Comprehensive Geriatric Assessment Scores Research Articles

A multicenter phase 4 geriatric assessment directed trial to evaluate gemcitabine +/- nab-paclitaxel in elderly pancreatic cancer patients (GrantPax).

TPS10124 Background: Nab-paclitaxel/gemcitabine ( nab-P/gem) is an effective 1st line regimen for metastatic pancreatic ductal adenocarcinoma (mPDAC). Elderly mPDAC patients (pts) may as well benefit from nab-P/gem. Geriatric assessments to evaluate the functional reserve of these pts may allow individualization of treatment. Therefore, the aim of this study is to determine whether comprehensive geriatric assessments (CGAs) can predict the benefit from combined nab-P/gem therapy for elderly mPDAC pts in 1st line. A stratified treatment approach shall result in patient groups with a stable or improving CGA performance during the 1st cycle of treatment. Methods: GrantPax (NCT02812992) is a multicenter, open label phase 4 interventional trial with stratified parallel treatment groups (n = 45 per arm). The hypothesis is that individualized assessment directed treatment algorithms identify elderly pts (≥70 yrs), who benefit from combined nab-P/gem therapy. The study uses a CGA to stratify pts as GOGO, SLOWGO or FRAIL. Depending on test outcome, pts receive chemotherapy (GOGO: nab-P/gem; SLOWGO: gem mono) or best supportive care (FRAIL). After 1st cycle of chemotherapy (4 wks) a CGA and safety assessment will be performed to assign pts to their definite treatment arm. The primary objective is that CGA-stratified pts do not decline in their CGA performance in response to chemotherapy, measured as a loss of 5 points or less in Barthels activities of daily living (ADL1 vs. ADL2 during CGA core assessment). The expected proportion of pts with ADL decline in each treatment group is 6%. Under this assumption it shall be shown with 80% power at one-sided significance level alpha of 0.05 that the proportion of pts with functional decline is less than 20% (n = 43 per group; ADL decline: n = 2 per group). Secondary endpoints are CGA scores during the course of therapy (CGA1-4), response rates, safety, survival rates, duration of treatment, cumulative dose, quality of life and discrepancy between CGA strata estimation by the investigator and true CGA assessment. GrantPax is the first trial realizing a CGA-driven treatment to individualize cancer therapy for elderly pts. Clinical trial information: NCT02812992.

The effect of comprehensive geriatric assessment on the therapeutic decision-makingin elderly patients with diffuse large B-cell lymphoma

Objective To evaluate the feasibility of using comprehensive geriatric assessment (CGA) in estimating if standard dose treatment is for the elderly patients with diffuse large B cell lymphoma. Methods Comprehensive geriatric assessments including three assessments of activity of daily living, instrumental activity of daily living and comorbidity scoring according to Cumulative Illness Rating Score for Geriatrics were adopted to assess if standard dose treatment is for the elderly patients in our prospective study.Thirty seven patients with diffuse large B cell lymphoma, aged >70 years were enrolled in the study, and grouped into fit, and groups according to comprehensive geriatric assessment scoring and their age. The treatment protocolswere not determined by comprehensive geriatric assessment scores, but by clinical judgments made by clinicians based on their clinical experience and disease features.The clinically effective response and overall survival (OS) were analyzed in the three groups. Results According to CGA scores, patients were grouped into fit 〔21 cases (56.8%)〕, unfit 〔7(18.9%)〕 and frail 〔9(24.3%)〕. 37 cases received 213 courses of treatment at average 5.76 courses per case.The overall response (complete / partial remission) rates were 〔85.7%(18/21) vs. 28.6% (2/7) vs. 44.4% (4/9), χ2=9.69, P=0.008〕 and median survival times were (44 months vs. 10 months vs. 9 months; χ2=7.03, P=0.03) among fit , unfit and frail groups with statistically significant differences.Total effective rate (achieving all clinical targets) in fit group of 21 cases were 100%(12/12)with receiving standard dose therapy, and 66.7% of(6/9)with low dose therapy(P=0.06). Overall response rate(total/partial remission) 〔85.7%(18/21) vs. 28.6%(2/7) vs. 44.4%(4/9), χ2=9.69, P=0.008〕 and median survival (44 months vs. 10 months vs. 9 months; χ2=7.03, P=0.03) among fit , unfit and frail groups.In fit group, the two-year overall survival was higher in patients receiving standard dose treatment than receivingpalliativetreatment, with statistical significance 〔83.3% (10/12) vs. 33.3% (3/9), P =0.032〕, without significant hematologic toxicity observed between the subgroups. Conclusions Comprehensive geriatric assessment can identify if elderly patients diffuse large B cell lymphoma can acquire a satisfactory curative effect from a standard dose treatment ofimmunochemotherapy. Key words: Lymphoma; Risk assessment

Comprehensive Geriatric Assessment (CGA) and ONCO-Mpi Predict Mortality in Diffuse Large B-Cell Lymphoma (DLBCL) in the Elderly: A Retrospective Evaluation in a Single Center Experience

DLBCL is the most common type of non-Hodgkin lymphoma and it usually affects elderly patients, with a median age at diagnosis of 70 years and an incidence that rises with increasing age. Nevertheless patients > 70 years are rarely included in clinical trials and the management is often different according to local practice. A pre-treatment evaluation based on Performance Status (PS) or comorbidity index is not sufficient to identify patients suitable for treatment with curative intent.We retrospectively reviewed 93 patients with newly diagnosed DLBCL, ≥65 years old , treated from January 2009 to December 2015 at Veneto Institute of Oncology-IRCCS (median age 76 years, range 65-96). Twenty-eight patients (28) were older than 80 years. All but one received at least first line treatment. All patients were evaluated with CGA at diagnosis, based on Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL) and Cumulative Illness Rating Scale (CIRS). According to these variables they were classified into three categories named ’fit’, ’vulnerable’ and ’frail’. In addition, a cancer-specific modified multidimensional prognostic index (MPI), called Onco-MPI, was calculated for all patients. Onco-MPI score identify three risk score categories (low, moderate and high risk) that predict one-year mortality in older cancer patients. Onco-MPI was calculated according to a validate algorithm as a weighted linear combination of the following CGA domains: age, sex, ADL, IADL, PS, mini-mental state examination, body mass index, CIRS, number of drugs and the presence of caregiver. Cancer sites were also included in the model.Other features analyzed included clinical characteristics, treatment management and outcomes.In our cohort 48% of patients were at advanced Ann Arbor stage (III-IV) with intermediate-high or high risk IPI score in 31%. In 61% of patients we observed extranodal disease, mainly Waldeyer’s ring and gastrointestinal tract. First line treatments received included R-CHOP (38%), R-COMP (R-CHOP with non-pegylated liposomial doxorubicin - 23%), R-CVP (14%), R-CEOP (3%), high dose methotrexate (4 patients with primary central nervous system lymphoma), R-VACOP-B (3%), R-Bendamustine in 2 patients and radiotherapy alone was used in 5 patients. Sixty-eight patients (84%) completed the planned cycles of immunochemotherapy. In this group 48,5% required dose reduction for subsequent cycles of treatment because of side effects, in particular hematological toxicities of grade 3-4 or neurological toxicities. In 23 chemotherapy-treated patients initial doses were reduced according to CGA . We observed, after first line therapy, complete response in 63% and partial response in 21%, 8% of patients experienced a disease progression at the end of treatment and 8% died during first line therapy because of lymphoma progression. At time of diagnosis 49% of patients were considered fit at CGA, 16% vulnerable and 35% frail. According to onco-MPI 24 patients (26%) were at low risk of one year mortality, 31 (33%) at medium risk and 38 (41%) at high risk. With a median follow up of 41,1 months the overall survival (OS) of our cohort is 55,9% (95% CI 25,3-56,9). OS correlates with CGA ( 84,4% in fit patients, 31,2 % in vulnerable and 28,1% in unfit, p< 0,001) and Onco-MPI score seems to discriminate our cohort for one-year mortality (95% in low risk, 77% in moderate and 63% in high, p<0,01). OS also correlates with anthracycline administration (67,8% vs 33,3%, p<0,001) as well as the use of consolidation radiotherapy after chemotherapy induction ( 75% vs 49,3%, p <0,01).Our retrospective, single Center experience demonstrates that elderly DLBCL need a multidimensional evaluation at diagnosis in order to identify patients candidate to treatment with curative intent. CGA confirm its role for choosing correct management. Also Onco-MPI can be a useful tool even if more data are needed in lymphoma patients. DisclosuresNo relevant conflicts of interest to declare.

Association study of comprehensive geriatric assessment and the mortality rate of elder inpatients with decompensated chronic heart failure

Objective To assess the relationship between the comprehensive geriatric assessment (CGA) score and the mortality rate of elder inpatients with decompensated chronic heart failure (CHF). Methods One hundred and thirty-four elder inpatients who were more than 75 years and diagnosed with decompensated CHF in Department of Geriatrics from July 2013 to July 2015 were included and assessed by CGA. Logistic regression analysis was used to evaluate the effects of CGA scores on the mortality rate of elderly inpatients with decompensated CHF. Results Significant differences between death patients and survival patients were found in age, serum lipid, atrial flutter/atrial fibrillation, mean blood pressure and cardiac function classification (P<0.05). In the CGA scoring system, significant differences between death patients and survival patients were found in health assessment, ability of daily life and mental state (P<0.05). The significant difference of the CGA scores between death patients and survival patients appeared in the score constitution(P<0.001). In Logistic regression analysis, age, lipid level, cardiac function classification, CGA score were screened as the risk factors of the death in the decompensated CHF inpatients, which together influenced the prognosis of inpatients, so the value of P(bilateral)<0.05. Conclusions In the study of elder inpatients with decompensated CHF, age, serum lipid, cardiac function classification and the CGA score are the risk factors of the mortality rate of inpatients with decompensated CHF. Key words: Heart failure; Comprehensive geriatric assessment; Mortality rate of inpatients

A poor performance in comprehensive geriatric assessment is associated with increased fall risk in elders with hypertension: a cross-sectional study.

BackgroundFall and serious fall injuries have become a major health concern for elders. Many factors including blood pressure and anti-hypertensive medication application were reported as hazards of fall. The purpose of this study was to determine if age related systemic functional decline related with increased fall risks in elderly patients with hypertension.MethodsA total of 342 elderly hypertension patients (age 79.5 ± 6.7 years, male 63.8%) were recruited to the study. Comprehensive geriatric assessment (CGA), including measurements about activity of daily living (ADL), nutrition, cognition, depression, numbers of prescription medication and number of clinical diagnosis, was conducted to evaluate the physical and mental status of each participants. Fall risk was evaluated by Morse fall scale, Tinetti performance oriented mobility assessment (POMA) and history of fall in the recent year. Participants were grouped into tertiles according to CGA score. Correlation between CGA and fall risk was analyzed through SPSS 18.0.ResultsParticipants with higher CGA score were likely to be older, had a lower body mass index (BMI), and a higher prevalence of cardiovascular disease, chronic obstructive pulmonary disease (COPD), cerebrovascular disease and osteoarthropathia. Participants in higher tertile of CGA score got increased prevalence of fall risk than those in lower tertile (P < 0.01 T3 vs. T1, P < 0.01 T3 vs. T2). Correlation analysis and regression analysis showed significant association between CGA and Morse fall scale (P < 0.001), as well as CGA and POMA (P < 0.001). Meanwhile, CGA components also showed co-relationships with increase fall risks. After adjusting age, BMI, benzodiazepine use, cardiovascular disease, cerebrovascular disease, COPD and osteoarthropathia, both history of fall in the recent year and rising Morse fall scale were significantly associated with ADL impairment (OR: 2.748, 95%CI: 1.598–4.725), (OR: 3.310, 95%CI: 1.893–5.788). Decreased Tinetti POMA score was associated with Mini-Mental State Examination (MMSE) (OR: 4.035, 95%CI: 2.100–7.751), ADL (OR: 2.380, 95%CI: 1.357−4.175) and shortened MNA form (MNA-SF) impairment (OR: 2.692, 95%CI: 1.147−6.319).ConclusionsIn elderly adults with hypertension, impaired physical and mental function is associated with increased fall risk. Further study is required to investigate possible mediators for the association and effective interventions.

Prognostic Value of Neuro-Psychological and Biological Factors in Clinically Fit Older Patients with Hematological Malignancies

BACKGROUND: A Comprehensive Geriatric Assessment (CGA) is recommended to detect vulnerable cancer patients for whom chemotherapy may lead to severe impairment on functionality, quality of life, or survival. Although CGA is useful for a better management of older patients with unsuspected problems, little is known about the reliability of CGA - or G8 screening tool - to optimize the therapeutic approach in a specific patient with a malignant hemopathy. Particularly, the prognostic value of cognitive functions, psychological status and other selected biological factors in older patients with hematological malignancies admitted to receive chemotherapy, are poorly investigated.AIM: To assess in clinically fit (go and slow go) patients with malignant hemopathies, the reliability of G8 screening and CGA as a prognostic tool to predict overall survival (OS) and particularly, the predictive value of neuro-psychological and biological factors, in terms of one-year OS.POPULATION AND METHODS: Between Oct 2010 and June 2013, G8 and CGA were proposed to 107 consecutive older patients (65+-yrs) with hematological malignancies, admitted to the hospital and judged clinically fit, by their refereeing physicians, to receive chemotherapy. An initial full-dose or reduced-dose chemotherapy has been administrated to these patients according to a multidisciplinary team decision. The nutritional status was screened by MNA and the cognitive functions by MMS and MoCARESULTS: Ninety patients -completely assessed for G8 and CGA- were evaluable for one year OS; Non Hodgkin’s Lymphoma (53%), Multiple myeloma (16%), Acute Myeloid Leukemia and Myelodysplastic Syndrome (15%), Chronic Lymphocytic Leukemia (14%) and Myeloproliferative Neoplasms (2%). Median age is 74 (65-89) yrs. 56% are males. 72% and 80%, were considered as “vulnerable” when evaluated with G8 (≤14.5) or CGA (≥2 impairments), respectively. The area under ROC-curve of G8 compared to CGA was 0.749 ± 0.051 (sensibility = 79.2% and specificity =55.6%). During the first year of follow-up, 28% (n=22) of older patients treated for hematological malignancies died. The leading cause of death (82%) was indeed the disease progression. Retrospectively, neither the G8 nor the CGA total score had an impact with the initial treatment choice and were not predictive for one-year OS. In addition, regarding patients characteristics, in a multivariate analysis (Cox proportional hazard model), age (p=0.015; HR=1.12) and diagnosis (p<0.001; HR=7.2), were major prognostic factors in terms of OS. Regarding specific CGA items, a multivariate analysis concluded that unsuspected cognitive impairment (evaluated with a MMS and a MoCA) had the strongest prognostic value (p=0.03; HR=3.560) in terms of OS.DISCUSSION: In our clinically fit hematological patients, a poor G8 or CGA score does not translate into a worse survival, more likely because of two reasons: the disease itself remains the major cause of death and malnutrition, a reversible impairment after effective treatments, strongly impacts on G8 and CGA. The objective of an effective screening tool should thus be the identification of the population who could benefit from optimal treatment combined with an comprehensive management of unsuspected specific problems.CONCLUSIONS: Our observations in “clinically fit” older hematological patients suggest that 1) the major cause of death is the disease itself and the priority should be to identify all patients susceptible to benefit from full dose chemotherapy 2) a poor G8 screening or an abnormal CGA are not specific enough and does not translate into a worse one year OS 3) some specific factors in the CGA (such as neuro-cognitive impairments) are highly correlated with one-year OS 4) age remain a continuous variable with a poor prognostic factor. Prospective trials are needed to further determine whether the combination of optimal treatment and improved management of impaired functions, including cognition, could lead to a better OS. DisclosuresNo relevant conflicts of interest to declare.

Comprehensive Geriatric Assessment and 2-Year Mortality in Elderly Patients Hospitalized for Heart Failure

In older adults hospitalized for heart failure, a poor score on a comprehensive geriatric assessment (CGA) is associated with worse prognosis during hospitalization and at 1 month after discharge. However, the association between the CGA score and long-term mortality is uncertain. This is a prospective study of 487 patients aged ≥75 years admitted for decompensated heart failure. At discharge, a CGA score (range, 0-10) was calculated based on limitation in activities of daily living, mobility limitation, comorbidity, cognitive decline, and previous medication use. The analysis of the association between the CGA score and 2-year subsequent mortality was performed with Cox regression and adjusted for the main confounders. A 1-point increase in the CGA score was associated with a 19% higher mortality (hazard ratio, 1.19; 95% confidence interval, 1.11-1.27). Results were similar regardless of age, sex, left ventricular ejection fraction, and the coexistence of atrial fibrillation, ischemic heart disease, or hypertensive cardiopathy. All components of the CGA score showed a consistent association with higher death risk: the hazard ratio (95% confidence interval) of mortality was 1.78 (1.25-2.54) with ≥3 versus 0 limitations in activities of daily living, 1.36 (1.0-1.86) with moderate or severe versus no or mild limitation in mobility, 1.98 (1.29-3.03) with a ≥5 versus ≤1 score on the Charlson index, 2.48 (1.84-3.34) with previous cognitive decline, and 1.77 (0.99-3.18) in those using ≥8 versus ≤3 medications. The score on a simple CGA is associated with long-term mortality in older patients hospitalized for heart failure.

Comprehensive geriatric assessment (CGA) in men age 70 or over with localized prostate cancer.

184 Background: There has been a four-fold increase in incidence of prostate cancer (PC) in men age 70 or older in England in the last 30 years. Which treatment (surgery, radiotherapy, or surveillance) is right for which patient depends on a number of factors including the risk of death from competing causes and fitness for the proposed treatment. Objective assessments such as those included in a Comprehensive Geriatric Assessment (CGA) might be helpful in this regard. The primary objective of this study is to describe CGA scores of a cohort of older men with PC. The secondary objectives are to examine if a single score (the Vulnerable Elders Survey [VES-13]), is a suitable screening test for a full CGA and to assess whether scores predict radiotherapy toxicity. Methods: Patients age 70 and older with localised PC completed a CGA prior to commencement of radical radiotherapy. The CGA assessed WHO performance status (PS), activities of daily living (ADL), instrumental activities of daily living (IADL), Charlson co-morbidity index, number of medications, mini-nutritional assessment (MNA), social network index (SNI), G8 score, and VES-13. Participants had acute radiotherapy toxicity assessed 12 weeks post-treatment completion. Results: As of September 2013, 100 patients had been recruited. Median age was 74.5 (range 70 to 82). Ninety five percent of patients had a PS less than two. Using the VES-13 tool, 5.2% scored greater than two. 22.6% scored less than 14 on G8 scoring. Additionally, 13.5% were not fully independent on ADLs, 4.2% were not fully independent on IADLs, 32.3% scored greater than one on the Charlson Index, 12.3% had a history of depression or dementia, and 52.9% were on more than three prescription medications. Fourteen percent were at risk of malnutrition and 2.3% were malnourished according to MNA scores, 25.0% had SNI scores less than three and 9.3% of patients had fallen at least once in the preceding three months. Twelve week follow-up data regarding acute radiotherapy toxicity is currently being collected; these will be correlated with the CGA components and presented at the 2014 ASCO Genitourinary Cancers Symposium. Conclusions: These data demonstrate that many older men with localised prostate cancer are vulnerable according to a CGA. Correlations observed between radiotherapy toxicity and CGA scores would have important implications for therapeutic decisions.

M19 The impact of co-morbidities on physical function and health status in chronic obstruction pulmonary disease (COPD): Abstract M19 Table 1.

Background Co-morbidities are of increasing importance in patients with COPD. However, the implications for function and health status have not been fully established. We hypothesised that the number of co-morbidities would relate to physical capacity, health status and impairments as measured by the comprehensive geriatric assessment (CGA) in COPD but not comparator subjects. Method As part of the longitudinal Assessment of Risk in Chronic Airways Disease Evaluation (ARCADE), 500 patients with stable COPD (confirmed with spirometry) were compared to 141 comparator subjects (past or current smokers) free from respiratory disease. In all subjects previously diagnosed co-morbidities including; hypertension, hypercholesterolemia, angina, myocardial infarction, Stroke/TIA, atrial fibrillation, diabetes, and osteoporosis were recorded using a standardised health questionnaire. Spirometry, BMI, six minute walk distance (6MWD), the Timed Up and Go (TUG), and the number of impairments were determined using the CGA. Patients with COPD also completed the St George’s Respiratory Questionnaire (SGRQ). Results Patients and comparators were similar in age, gender and BMI, but differed in FEV1% predicted 59 (20) and 105 (14) respectively (p < 0.01). Patients had more co-morbidities median (range) 2 (0–6) than comparators 1 (0–3) (p < 0.01). Of the patients, 24% had no co-morbidity, 54% had 1–2 co-morbidities and 22% had over 3 co-morbidities, while 54% of comparators had no co-morbidities and 45% had 1–2 co-morbidities (p < 0.01). Patients also had more impairments (CGA score), reduced 6MWD and increased TUG (all p < 0.001). The number of co-morbidities related to age, BMI, 6MWD, TUG, fibrinogen, the CGA and SGRQ and but not FEV1 in patients with COPD, and only to CGA score in comparators (Table 1).

Immune senescence and cancer in elderly patients: Results from an exploratory study

BackgroundThe challenge of immune senescence has never been addressed in elderly cancer patients. This study compares the thymic output and peripheral blood telomere length in ≥70year old cancer patients. Patients and methodsFifty-two elderly cancer patients and 39 age-matched controls without personal history of cancer were enrolled. All patients underwent a Comprehensive Geriatric Assessment (CGA), from which a multidimensional prognostic index (MPI) score was calculated. Peripheral blood samples were studied for naïve and recent thymic emigrant (RTE) CD4+ and CD8+ cells by flow cytometry. T-cell receptor rearrangement excision circle (TREC) levels, telomere length and telomerase activity in peripheral blood cells were quantified by real-time PCR. ResultsThe percentages of CD8+ naïve and CD8+ RTE cells and TREC levels were significantly lower in cancer patients than in controls (p=0.003, p=0.004, p=0.031, respectively). Telomere lengths in peripheral blood cells were significantly shorter in cancer patients than in controls (p=0.046) and did not correlate with age in patients, whereas it did in controls (r=−0.354, p=0.031). Short telomere (≤median)/low TREC (≤median) profile was associated with higher risk of cancer (OR=3.68 [95% CI 1.22–11.11]; p=0.021). Neither unfitness on CGA nor MPI score were significantly related to thymic output or telomere length in either group. ConclusionsImmune senescence is significantly worse in elderly cancer patients than in age-matched controls. The low thymic output and the shorter telomeres in peripheral blood cells of cancer patients may reflect a pre-existing condition which facilitates the onset of malignancies in elderly people.

Comprehensive geriatric assessment and hospital mortality among older adults with decompensated heart failure

The aim of this study is to assess whether a simple comprehensive geriatric assessment (CGA) score predicts hospital mortality among very elderly patients admitted with heart failure (HF). This is a prospective follow-up of 581 individuals aged ≥75 years admitted for decompensated HF to an acute geriatric unit from October 2006 to September 2009. A CGA score (range, 0-10) was constructed using baseline individual data on 5 domains: dependence in activities of daily living (Katz index), mobility (qualitative mobility scale), cognition (Mini-Mental State Examination), comorbidity (Charlson index), and number of prescribed medications. Mean age of patients was 85.8 ± 5.8 years, 67% were women, and 75% had preserved ventricular function (ejection fraction >45%). Fifty percent of patients required assistance in ≥1 activities of daily living, 66% had mobility problems, 45% had cognitive impairment, the mean Charlson index was 3.97 ± 3.01, and 36% had >7 medications prescribed. As a result, the mean CGA score was 4.8 ± 2.2. Hospital mortality was 8.2%. In multivariate analysis, variables associated with hospital mortality included New York Heart Association functional class III (odds ratio [OR] 4.1, 95% CI 1.5-10.8), class IV (OR 19.6, 95% CI 6.3-61), pulmonary edema on chest radiography (OR 3.0, 95% CI 1.3-6.6), renal failure (OR 2.8, 95% 1.2-6.2), and the CGA score (OR 1.2, 95% CI 1.02-1.4 for each point of increment). The area under the receiver operating characteristic curve was 0.856 (95% CI 0.790-0.921), and the model classified 93.4% of cases correctly. In our cohort of very old patients with HF, a simple CGA score predicts hospital mortality.

Treatment decisions for elderly patients with haematological malignancies: a dilemma

Over the past decade, haematological malignant diseases have been diagnosed with increasing frequency in patients older than 65 years. The management of these diseases is particularly difficult in elderly patients, as non-tumour-related life expectancy is highly variable and the benefit-to-risk ratio for oncological treatments depends on comorbidities and pharmacological factors. Very few data are available in very old or frail patients, and management decisions are usually based on data obtained in younger patients. Patients might, therefore, be overtreated or undertreated without clear clinical or biological justification. In this Review we discuss the management of haematological malignant diseases in the elderly, with respect to biology or pharmacokinetic and pharmacodynamic features. We focus on acute myeloid leukaemia and aggressive lymphoma. Additionally, we discuss how the implementation of geriatric tools, such as comprehensive geriatric assessment scores, in the clinical management of elderly patients might help to adapt treatment to meet individual patients' needs.

Incorporation of a comprehensive geriatric assessment (CGA) into a randomized phase III trial for metastatic breast cancer (MBC): The PELICAN study.

1070 Background: PELICAN is a randomized phase III trial evaluating efficacy and safety of pegylated liposomal doxorubicin (PLD) vs. capecitabine (CAP) as first-line therapy in patients (pts) with MBC. CGA results and correlation to time to progression (TTP), overall survival (OS), and time to treatment failure (TTF) were evaluated. Methods: CGA comprised data on activities of daily living (ADL), instrumental sctivities of daily living (IADL), Karnofsky performance status (KPS), comorbidity (CIRS-G), and the number of comedications. According to CGA, pts were classified into 3 groups. Single and combined CGA items were analyzed for association with treatment burden and efficacy outcome (TTP, OS, TTF) using Fisher's exact test, Wilcoxon test, and logistic regression. Results: Data from 210 pts (105 PLD, 105 CAP) with a median age of 62 y (22-85) were analyzed. 123 pts (59%) were <65 y and 87 pts (41%) ≥65 y. CGA scores were available from 152 pts. According to CGA, 113 pts were considered fit (group 1, 74%), 15 compromised (group 2, 10%), and 24 frail (group 3, 16%). Pts with a good KPS (≥ 90%) (n=46) had a significantly longer TTP vs. pts with a worse KPS (n=44) (median KPS 100%: 8.7 mo; 90%: 8.6 mo; ≤ 90%: 3.8 mo; p=0.0027). CGA, ADL, and IADL scores, and CIRS-G did not have a significant impact on TTP. In terms of OS, a high KPS (≥ 90%) significantly increased OS (median 100%: 27.5 mo; 90%: 32.1; <90%: 18.4 mo; p=0.0034). IADL score 8 and CIRS-G 0-3 also correlated with longer OS vs. IADL score <8 (24.1 vs. 17.8 mo, p=0.0061) and CIRS-G >3 (median 0-1: 30.0 mo; 2-3: 32.1 mo; >3: 17.8 mo; p<0.0001). A high KPS increased TTF significantly (median 100%: 5.8.mo; 90%: 4.6 mo, ≤ 90%: 3.0 mo; p=0.0076). Pts with IADL score <8 had a longer TTP (13.7 vs 2.6 mo, p=0.0272), OS (22.7 vs. 4.0 mo, p=0.0031) and TTF (4.6 vs. 2.5 mo, p=0.0043) in the PLD vs. CAP arm. Conclusions: KPS was the most striking predictive factor in this analysis with respect to correlation to TTF and OS. Pts with IADL score <8 treated with PLD had better outcome than pts in CAP arm. Incorporation of CGA into a phase III trial is feasible and yields valuable information for deciding best therapy for MBC patients. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Essex Pharma Essex Pharma, Schering-Plough Essex Pharma, Schering-Plough Schering-Plough, University Hospital Hamburg-Eppendorf Schering-Plough

A multicenter phase II randomized study of gemcitabine (G) weekly followed by erlotinib (E) after progression versus E followed by G after progression in advanced non-small cell lung cancer (NSCLC) in vulnerable elderly patients selected with a comprehensive geriatric assessment (CGA) (GFPC*0505).

e18002 Background: Elderly patients (pts) are a heterogeneous population in which anticancer therapeutic decision is often difficult. The objective of this study was to evaluate the feasibility and activity of weekly G followed by E after progression versus E following by G after progression in vulnerable elderly advanced NSCLC patients selected on the basis of a CGA and Charlson score (CS). Methods: This multicenter phase II study randomized chemonaive pts with stage IV and IIIB with pleural effusion received G 1,250mg/m2 days 1, 8, for a maximum of 18 weeks or until progression, followed by E until second progression (arm A) versus E in first line followed by G until second progression (arm B).Only vulnerable pts (without dependence for ADL and geriatric syndrome) selected by CGA using a software (EGSK) included in a palm assistant with 10 items: socio-economic conditions, cognitive assessment, depression scale, nutritional risk, quality of life(QOL), ADL, IADL (Lawton), incontinence, falls, pain. Major endpoint was time to second progression (TTP2), secondary endpoints were response, time to first progression (TTP1), safety, QOL. Results: 95 pts (67 available today) were enrolled from Aug 2006 to Dec 2009. Patients: Male/Female 54/13, median age 78.1; PS 0/1/2:22/33/10, median co-morbidity (CS) 1.85 (1-3), median IADL score 3.48 (1-4), median global geriatric index: 17.7/20. Respectively for arm A and B, partial response was 18% and 7%, stable disease 18% and 27%, progressive disease 64% and 67%,TTP1 81 and 63 days, median survival 4.3 and 3.9 months. The main WHO grade 3/4 toxicity was anemia 12.5% and fatigue 12.5% in arm A and fatigue 28.6% and anemia 5.7% in B. Conclusions: Preliminary analysis suggests that either the G followed by E or E followed by G appears to have acceptable toxicity but moderate activity, comparable in terms of efficacy to prior data in this vulnerable elderly NSCLC pts population with significant co-morbidities. Our trial confirms the necessity to identify the better tools in CGA to distinguish frail pts. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, Boehringer Ingelheim, Lilly, Roche Amgen, Lilly, Roche Amgen, Lilly, Roche

A multicenter phase II randomized study of docetaxel (D)/gemcitabine (G) weekly followed by erlotinib (E) after progression versus erlotinib followed by docetaxel/gemcitabine after progression in advanced non-small cell lung cancer (NSCLC) in fit elderly patients selected with a comprehensive geriatric assessment (CGA): Groupe Français de Pneumocancerologie (GFPC)*0504.

7536 Background: Elderly pts is an heterogeneous population in which anticancer therapeutic decision is often difficult. The objective of this study was to evaluate the feasibility and activity of weekly D/G followed by E after progression versus E following by D + G after progression in fit elderly advanced NSCLC patients selected on the basis of a CGA and Charlson score. Methods: This multicenter phase II study randomized chemonaive pts with stage IV and IIIB with pleural effusion received D 30 mg/m2 weekly for 6 consecutive weeks (wks) plus G 900 mg/m2 days 1, 8, 22, 29 followed by 2 wks off, for a maximum of 24 wks or until progression, followed by E until second progression (arm A) versus E in first line followed by D+G until second progression (arm B). Only fit pts (without dependence for ADL or IADL and geriatric syndrom) selected by CGA using a software (EGSK) included in a palm assistant with 10 items: socio-economic conditions, cognitive assessment,depression scale, nutritional risk, quality of life (QOL), ADL, IADL, incontinence, falls, pain. Major endpoint was time to second progression (TTP2), secondary endpoints were response, time to first progression (TTP1), safety, QOL. Results: 100 pts (99 available) were enrolled from July 2006 to November 2008. Patients: Male/Female 59/40, median age 75.9; PS 0/1/2:43/49/6, median comorbidity 0, 4 (0-4) median global geriatric index: 18.5/20. Respectively for arm A and B: partial response was 26.3% and 18.8%, stable disease 42.1% and 33.3%, progressive disease 31.6% and 47.9%,TTP1: 4.7 and 3.1 months, TTP2: 7.7 and 6.6 months, median survival 9.4 and 7.1 months. The main WHO grade 3/4 toxicity was neutropenia 29.2% and fatigue 10.4% in arm A and fatigue 11.8% and cutaneous 11.8% in B. Conclusions: Preliminary analysis suggests that either the combination of weekly D and G followed by E or E followed by D+G appears to be promising with a favourable toxicity profile in fit elderly NSCLC pts with mild comorbidity. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, Boehringer Ingelheim, Lilly, Roche Amgen, Lilly, Roche Amgen, Lilly, Pfizer, Roche, sanofi-aventis

Comprehensive geriatric assessment (CGA)-adapted chemotherapy (CT) in 100 elderly patients (pts) (&gt;70 years) with diffuse large B-cell non-Hodgkin’s lymphoma (DLBCL)

19515 Rituximab+CHOP (R-CHOP) is the standard CT regimen for elderly pts with CD20+ DLBCL. However, many pts ≥70 yrs are often unable to received R-CHOP and are excluded from clinical trials. Moreover, CGA has been demonstrated a useful instrument to predict the clinical outcome of elderly cancer pts even if it has never been tested prospectively. Within the GOL (Onco-hematological Lymphoma Group) from June 2000 to March 2006 we started a phase II prospective study to evaluate the feasibility and activity of a CGA-driven CT for elderly pts with DLBCL. Rituximab was used in all pts after February 2002. Pts with no comorbidity received CHOP or R-CHOP; in pts with mild cardiopathy epirubicin was used instead of doxorubicin (CEOP or R-CEOP); in pts with moderate or severe cardiopathy the use of antracyclines was omitted (CVP or R-CVP). CT dosage was decided according to CGA: pts with a good CGA score (ADL=6, IADL&gt;6) received full doses of CT; pts with an intermediate score (ADL=5, IADL&gt;4) received 75% of the planned dose; pts with a poor score (ADL&lt;5, IADL&lt;5) received 50% dose. All pts received prophylactic filgrastim; 100 pts (41 males and 59 females) have been treated and no pt was excluded from this approach. Median age was 75 yrs (range 70–89) and 51% were stages III-IV. Sixty-one per cent of pts received full doses of CT, 86% received antracycline (doxorubicin in 56% and epirubicin in 30%) and 54% received rituximab plus CT. The following regimens were used: R-CHOP 22%, CHOP 16%, 75%-R-CHOP 10%, 75%-CHOP 8%, CEOP 11%, R-CEOP 4%, 75%-R-CEOP 9%, 75%-CEOP 6%. The remaining pts received CVP in 5% of cases and reduced R-CVP in 9% of cases. The toxicity was quite acceptable, however 4 toxic deaths occurred (2 septic shock, 1 acute respiratory failure and 1 acute myocardial infarction). Overall, 76% achieved CR and with a median follow-up of 24 months (range 1–71 months) only 16% relapsed. Seventy-three pts are alive and 63% in CR. Our results demonstrated that a CGA-driven approach is feasible and highly active in elderly pts with DLBCL. Moreover this strategy allows a potentially curative approach to all pts with aggressive NHL avoiding both to under-treat elderly pts with a curable disease and to over-treat elderly pts with comorbidities. No significant financial relationships to disclose.

Comprehensive geriatric assessment for community‐dwelling elderly in Asia compared with those in Japan: III. Phuto in Vietnam

Background: The objective of the present study is to compare the findings of comprehensive geriatric assessment between community‐dwelling elderly aged 60 years and older living in Vietnam and in Japan.Methods: A cross‐sectional, interview‐ and examination‐based study was undertaken of community‐dwelling elderly people living in under‐developed Ngoc Quan village, semideveloped Viet‐tri city in Phuto province, both in Vietnam and in Sonobe town in Kyoto, Japan. One hundred and ninety‐nine and 188 community‐dwelling elderly aged 60 years or older in two developmentally different areas in Vietnam and 411 community‐dwelling elderly aged 65 years or older in Japan, were examined using a common comprehensive geriatric assessment tool. Interviews pertaining to activities of daily living (ADL), medical and social history, quality of life (QOL) and the 15‐item Geriatric Depression Scale as well as anthropometrical and blood chemical examinations were included in the assessment. Using anova and χ2 test, findings from the three groups were compared.Results: In a comparison of comprehensive geriatric assessment findings among community‐dwelling elderly in under‐developed Ngoc Quan village, in semideveloped Viet‐tri city in Vietnam and in highly developed Kyoto in Japan, all activities of daily living scores except those relating to social role, all quality of life scores, body mass index, serum lipid levels and hemoglobin concentrations were lowest in Ngoc Quan and highest in Kyoto. Mean blood pressure measurements, prevalence of hypertension and prevalence of impaired glucose tolerance were higher in Vietnam than in Japan. The prevalence of depression was lower in the elderly in Viet‐tri in Vietnam than those in Ngoc Quan in Vietnam or in Kyoto in Japan.Conclusion: It is supposed that economic and social development might bring higher comprehensive geriatric assessment scores, better‐nutritional states and more appropriate controls for risk factors in community‐dwelling elderly in a economically developmental dose responsive manner.