Cerebral Perfusion and Gray Matter Changes Associated With Chemotherapy-Induced Peripheral Neuropathy

Abstract

Purpose To investigate the longitudinal relationship between chemotherapy-induced peripheral neuropathy (CIPN) symptoms (sx) and brain perfusion changes in patients with breast cancer. Interaction of CIPN-sx perfusion effects with known chemotherapy-associated gray matter density decrease was also assessed to elucidate the relationship between CIPN and previously reported cancer treatment–related brain structural changes. Methods Patients with breast cancer treated with (n = 24) or without (n = 23) chemotherapy underwent clinical examination and brain magnetic resonance imaging at the following three time points: before treatment (baseline), 1 month after treatment completion, and 1 year after the 1-month assessment. CIPN-sx were evaluated with the self-reported Functional Assessment of Cancer Therapy/Gynecologic Oncology Group–Neurotoxicity four-item sensory-specific scale. Perfusion and gray matter density were assessed using voxel-based pulsed arterial spin labeling and morphometric analyses and tested for association with CIPN-sx in the patients who received chemotherapy. Results Patients who received chemotherapy reported significantly increased CIPN-sx from baseline to 1 month, with partial recovery by 1 year (P< .001). CIPN-sx increase from baseline to 1 month was significantly greater for patients who received chemotherapy compared with those who did not (P= .001). At 1 month, neuroimaging showed that for the group that received chemotherapy, CIPN-sx were positively associated with cerebral perfusion in the right superior frontal gyrus and cingulate gyrus, regions associated with pain processing (P<.001). Longitudinal magnetic resonance imaging analysis in the group receiving chemotherapy indicated that CIPN-sx and associated perfusion changes from baseline to 1 month were also positively correlated with gray matter density change (P< .005). Conclusion Peripheral neuropathy symptoms after systemic chemotherapy for breast cancer are associated with changes in cerebral perfusion and gray matter. The specific mechanisms warrant further investigation given the potential diagnostic and therapeutic implications.

Gait, balance, and patient-reported outcomes during taxane-based chemotherapy in early-stage breast cancer patients

“…While the patient-reported sensory symptoms and decreased pin prick sensitivity may suggest that damage to peripheral somatosensory nerves contributed to these deficits, it is unknown whether previously reported cases of taxane toxicity to optic [37,38] and/or motor nerves [39] or the central nervous system [40] were also contributors. As these systems are all integral to postural control and physical function, future research is warranted to elucidate contributors to the functional deficits suggested by this study.…”

“…The comparatively large changes in balance parameters suggest that tracking patient balance may provide an objective measure to detect changes early in treatment. The utility of including an objective measure in clinical assessments of CIPN is supported by Nudelman et al, who suggested that the changes to cerebral structures associated with developing CIPN may increase the risk of patients to underreport symptoms on patient-reported outcomes [40]. By including an objective measure of patient function, clinicians may be better able to detect CIPN symptoms compared to relying solely on patient-reported measures.…”

Brain structure and function in patients with ovarian cancer treated with first-line chemotherapy: a pilot study

“…However, it has been noted that methodological factors pertaining to imaging analyses, such as selection of statistical thresholds, may in part influence the pattern and extent of regional findings when different analytic approaches are used (McDonald and Saykin 2013). We derived our cluster extent threshold empirically taking into account the voxel size used in the structural and functional MRI data, which is equally or more conservative than other imaging studies in cancer survivors (de Ruiter et al 2011; Deprez et al 2014; Stouten-Kemperman et al 2015; Nudelman et al 2016). The validity of our reported findings is further strengthened by the fact that structural and functional differences overlapped or were regionally adjacent, suggesting structural differences may have contributed to functional differences between groups.…”

Evaluating the impact of chemotherapy-induced peripheral neuropathy symptoms (CIPN-sx) on perceived ability to work in breast cancer survivors during the first year post-treatment

“…Exclusion criteria included a self-reported history of prior cancer; substance abuse; and other medical, neurological, and psychiatric risk factors with the potential to affect central or peripheral neurological structure/function [30, 31]. All Ctx+ women were treated with standard doses of chemotherapy agents known to cause CIPN-sx, such as taxanes and platinum compounds.…”