Highlights
- •A baseline machine learning-derived signature predicted survival on immunotherapy.
- •LDHhi (elevated serum LDH) and LM+ (liver metastasis) forecasted short survival.
- •LDHlow LM-forecasted longer survival with immunotherapy than other systemic therapies.
- •LDH LM status could guide clinical decision making for advanced cancer patients.
Abstract
Aim
Anti-PD-(L)1 immunotherapies improve survival in multiple cancers but remain ineffective
for most patients. We applied machine-learning algorithms and multivariate analyses
on baseline medical data to estimate their relative impact on overall survival (OS)
upon anti-PD-(L)1 monotherapies.
Method
This prognostic/predictive study retrospectively analysed 33 baseline routine medical
variables derived from computed tomography (CT) images, clinical and biological meta-data.
695 patients with a diagnosis of advanced cancer were treated in prospective clinical
trials in a single tertiary cancer centre in 3 cohorts including systemic anti-PD-(L)1
(251, 235 patients) versus other systemic therapies (209 patients). A random forest
model combined variables to identify the combination (signature) which best estimated
OS in patients treated with immunotherapy. The performance for estimating OS [95%CI]
was measured using Kaplan–Meier Analysis and Log–Rank test.
Results
Elevated serum lactate dehydrogenase (LDHhi) and presence of liver metastases (LM+) were dominant and independent predictors
of short OS in independent cohorts of melanoma and non-melanoma solid tumours. Overall,
LDHhiLM+ patients treated with anti-PD-(L)1 monotherapy had a poorer outcome (median OS:
3.1[2.4–7.8] months]) compared to LDHlowLM-patients (median OS: 15.3[8.9-NA] months; P < 0.0001). The OS of LDHlowLM-patients treated with immunotherapy was 28.8[17.9-NA] months (vs 13.1[10.8–18.5],
P = 0.02) in the overall population and 30.3[19.93-NA] months (vs 14.1[8.69-NA], P = 0.0013)
in patients with melanoma.
Conclusion
LDHhiLM+ status identifies patients who shall not benefit from anti-PD-(L)1 monotherapy.
It could be used in clinical trials to stratify patients and eventually address this
specific medical need.
Keywords
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Article info
Publication history
Published online: November 01, 2022
Accepted:
August 27,
2022
Received:
June 29,
2022
Identification
Copyright
© 2022 Elsevier Ltd. All rights reserved.
