Hearing loss and intellectual outcome in children treated for embryonal brain tumors: Implications for young children treated with radiation sparing approaches.

PURPOSE: We investigate the impact of severe sensorineural hearing loss (SNHL) and for the first time evaluate the effect of unilateral versus bilateral SNHL on intellectual outcome in a cohort of children with embryonal brain tumors treated with and without radiation. METHODS: Data were from 94 childhood survivors of posterior fossa (PF) embryonal brain tumors who were treated with either: (1) chemotherapy alone (n = 16, 7.11 [3.41] years, 11M/5F), (2) standard-dose craniospinal irradiation (CSI) and/or large boost volumes (n = 44, 13.05 [3.26] years, 29M/15F), or (3) reduced-dose CSI with a boost restricted to the tumor bed (n = 34, 11.07 [3.80] years, 19M/15F). We compared intellectual outcome between children who: (1) did and did not develop SNHL and (2) developed unilateral versus bilateral SNHL. A Chang grade of ≥2b that required the use of a hearing aid was considered severe SNHL. Comparisons were made overall and within each treatment group separately. RESULTS: Patients who developed SNHL had lower full scale IQ (p = 0.007), verbal comprehension (p = 0.003), and working memory (p = 0.02) than patients without SNHL. No differences were observed between patients who had unilateral versus bilateral SNHL (all p > 0.05). Patients treated with chemotherapy alone who developed SNHL had lower mean working memory (p = 0.03) than patients who did not develop SNHL. Among patients treated with CSI, no IQ indices differed between those with and without SNHL (all p > 0.05). CONCLUSIONS: Children treated for embryonal brain tumors who develop severe SNHL have lower intellectual outcome than patients with preserved hearing: this association is especially profound in young children treated with radiation sparing approaches. We also demonstrate that intellectual outcome is similarly impaired in patients who develop unilateral versus bilateral SNHL. These findings suggest that early intervention to preserve hearing is critical.

Cognitive Functions under Anti-HER2 Targeted Therapy in Cancer Patients: A Scoping Review.

Pharmacological therapy targeting the HER2 protein is one of the major breakthroughs in the treatment of cancer patients overexpressing HER2 who have increased survival rates. Despite improved survival, it is important to determine the less frequent adverse effects in order to tailor treatments more personalized to the patients' features. The possible impact of cancer treatments on cognitive functions is huge, and the effects of anti-HER 2 therapies on this issue have not been reviewed and are the objective of this study. Analysis of PubMed, Scopus, Cochrane library and Web of Science databases revealed six studies performed in breast and serous uterine cancer patients analyzing cognitive function under chemotherapy regimens including anti-HER2 drugs. Four of these studies reported small to significant worsening of cognitive function following chemotherapy regimens containing trastuzumab (the most widely used anti-HER2 drug). In neoadjuvant settings, and in breast cancer patients, treatment with the new anti-HER-2 drug trastuzumab emtansine seems to induce less cognitive impairment than therapeutic regimens containing chemotherapy and trastuzumab. Acute administration of trastuzumab induced cognitive impairment in gastric cancer mice models, confirming its ability to alter cognitive function in patients. More studies analyzing the impact of anti-HER2 therapy on cognitive function are necessary at preclinical and clinical levels in order to personalize pharmacological treatment and offer cancer patients a better quality of life.

Chemotherapy-induced cognitive impairment from the forensic medicine perspective: A review of the updated literature.

Chemotherapy treatments in some neoplastic patients can cause unwanted side-effects that can be accompanied by a physical weakening due to changes in executive functioning, processing speed and reaction times with a consequent inability to carry out daily life activities (ADL) or a working disability due to the loss of working memory and the inability to organize fundamental skills, influencing the quality of everyday life. Although chemotherapy-induced cognitive impairment (CICI), also known as post-chemotherapy cognitive impairment (PCCI), chemo-brain or chemo-fog, has been described in the literature since the late 1980s, the neurobiological factors behind this pathology to date are not yet fully understood. According to the finding of most studies conducted on patients affected by different forms of neoplastic diseases, there are strong enough evidence of a prominent role of some drug such as doxorubicin, cyclophosphamide, cytarabine, methotrexate, 5-fluorouracil and cisplatin in causing chemo-fog related neurological impairment. The physical incapacity that affects the patients seems, therefore, to be related to the cytotoxic effects that the chemotherapy drugs exert on the central nervous system, causing a short or long-term neurological decline. Cognitive dysfunctions could influence individual self-determination by configuring a state of transient or habitual mental infirmity capable of altering the preservation of the person's voluntary faculties, with potential consequences on the legal validity of any deeds signed by the person. The growing interest in this pathological condition by the forensic medicine community is due precisely to the non-negligible medico-legal implications that derive from it affecting aspects of private law. In this article, a review of the literature on chemotherapy-induced cognitive impairment and related issues that may arise in forensic medicine and private law was conducted.

Potential for identification of memory problems in the cancer clinic to enable improved treatment experience and outcomes: Mixed methods case study research.

PURPOSE: To inform improvement in cancer treatment experience and outcomes for people with dementia or milder cognitive impairment. People with dementia, compared to those without, experience more side effects from cancer treatment and have poorer outcomes including poorer survival. METHODS: The research was a mixed methods exploratory case study. Each case was a cancer treatment in a person with memory loss, a common symptom of dementia. Observations were conducted in 30 clinic sessions at one cancer centre between September 2014 and February 2015. Thirty-three encounters between people with a memory problem and a staff member were observed and ten consultations recorded. Interviews were conducted with five staff members and six people receiving cancer treatment, five accompanied by their carer. Analysis, informed by hermeneutic phenomenology, enabled the treatment pathway to be mapped and modelled to reveal sites for intervention. FINDINGS: Five potential sites of intervention were identified in the treatment pathway. Five actions at the sites of intervention that may improve patient experience and outcomes include, raising awareness of common problems for people with cognitive impairment receiving cancer treatment, encouraging disclosure of memory problems, staff training to identify memory problems and to know what to do, offering tools and techniques to aid self-management of memory problems, and addressing carer support needs. CONCLUSION: Embedding biomedical treatment of cancer within a dementia-friendly psychosocial system may enable safe cancer treatment for a greater number of people with dementia or milder cognitive impairment.

Doxorubicin chemotherapy-induced "chemo-brain": Meta-analysis.

Doxorubicin is a leading chemotherapeutic halting cellular replication and inducing p53-dependent apoptosis in cancerous tissue. Like many chemotherapies, doxorubicin damages healthy tissue throughout the body through cellular mechanisms independent of its chemotherapeutic action. Although cognitive impairment is commonly recorded in patients after chemotherapy, the occurrence of doxorubicin-induced "chemo-brain" is debated, as doxorubicin cannot cross the blood-brain barrier. However, the potential of indirect doxorubicin neurotoxicity remains, providing a foundation for doxorubicin-mediated chemo-brain. We present the first meta-analysis of defined cognitive performance of doxorubicin-treated patients. A search of PubMed and MedLine collected 494 studies, 14 of which met analysis criteria. Performance of 511 doxorubicin-treated women with breast cancer was compared to that of 306 healthy controls across measures of defined cognitive modalities. Treated patients experience significant impairment in global cognition compared to controls (g= -0.41, P < 0.001), with select impairment in executive function (g = -0.25, P < 0.0001), language (g = -0.30, P < 0.0001), memory (g = -0.12, P < 0.01) and processing speed (g = -0.28, P < 0.01). Within memory, short-term verbal memory is most significantly affected (g = -0.21, P < 0.01). Impairment in select cognitive modalities (executive function, language, memory, short-term verbal memory, processing speed) is prevalent in doxorubicin-treated patients, with some cognitive functions remaining intact (attention, motor function, visuospatial abilities). This information can guide the development of future interventions to improve quality-of-life (QOL) and doxorubicin-derived therapies that target cytotoxicity to cancerous tissue, avoiding healthy tissue damage, which is mediated by seemingly independent mechanisms.

Chemotherapy-related cognitive impairment in patients with breast cancer based on MRS and DTI analysis.

The purpose of this study is to investigate chemotherapy-related cognitive impairment (CRCI) in breast cancer patients, analyze absolute concentration and structural changes of metabolites in different brain regions by multimodal neuroimaging technology, and explore correlation between them. Breast cancer patients with chemotherapy treatment group (Ctx+, N = 24) and control group without treatment (Ctx-, N = 20) underwent neuropsychological tests, multivoxel magnetic resonance spectroscopy (MRS), and diffusion tensor imaging (DTI) before and after chemotherapy. Regions of interest (ROls) in magnetic resonance scan include bilateral posterior cingulate gyrus (PCG), bilateral dorsal thalamus (DT), bilateral lenticular nucleus (LN), bilateral posterior horn of the lateral ventricle paratrigonal white matter (PWM). In MRS, absolute concentrations of N-acetylaspartate (NAA), myo-inositol (MI), choline-containing compounds (Cho), total creatine (tCr), glutamine + glutamate (Glx) were quantified using LC Model and SAGE software. In DTI, we used fractional anisotropy (FA) and mean diffusivity (MD) to reflect white matter integrity. In Ctx+ patients, scores of functional assessment of cancer treatment cognition test (FACT-Cog), perceived cognitive impairments (PCI), impact of perceived impairments on quality of life (QOL), perceived cognitive abilities (PCA), auditory-verbal learning test (AVLT) recognition and clock drawing test (CDT) were lower than those before chemotherapy (p < 0.05). In MRS, Ctx+ patients had significantly lower NAA values in bilateral PCG, DT, respectively. The concentrations of tCr were observed to decline in bilateral PCG and right DT. Glx values decreased in right DT. Cho values decreased significantly in bilateral DT. In DTI, Ctx+ patients had lower FA values in bilateral PCG compared with patients before chemotherapy. Among imaging metrics and cognitive scores, positive correlations were observed between changes in AVLT recognition scores and changes in NAA values in bilateral PCG (left PCG: r = 0.470, p < 0.01; right PCG: r = 0.500, p < 0.01). Positive correlations were also found between changes in AVLT recognition and changes in FA values in bilateral PCG (left PCG: r = 0.513, p < 0.01; right PCG: r = 0.563, p < 0.01). Chemotherapy can lead to a decrease in memory function, accompanied by changes in brain metabolite concentration and white matter integrity in some parts of brain.