P09.63 Postmortem evaluation of end-organ toxicity in patients with glioblastoma treated with temozolomide, bevacizumab and irinotecan

• Published in: Neuro-oncology (Charlottesville, Va.) Va.), 2017-05, Vol.19 (suppl_3), p.iii84-iii84
• Main Authors: Lu, G., Rao, M., Zhu, P., Tian, X., Linendoll, N., Pilichowska, M., Glass, W. F., Hunter, R., Zhu, J.
• Format: Article
• Language: English
• Subjects: POSTER PRESENTATIONS
• ISSN: 1522-8517; 1523-5866
• DOI: 10.1093/neuonc/nox036.318

Chemotherapies [temozolomide (TMZ), bevacizumab (BEV), irinotecan (IRI)] are commonly used drugs treating glioblastoma multiforme (GBM). The side effects from individual drug are well-known clinically and are manageable. Most of side effects are reversible after discounting the suspected drug(s). Combination chemotherapies either concurrently or in sequence are common in oncology practice. Most GBM patients received TMZ first followed by BEV with or without IRI. However, the side effects or permanent end-organs injuries of cumulative toxicity profiles are not well established. Whether these chemotherapies will lead to permanent end-organ damage by post-mortem pathological examination after long term use of either single drug or combination of two or three of the above listed chemotherapy drugs has never been studied in detail. In this study, 45 post-mortem pathological examination and some with electronic microscopic examinations are performed to study possible end-organ toxicity attributed to chemotherapies. Consent for autopsy were obtained from next of kin from each of the subjects. Postmortem organ specific studies including gross exam, H&E, immunohistochemistry study, electron microscopy (EM) (n=8) and immunofluorescence (IF). Autopsy cases include 35 GBMs, 6 brain metastatic cancers, 1 grade II and 2 grade III gliomas, 1 spinal glioma from UTHealth and Tufts medical center since 2007 to 2016. Twenty eight male and 17 female subjects were included with ages ranging from 20 to 79 years old (median 62 years old). Clinical toxicities and laboratory abnormalities were collected and correlated with autopsy results. At autopsy, there was no significant morphologic evidence of TMZ/BEV or TMZ/BEV/IRI-related injury in heart, lung, liver, adrenal glands, thyroid, pancreas, spleen, bladder or bone marrow which we did not know clinically. The cause of death in most patients was bronchopneumonia. Pulmonary embolism was confirmed in 4 cases with 2 case showing additional alveolar hemorrhage. One case had peritonitis with diverticular perforation diagnosed pre-mortem during BEV therapy. EM evaluation of renal glomerular ultrastructure reveal extensive postmortem autolytic change; however there was sufficient preservation to determine that podocyte foot processes were mostly preserved, but glomeruli had segmental to global subendothelial expansion by edematous, flocculent, matrix indicative of endothelial injury. IF examination showed no immune complex deposition. W