VALUTAZIONE GERIATRICA MULTIDIMENSIONALE ED INDICE PROGNOSTICO DI MORTALITA' IN PAZIENTI ANZIANI AFFETTI DA NEOPLASIA

Background: the Comprehensive Geriatric Assessment (CGA) is considered a valid tool in geriatrics medicine; this kind of instrument is not use only for the assessment and the diagnosis but, from an operative point of view, it extends itself to the patient’s management as well. Being the interdisciplinary the main feature of it, CGA results an useful investigation tool towards the frail elderly. CGA is acquiring interest in geriatric oncology for two main reasons: first of all, for the need to distinguish the features linked to the geriatrics syndromes from those ones which are strictly connected to the cancer pathology; secondly, for its potential prognostic value related to these clinically complex patients. A Multidimensional Prognostic Index (MPI) based on a CGA has been recently developed in hospitalized patients; it was observed that a more severe MPI is positively associated to an high risk of mortality and the prognostic value of CGA was confirmed by this index. Aim: the aim of the present study was to collect a sample of elderly cancer patents in order to: 1) propose the methodology of CGA using the domains of MPI and valuate its validity - which has already been assessed in geriatric patients with acute pathology or reemerging chronic pathology - and if it maintains its prognostic value in geriatric cancer patients too; 2) evaluate the 6-month mortality (as regards to the date recruitment) and the possible relationship between mortality and the worsening on MPI domains, or the severity of MPI itself; 3) verify the relationship between the domains not included in MPI scales and a major MPI severity. 4) identify other possible prognostic mortality factors associated to the parameters not included in the MPI development and validation. Materials and Methods: the study population included 160 patients with cancer aged ≥70 years admitted from the April 17th 2008 to the January 15th 2009 to the 3 Operative Units of Padua’s Hospital (Geriatric Clinic, Geriatric Surgical Unit and Medical Oncology). It was provided an informed consent and then a complete CGA was evaluated for each one. The 160 items collected from the general features and from 14 geriatric assessment scales related to each patient were the following: ADL (Activities of Daily Living), IADL (Instrumental Activities of Daily Living), SPMSQ (Short Portable Mental Status Questionnaire), MNA (Mini-Nutritional Assessment), ESS (Exton-Smith Scale), CIRS (Cumulative Illness Rating Scale- Comorbility), VNS (Visual Numeric Scale), MMSE (Mini Mental State Examination), GDS (Geriatric Depression Scale), NPI (UCLA-Neuropsychiatric Inventory), CBI (Caregiver Burden Inventory), SR ( Responsibility Scale), LPSV (Protection Level of the Life Space), ICA (Welfare Coverage Index). The observation period was of 180 days for the patients who were still alive or until the day of death for the dead ones. Results: 160 patients were considered, but only 150 patients were included in the study (82 females and 68 males; mean age: 79.2 ± 5.6 years, range: 69-93; mean education: 6.4 ± 3.7 years, range: 0-19). The main sites of primitive cancer were: colon (30%), breast (22%) and lung (17%). In relation to the different grades of MPI the sample were classified as following: 54% with low MPI, 76% with moderate MPI and 20% with severe MPI. The 35.3% of the patients (n=53) died within the 6 months of observation against the 15.7% on the development and validation study; of these the 64.2% (n=34) were died in the first 90 days and the 35.8% (n=19) between the 90 and 180 days. It was observed a significant association between MPI and 6-month mortality (low MPI: 5.6% - moderate MPI: 44.7% - severe MPI: 80%; p<0.0001). Furthermore it was detected a significant association between MPI and the following features: age, weight, BMI, numbers of drugs, social condition (“Living alone” and “Institutionalized”), admission to the Geriatric Clinic; in fact this Unit presented the major percentage of deaths compare to the Geriatric Surgical Unit and the Medical Oncology, 49.1%, 7.5%, and 43.4% (p<0.0001), respectively. There was no significant association between MPI and: educational level, sex, height and BSA. A most severe MPI resulted associated with the worsening of the following scales: MNA, ADL, IADL, CIRS-SI, CIRS-CI, ESS (MPI domains) and MMSE, VNS, GDS, CBI, NPI, SR (not included in MPI domains). No significant association was found between MPI and SPMSQ and between MPI and LPSV and ICA. An agreement between the estimated mortality and the observed mortality was not found in the severe MPI (HR = 1.553; IC 95% = 0.904-2.669; observed mortality = 0.800; ∆ = 0.753) compare to low and moderate MPI (HR = 0.056; IC 95% = 0.018-0.173; observed mortality= 0.056; ∆= 0.000 e HR = 0.584; IC 95%= 0.415-0.823; observed mortality= 0.447; ∆ = 0.137, respectively). Independently from MPI, it was observed a significant association between mortality risk and: MNA, ADL, IADL, CIRS-SI, CIRS-CI, ESS, SPMQ (MPI domains) and VNS, GDS, CBI, NPI. Sex, educational level, MMSE, number of drugs, social condition and social scales (SR, LPSV, ICA) were not significantly associated with mortality risk. Conclusions: from the present study emerges that MPI (derived from a CGA) shows a significant prognostic value in the cancer elderly patients, although it seems to overestimate the mortality risk. An higher mortality in the considered sample - than in the MPI development or validation cohort - was remarkable as well; these data confirm the severity of cancer in geriatrics. Mortality was significantly associated with higher MPI grade and a worsening in all the domains of MPI, with the exception of SPMSQ. Furthermore, It was detected a significant association between the MPI severity and the admission to the Geriatric Unit and also between severe MPI and the mortality within 6-month. As regards to the considered domains (not included in the MPI), it was possible registered a positive association between severe MPI and MMSE, VNS, GDS, CBI, NPI and SR. The analysis among all the parameters evaluated and the association of the mortality risk showed a significant association between the worsening of all the variables considered and an higher mortality risk, except for sex, educational level, height, number of drugs, social condition and MMSE. In spite of the still small number of the subjects valuated, the sample was sufficiently high to confirm the validity of MPI in oncology.Background: la metodologia della Valutazione Multidimensionale (VMD) è considerata un valido strumento della medicina geriatrica che lo ha elaborato e validato; esso non si limita al solo momento valutativo-diagnostico ma dal punto di vista operativo si estende anche alla gestione del paziente. Essendo l’interdisciplinarità l’elemento caratterizzante la VMD, risulta un valido strumento di indagine nei confronti dell’anziano fragile. La VMD sta acquisendo un crescente interesse in oncologia geriatrica per due ordini di motivi: in primo luogo per la necessità di riuscire a discriminare tra gli aspetti legati alle sindromi geriatriche e quelli strettamente correlati alla patologia tumorale; in secondo luogo, per il suo potenziale valore prognostico in pazienti così clinicamente complessi. Recentemente è stato sviluppato un Indice Prognostico di Mortalità (MPI) - basato sull’utilizzo di una VMD Geriatrica - in pazienti anziani ospedalizzati; è stato dimostrato come ad un MPI più severo sia positivamente associato un rischio di mortalità più elevato. Scopo: il presente lavoro si è posto l’obiettivo di raccogliere una casistica di pazienti anziani affetti da neoplasia al fine di: 1) applicare la metodologia della VMD utilizzando i domini del MPI e valutare se la sua validità - ad oggi accertata nei pazienti geriatrici con patologie acute o riacutizzazioni di patologie croniche - mantenga il suo valore prognostico anche nei pazienti anziani neoplastici; 2) valutare la mortalità dei pazienti oncologici a 6 mesi rispetto alla data di reclutamento ed identificarne una possibile relazione con il peggioramento dei domini del MPI e con una maggiore severità dello stesso; 3) ricercare una possibile relazione tra i domini non inclusi nelle scale del MPI e una maggiore severità del MPI; 4) individuare altri possibili predittori della mortalità associati ai parametri non presenti nello sviluppo e validazione del MPI. Materiali e Metodi: è stato considerato un campione di pazienti affetti da neoplasia maligna di età maggiore o uguale a 70 anni, ricoverati dal 17 Aprile 2008 al 15 Gennaio 2009 presso le tre Unità Operative dell’Ospedale di Padova (Clinica Geriatrica, Clinica Chirurgica Geriatrica e Oncologia Medica II). Previo consenso scritto e possibilità di raccogliere una VMD completa, sono stati raccolti per ogni paziente 160 items derivanti dalle caratteristiche generali e dalla somministrazione di 14 diverse scale di valutazione geriatrica: ADL (Activities of Daily Living), IADL (Instrumental Activities of Daily Living), SPMSQ (Short Portable Mental Status Questionnaire), MNA (Mini-Nutritional Assessment), ESS (Exton-Smith Scale), CIRS (Cumulative Illness Rating Scale Comorbility), VNS (Visual Numeric Scale), MMSE (Mini Mental State Examination), GDS (Geriatric Depression Scale), NPI (UCLA-NeuroPsychiatric Inventory), CBI (Caregiver Burden Inventory), SR (Scala di Responsabilizzazione), LPSV (Livello di Protezione dello Spazio di Vita), ICA (Indice di Copertura Assistenziale). Il periodo di osservazione è stato di 180 giorni per i sopravvissuti o rientrante entro tale intervallo di tempo per i deceduti. Risultati: sono stati considerati 160 pazienti di cui 150 sono rientrati nei criteri di inclusione previsti dal protocollo di studio (82 femmine e 68 maschi; età media: 79.2 ± 5.6 anni, range: 69-93; scolarità media: 6.4 ± 3.7, range: 0-19). Le sedi principali di insorgenza del tumore primitivo erano: colon (30%), mammella (22%) e polmone (17%). Il 54% dei pazienti presentavano un MPI basso, il 76% un MPI moderato e il 20% un MPI severo. Il 35.3% dei pazienti (n = 53) sono deceduti entro i 6 mesi di osservazione contro il 15.7% dello studio di riferimento; di questi il 64.2% (n = 34) è deceduto entro i primi 90 giorni contro il 35.8% (n = 19) di essi che sono morti tra i 90 ed i 180 giorni. È stata osservata una significativa associazione tra l’MPI e la mortalità a 6 mesi (MPI basso: 5.6% - MPI moderato: 44.7% - MPI severo, 80%; p<0.0001). È stata, inoltre, rilevata una significativa associazione tra l’MPI e le seguenti caratteristiche: età, peso, BMI, numero di farmaci assunti, condizione sociale (vivere soli ed in RSA), ricovero presso la U.O. Clinica Geriatrica; infatti la Clinica Geriatrica presenta una percentuale significativamente maggiore di decessi rispetto alla Chirurgia Geriatrica e all’Oncologia Medica II rispettivamente: 49.1%, 7.5% e 43.4% (p