title: Immune Reactivity and Pseudoprogression or Tumor Flare in a Serially Biopsied Neuroendocrine Patient Treated with the Epigenetic Agent RRx-001.
abstract: Neuroendocrine tumors (NETs) are grouped together as a single class on the basis of histologic appearance, immunoreactivity for the neuroendocrine markers chromogranin A and synaptophysin, and potential secretion of hormones, neurotransmitters, neuromodulators and neuropeptides. Nevertheless, despite these common characteristics, NETs differ widely in terms of their natural histories: high-grade NETs are clinically aggressive and, like small cell lung cancer, which they most closely resemble, tend to respond to cisplatin and etoposide. In contrast, low-grade NETs, which as a rule progress and behave indolently, do not. In either case, the treatment strategy, apart from potentially curative surgical resection, is very poorly defined. This report describes the case of a 28-year-old white male with a diagnosis of high-grade NET of undetermined primary site metastatic to the lymph nodes, skin and paraspinal soft tissues, treated with the experimental anticancer agent RRx-001, in the context of a phase II clinical trial called TRIPLE THREAT (NCT02489903); serial sampling of tumor material through repeat biopsies demonstrated an intratumoral inflammatory response, including the amplification of infiltrating T cells, which correlated with clinical and symptomatic benefit. This case suggests that pseudoprogression or RRx-001-induced enlargement of tumor lesions, which has been previously described for several RRx-001-treated patients, is the result of tumoral lymphocyte infiltration.
authors.affiliation: Walter Reed National Military Medical Center, Bethesda, Md., USA.
authors.forename: Corey A
authors.initials: CA
authors.lastname: Carter
authors.affiliation: Walter Reed National Military Medical Center, Bethesda, Md., USA.
authors.forename: Bruno
authors.initials: B
authors.lastname: Schmitz
authors.affiliation: Walter Reed National Military Medical Center, Bethesda, Md., USA.
authors.forename: P Gabriel
authors.initials: PG
authors.lastname: Peterson
authors.affiliation: Walter Reed National Military Medical Center, Bethesda, Md., USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Quinn
authors.affiliation: Walter Reed National Military Medical Center, Bethesda, Md., USA.
authors.forename: Aiste
authors.initials: A
authors.lastname: Degesys
authors.affiliation: Walter Reed National Military Medical Center, Bethesda, Md., USA.
authors.forename: John
authors.initials: J
authors.lastname: Jenkins
authors.affiliation: EpicentRx, Inc., Mountain View, Calif., USA.
authors.forename: Bryan
authors.initials: B
authors.lastname: Oronsky
authors.affiliation: EpicentRx, Inc., Mountain View, Calif., USA.
authors.forename: Jan
authors.initials: J
authors.lastname: Scicinski
authors.affiliation: EpicentRx, Inc., Mountain View, Calif., USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Caroen
authors.affiliation: Moores Cancer Center, La Jolla, Calif., USA.
authors.forename: Tony R
authors.initials: TR
authors.lastname: Reid
authors.affiliation: Department of Bioengineering, University of California San Diego, La Jolla, Calif., USA.
authors.forename: Pedro
authors.initials: P
authors.lastname: Cabrales
authors.affiliation: Walter Reed National Military Medical Center, Bethesda, Md., USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Brzezniak
keywords: Immune reactivity; Neuroendocrine tumor; Pseudoprogression; RRx-001; Serial biopsy; Tumor flare