Overcoming autopsy barriers in pediatric cancer research.

Although survival rates have greatly increased over the past decades for some pediatric cancers, other subtypes including high-risk sarcomas and diffuse intrinsic pontine gliomas (DIPG) have an unimproved or near-zero survival rate despite novel therapies [3,4]. This observation highlights the need for improved treatments and new research approaches for rare pediatric tumors. One way to advance knowledge of rare cancers is to study the disease at all stages including the point when treatment has failed and the child has succumbed to the disease. Obtaining quality tumor samples that may be donated directly to a research laboratory or frozen in a biorepository for future research has several important benefits. Autopsy samples allow researchers to collect the most biologically aggressive component of the tumor which has not been eradicated by any treatment administered, to sample multiple sites of disease, and to collect larger specimens than might be possible in a living patient [5]. Fresh samples may provide highly valuable tissue for researchers to study because living cell tumor cultures can sometimes be established; nevertheless, frozen or even paraffin-fixed samples have already proven to be of great value and numerous examples can be cited how such autopsy samples have revealed fundamental mechanisms of tumor progression [5–12]. Despite these significant advances in the understanding of pediatric cancers facilitated by autopsy tissue for research, the number of tumor donations from autopsies remains small. To some extent this reflects a general decline in the frequency of autopsies over the decades in the United States where the autopsy is only performed in 5% of all hospital deaths [13]. This decline has been attributed to physicians’ minimal knowledge regarding the procedure, physicians’ unwillingness to ask for consent, the assumption that families will not consent, uncertainty of how to approach the family, and the rationale that improved imaging and clinical laboratory tests already shed light on the cause of death [13–15]. However, some studies suggest that autopsy continues to identify unrecognized medical problems even in patients dying of cancer [16,17]. Many physicians currently have not had adequate training in the autopsy procedure [18] and as a result may be insufficiently aware of the benefits. Not only do tumor samples from an autopsy for research offer a potentially important scientific impact, but the opportunity to contribute a Legacy Gift (i.e., the donation of autopsy tumor tissue to science) may also create a small positive aspect for an otherwise devastative event for the grieving family. The goal of this study was to identify barriers to performing pediatric autopsies for research purposes and to develop guidelines that institutions may use to encourage physicians to address tumor donation with families.