Impact of Cryotherapy on Sensory, Motor, and Autonomic Neuropathy in Breast Cancer Patients Receiving Paclitaxel: A Randomized, Controlled Trial.

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: ß = -3.6, 95%CI = -10.5-3.4, p = 0.308; motor: ß = -7.3, 95%CI = -14.6-0, p = 0.051). Additionally, cryotherapy subjects have lower CIPN20 autonomic score (ß = -5.84, 95%CI = -11.15 to -0.524, p = 0.031) and higher sympathetic skin response hand amplitudes (ß = 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.

Replication and Meta-analysis of the Association between BDNF Val66Met Polymorphism and Cognitive Impairment in Patients Receiving Chemotherapy.

Cancer-related cognitive impairment (CRCI) adversely affects cancer patients. We had previously demonstrated that the BDNF Val66Met genetic polymorphism is associated with lower odds of subjective CRCI in the multitasking and verbal ability domains among breast cancer patients receiving chemotherapy. To further assess our previous findings, we evaluated the association of BDNF Val66Met polymorphism with subjective and objective CRCI in a temporally separate cohort of patients and pooled findings from both the original (n = 145) and current (n = 193) cohorts in a meta-analysis. Subjective CRCI was assessed using FACT-Cog. Objective CRCI was evaluated using computerized neuropsychological tests. Genotyping was carried out using Sanger sequencing. The association of BDNF Val66Met genotypes and CRCI was examined with logistic regression. A fixed-effect meta-analysis was conducted using the inverse variance method. In the meta-analysis (n = 338), significantly lower odds of CRCI were associated with Met allele carriers based on the global FACT-Cog score (OR = 0.52, 95% CI 0.29-0.94). Furthermore, Met allele carriers were at lower odds of developing impairment in the domains of memory (OR = 0.34, 95% CI: 0.17-0.70), multitasking (OR = 0.33, 95% CI: 0.18-0.59), and verbal ability (OR = 0.46, 95% CI: 0.24-0.88). Consistent with the previous study, lower odds of subjective CRCI among patients with the BDNF Met allele was observed after adjusting for potential confounders in the multitasking (OR = 0.30, 95% CI: 0.14-0.67) domain. In conclusion, carriers of the BDNF Met allele were protected against global subjective CRCI, particularly in the domains of memory, multitasking, and verbal ability. Our findings further contribute to the understanding of CRCI pathophysiology.

Association of mitochondrial DNA content in peripheral blood with cancer-related fatigue and chemotherapy-related cognitive impairment in early-stage breast cancer patients: a prospective cohort study.

PURPOSE: Cancer-related fatigue (CRF) and chemotherapy-related cognitive impairment (CRCI) are reported to be associated with mitochondrial dysfunction. Hence, mitochondrial DNA (mtDNA) content, a biomarker of mitochondrial dysfunction, is hypothesized to correlate with the onset of CRF and CRCI. This study aims to evaluate the association between peripheral blood mtDNA content reduction and severity of CRF and CRCI in patients receiving chemotherapy. METHODS: This was a prospective cohort study. Early-stage breast cancer patients receiving anthracycline- or taxane-based chemotherapy were recruited. CRF was assessed using MFSI-SF, and CRCI was assessed using FACT-Cog and CANTAB at two timepoints: baseline (T1; prior to treatment) and 6 weeks after initiation of treatment (T2). mtDNA content was measured at both timepoints using real-time quantitative polymerase chain reaction. Multiple logistic regression was utilized to evaluate the association between mtDNA reduction and worsening of CRF and CRCI, adjusting for age, anxiety, insomnia, plasma cytokines concentrations, and other clinically important covariates. RESULTS: A total of 108 patients (age 52.0 ± 9.2 years; 82.4% Chinese; 64.8% receiving anthracycline-based chemotherapy) were recruited. Proportions of patients with worsening of CRF increased from the lower to the upper quartiles of mtDNA reduction (22.2, 33.3, 55.6, and 63.0% in quartiles 1, 2, 3, and 4, respectively, p = 0.001 for trend). Reduction of mtDNA content was significantly greater among those with worsening of CRF and CRCI compared to those without CRF [mean reduction (± SD): 36.5 (46.1) vs. 9.4 (34.5), p < 0.001]. After adjusting for covariates, every 1-unit reduction of the mtDNA content was associated with a 4% increased risk for worsening of CRF (95% CI, 1-6%; p = 0.009). CONCLUSIONS: This is the first study to show that the reduction of mtDNA content in peripheral blood is associated with the onset of CRF in patients receiving chemotherapy. Further validation studies are required to confirm the findings.

Addressing the needs of colorectal cancer survivors: current strategies and future directions.

Colorectal cancer (CRC) is one of the three topmost common cancers in men and the second most common cancer in women worldwide. With current advances in the medical and surgical treatment of CRC, care has slowly transformed to curative treatment. With these advances, CRC survivors are increasing in numbers and these patients have a unique range of medical, physical and psychological needs that require regular follow-up. In 2006, the Institute of Medicine recommended that cancer survivors who are completing primary treatment receive a survivorship care plan. There are many different programs of different complexity that are implemented for CRC survivors. This review outlines the needs of CRC survivors, the current surveillance techniques used in the continuing care of patients with CRC after curative treatment and the evidence behind these strategies.