Hoda Anwar1, Christos Sachpekidis2, Julia Winkler3, Annette Kopp-Schneider4, Uwe Haberkorn2,5, Jessica C Hassel3, Antonia Dimitrakopoulou-Strauss2. 1. Medical PET Group-Biological Imaging, Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Im Neuenheimer Feld 280, 69210, Heidelberg, Germany. hoda.nagui@gmail.com. 2. Medical PET Group-Biological Imaging, Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Im Neuenheimer Feld 280, 69210, Heidelberg, Germany. 3. Department of Dermatology and National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany. 4. Department of Biostatistics, German Cancer Research Center, Heidelberg, Germany. 5. Division of Nuclear Medicine, University of Heidelberg, Heidelberg, Germany.
Abstract
PURPOSE: Evaluation of response to immunotherapy is a matter of debate. The aim of the present study was to evaluate the response of metastatic melanoma to treatment with ipilimumab by means of 18F-FDG PET/CT, using the patients' clinical response as reference. METHODS: The final cohort included in the analyses consisted of 41 patients with metastatic melanoma who underwent 18F-FDG PET/CT before and after administration of ipilimumab. After determination of the best clinical response, the PET/CT scans were reviewed and a separate independent analysis was performed, based on the number and functional size of newly emerged 18F-FDG-avid lesions, as well as on the SUV changes after therapy. RESULTS: The median observation time of the patients after therapy was 21.4 months (range 6.3-41.9 months). Based on their clinical response, patients were dichotomized into those with clinical benefit (CB) and those without CB (No-CB). The CB group (31 patients) included those with stable disease, partial remission and complete remission, and the No-CB group (10 patients) included those with progressive disease. The application of a threshold of four newly emerged 18F-FDG-avid lesions on the posttherapy PET/CT scan led to a sensitivity (correctly predicting CB) of 84% and a specificity (correctly predicting No-CB) of 100%. This cut-off was lower for lesions with larger functional diameters (three new lesions larger than 1.0 cm and two new lesions larger than 1.5 cm). SUV changes after therapy did not correlate with clinical response. Based on these findings, we developed criteria for predicting clinical response to immunotherapy by means of 18F-FDG PET/CT (PET Response Evaluation Criteria for Immunotherapy, PERCIMT). CONCLUSION: Our results show that a cut-off of four newly emerged 18F-FDG-avid lesions on posttherapy PET/CT gives a reliable indication of treatment failure in patients under ipilimumab treatment. Moreover, the functional size of the new lesions plays an important role in predicting the clinical response. Validation of these results in larger cohorts of patients is warranted.
PURPOSE: Evaluation of response to immunotherapy is a matter of debate. The aim of the present study was to evaluate the response of metastatic melanoma to treatment with ipilimumab by means of 18F-FDG PET/CT, using the patients' clinical response as reference. METHODS: The final cohort included in the analyses consisted of 41 patients with metastatic melanoma who underwent 18F-FDG PET/CT before and after administration of ipilimumab. After determination of the best clinical response, the PET/CT scans were reviewed and a separate independent analysis was performed, based on the number and functional size of newly emerged 18F-FDG-avid lesions, as well as on the SUV changes after therapy. RESULTS: The median observation time of the patients after therapy was 21.4 months (range 6.3-41.9 months). Based on their clinical response, patients were dichotomized into those with clinical benefit (CB) and those without CB (No-CB). The CB group (31 patients) included those with stable disease, partial remission and complete remission, and the No-CB group (10 patients) included those with progressive disease. The application of a threshold of four newly emerged 18F-FDG-avid lesions on the posttherapy PET/CT scan led to a sensitivity (correctly predicting CB) of 84% and a specificity (correctly predicting No-CB) of 100%. This cut-off was lower for lesions with larger functional diameters (three new lesions larger than 1.0 cm and two new lesions larger than 1.5 cm). SUV changes after therapy did not correlate with clinical response. Based on these findings, we developed criteria for predicting clinical response to immunotherapy by means of 18F-FDG PET/CT (PET Response Evaluation Criteria for Immunotherapy, PERCIMT). CONCLUSION: Our results show that a cut-off of four newly emerged 18F-FDG-avid lesions on posttherapy PET/CT gives a reliable indication of treatment failure in patients under ipilimumab treatment. Moreover, the functional size of the new lesions plays an important role in predicting the clinical response. Validation of these results in larger cohorts of patients is warranted.
Authors: Steve Y Cho; Evan J Lipson; Hyung-Jun Im; Steven P Rowe; Esther Mena Gonzalez; Amanda Blackford; Alin Chirindel; Drew M Pardoll; Suzanne L Topalian; Richard L Wahl Journal: J Nucl Med Date: 2017-03-30 Impact factor: 10.057
Authors: Sree Harsha Tirumani; Nikhil H Ramaiya; Abhishek Keraliya; Nancy D Bailey; Patrick A Ott; F Stephen Hodi; Mizuki Nishino Journal: Cancer Immunol Res Date: 2015-06-22 Impact factor: 11.151
Authors: H Young; R Baum; U Cremerius; K Herholz; O Hoekstra; A A Lammertsma; J Pruim; P Price Journal: Eur J Cancer Date: 1999-12 Impact factor: 9.162
Authors: Antoni Ribas; Matthias R Benz; Martin S Allen-Auerbach; Caius Radu; Bartosz Chmielowski; Elizabeth Seja; John L Williams; Jesus Gomez-Navarro; Timothy McCarthy; Johannes Czernin Journal: J Nucl Med Date: 2010-02-11 Impact factor: 10.057
Authors: Jedd D Wolchok; Axel Hoos; Steven O'Day; Jeffrey S Weber; Omid Hamid; Celeste Lebbé; Michele Maio; Michael Binder; Oliver Bohnsack; Geoffrey Nichol; Rachel Humphrey; F Stephen Hodi Journal: Clin Cancer Res Date: 2009-11-24 Impact factor: 12.531
Authors: Benjamin Y Kong; Alexander M Menzies; Catherine A B Saunders; Elizabeth Liniker; Sangeetha Ramanujam; Alex Guminski; Richard F Kefford; Georgina V Long; Matteo S Carlino Journal: Pigment Cell Melanoma Res Date: 2016-08-04 Impact factor: 4.693
Authors: Kimiteru Ito; Rebecca Teng; Heiko Schöder; John L Humm; Ai Ni; Laure Michaud; Reiko Nakajima; Rikiya Yamashita; Jedd D Wolchok; Wolfgang A Weber Journal: J Nucl Med Date: 2018-11-09 Impact factor: 10.057
Authors: Timo E Schank; Andrea Forschner; Michael Max Sachse; Antonia Dimitrakopoulou-Strauss; Christos Sachpekidis; Albrecht Stenzinger; Anna-Lena Volckmar; Alexander Enk; Jessica C Hassel Journal: Cancers (Basel) Date: 2021-05-26 Impact factor: 6.639