Measuring Aging and Identifying Aging Phenotypes in Cancer Survivors.


Observational data have shown that some cancer survivors develop chronic conditions like frailty, sarcopenia, cardiac dysfunction, and mild cognitive impairment earlier and/or at a greater burden than similarly aged individuals never diagnosed with cancer or exposed to systemic or targeted cancer therapies. In aggregate, cancer- and treatment-related physical, cognitive, and psychosocial late- and long-term morbidities experienced by cancer survivors are hypothesized to represent accelerated or phase-shift aging trajectories. However, conceptual, measurement, and methodological challenges have constrained efforts to identify, predict, and mitigate aging-related consequences of cancer and cancer treatment. In July 2018, the National Cancer Institute convened basic, clinical, and translational science experts for a think tank titled "Measuring Aging and Identifying Aging Phenotypes in Cancer Survivors." Through the resulting deliberations, several research and resource needs were identified, including longitudinal studies to examine aging trajectories that include detailed data from before, during, and after cancer treatment; mechanistic studies to elucidate the pathways that lead to the emergence of aging phenotypes in cancer survivors; long-term clinical surveillance to monitor survivors for late-emerging effects; and tools to integrate multiple data sources to inform understanding of how cancer and its therapies contribute to the aging process. Addressing these needs will help expand the evidence base and inform strategies to optimize healthy aging of cancer survivors.

Published by Oxford University Press 2019.

Guida JL, et al., J Natl Cancer Inst. 2019 Jul 18. pii: djz136. doi: 10.1093/jnci/djz136. [Epub ahead of print]

Commento: L’invecchiamento precoce rappresenta una esperienza per i pazienti oncologici e una sfida per la ricerca. Lo studio suggerisce strumenti per minimizzare questa seria complicanza della malattia neoplastica e dei suoi trattamenti.

Moving beyond symptom management towards cancer rehabilitation for older adults: Answering the 5W's


Older adults with cancer are quickly becoming the largest group of cancer survivors. Chronological age is a poor predictor of cancer treatment outcomes and of the need for rehabilitation services. While newer symptom management systems and assessments are slowly becoming used in the clinic to improve communication between providers and survivors, such assessments are rarely used to trigger a referral to rehabilitation. Cancer rehabilitation for older adults with cancer has the potential to improve the quality of life and decrease disability caused by cancer and its treatments. One barrier to referral to cancer rehabilitation remains an understanding of what cancer rehabilitation is, and who, when, where, and why to refer to rehabilitation services. This report utilizes examples of three popular geriatric, distress and symptom measures to help answer these questions.

Pergolotti M et al, J Geriatr Oncol. 2017 Dec 3. pii: S1879-4068(17)30248-5. doi: 10.1016/j.jgo.2017.11.009. [Epub ahead of print]


Commento: La riabilitazione negli anziani affetti da cancro migliora la qualità di vita .Chi è il target della riabilitazione da cancro? In questo articolo si cerca di rispondere a questa ed altre domande ad essa correlata.  

Impact of Preexisting Mental Illness on All-Cause and Breast Cancer–Specific Mortality in Elderly Patients With Breast Cancer


Limited data are available on the survival of patients with breast cancer with preexisting mental illness, and elderly women are of special interest because they experience the highest incidence of breast cancer. Therefore, we compared all-cause and breast cancer–specific mortality for elderly patients with breast cancer with and without mental illness.

A retrospective cohort study was conducted by using SEER-Medicare data, including 19,028 women ≥ 68 years of age who were diagnosed with stage I to IIIa breast cancer in the United States from 2005 to 2007. Patients were classified as having severe mental illness if an International Classification of Diseases, Ninth Edition, Clinical Modification code for bipolar disorder, schizophrenia, or other psychotic disorder was recorded on at least one inpatient or two outpatient claims during the 3 years before breast cancer diagnosis. Patients were followed for up to 5 years after breast cancer diagnosis to assess survival outcomes, which were then compared with those of patients without mental illness.

Nearly 3% of patients had preexisting severe mental illness. We observed a two-fold increase in the all-cause mortality hazard between patients with severe mental illness compared with those without mental illness after adjusting for age, income, race, ethnicity, geographic location, and marital status (adjusted hazard ratio, 2.19; 95% CI, 1.84 to 2.60). A 20% increase in breast cancer–specific mortality hazard was observed, but the association was not significant (adjusted hazard ratio, 1.20; 95% CI, 0.82 to 1.74). Patients with severe mental illness were more likely to be diagnosed with advanced breast cancer and aggressive tumor characteristics. They also had increased tobacco use and more comorbidities.

Patients with severe mental illness may need assistance with coordinating medical services.

Commento: In questo studio retrospettivo viene evidenziato l’impatto che ha una precedente malattia mentale sulla mortalita’ da cancro della mammella e da tutte le altre cause.


Cardio-oncology in the older adult


Heart disease and cancer are the leading causes of death in older adults. Many first-line cancer treatments have the potential for cardiotoxicity. Age-related risk factors, pre-existing cardiac disease, and a high prevalence of comorbidities are reasons for increased cardiotoxicity in older adults. Concerns regarding cardiotoxicity may lead to frailty bias and undertreatment, resulting in suboptimal outcomes. There is an urgent need for geriatric-specific evidence and guidelines to help tailor care for this vulnerable group. A multi-disciplinary approach based on close collaboration between oncologists, cardiologists, and geriatricians, among other specialist clinicians is essential.

Reddy P, et al, Cardio-oncology in the older adult, J Geriatr Oncol (2017),

La maggior parte dei pazienti affetti da patologie cardiovascolari sono ultra sessantacinquenni. In questa stessa fascia di età ricadono anche la maggior parte delle diagnosi oncologiche.

La cardio-oncologia è un aspetto di particolare interesse che sottolinea ulteriormente come l’oncologia sia una disciplina che non può  non valutare il paziente a 360 gradi, a maggior ragione quando si tratta di soggetti potenzialmente fragili. A tal proposito, è stato pubblicato sulla rivista Journal of Geriatric Oncology, questo interessante articolo inerente il ruolo della cardio-oncocologia  nella valutazione multidisciplinare del paziente oncologico anziano.

Immunosenescence and immunecheckpoint inhibitors in non-small celllung cancer patients: Does age really matter?

Immunotherapy has dramatically changed the therapeutic scenario in non-small cell lung cancer (NSCLC), extending overall survival, with a favorable safety profile. However, there is still a gap of knowledge about the efficacy of immune checkpoint inhibitors (ICIs) in elderly patients. Data from randomized clinical trials testing ICIs are conflicting and often lack adequate statistical power. Although two large meta-analyses suggested an absence of a significant survival benefit in patients older than 75 years, expanded access programs and retrospective cohort studies of ICIs in the real-life setting, showed comparable survival outcomes and safety profiles between older and younger patients. In this complex scenario, a further unresolved issue is the potential correlation between older age and immunotherapy primary resistance, a phenomenon probably linked to the continuous and progressive remodeling of immune functions with ageing, known as immunosenescence. Defining the role of ICIs in elderly NSCLC patients and exploring the molecular mechanisms underlying a possible lack of benefit or even accelerated tumor growth during immunotherapy are two major challenges for future research in this field of cancer treatment. In this review, we describe the major hallmarks of immunosenescence and we summarize the existing clinical data of ICIs in elderly NSCLC patients.

L’impiego dell’immunoterapia ha permesso di migliorare la sopravvivenza in una quota parte di tumori. Questa reviews rappresenta un interessante spunto di riflessione sul rapporto esistente tra efficacia dei trattamenti immunoterapici e immunosenescenza. 

Cancer Treatment Reviews 60 (2017) 60–68

Identifying predictive motor factors for falls in post-menopausal breast cancer survivors

Objective: Breast cancer treatment, including radical surgery, is also pursued as late as the 7th - 8th decade of women's lives. Standard physical rehabilitation procedures offered to those women are predominantly focused on attenuating specific functional deficits of the upper limb and trunk. Seldom do they entail any regimens specifically aimed at recovering overall functionality, and reducing exposure to falls-risk. The study aimed to assess potential interrelationships between the self-reported falls, individual functional capabilities and appreciably reducing exposure to falls-risk in a group of post-menopausal, post-surgical breast cancer survivors.

Methods: The study recruited 102 women (aged 65-79; mean age 70.2), post-surgical breast cancer survivors. The subjects were stratified by age into three groups: Group 1 (65-69 years); Group 2 (70-74 years), and Group 3 (75-79 years). Individual functional capabilities were assessed with Eight-foot up & go test (8UG), chair stand test (CST), and 2-minute step test (2ST). Tinetti POMA test was applied to assess gait and balance disorders. Self-reported falls in the past year were ascertained through a questionnaire. 

Results: Assessment of individual aerobic endurance (2ST) also demonstrated a clear deficit in the mean scores category in all respective age sub-groups, as compared against the reference values. The deficits ranged from 4.86 to 15.90 steps less than the normative values; the oldest subjects demonstrating the largest deficit. The aerobic endurance tests results significantly impacted the ultimate assessment of an individual falls-risk in the oldest group. The analysis of the number of falls sustained within the recent year indicated that 43.67% of the subjects fell victim of such incidents.

Conclusion: An individual exposure to falls-risk was found to be appreciably more dependent upon individual aerobic endurance rather than overall strength of the lower part of the body in the breast cancer survivors over 75.

Comparative effectiveness of chemotherapy versus resection of the primary tumor as the initial treatment in older patients with stage IV colorectal cancer.


 Aim: The objective was to determine trends in the use of chemotherapy as the initial treatment and evaluate the comparative effectiveness of initial chemotherapy versus resection of the primary tumour on survival (intention-to-treat analysis) in stage IV colorectal cancer (CRC).

Methods: This cohort study used Surveillance Epidemiology, and End Results (SEER)-Medicare (2000-2011) data, including patients ≥66 years presenting with stage IV CRC. Cox proportional hazards models and instrumental variable analysis were used to determine the association of chemotherapy versus resection of the primary tumour as the initial treatment with 2-year survival. 

Results: The use of chemotherapy as the first treatment increased over time, from 26.8% in 2001 to 46.9% in 2009 (p<0.0001). The traditional Cox model showed that chemotherapy as the initial treatment was associated with the higher risk of mortality (HR, 1.35; 95% CI, 1.27-1.44). When accounting for known and unknown confounders in an instrumental variable analysis, chemotherapy as the initial treatment suggested benefit on 2-year survival (HR, 0.68; 95% CI, 0.44-1.04); however, the association did not reach statistical significance. The study findings were similar in six subgroup analysis. 

Conclusions: The use of chemotherapy as the initial therapy increased substantially in the last decade. Instrumental variable analysis found that chemotherapy as the initial treatment offers similar or better 2-year survival in patients with stage IV CRC. Given the morbidity and mortality associated with colorectal resection in elderly patients, chemotherapy provides an option to patients who are not good candidates for resection. This article is protected by copyright. All rights reserved.



Comorbidities and Risk of Chemotherapy-Induced Peripheral Neuropathy Among Participants 65 Years or Older in Southwest Oncology Group Clinical Trials.


Background. Neuropathy is a debilitating toxicity associated with various chemotherapy agents.We evaluated the association between common comorbid conditions and the development of peripheral neuropathy in patients treated with taxane-based chemotherapy.

Methods. We examined the Southwest Oncology Group database to identify phase II and III trials that included taxane therapy from 1999 to 2011. We linked the Southwest Oncology Group clinical records to Medicare claims data according to Social Security number, sex, and date of birth. The following disease conditions potentially associated with peripheral neuropathy were evaluated: diabetes, hypothyroidism, hypercholesterolemia, hypertension, varicella zoster, peripheral vascular disease, and autoimmune diseases. Multivariate logistic regression was used to model the odds of experiencing grade 2 to 4 neuropathy.

Results. A total of 1,401 patients from 23 studies were included in the analysis. Patients receiving paclitaxel were more likely to experience grade 2 to 4 neuropathy compared with docetaxel (25% v 12%, respectively; OR, 2.20; 95% CI, 1.52 to 3.18; P , .001). The inclusion of a platinum agent was also associated with greater neuropathy (OR, 1.68; 95% CI, 1.18 to 2.40; P = .004). For each increase in age of 1 year, the odds of neuropathy increased 4% (P = .006). Patients with complications from diabetes had more than twice the odds of having neuropathy (OR, 2.13; 95% CI, 1.31 to 3.46; P = .002) compared with patientswith no diabetes. In contrast, patientswith autoimmune diseasewere half as likely to experience neuropathy (OR, 0.49; 95% CI, 0.24 to 1.02; P = .06). The other conditions were not associated with neuropathy.

Conclusion. We found that in addition to drug-related factors, age and history of diabetes were independent predictors of the development of chemotherapy-induced peripheral neuropathy. Interestingly, we also observed that a history of autoimmune disease was associated with reduced odds of neuropathy. Patients with diabetic complications may choose to avoid paclitaxel or taxane plus platinumcombination therapies if other efficacious options exist.

 J Clin Oncol 34:3014-3022. © 2016 by American Society of Clinical Oncology


Inclusion of elderly patients in oncology clinical trials

Background. Physicians need clinical trials assessing benefits and harms of treatments to avoid under-treatment or over-treatment of elderly patients. The main objectives of this report were to examine how data regarding elderly oncology patients were presented in medical literature; and to assess the evolution of this presentation between two time periods.

Patients and methods. All phases I, II and III trials dedicated to the treatment of cancer among elderly patients published between 2001 and 2004 and between 2011 and 2014 were reviewed. All phase III clinical trials assessing cancer treatments among adults in the same periods were also reviewed to evaluate potential subgroup analyses in elderly patients in these studies. Key characteristics of interest were extracted by two investigators before descriptive and comparative analyses were undertaken.

Results. A total of 1084 trials were included: 366 and 718 from the first and second time period, respectively. Twenty-seven and 193 of these trials were phase I and II trials dedicated to elderly or frail patients, respectively. A large proportion of phase III trials published between 2011 and 2014 reported at least one analysis dedicated to elderly patients (46.7%) versus 19.3% during the first time period. The use of subgroup analyses of elderly patients in phase III trials was the most frequent source of information. Subgroup analyses were more frequent among trials with industrial funding, trials published in high impact factor journal, intercontinental trials and trials with large sample size. The age threshold defining the elderly subgroup increased over time.

Conclusion. Elderly patients have become a topic of interest during the past decade. However, data available are mostly extracted from subgroup analyses, which can only be regarded as preliminary evidence.

Ann Oncol (2016) 27 (9): 1799-1804.