Review articleComorbidity and geriatric assessment for older patients with hematologic malignancies: A review of the evidence
Introduction
The majority of patients with hematologic malignancies are over the age of 65. In the US, the median age at diagnosis is 65 years for chronic myelogenous leukemia (CML), 67 years for acute myelogenous leukemia (AML) and non-Hodgkin's lymphoma (NHL), 69 years for multiple myeloma, and 72 years for chronic lymphocytic leukemia (CLL). Hodgkin's disease remains diagnosed mostly in young people, with a median age of 38 years. Acute lymphoblastic leukemia (ALL) has a bimodal distribution with an incidence peak in early childhood and another one in the elderly (http://seer.cancer.gov/). Older patients have a significant amount of comorbidity, functional decline, and geriatric syndromes that might impact the treatment selection and outcome of their hematologic malignancy. Whereas healthy older patients can receive treatment similar to younger ones for most hematologic malignancies, at the cost of some increased toxicity, patients with a heavy comorbidity burden have more limited benefits and increased toxicity and might benefit from alternate treatment options. Comorbidity and geriatric assessment have been extensively studied, but most studies and reviews have focused either exclusively on solid tumors, or on a general sample with a minority of hematologic malignancies. Yet hematologic malignancies have some unique features: e.g. frequent bone marrow involvement; rapid response to chemotherapy, which might lead to dramatic functional improvement; and even in advanced stages, treatments offering good chances of cure or long-term remissions. The purpose of this review is to assess what is known about the impact of these comorbid conditions and what tools might be used to guide therapeutic decisions.
Section snippets
Comprehensive Geriatric Assessment (CGA)
Accurate and consistent assessment of patient fitness is of paramount importance for administering effective and safe treatment to elderly cancer patients. Evidence demonstrates that chronological age alone is not a good predictor of life expectancy, functional reserve, or likelihood of treatment-related complications, and therefore guidelines such as those of the National Comprehensive Cancer Network (NCCN) or the International Society of Geriatric Oncology (SIOG) recommend a CGA of older
Comorbidity
Comorbidity has long been studied for its association with outcomes in several malignancies. The most frequently used instruments are the Charlson comorbidity index (hereafter “Charlson”) and the Cumulative Illness Rating Scale for Geriatrics (CIRS-G).[13], [14] The properties of those instruments, as well as their advantages over ad hoc lists of diseases, have been discussed elsewhere.15 Most of the studies included either all types of cancers confounded or solid tumors only. Some studies,
Functional Status
ECOG performance status is a strong predictor of outcome in older AML patients. A recent study from the Swedish Acute Leukemia Registry demonstrated several aspects of that relationship.39 Older patients with a low PS score had more early deaths than those with good PS, no matter what their age. However, within each age and PS category, the patients who did receive intensive treatment had lower early death rates than the others (Table 2). Although they may represent selection bias, these
Frailty Definitions in Hematologic Clinical Trials
Several lymphoma/leukemia studies have used empirical definitions of frailty to design adapted regimens:
The EORTC 20992 study defined a frail patient as one aged 70 years or older and having either severe comorbidities (by CIRS-G), WHO performance status of 3 or 4, cardiac contraindication to anthracyclines, creatinine clearance < 50 mL/min, baseline neutropenia, or thrombopenia.46 These criteria were chosen as predictors of inability to receive CHOP for large cell lymphoma, and the patients were
Tools Focusing on The Risk of Toxicity From Chemotherapy
Until recently, there were no tools available that could reliably evaluate the individual risk of severe toxicity from different chemotherapy regimens across a range of tumor types. Two new assessment methods that specifically look at the older patient's ability to tolerate chemotherapy were presented at the American Society of Clinical Oncology (ASCO) 2010 Annual Meeting and are in the process of further evaluation: The Chemotherapy Risk Assessment Scale for High-age patients (CRASH) and the
Conclusions and Perspective
Comorbidity does impact the prognosis of older patients with hematologic malignancies. The other parameters of the geriatric assessment have so far received less attention. The end point that has received the most attention is tolerance to treatment, especially neutropenia and febrile neutropenia. This is most likely because of the availability of a prophylactic intervention with growth factors. However, nonhematologic toxicities as a whole are as frequent and are in need of predictive
Disclosures
The authors have no conflict of interest to disclose.
Author Contributions
Concept and design: ME.
Data collection: ME, UW.
Analysis and interpretation of data: ME, UW.
Manuscript writing and approval: ME, UW.
Acknowledgements
John Carron, from Health Interactions, Manchester, UK, contributed to the literature review and the writing of the manuscript. Support for third-party writing assistance for this manuscript was provided by F. Hoffmann-La Roche Ltd. Roche had no input in the scientific content of the article.
References (57)
- et al.
Use of comprehensive geriatric assessment in older cancer patients: recommendations from the task force on CGA of the International Society of Geriatric Oncology (SIOG)
Crit Rev Oncol Hematol
(2005) - et al.
A comprehensive geriatric intervention detects multiple problems in older breast cancer patients
Crit Rev Oncol Hematol
(2004) - et al.
Comprehensive geriatric assessment predicts tolerance to chemotherapy and survival in elderly patients with advanced ovarian carcinoma: a GINECO study
Ann Oncol
(2005) - et al.
A new method of classifying prognostic comorbidity in longitudinal studies: development and validation
J Chronic Dis
(1987) - et al.
Rating chronic medical illness burden in geropsychiatric practice and research: application of the Cumulative Illness Rating Scale
Psychiatry Res
(1992) Measuring comorbidity in older cancer patients
Eur J Cancer
(2000)- et al.
Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT
Blood
(2005) - et al.
Comorbidity as prognostic variable in MDS: comparative evaluation of the HCT-CI and CCI in a core dataset of 419 patients of the Austrian MDS Study Group
Ann Oncol
(2010) - et al.
Independent prognostic effect of co-morbidity in lymphoma patients: results of the population-based Eindhoven Cancer Registry
Eur J Cancer
(2005) - et al.
Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial
Lancet
(2010)
Comorbidities, not age, impact outcomes in autologous stem cell transplant for relapsed non-Hodgkin lymphoma
Biol Blood Marrow Transplant
Utility of comorbidity assessment in predicting transplantation-related toxicity following autologous hematopoietic stem cell transplantation for multiple myeloma
Biol Blood Marrow Transplant
Performance status and comorbidity predict transplant-related mortality after allogeneic hematopoietic cell transplantation
Biol Blood Marrow Transplant
Assessment of the hematopoietic cell transplantation comorbidity index in non-Hodgkin lymphoma patients receiving reduced-intensity allogeneic hematopoietic stem cell transplantation
Biol Blood Marrow Transplant
Age and acute myeloid leukemia: real world data on decision to treat and outcomes from the Swedish Acute Leukemia Registry
Blood
Safety and tolerability of phase I/II clinical trials among older and younger patients with acute myelogenous leukemia
J Geriatr Oncol
Patterns of care and survival in cancer patients with cognitive impairment
Crit Rev Oncol Hematol
Diffuse large B-cell and peripheral T-cell non-Hodgkin's lymphoma in the frail elderly. A phase II EORTC trial with a progressive and cuatious treatment emphasizing geriatric assessment
J Geriatr Oncol
Vinorelbine and prednisone in frail elderly patients with intermediate-high grade non-Hodgkin's lymphomas
Ann Oncol
MAX2—a convenient index to estimate the average per patient risk for chemotherapy toxicity; validation in ECOG trials
Eur J Cancer
Can first cycle CBCs predict older patients at very low risk of neutropenia during further chemotherapy?
Crit Rev Oncol Hematol
NCCN Guidelines™
Cancer screening in elderly patients: a framework for individualized decision making
JAMA
Management of cancer in the older person: a practical approach
Oncologist
Basic Assessment of the Older Cancer Patient
Curr Treat Options Oncol
A specialized home care intervention improves survival among older post-surgical cancer patients
J Am Geriatr Soc
Comprehensive Geriatric Assessment in the Decision-Making Process in Elderly Patients With Cancer: ELCAPA Study
J Clin Oncol
Shall we operate? Preoperative assessment in elderly cancer patients (PACE) can help. A SIOG surgical task force prospective study
Crit Rev Oncol Hematol
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