Modulation by Ozone Therapy of Oxidative Stress in Chemotherapy-Induced Peripheral Neuropathy: The Background for a Randomized Clinical Trial.

(1) Background: Chemotherapy-induced peripheral neuropathy (CIPN) decreases the quality of life of patients and can lead to a dose reduction and/or the interruption of chemotherapy treatment, limiting its effectiveness. Potential pathophysiological mechanisms involved in the pathogenesis of CIPN include chronic oxidative stress and subsequent increase in free radicals and proinflammatory cytokines. Approaches for the treatment of CIPN are highly limited in their number and efficacy, although several antioxidant-based therapies have been tried. On the other hand, ozone therapy can induce an adaptive antioxidant and anti-inflammatory response, which could be potentially useful in the management of CIPN. (2) Methods: The aims of this works are: (a) to summarize the potential mechanisms that could induce CIPN by the most relevant drugs (platinum, taxanes, vinca alkaloids, and bortezomib), with particular focus on the role of oxidative stress; (b) to summarize the current situation of prophylactic and treatment approaches; (c) to describe the action mechanisms of ozone therapy to modify oxidative stress and inflammation with its potential repercussions for CIPN; (d) to describe related experimental and clinical reports with ozone therapy in chemo-induced neurologic symptoms and CIPN; and (e) to show the main details about an ongoing focused clinical trial. (3) Results: A wide background relating to the mechanisms of action and a small number of experimental and clinical reports suggest that ozone therapy could be useful to prevent or improve CIPN. (4) Conclusions: Currently, there are no clinically relevant approaches for the prevention and treatment of stablished CIPN. The potential role of ozone therapy in this syndrome merits further research. Randomized controlled trials are ongoing.

Effects of ozone therapy on anxiety and depression in patients with refractory symptoms of severe diseases: a pilot study.

Background: Patients with refractory symptoms of severe diseases frequently experience anxiety, depression, and an altered health-related quality of life (HRQOL). Some publications have described the beneficial effect of ozone therapy on several symptoms of this kind of patient. The aim of this study was to preliminarily evaluate, in patients treated because of refractory symptoms of cancer treatment and advanced nononcologic diseases, if ozone therapy has an additional impact on self-reported anxiety and depression. Methods: Before and after ozone treatment, we assessed (i) anxiety and depression according to the Hospital Anxiety and Depression Scale (HADS); (ii) the HRQOL (according to the EQ-5D-5L questionnaire), which includes a dimension on anxiety and depression and a visual analog scale (VAS) measuring self-perceived general health. Results: Before ozone therapy, 56% of patients were on anxiolytic and/or antidepressant treatment. Before and after ozone therapy, the anxiety and depression HADS subscales (i) significantly correlated with the anxiety/depression dimension of the EQ-5D-5L questionnaire and (ii) inversely correlated with the health status as measured by the VAS. After ozone therapy, we found a significant improvement in anxiety and depression measured by both the (i) HADS subscales and (ii) EQ-5D-5L questionnaire. Conclusion: The addition of ozone therapy for patients with refractory symptoms of cancer treatment and advanced chronic nononcologic diseases can decrease anxiety and depression severity levels. Additional, more focused studies are ongoing to provide the needed explanatory information for this finding.

Effects of Ozone Treatment on Health-Related Quality of Life and Toxicity Induced by Radiotherapy and Chemotherapy in Symptomatic Cancer Survivors.

(1) Background: The continuous improvement in cancer treatment has led to improvement in patients' survival and a subsequent increase in the number of cancer survivors living with adverse side effects of cancer treatments, sometimes with a high and adverse impact on their health-related quality of life (HRQOL). Side effects of cancer treatments are frequently associated with chronic status of oxidative stress, inflammation, and/or ischemia. The potential for ozone treatment to modulate those processes and improve some of those adverse effects has previously been described. The aim of this study was to evaluate the effect of ozone treatment on the HRQOL and grade of toxicity in symptomatic cancer survivors. (2) Methods: Before and after ozone treatment, we assessed (i) the HRQOL (according to the EQ-5D-5L questionnaire) and (ii) the grade of toxicity (according to the Common Terminology Criteria for Adverse Events of the National Cancer Institute of EEUU (CTCAE v.5.0)) in 26 cancer survivors with chronic side effects of radiotherapy and chemotherapy. (3) Results: There was a significant (p < 0.001) improvement in the EQ-5D-5L index as per the self-reported outcome evaluation of patients' health status. All the dimensions of the EQ-5D-5L questionnaire (mobility, self-care, activities, pain/discomfort, and anxiety/depression) and the self-evaluation of the health status using the visual analog scale were significantly improved (p < 0.05). The grade of toxicity was also significantly decreased (p < 0.001). (4) Conclusions: In cancer survivors with chronic side effects of cancer treatment, ozone treatment can improve the grade of toxicity and the HRQOL. These results merit additional research. Further studies are ongoing.

Impact of body mass index on pathological complete response and survival of breast cancer patients receiving neoadjuvant chemotherapy.

BACKGROUND: High body mass index (BMI) is regarded as a poor prognostic factor in breast cancer (BC). However, its association with pathological complete response (pCR) and survival after neoadjuvant chemotherapy (NAC) remains controversial. OBJECTIVE: We wanted to assess the prognostic impact of BMI in this setting. METHODS: Single-center, retrospective review of 314 BC patients undergoing NAC from 2010 to 2018. Patients were categorized as underweight/normal weight (UW/NW) (BMI < 25) or overweight/obese (OW/OB) (BMI ≥ 25). The relationship between BMI and other traditional clinical-pathological prognostic variables with the pCR rate was investigated using logistic regression analysis. The effect on event-free survival (EFS) and overall survival (OS) was estimated by the Cox proportional hazards regression analysis. RESULTS: One hundred and twenty-two patients were UW/NW while 192 were OW/OB. Multivariate analysis revealed that hormonal receptors negative, HER2 positive, and clinical tumor stage (cT) 1-2 were independent predictor factors for pCR. Multivariate analysis confirmed tumor grade G3 and lack of pCR as independent adverse prognostic factors for EFS, while factors associated with worse OS were cT3-4, hormone receptors negative, and lack of pCR. Non-significant differences in pCR, EFS, or OS were observed between the two baseline BMI categories. CONCLUSIONS: In our experience, BMI is not associated with pCR, EFS, or OS in BC patients receiving NAC. Achieving pCR is the most consistent factor associated with EFS and OS. Prospective and well-designed studies taking into account other important biological and anthropometric factors are needed to determine the exact role of BMI in this setting.

Long-term improvement by ozone treatment in chronic pain secondary to chemotherapy-induced peripheral neuropathy: A preliminary report.

Background: Pain secondary to chemotherapy-induced peripheral neuropathy (CIPN) can limit the administration of chemotherapy, cancer-treatment outcomes, and the quality of life of patients. Oxidative stress and inflammation are some of the key mechanisms involved in CIPN. Successful treatments for CIPN are limited. This report shows our preliminary experience using ozone treatment as a modulator of oxidative stress in chronic pain secondary to CIPN. Methods: Ozone treatment, by rectal insufflation, was administered in seven patients suffering from pain secondary to grade II or III CIPN. Pain was assessed by the visual analog scale (VAS). Results: All patients, except one, showed clinically relevant pain improvement. Median pain score according to the VAS was 7 (range: 5-8) before ozone treatment, 4 (range: 2-6) at the end of ozone treatment (p = 0.004), 5.5 (range: 1.8-6.3) 3 months after the end of ozone treatment (p = 0.008), and 6 (range: 2.6-6.6) 6 months after the end of ozone treatment (p = 0.008). The toxicity grade, according to the Common Terminology Criteria for Adverse Events (CTCAE v.5.0), improved in half of the patients. Conclusion: This report shows that most patients obtained clinically relevant and long-lasting improvement in chronic pain secondary to CIPN after treatment with ozone. These observed effects merit further research and support our ongoing randomized clinical trial (NCT04299893).