Sarcopenia Diagnosis and Management in Hematological Malignancies and Differences with Cachexia and Frailty.

Sarcopenia is a geriatric syndrome characterized by a progressive loss of systemic muscle mass and decreased muscle strength or physical function. Several conditions have a role in its pathogenesis, significantly impacting adverse outcomes such as falls, functional decline, frailty, disability, multiple hospitalizations, and mortality. In the oncological setting, sarcopenia is associated with an increased risk of treatment toxicity, postoperative complications, and a higher mortality rate related to other causes (e.g., pneumonia). In the hematological field, even more so, sarcopenia predicts toxicity and response to treatments. In patients with hematologic malignancy, low muscle mass is associated with adverse outcomes and is a predictor of overall survival and non-relapse mortality. Therefore, it is essential to correctly recognize sarcopenia, evaluate the risk factors and their impact on the patient's trajectory, and effectively treat sarcopenia. Sarcopenia is a reversible condition. The most effective intervention for reversing it is physical exercise combined with nutrition. The objective of clinical assessment focused on sarcopenia is to be able to carry out a "tailor-made treatment".

Frailty modifies the effect of polypharmacy and multimorbidity on the risk of death among nursing home residents: Results from the SHELTER study.

Background: Frailty, disability, and polypharmacy are prevalent in nursing home (NH) residents, often co-occurring with multimorbidity. There may be a complex interplay among them in terms of outcomes such as mortality. Aims of the study were to (i) assess whether nursing home residents with polypharmacy (5-9 medications) or hyperpolypharmacy (≥10 drugs), have an increased risk of death and (ii) whether any association is modified by the co-presence of frailty or disability. Methods: Cohort study with longitudinal mortality data including 4,023 residents from 50 European and 7 Israeli NH facilities (mean age = 83.6 years, 73.2% female) in The Services and Health for Elderly in Long Term care (SHELTER) cohort study. Participants were evaluated with the interRAI-LongTerm Care assessment tool. Frailty was evaluated with the FRAIL-NH scale. Hazard ratio (HR) of death over 12 months was assessed with stratified Cox proportional hazards models adjusted for demographics, facilities, and cognitive status. Results: 1,042 (25.9%) participants were not on polypharmacy, 49.8% (n = 2,002) were on polypharmacy, and 24.3% (n = 979) on hyperpolypharmacy. Frailty and disability mostly increased risk of death in the study population (frailty: HR = 1.85, 95%CI 1.49-2.28; disability: HR = 2.10, 95%CI 1.86-2.47). Among non-frail participants, multimorbidity (HR = 1.34, 95%CI = 1.01-1.82) and hyperpolypharmacy (HR = 1.61, 95%CI = 1.09-2.40) were associated with higher risk of death. Among frail participants, no other factors were associated with mortality. Polypharmacy and multimorbidity were not associated with mortality after stratification for disability. Conclusions: Frailty and disability are the strongest predictors of death in NH residents. Multimorbidity and hyperpolypharmacy increase mortality only in people without frailty. These findings may be relevant to identify patients who could benefit from tailored deprescription.

Rapidly Progressive Malignant Pelvic Perivascular Epithelioid Cell Neoplasm (PEComa) Associated with Eggerthella lenta Bloodstream Infection.

Perivascular epithelioid cell tumors (PEComa) are rare mesenchymal neoplasms composed of cells that express melanocytic and myogenic markers and grow around small blood vessels. PEComa often show benign behaviors but can also be highly aggressive. In frail and more complex patients, many conditions can overlap, compounding the diagnostic and therapeutic difficulties inherent in rare diseases. Moreover, the complexity of modern patients introduces new and significant players in host-microbe interactions, and emerging pathogens represent a relevant challenge to modern healthcare. Among these pathogens is Eggerthella lenta, an anaerobic gram-positive bacterium of the normal gut microbiota associated with life-threatening infections. Here, we present a case of malignant pelvic PEComa with rapid metastatic progression in a 73-year-old man who presented with an E. lenta bloodstream infection. Approaching differential diagnosis with open-mindedness may assist in better imaging interpretation, surgery scheduling, and proper treatment planning. The non-specific clinical presentation might delay timely diagnosis, while the absence of well-consolidated guidelines undermines the accurate management of the disease, for which strict follow-up can favor better outcomes. Progress in diagnostic techniques, such as the implementation of MALDI-TOF (matrix-assisted laser desorption/ionization-time of flight) mass spectrometry for micro-organism identification, helps with a more accurate pathogen diagnosis and characterization. This allows the implementation of the most appropriate therapy, as well as better surveillance of antibiotic resistance, infection prevention, and control measures. Nevertheless, a good dose of wisdom is vital to avoid overlooking potentially harmful pathogens, particularly in frail individuals.

Characteristics of patients with cancer in European long-term care facilities.

PURPOSE: Up to 26% of residents in nursing homes (NHs) are affected by cancer. Their care represents a challenge, because NHs are not usually considered a setting focused on oncologic management and care. The aim of this paper is to describe socio-demographic and clinical features of patients with cancer residing in European NHs. METHODS: Cross-sectional study based on data from the Services and Health for Elderly in Long TERm care (SHELTER) study. Participants were assessed through the interRAI-LTCF, which includes cancer assessment. RESULTS: Among 4140 participants (mean age 83.4 years; female 73%), 442 (10.7%) had cancer. Patients with cancer had a higher prevalence of do-not-resuscitate directives compared to those without cancer (21.1% vs 16.5%, p = 0.019). Variables directly associated with cancer were male sex (adj OR 1.67, 95% CI 1.36-2.05), pain (adj OR 1.43, 95% CI 1.16-1.77), fatigue (adj OR 1.25, 95% CI 1.01-1.55), polypharmacy (adj OR 1.59, 95% CI 1.21-2.08) and falls (adj OR. 1.30, 95% CI 1.01-1.67). Dementia was inversely associated with cancer (adj OR 0.74, 95% CI 0.58-0.94). Symptomatic drugs such as opioids (23.5% vs 12.2, p < .001), NSAIDS (7.2% vs 3.9%, p = 0.001), antidepressants (39.1% vs 33.8%, p = 0.026) and benzodiazepines (40.3% vs 34.3, p = 0.012) were all prescribed more in participants with cancer compared to those without cancer. CONCLUSIONS: Cancer patients are prevalent in European NHs and they show peculiar characteristics. Studies are needed to evaluate the impact of a supportive care approach on the management of NHs residents with cancer throughout all its phases, until the end-of-life care.

Different Impact of Definitions of Sarcopenia in Defining Frailty Status in a Population of Older Women with Early Breast Cancer.

Sarcopenia is a geriatric syndrome characterized by losses of quantity and quality of skeletal muscle, which is associated with negative outcomes in older adults and in cancer patients. Different definitions of sarcopenia have been used, with quantitative data more frequently used in oncology, while functional measures have been advocated in the geriatric literature. Little is known about the correlation between frailty status as assessed by comprehensive geriatric assessment (CGA) and sarcopenia in cancer patients. We retrospectively analyzed data from 96 older women with early breast cancer who underwent CGAs and Dual X-ray Absorptiometry (DXA) scans for muscle mass assessment before cancer treatment at a single cancer center from 2016 to 2019 to explore the correlation between frailty status as assessed by CGA and sarcopenia using different definitions. Based on the results of the CGA, 35 patients (36.5%) were defined as frail. Using DXA Appendicular Skeletal Mass (ASM) or the Skeletal Muscle Index (SMI=ASM/height^2), 41 patients were found to be sarcopenic (42.7%), with no significant difference in prevalence between frail and nonfrail subjects. Using the European Working Group on Sarcopenia in Older People (EWGSOP2) definition of sarcopenia (where both muscle function and mass are required), 58 patients were classified as "probably" sarcopenic; among these, 25 were sarcopenic and 17 "severely" sarcopenic. Only 13 patients satisfied both the requirements for being defined as sarcopenic and frail. Grade 3-4 treatment-related toxicities (according to Common Terminology Criteria for Adverse Events) were more common in sarcopenic and frail sarcopenic patients. Our data support the use of a definition of sarcopenia that includes both quantitative and functional data in order to identify frail patients who need tailored treatment.

Perspectives and limits of cancer treatment in an oldest old population.

BACKGROUND: Population of oldest old will grow dramatically in the next future and cancer, physiologically related to aging, will be very prevalent among them. Lack of evidence is a huge problem to manage cancer in oldest old and will be more and more in the next years. AIMS: Our purpose was to investigate the characteristics of a population of oldest old patients with cancer treated in the Radiation Oncology Unit of Fondazione Policlinico A. Gemelli IRCCS. METHODS: We conducted a retrospective study. The primary outcome was to evaluate which characteristics of the population could influence the choice of oncological treatment (with radical or non-radical intent). RESULTS: We identified a total of 348 patients: 140 were on follow-up; 177 were under treatment; 31 were considered not eligible for treatments. Patients under treatment had a high comorbidity index (mean Charlson Comorbidity Index 5.4), and a high prevalence of polypharmacy (mean number of drugs 5.6). More than half (53.1%) was treated with radical intent. Patients treated with radical intent were 1 year younger (87.1 years old vs 88.1 years old), more performant (ECOG 0.7 vs 1.3), and had less prevalence of metastatic neoplasia (6.4% vs 34.9%); comorbidities and drugs did not show differences in the two groups. CONCLUSION: Oldest old, usually not considered in international guidelines, are treated for oncological disease, often with radical intent. The treatment seems not to be tailored considering comorbidities but on performance status.

Comprehensive geriatric assessment in older adults with cancer: Recommendations by the Italian Society of Geriatrics and Gerontology (SIGG).

INTRODUCTION: Optimizing the approach to older adults with cancer is now a priority given the increasing frequency of new cancer diagnoses that are made in the older population. The comprehensive geriatric assessment (CGA) represents the gold-standard for (1) defining prognosis and ability to withstand cancer treatments, (2) exploring the multiple aspects that define the complexity of frail older persons, and (3) designing person-tailored interventions. MATERIALS AND METHODS: In this document, based on a comprehensive revision of the literature, the Italian Society for Geriatrics and Gerontology proposes a CGA model (ONCOGER CGA) to be adopted by oncology centers for their routine approach to older patients with cancer. RESULTS AND DISCUSSION: A widespread use of this standardized CGA format will facilitate comparisons across institutions, promote studies based on a multidimensional patient assessment, and foster the inclusion of geriatric endpoints in oncological clinical trials. Furthermore, we predict that the use of a standardized CGA approach will increase the integration of geriatricians into oncology care teams with the final result of improving therapeutic choices and clinical outcomes.

The importance of geriatric and surgical co-management of elderly in muscoloskeletal oncology: A literature review.

People over 65 years old are the fastestgrowing part of the population and also the most common population in oncological practice. The geriatric co-assessment when involved in the management of orthopedic elderly patients could improve the survival and clinical outcomes of the patients. The aim of this review is to understand the importance of comprehensive geriatric assessment in elderly cancer orthopaedic patients affected by bone and soft tissue sarcoma in order to apply it and identify the mean surgical prognostic factors of this population.

Biological and Functional Biomarkers of Aging: Definition, Characteristics, and How They Can Impact Everyday Cancer Treatment.

PURPOSE OF REVIEW: Recognize which are the elements that predict why a person is aging faster or slower and which intervention we can arrange to slow down the process, which permits to prevent or delay the progression of multimorbidity and disability. RECENT FINDINGS: Aging is a complex process that leads to changes in all the systems of the body and all the functions of the person; however, aging develops at different rates in different people, and chronological age is not always consistent with biological age. Gerontologists are focused not only on finding the best theory able to explain aging but also on identifying one or more markers, which are able to describe aging processes. These biomarkers are necessary to better define the aging-related pathologies, manage multimorbidity, and improve the quality of life. The aim of this paper is to review the most recent evidence on aging biomarkers and the clusters related to them for personalization of treatments.

Cognitive decline in older long-term survivors from Non-Hodgkin Lymphoma: a multicenter cross-sectional study.

OBJECTIVES: To compare cognition in a group of older long-term survivors from Non-Hodgkin Lymphoma (NHL) and in a corresponding group of non-cancer controls of the same age. Functional status, polypharmacy and multimorbidity were also evaluated. METHODS: A cross-sectional study was performed in a population of 63 outpatient long-term survivors from NHL, aged 65 or more and 61 non-cancer controls. Socio-demographic, clinical and functional data were collected. Cognitive function was assessed through neuropsychological tests. RESULTS: NHL survivors showed a slightly worse functional status than controls, they were affected by more chronic conditions (3.4 vs 2.3; p = .003) and were taking a higher number of medications (3.4 vs 2.3; p = .03). The Mini Mental State Examination (MMSE) was not significantly different between the groups. NHL survivors performed worse than controls in executive functioning (Trail Making Test B-A 47.9 vs 32.1 p = .04, OR for Stroop test time over 75th percentile in survivors: 2.66; CI 95% 1.04-6.61; OR for Multiple Features Target Cancellation time over 75th percentile in survivors: 2.84; CI 95% 1.10-7.31). A small, statistically significant difference was also observed in verbal memory scores between the two groups. . CONCLUSIONS: The findings of this study suggest that, compared with non-cancer controls, older survivors from NHL may have a lower cognitive performance, especially in the executive functioning and attention domains, regardless of multimorbidity and polypharmacy. Further evidence from larger samples is needed to confirm such findings and better characterize cognitive decline in NHL survivors.

Comorbidity assessment to determine prognosis in older adult patients with classical Hodgkin lymphoma.

The clinical management of older adult patients with Hodgkin lymphoma (HL) remains a major challenge. The aim of this study was to evaluate the impact of comorbidity assessment according to a standardized approach, the Cumulative Illness Rating Scale (CIRS), on prognosis in patients with classical HL aged 60 years and older. We studied 76 consecutive older adult patients with HL (median age 69 y, range 60-84) who had been treated in our institution between 1999 and 2018. Comorbidity was assessed at diagnosis according to CIRS. Anthracycline-containing chemotherapy with curative intent was administered in 59 (78%) patients. We identified 41 (54%) patients with at least one severe comorbidity rated on CIRS grade ≥ 3. Patients with severe comorbidity were more likely to have advanced-stage disease (P = .003), to have an International Prognostic Score (IPS) > 3 (P = .03), and to not receive anthracycline-containing chemotherapy (P = .008). The probability of overall survival (OS) at 3 years was 88% (95% CI, 71%-95%) in patients without severe comorbidities, while it was only 46% (95% CI, 29%-62%) in patients with a comorbidity CIRS grade ≥ 3 (P = .0001). The impact of comorbidity on prognosis was also evident when restricting the analysis to patients treated with anthracycline-containing therapy. The 3-year OS was 93% (95% CI, 76%-98%) (P = .004) in patients without severe comorbidity and 72% (95% CI, 47%-87%) in patients with severe comorbidity (P = .004). In a multivariate analysis, presence of comorbidity, but not age, was a significant factor for OS. Therefore, we conclude that a significant proportion of older adult patients with HL has severe comorbidity on the CIRS scale, which impacts more importantly than age on prognosis.

ToleRability of BevacizUmab in elderly Ovarian cancer patients (TURBO study): a case-control study of a real-life experience.

OBJECTIVE: Bevacizumab maintenance following platinum-based chemotherapy is an effective treatment for epithelial ovarian cancer (EOC), both in primary and recurrent disease. Our aim was to identify criteria to select elderly patients who can safely benefit from bevacizumab addition. METHODS: This is a case-control study on patients with primary or recurrent EOC who received platinum-based chemotherapy plus bevacizumab, between January 2015 and December 2016. Patient characteristics, treatment details and adverse events were reviewed and analyzed in 2 settings: younger (<65 years, group 1) and elderly (≥65 years, group 2). A binary logistic model was applied to correlate clinical variables and severe (grade ≥3) toxicity risk. RESULTS: Overall, 283 patients with EOC were included, with 72 (25.4%) older patients compared with 211 (74.6%) younger women. Bevacizumab had been administered to 234 patients (82.7%) as first-line treatment and in 49 (17.3%) with recurrent disease. At diagnosis, elderly patients presented with at least one comorbidity and were taking at least 1 medication in 84.7% and 80.6% of the cases respectively, compared with correspondingly 47.4% and 37.4% in group 1 (p<0.001). Nonetheless, the occurrence of serious (grade ≥3) adverse events did not increase among the older group. Creatinine serum levels >1.1 g/dL, estimated glomerular filtration rate (eGFR) ≤60 mL/min, ≥3 comorbidities were independently associated with a higher severe toxicity. CONCLUSIONS: Elderly patients with EOC can safely be treated with bevacizumab; factors other than age, as higher creatinine serum levels, eGFR and number of comorbidities should be considered to better estimate bevacizumab-related toxicity risk.

Ovarian Cancer Management in the Oldest Old: Improving Outcomes and Tailoring Treatments.

Ovarian cancer is the most common cause of death from gynecological cancers in developed countries. It is a common disease of older women at or above 63 years upon diagnosis. Thanks to advance in new treatments, mortality from ovarian cancer has declined in developed countries in the last decade. This decline in mortality rate is unevenly distributed across the age-spectrum. While mortality in younger women has decreased 21.7%, for elderly women it has declined only 2.2%. Even if ovarian cancer is clearly a disease of the elderly, older women are underrepresented in clinical trials, and scant evidence exists for the treatment of women older than 80 years. Moreover, older women are frequently undertreated, receive less chemotherapy and less combination of surgery and chemotherapy, despite the fact that this is considered the optimal treatment modality. This may be mainly due to the lack of evidence and physician's confidence in the management of elderly women with ovarian cancer. In this review, we focus on the management of older women with ovarian cancer, considering geriatric features tied to this population.

Effects of antioxidant supplementation on the aging process.

The free radical theory of aging hypothesizes that oxygen-derived free radicals are responsible for the age-related damage at the cellular and tissue levels. In a normal situation, a balanced-equilibrium exists among oxidants, antioxidants and biomolecules. Excess generation of free radicals may overwhelm natural cellular antioxidant defences leading to oxidation and further contributing to cellular functional impairment. The identification of free radical reactions as promoters of the aging process implies that interventions aimed at limiting or inhibiting them should be able to reduce the rate of formation of aging changes with a consequent reduction of the aging rate and disease pathogenesis. Even if antioxidant supplementation is receiving growing attention and is increasingly adopted in Western countries, supporting evidence is still scarce and equivocal. Major limitations in literature are still needed to be addressed to better evaluate the potential benefits from antioxidant supplementation: 1) an improved understanding of oxidation mechanisms possibly at the basis of the aging process, 2) the determination of reliable markers of oxidative damage and antioxidant status, 3) the identification of a therapeutic window in which an eventual antioxidant supplementation may be beneficial, 4) a deeper knowledge of the antioxidant molecules which in several conditions act as pro-oxidants. In the present paper, after a preliminary introduction to the free radical theory of aging and the rationale of antioxidant supplementation as an anti-aging intervention, we will present an overview of evidence relating antioxidant supplementations with clinical conditions typical of older age (ie, cardiovascular disease, Alzheimer's disease, cancer). We will also discuss studies that have evaluated whether antioxidant supplementation might improve major outcomes of interest in older persons (ie, physical performance, muscle strength, longevity). Given the large amount of data available on the antioxidant supplementation topic, this overview is not intended to be exhaustive. The aim of this paper is to provide the main basis from which future studies should start and indicate which the main limitations that need to be addressed are.

Preoperative assessment and risk factors in the surgical treatment of lung cancer: the role of age.

The incidence of lung cancer in the elderly is increasing in Western countries. This disease represents the second leading cause of cancer death in this age group and it is also responsible for a substantial increment in morbidity and health care costs. Several studies suggested that age per se should not be considered a risk factor for surgical mortality and morbidity in lung cancer patients and access to surgical treatment should not be denied only on the basis of age. Indeed, advanced age may represent an indicator of several factors such as comorbidity or poor physical performance which in turn can increase surgical risk and dramatically reduce life expectancy. Therefore, a careful preoperative assessment of these factors, with particular regard to comorbid conditions (such as cardiovascular and pulmonary diseases or secondary malignancy) is necessary in older adults. In consideration of the need of a multidisciplinary assessment to identify comorbidities and operative risk a close collaboration between pneumologists, radiologists, oncologists, thoracic surgeons, anesthesiologists, cardiologists, geriatric specialists, physical therapists is highly recommended.