Initial metastatic kinetics is the best prognostic indicator in stage IV metastatic melanoma.
OBJECTIVE
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.


METHODS
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.


CONCLUSIONS
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.
Dermatology and skin cancers Department, Aix-Marseille University, APHM, Marseille, France. Electronic address: Caroline.Gaudy@ap-hm.fr.
Caroline
C
Gaudy-Marqueste
Dermatology and skin cancers Department, Aix-Marseille University, APHM, Marseille, France.
Elodie
E
Archier
Radiology Department, Aix-Marseille University, APHM, Marseille, France.
Anaïs
A
Grob
Radiology Department, Aix-Marseille University, APHM, Marseille, France.
Olivier
O
Durieux
Public Health Department, Aix-Marseille University, APHM, Marseille, France.
Anderson
A
Loundou
Dermatology and skin cancers Department, Aix-Marseille University, APHM, Marseille, France.
Marie-Aleth
MA
Richard
Dermatology and skin cancers Department, Aix-Marseille University, APHM, Marseille, France.
Jean-Jacques
JJ
Grob
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D006801:Humans; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D012189:Retrospective Studies; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome; D047368:Tumor Burden; D057832:Watchful Waiting / Q000379:methods*; D055815:Young Adult
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D007770:L-Lactate Dehydrogenase
Kinetics; Melanoma; Prognosis