Multisystem Toxicity in Cancer: Lessons from NASA's Countermeasures Program

Abstract

Astronauts and cancer patients are subject to similar multisystem physiological toxicities. Over the past sixty years, NASA developed a state-of-the-art countermeasures program (CMP) to characterize and mitigate the physiological consequences of spaceflight. Here, we propose a NASA-modeled CMP to elucidate and abrogate physiological toxicities in patients with cancer.

Figure 1.. Multiple Hit-Induced Multisystem Toxicity in Astronauts and Cancer Patients

(A) There are numerous analogous multiple hits (i.e., baseline risk factors; direct and indirect insults) (Jones et al., 2007) and resultant multisystem toxicities between astronauts (left) and cancer patients (right). (B) Contemporary toxicity characterization approaches in astronauts (top) and cancer patients (bottom). Astronauts are profiled using multidimensional and longitudinal phenotyping (solid line), whereas cancer patients are profiled using the single-organ level during resting states (when reserve capacity is high) and/or performance status intermittently before, during, and after therapy (dotted line). Several trajectories of change post-therapy have been observed including: continued declines, spontaneous acute recovery, and plateau. (C) Contemporary toxicity management approaches in astronauts (top) and cancer patients (bottom). In astronauts, toxicities are managed with mandatory exercise therapy: pre-flight to augment reserve, in-flight to mitigate spaceflight-related physiological toxicities, and post-flight to reverse any toxicities. In cancer patients, toxicities are managed using pre-therapy dose modification, during-therapy dose modification, dose interruption or discontinuation and/or pharmacological supportive care, and post-therapy pharmacological supportive care. Down arrow, dose modification; pill bottle, pharmacological supportive care.

Figure 2.. Cancer Countermeasures Program

(A) Multidimensional and longitudinal characterization pre-, during, and post-therapy and exemplar trajectories of change in CRF. Acquisition of clinically important physiological parameters is now feasible with automated, “real-world” devices and digitized platforms (e.g., home-based blood draws, smart watches tracking vital signs and sleep, scales, and blood pressure devices). (B) Toxicity management with exercise therapy (1) pre-surgery to augment CRF, (2) during therapy to abrogate CRF decline, and (3) post-therapy to return CRF to baseline levels. Like NASA’s countermeasures program, exercise is individualized and is delivered and supervised remotely with continuous data capture to ensure safety and efficacy of intervention. CRF, cardiorespiratory fitness.