Caroline Gaudy-Marqueste1, Elodie Archier2, Anaïs Grob3, Olivier Durieux3, Anderson Loundou4, Marie-Aleth Richard2, Jean-Jacques Grob2. 1. Dermatology and skin cancers Department, Aix-Marseille University, APHM, Marseille, France. Electronic address: Caroline.Gaudy@ap-hm.fr. 2. Dermatology and skin cancers Department, Aix-Marseille University, APHM, Marseille, France. 3. Radiology Department, Aix-Marseille University, APHM, Marseille, France. 4. Public Health Department, Aix-Marseille University, APHM, Marseille, France.
Abstract
AIM: In metastatic melanoma (MM) there is an agreement that a fast or slow progression should influence the choice between drugs with immediate impact (BRAF-inh) or delayed (ipilimumab) activity. MM kinetics thus appears crucial for medical decision, although only estimated through surrogate markers (tumour load or lactate dehydrogenase (LDH)). Our objective was to show that 1-MM kinetics can be measured and 2- is a real prognostic factor. METHOD: Among all stage IV MM, we retrospectively select those with long follow-up who had two comparable total body computed tomography (CT) scans within the first 3 months, and did not receive meantime any treatment with a likely impact on MM kinetics. Kinetics index (KI) was calculated from changes in total metastatic volume (ΔTMV/ΔT). RESULTS: In 126 patients, KI of progression ranges from 0 to 24,839 mm3/day. Overall survival (OS) was significantly much lower in the higher terciles of KI than in the lower ones (median OS of 459, 388 and 183 days, for KI of 0-99, 100-999 and > or =1000 mm3/day, respectively). In the multivariate analysis, KI was more predictive of OS than LDH or tumour load. CONCLUSION: Delaying major treatments in stage IV MM for a few weeks permits a measure of KI, which is the best prognostic indicator in MM. The huge range of KI probably reflects major differences in aggressiveness that any therapeutic decision should take into account. KI could be used to assess prospectively how much the efficacy of each new MM drugs is influenced by MM initial kinetics.
AIM: In metastatic melanoma (MM) there is an agreement that a fast or slow progression should influence the choice between drugs with immediate impact (BRAF-inh) or delayed (ipilimumab) activity. MM kinetics thus appears crucial for medical decision, although only estimated through surrogate markers (tumour load or lactate dehydrogenase (LDH)). Our objective was to show that 1-MM kinetics can be measured and 2- is a real prognostic factor. METHOD: Among all stage IV MM, we retrospectively select those with long follow-up who had two comparable total body computed tomography (CT) scans within the first 3 months, and did not receive meantime any treatment with a likely impact on MM kinetics. Kinetics index (KI) was calculated from changes in total metastatic volume (ΔTMV/ΔT). RESULTS: In 126 patients, KI of progression ranges from 0 to 24,839 mm3/day. Overall survival (OS) was significantly much lower in the higher terciles of KI than in the lower ones (median OS of 459, 388 and 183 days, for KI of 0-99, 100-999 and > or =1000 mm3/day, respectively). In the multivariate analysis, KI was more predictive of OS than LDH or tumour load. CONCLUSION: Delaying major treatments in stage IV MM for a few weeks permits a measure of KI, which is the best prognostic indicator in MM. The huge range of KI probably reflects major differences in aggressiveness that any therapeutic decision should take into account. KI could be used to assess prospectively how much the efficacy of each new MM drugs is influenced by MM initial kinetics.
Authors: Nikolaus B Wagner; Max M Lenders; Kathrin Kühl; Lydia Reinhardt; Fiona André; Milena Dudda; Natalie Ring; Chiara Ebel; Ramon Stäger; Caroline Zellweger; Roland Lang; Michael Paar; Philipp Gussek; Georg Richtig; Suzan H Stürmer; Susanne Kimeswenger; Angela Oellinger; Andrea Forschner; Ulrike Leiter; Benjamin Weide; Maximilian Gassenmaier; Amadeus Schraag; Bernhard Klumpp; Wolfram Hoetzenecker; Carola Berking; Erika Richtig; Mirjana Ziemer; Johanna Mangana; Patrick Terheyden; Carmen Loquai; Van Anh Nguyen; Christoffer Gebhardt; Friedegund Meier; Stefan Diem; Antonio Cozzio; Lukas Flatz; Martin Röcken; Claus Garbe; Thomas K Eigentler Journal: J Immunother Cancer Date: 2021-05 Impact factor: 13.751