Universität zu Köln

Trommer, Maike, Yeo, Sin Yuin, Persigehl, Thorsten, Bunck, Anne, Gruell, Holger, Schlaak, Max, Theurich, Sebastian ORCID: 0000-0001-5706-8258, Von Bergwelt, Michael, Morgenthaler, Janis, Herter, Jan M., Celik, Eren, Marnitz, Simone and Baues, Christian (2019). Abscopal Effects in Radio-Immunotherapy - Response Analysis of Metastatic Cancer Patients With Progressive Disease Under Anti-PD-1 Immune Checkpoint Inhibition. Front. Pharmacol., 10. LAUSANNE: FRONTIERS MEDIA SA. ISSN 1663-9812

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Abstract

Immune checkpoint inhibition (ICI) targeting the programmed death receptor 1 (PD-1) has shown promising results in the fight against cancer. Systemic anti-tumor reactions due to radiation therapy (RT) can lead to regression of non-irradiated lesions (NiLs), termed abscopal effect (AbE). Combination of both treatments can enhance this effect. The aim of this study was to evaluate AbEs during anti-PD-1 therapy and irradiation. We screened 168 patients receiving pembrolizumab or nivolumab at our center. Inclusion criteria were start of RT within 1 month after the first or last application of pembrolizumab (2 mg/kg every 3 weeks) or nivolumab (3mg/kg every 2 weeks) and at least onemetastasis outside the irradiation field. We estimated the total dose during ICI for each patient using the linear quadratic (LQ) model expressed as 2Gy equivalent dose (EQD2) using alpha/beta of 10Gy. Radiological images were required showing progression or no change in NiLs before and regression after completion of RT(s). Images must have been acquired at least 4 weeks after the onset of ICI or RT. The surface areas of the longest diameters of the short-and long-axes of NiLs were measured. One hundred twenty-six out of 168 (75%) patients received ICI and RT. Fifty-three percent (67/126) were treated simultaneously, and 24 of these (36%) were eligible for lesion analysis. AbE was observed in 29% (7/24). One to six lesions (mean = 3 +/- 2) in each AbE patient were analyzed. Patients were diagnosed with malignant melanoma (MM) (n = 3), non-small cell lung cancer (NSCLC) (n = 3), and renal cell carcinoma (RCC) (n = 1). They were irradiated once (n = 1), twice (n = 2), or three times (n = 4) with an average total EQD2 of 120.0 +/- 37.7Gy. Eighty-two percent of RTs of AbE patients were applied with high single doses. MMpatients received pembrolizumab, NSCLC, and RCC patients received nivolumab for an average duration of 45 +/- 35 weeks. We demonstrate that 29% of the analyzed patients showed AbE. Strict inclusion criteria were applied to distinguish the effects of AbE from the systemic effect of ICI. Our data suggest the clinical existence of systemic effects of irradiation under ICI and could contribute to the development of a broader range of cancer treatments.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Trommer, Maike UNSPECIFIED UNSPECIFIED UNSPECIFIED Yeo, Sin Yuin UNSPECIFIED UNSPECIFIED UNSPECIFIED Persigehl, Thorsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Bunck, Anne UNSPECIFIED UNSPECIFIED UNSPECIFIED Gruell, Holger UNSPECIFIED UNSPECIFIED UNSPECIFIED Schlaak, Max UNSPECIFIED UNSPECIFIED UNSPECIFIED Theurich, Sebastian UNSPECIFIED orcid.org/0000-0001-5706-8258 UNSPECIFIED Von Bergwelt, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Morgenthaler, Janis UNSPECIFIED UNSPECIFIED UNSPECIFIED Herter, Jan M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Celik, Eren UNSPECIFIED UNSPECIFIED UNSPECIFIED Marnitz, Simone UNSPECIFIED UNSPECIFIED UNSPECIFIED Baues, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-148240
DOI:	10.3389/fphar.2019.00511
Journal or Publication Title:	Front. Pharmacol.
Volume:	10
Date:	2019
Publisher:	FRONTIERS MEDIA SA
Place of Publication:	LAUSANNE
ISSN:	1663-9812
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language COMBINING RADIOTHERAPY; IONIZING IRRADIATION; ANTITUMOR IMMUNITY; ADVANCED MELANOMA; OPEN-LABEL; RADIATION; NIVOLUMAB; TUMOR; PEMBROLIZUMAB; MULTICENTER Multiple languages Pharmacology & Pharmacy Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/14824