December 2012) had received a median of three prior therapies. The median time from physician order to receipt of molecular diagnostic test results was 27 days (range: 14-77 days). Patients had a median of 4 molecular abnormalities (range: 1-14 abnormalities) found by next-generation sequencing (182- or 236-gene panels). Seventy-four genes were involved, with 123 distinct abnormalities. Importantly, no two patients had the same aberrations, and 107 distinct abnormalities were seen only once. Among the 11 evaluable patients whose treatment had been informed by molecular diagnostics, 3 achieved partial responses (progression-free survival of 3.4 months, ≥6.5 months, and 7.6 months). The most common reasons for being unable to act on the molecular diagnostic results were that patients were ineligible for or could not travel to an appropriately targeted clinical trial and/or that insurance would not cover the cognate agents.
Genomic sequencing is revealing complex molecular profiles that differ by patient. Multidisciplinary molecular tumor boards may help optimize management. Barriers to personalized therapy include access to appropriately targeted drugs.
DNA测序检测使医生能够探究患者肿瘤的分子特征,但大多数肿瘤学家并未接受过高级基因组学方面的培训。我们启动了一个分子肿瘤专家委员会,为这些患者提供多学科专家意见。
一个团队参会,成员包括临床医生、基础科学家、遗传学家以及在各种癌症类型方面具有专业知识的生物信息学/通路科学家。分子检测在符合临床实验室改进修正案要求的环境中进行。
自2012年12月以来的34例患者此前接受的治疗中位数为3种。从医生下达医嘱到收到分子诊断检测结果的中位时间为27天(范围:14 - 77天)。通过二代测序(182基因或236基因检测板),患者发现的分子异常中位数为4个(范围:1 - 14个异常)。涉及74个基因,有123种不同的异常。重要的是,没有两名患者具有相同的畸变,107种不同的异常仅出现过一次。在11例其治疗决策受分子诊断影响的可评估患者中,3例获得部分缓解(无进展生存期分别为3.4个月、≥6.5个月和7.6个月)。无法根据分子诊断结果采取行动最常见的原因是患者不符合参加或无法前往合适的靶向临床试验的条件,和/或保险不涵盖相关药物。
基因组测序揭示了因患者而异的复杂分子特征。多学科分子肿瘤专家委员会可能有助于优化治疗管理。个性化治疗的障碍包括获得合适的靶向药物。