Cancer-related cognitive impairment in patients with non-central nervous system malignancies: an overview for oncology providers from the MASCC Neurological Complications Study Group.

Cancer-related cognitive impairment (CRCI) is commonly experienced by individuals with non-central nervous system cancers throughout the disease and treatment trajectory. CRCI can have a substantial impact on the functional ability and quality of life of patients and their families. To mitigate the impact, oncology providers must know how to identify, assess, and educate patients and caregivers. The objective of this review is to provide oncology clinicians with an overview of CRCI in the context of adults with non-central nervous system cancers, with a particular focus on current approaches in its identification, assessment, and management.

Malnutrition and overall survival in older patients with cancer.

BACKGROUND & AIMS: In this study, we assessed the prevalence of malnutrition and its association with overall survival among patients with cancer aged 65 years and older. METHODS: In this retrospective cohort study, patients receiving cancer care underwent a comprehensive geriatric assessment (CGA). Malnutrition status was determined through the CGA. We used univariate and multivariable Cox regression survival analyses to assess the association between baseline malnutrition and survival. RESULTS: A total of 454 patients with cancers were included in the analysis. The median age was 78 years and men and women were equally represented. Forty-two percent (n = 190) were malnourished at baseline, and 33% died during the follow-up (range 0.2-51.1 month). Univariate analysis showed that malnutrition increased the risk of all-cause mortality in older patients with cancer (HR, 1.49; 95% CI, 1.08-2.05; p = 0.01). In the multivariate Cox regression model, malnutrition increased the risk of all-cause mortality (HR, 1.87; 95% CI, 1.10-3.17; p = 0.02) in older patients with solid tumors. However, malnutrition did not increase the risk of all-cause mortality for hematologic malignancies. CONCLUSIONS: In our study, we found that malnutrition was a risk factor for mortality in older cancer patients, especially in older patients with solid tumors. Prospective inter ventional studies are recommended.

Exposure to Domestic Violence during Adolescence: Coping Strategies and Attachment Styles as Early Moderators and their Relationship to Functioning during Adulthood.

The present study aimed to investigate the impact of exposure to domestic violence during adolescence on an individual's psychological health, ability to regulate emotions, and sense of satisfaction with life, during adulthood. Additionally, it aimed to investigate the long-term role of different coping strategies and attachment with primary caregiver, during adolescence, as potential moderators in the relationship between severity of domestic violence exposure during adolescence and an individual's functioning during adulthood. A total of 218 adult participants completed measures regarding exposure to domestic violence, engagement in coping strategies, and attachment with primary caregiver, during adolescence, and psychological health, ability to regulate emotions, and sense of satisfaction with life, during adulthood. Ninety-two participants reported domestic violence exposure during adolescence. Two-way analyses of variance indicated that participants who were exposed to domestic violence during adolescence were more likely to report negative functioning during adulthood. Correlational analysis indicated that severity of domestic violence exposure during adolescence was positively correlated with engagement in avoidance-focused coping strategies and insecure attachment, during adolescence, and negative functioning during adulthood. Moderation analyses indicated that engagement in avoidance-focused coping strategies and insecure attachment with primary caregiver, during adolescence, moderated the relationship between severity of domestic violence exposure during adolescence and functioning during adulthood, but only in low-moderate severity of exposure to domestic violence. These findings confirm the long-term impact of domestic violence exposure during adolescence on an individual's functioning during adulthood, and provide new information that certain coping strategies and attachment with primary caregiver during adolescence may buffer against the impact.

Geriatric assessment in older alloHCT recipients: association of functional and cognitive impairment with outcomes.

Use of allogeneic hematopoietic cell transplantation (alloHCT) is increasing in older patients with hematologic malignancies. Studies suggest that geriatric assessment (GA), incorporating functional measures such as instrumental activities of daily living (IADL), delineates subtle age-related impairments that enhance risk-stratification. The objective of this multi-institutional retrospective study was to evaluate the prognostic utility of GA metrics collected pre-alloHCT. Eligibility criteria included age ≥50 and pre-alloHCT GA inclusive of at least IADL. Beyond IADL, additional geriatric metrics were collected where available and included Medical Outcomes Study Physical Health score (MOS-PH), Timed Up and Go (TUG), and cognition by Blessed Orientation Memory Concentration (BOMC). Three hundred thirty subjects were included, with a median age of 63 (range 50 to 77). Impairments were frequent: 36% had at least 1 IADL impairment; 14% had TUG ≥13.5 seconds; and 17% had cognitive impairment (BOMC ≥ 7). Median MOS-PH score was 80. IADL and age were not significantly associated with nonrelapse mortality (NRM) or overall survival (OS). In multivariate analysis, only impaired cognition and Hematopoietic Cell Transplant-Comorbidity Index score ≥3 showed an independent association with 1-year NRM (subdistribution hazard ratio [SHR], 2.36; P = .01; and SHR, 2.19; P = .009, respectively). Cognitive impairment independently conferred inferior 1-year OS (hazard ratio, 1.94; P = .01). In a preplanned subgroup analysis in 224 patients aged ≥60 years, cognitive impairment remained the sole GA metric predictive of NRM (2-year NRM: SHR, 2.72; P = .007). These data suggest that cognitive impairment elevates risk of post-alloHCT NRM in older patients.

The validity of three malnutrition screening markers among older patients with cancer.

BACKGROUND: Malnutrition is common in older adults with cancer and is associated with adverse clinical outcomes. We assessed and compared the validity of three tools commonly used to screen for malnutrition: The Mini Nutritional Assessment (MNA), weight loss and body mass index (BMI). METHODS: In this retrospective study, we reviewed patients over age 65 with a diagnosis of cancer who were treated at the MD Anderson Cancer Center between 1 January 2013 and 31 March 2017. All patients in this study were evaluated by a trained geriatrician as part of a comprehensive geriatric assessment (CGA). Malnutrition was diagnosed by both CGA and clinical examination. The sensitivity, specificity and Cohen's κ of each tool was also compared with the clinical diagnosis. RESULTS: A total of 454 older patients with cancer who had malnutrition information available were included in the analyses. The median age was 78%, and 42% (n=190) were clinically diagnosed with malnutrition at baseline. When the MNA was performed, 105 out of 352 patients (30%) were malnourished, and 122 (35%) at risk of malnutrition. Weight loss >3 kg was seen in 183 out of 359 (51%) patients, and BMI <20 kg/m2 was found in 30 of the 454 (7%) patients. MNA had the highest validity (area under curve (AUC)=0.83) and reliability (κ=0.67), weight loss had moderate validity (AUC=0.73) and reliability (κ=0.46), while BMI had the lowest validity (AUC=0.55) and reliability (κ=0.55). CONCLUSIONS: For clinical practice, MNA should be incorporated for standard assessment/screening for these older patients with cancer.

Overall survival in older patients with cancer.

OBJECTIVES: A growing number of patients with cancer are older adults. We sought to identify the predictors for overall survival (OS) in older adults with solid tumour and haematological malignancies between January 2013 and December 2016. METHODS: Retrospective cohort study. A comprehensive geriatric assessment was performed, with a median follow-up of 12.8 months. ANALYSIS: univariate and multivariate Cox proportional hazards regression analysis. RESULTS: In this study, among the 455 patients with last follow-up date or date of death, 152 (33.4%) died during the follow-up. The median follow-up is 12.8 months (range 0.2-51.1 months) and the median OS is 20.5 months (range 0.3-44.5 months). Among all older patients with cancer, predictors of OS included male gender, cancer stage, malnutrition, history of smoking, heavy alcohol use, frailty, weight loss, major depression, low body weight and nursing home residence. Traditional performance scores (Eastern Cooperative Oncology Group (ECOG) and Karnofsky Performance Scale (KPS)) were predictors of OS. Independent predictors included age >85 years and haematological malignancies. Among solid tumours (n=311) in addition to the above predictors, comorbidity, gait speed and vitamin D deficiency were associated with OS. CONCLUSIONS: We identified specific geriatric factors associated with OS in older patients with cancer, and comparable in predictive ability to traditional performance scores such as KPS and ECOG. Prospective studies will be necessary to confirm our findings.

Biological predictors of chemotherapy-induced peripheral neuropathy (CIPN): MASCC neurological complications working group overview.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating condition associated with a number of chemotherapeutic agents. Drugs commonly implicated in the development of CIPN include platinum agents, taxanes, vinca alkaloids, bortezomib, and thalidomide analogues. As a drug response can vary between individuals, it is hypothesized that an individual's specific genetic variants could impact the regulation of genes involved in drug pharmacokinetics, ion channel functioning, neurotoxicity, and DNA repair, which in turn affect CIPN development and severity. Variations of other molecular markers may also affect the incidence and severity of CIPN. Hence, the objective of this review was to summarize the known biological (molecular and genomic) predictors of CIPN and discuss the means to facilitate progress in this field.

Prevalence and factors associated with malnutrition in older patients with cancer.

BACKGROUND: >60% of patients with cancer are 65 years of age and older, and malnutrition is commonly encountered in older adults. OBJECTIVE: To assess the prevalence and factors associated with malnutrition in older patients with cancer. METHODS: In this cross-sectional study, patients with cancer underwent a comprehensive geriatric assessment (CGA). Malnutrition status was diagnosed by clinical assessment including screening tools such as Mini Nutrition Assessment (MNA), weight loss, and BMI. ANALYSIS: Descriptive statistics, chi-Square and logistic regression analysis were used to assess factors associated with malnutrition. RESULTS: A total of 454 patients with malnutrition information available were included in analysis. The median age was 78, range 65-96 years and comorbid diagnoses included dementia, mild cognitive impairment, frailty, and functional impairment. A total of 41.9% (n = 190) were diagnosed with malnutrition during the CGA. In the multivariable analysis, major depression and frailty were significantly associated with malnutrition. After controlling for potential confounders, patients who had malnutrition were 2.53-times more likely to have major depression (OR = 2.53, 95% CI: 1.23-5.24, p = 0.01) and 3.82 times more likely to have frailty (OR = 3.82, 95% CI: 1.35-10.84, p = 0.01) than those without malnutrition. CONCLUSIONS: Despite significant advances in cancer and supportive care, malnutrition remains a significant and highly prevalent public health problem among older patients with cancer. Identifying factors associated with risk for malnutrition in this patient population can help develop preventive strategies as part of care. Prospective studies are recommended.

Malnutrition and overall survival in older adults with cancer: A systematic review and meta-analysis.

BACKGROUND: Some studies have shown that malnutrition is associated with increased risk of mortality in older adults with cancer. However, evidence of its effect is limited and inconsistent. To assess the effect of malnutrition on overall survival in older adults with cancer, we performed a meta-analysis of available studies. METHODS: We systematically searched MEDLINE, EMBASE, Web of Science, CINAHL, and PsycINFO for observational studies that examined the association between malnutrition and risk of mortality in older adults with cancer (≥65 years). Malnutrition is defined according to assessment and screening tools in different studies. Older adults with malnutrition were compared with those with normal nutrition for overall survival. A random-effect model was fitted to estimate the summary relative risk (RR) and 95% confidence interval (CI). Between-studies heterogeneity was measured with the I2 statistic. RESULTS: Ten studies met the inclusion criteria, and a total of 4692 older adults with cancer were included in the meta-analysis. Heterogeneity existed among the different studies (I2 = 73.7%, p < 0.01). Malnutrition was significantly positively associated with increased risk of all-cause mortality (RR: 1.73; 95% CI: 1.23-2.41) compared with those with good nutrition status. A sensitivity analysis of 2773 older adults with cancer on the malnutrition assessed by Mini Nutrition Assessment (MNA), found that malnutrition is still associated with higher risk for all-cause mortality (RR = 2.13, 95% CI: 1.34-3.39). CONCLUSION: Our meta-analysis of observational studies found a significant effect of malnutrition on overall survival in older adults with cancer.

Symptom frequency and change of oldest old cancer patients.

PURPOSE: The oldest old, described as those aged 85 and older, is a growing cancer population. There are limited studies evaluating the symptoms of the oldest old cancer patient population. Our study aimed to evaluate symptom frequency and clinical symptom change as assessed by the Edmonton Symptom Assessment System (ESAS) of the oldest old (≥ 85) compared to older adult (65-84) and general adult (18-64) outpatient cancer patients on initial consult and follow-up visit. METHODS: Retrospective review of a total of 441 patients, 200 randomly sampled patients in the general and older adult group and 41 consecutive patients in the oldest old group. Chart review was performed for demographic and clinical information including ESAS. RESULTS: The oldest old group had less advanced tumors and worse performance status and was receiving less cancer therapy. Eighty percent or more of these patients reported fatigue, sleep disturbance, appetite, and drowsiness. They experienced lower frequencies of pain (p < 0.0001), fatigue (p = 0.0338), nausea (p = 0.0151), feeling of well-being (p = 0.0245), sleep disturbance (p = 0.0484), financial distress (p = 0.0002), and spiritual distress (p = 0.0010) compared to the younger groups. Twenty-six to fifty-one percent of the oldest old patients' symptoms improved on the first follow-up visit. CONCLUSIONS: Oldest old cancer patients have high frequencies of multiple symptoms on initial referral. However, these symptom frequencies are lower when compared to younger age groups. Additionally, many of their symptoms improved on first follow-up visit in the palliative care clinic. More research is needed to address the needs of this growing cancer population and focus symptoms that can improve with palliative care intervention.

Novel Cancer Therapeutics in Geriatrics: What is Unique to the Aging Patient?

With the worldwide trend of aging populations, the number of older adults who develop and survive cancer is likely to increase. In the last decade, oncology drug development has shifted away from conventional chemotherapeutics towards agents that can 'target' a driver mutation of a specific cancer or 'unleash' the patient's native immune system to attack the cancer-so-called molecularly targeted therapies and immunotherapeutics. The basic algorithms of cancer treatment in elderly patients are essentially the same as in younger patients; however, one needs to pay exceptional attention to the effects of co-morbidities, interaction with other drugs, and the organ function reserve of an older individual before determining his/her 'eligibility' for a specific cancer treatment modality. Despite the growing evidence of safety and effectiveness of combination chemotherapy in fit elderly patients, the data are still lacking concerning the use of currently approved targeted agents and immunotherapies. The current evidence, though limited, suggests reasonable tolerability with comparable efficacy in patients > 65 years old treated with immune-based therapies to that in younger controls; however, it is unclear if this leads to significant patient-relevant gains such as improved survival with an acceptable quality of life. Nonetheless, these newer agents remain better tolerated than cytotoxic chemotherapy in clinical practice, particularly in older patients. Alternatively, a personalized approach for elderly patients with consideration of the incidence and management of adverse effects, as well as strategies for optimizing efficacy in the context of an aging immune system, would be of utmost value in our aging cancer population. Future trials should also explore immune markers to predict response to these therapeutics in elderly patients, taking into consideration the effects of immunosenescence and immune modulation in aging hosts.

Medical students' reflections of a posthospital discharge patient visit.

Transitions of care is an important part of patient safety that is not often taught in medical schools. As part of a curriculum for patient safety and transitions of care, third-year medical students followed patients they cared for during their inpatient rotations on a posthospital discharge visit. Students answered reflection questions on these visits, which were reviewed at a group debriefing session. The written reflections and oral debriefings were analyzed qualitatively to identify what medical students were able to learn from a posthospital discharge visit. Of the students who visited patients, 265 participated in the debriefing sessions, and their responses were grouped into 7 domains and 33 themes. Students commented most often on the importance of family and caregivers who provided support for the patient after hospitalization. They identified problems specific to the discharge process and factors that helped or hindered transitions, noted new experiences visiting postacute care facilities, and also developed solutions to improve transitions. Postdischarge visits combined with brief reflection writing and debriefing allowed students to better understand difficulties that can be faced in care transitions.

Risk factors for falls in older patients with cancer.

OBJECTIVES: A rising number of patients with cancer are older adults (65 years of age and older), and this proportion will increase to 70% by the year 2020. Falls are a common condition in older adults. We sought to assess the prevalence and risk factors for falls in older patients with cancer. METHODS: This is a single-site, retrospective cohort study. Patients who were receiving cancer care underwent a comprehensive geriatric assessments, including cognitive, functional, nutritional, physical, falls in the prior 6 months and comorbidity assessment. Vitamin D and bone densitometry were performed. ANALYSIS: Descriptive statistics and multivariable logistic regression. RESULTS: A total of 304 patients aged 65 or above were enrolled in this study. The mean age was 78.4±6.9 years. They had haematological, gastrointestinal, urological, breast, lung and gynaecological cancers. A total of 215 patients with available information about falls within the past 6 months were included for final analysis. Seventy-seven (35.8%) patients had at least one fall in the preceding 6 months. Functional impairment (p=0.048), frailty (p<0.001), dementia (p=0.021), major depression (p=0.010) and low social support (p=0.045) were significantly associated with the fall status in the univariate analysis. Multivariate logistic regression analysis identified frailty and functional impairment to be independent risk factors for falls. CONCLUSIONS: Falls are common in older patients with cancer and lead to adverse clinical outcomes. Major depression, functional impairment, frailty, dementia and low social support were risk factors for falls. Heightened awareness and targeted interventions can prevent falls in older patients with cancer.

Hallucinations Experienced by Visually Impaired: Charles Bonnet Syndrome.

: Charles Bonnet Syndrome is a condition where visual hallucinations occur as a result of damage along the visual pathway. Patients with Charles Bonnet Syndrome maintain partial or full insight that the hallucinations are not real, absence of psychological conditions, and absence of hallucinations affecting other sensory modalities, while maintaining intact intellectual functioning. Charles Bonnet Syndrome has been well documented in neurologic, geriatric medicine, and psychiatric literature, but there is lack of information in optometric and ophthalmologic literature. Therefore, increased awareness of signs and symptoms associated with Charles Bonnet Syndrome is required among practicing clinicians. This review of the literature will also identify other etiologies of visual hallucinations, pathophysiology of Charles Bonnet Syndrome, and effective management strategies.

Characterization of ductal and lobular breast carcinomas using novel prolactin receptor isoform specific antibodies.

BACKGROUND: Prolactin is a polypeptide hormone responsible for proliferation and differentiation of the mammary gland. More recently, prolactin's role in mammary carcinogenesis has been studied with greater interest. Studies from our laboratory and from others have demonstrated that three specific isoforms of the prolactin receptor (PRLR) are expressed in both normal and cancerous breast cells and tissues. Until now, reliable isoform specific antibodies have been lacking. We have prepared and characterized polyclonal antibodies against each of the human PRLR isoforms that can effectively be used to characterize human breast cancers. METHODS: Rabbits were immunized with synthetic peptides of isoform unique regions and immune sera affinity purified prior to validation by Western blot and immunohistochemical analyses. Sections of ductal and lobular carcinomas were stained with each affinity purified isoform specific antibody to determine expression patterns in breast cancer subclasses. RESULTS: We show that the rabbit antibodies have high titer and could specifically recognize each isoform of PRLR. Differences in PRLR isoform expression levels were observed and quantified using histosections from xenografts of established human breast cancer cells lines, and ductal and lobular carcinoma human biopsy specimens. In addition, these results were verified by real-time PCR with isoform specific primers. While nearly all tumors contained LF and SF1b, the majority (76%) of ductal carcinoma biopsies expressed SF1a while the majority of lobular carcinomas lacked SF1a staining (72%) and 27% had only low levels of expression. CONCLUSIONS: Differences in the receptor isoform expression profiles may be critical to understanding the role of PRL in mammary tumorigenesis. Since these antibodies are specifically directed against each PRLR isoform, they are valuable tools for the evaluation of breast cancer PRLR content and have potential clinical importance in treatment of this disease by providing new reagents to study the protein expression of the human PRLR.