Introduction: We conducted a randomized controlled trial evaluating the efficacy and tolerability of cryotherapy in preventing chemotherapy-induced peripheral neuropathy (CIPN) in patients with early breast cancer receiving neo/adjuvant weekly paclitaxel.Methods: Patients were recruited from the National Cancer Centre Singapore and randomized (1:1) to receive either cryotherapy or usual care. Cryotherapy was applied as frozen gloves and socks on all extremities from 15 min before paclitaxel until 15 min post-infusion every cycle. Efficacy was measured by patient-reported outcomes (Patient Neurotoxicity Questionnaire [PNQ] and EORTC QLQ-CIPN20) and electrophysiological assessments. The primary endpoint was PNQ severity at 2 weeks after 12 cycles of weekly paclitaxel.Results: A total of 46 patients were recruited, of which 8 dropped out before paclitaxel treatment, leaving 38 evaluable. There was no significant difference in PNQ severity between cryotherapy and usual care at 2 weeks after paclitaxel treatment (sensory: p = 0.721; motor: p = 1.000). A benefit was observed at 3 months post-paclitaxel based on PNQ (sensory: 14.3 vs. 41.2%, p = 0.078; motor: 0 vs. 29.4%, p = 0.012) and CIPN20 (sensory: β = −3.6, 95%CI = −10.5–3.4, p = 0.308; motor: β = −7.3, 95%CI = −14.6–0, p = 0.051). Additionally, cryotherapy subjects have lower CIPN20 autonomic score (β = −5.84, 95%CI = −11.15 to −0.524, p = 0.031) and higher sympathetic skin response hand amplitudes (β = 0.544, 95%CI = 0.108–0.98, p = 0.014), suggesting possible autonomic benefits from cryotherapy. Temporary interruption with cryotherapy occurred in 80.9% of the subjects due to cold intolerance.Conclusions: There is insufficient evidence that cryotherapy prevents sensory neuropathy which may be due to the high rates of cryotherapy interruption in this study. The autonomic benefits of cryotherapy should be further investigated with appropriate outcome measures.Clinical Trial Registration:ClinicalTrials.gov: NCT03429972.
Background: There is little information about cancer-related cognitive impairment (CRCI) in adolescent and young adults (AYA, 15-39 years old) due to its rare incidence. Here, we present the pre-treatment (before chemotherapy or radiotherapy) evaluation of cognitive function and ability of AYA with cancer (AYAC) in a multicentered cohort study.
Methods: Newly diagnosed AYAC and age-matched healthy controls (HC) were recruited between 2018 and 2021. The primary outcome was the comparison of pre-treatment cognitive impairment defined as 2 standard deviations (SDs) below the HC on ≥1 cognitive test, or >1.5 SDs below on ≥2 tests using CANTAB® between AYAC and HC. Secondary outcomes included self-perceived cognitive ability assessed by FACT-Cog v3 and biomarkers (inflammatory cytokines and brain-derived neurotrophic factor [BDNF]).
Results:We recruited 74 AYAC (median age = 34) and 118 HC (median age = 32). On objective cognitive testing, we observed three times more AYAC patients performed poorly on at least 2 cognitive tests compared to HC (40.5% vs. 13.6%, p < 0.001). AYAC self-perceived less degree of cognitive impairment than HC (p < 0.001). However, AYAC perceived a greater impact of cognitive changes on their quality of life compared to HC (p = 0.039). Elevated baseline inflammatory markers (IL-2, IL-4, IL-6, IL-8, IL-10 and IFN-γ) were observed among AYAC compared to HC, and baseline BDNF was lower in AYAC compared to HC. Interaction effects between cancer diagnosis and biomarkers were observed in predicting cognitive function.
Conclusion:With the pre-existence of CRCI and risk factors of neuroinflammation even prior to systemic therapy, AYAC should receive early rehabilitation to prevent further deterioration of cognitive function after initiation of systemic therapies. (Clini calTr ials.gov Identifier: NCT03476070).
Cognitive impairment due to cancer and its therapy is a major concern among cancer patients and survivors. Extracellular vesicle (EVs) composition altered by cancer and chemotherapy may affect neurological processes such as neuroplasticity, potentially impacting the cognitive abilities of cancer patients and survivors. We investigated the EV proteome of breast cancer patients with and without cognitive impairment following anthracycline-based chemotherapy from longitudinally collected plasma. EVs were cup-shaped and positive for Flotillin-1 and TSG-101. We identified 517 differentially expressed EV proteins between the cognitive impaired and non-impaired groups during and post-chemotherapy. The observed decreased expression of p2X purinoceptor, cofilin-1, ADAM 10, and dynamin-1 in the plasma EVs of the cognitive impaired group may suggest alterations in the mechanisms underlying synaptic plasticity. The reduced expression of tight junction proteins among cognitive-impaired patients may imply weakening of the blood-brain barrier. These EV protein signatures may serve as a fingerprint that underscores the mechanisms underlying cognitive impairment in cancer patients and survivors.
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