Vai ai contenuti. | Spostati sulla navigazione | Spostati sulla ricerca | Vai al menu | Contatti | Accessibilità

| Crea un account

Falco, Cristina (2015) Exploring the Relationship between Ageing and Cancer: from Translational to Clinical Research. [Tesi di dottorato]

Full text disponibile come:

[img]
Anteprima
Documento PDF
3450Kb

Abstract (inglese)

A better understanding of the physiological and functional changes that occur with aging will enable to improve strategies for treating elderly cancer patients. For istance, hemathological toxicity is a major obstacle to the administration of chemotherapy in elderly cancer patients and ageing per sé is a major risk factor for cancer development, but the age-related impairment of immune system has never been studied in cancer patients.
For this reason, the present Doctoral Course has been committed to provide the first description of immune senescence observed in cancer patients. In the context of a prospective, exploratory study, TREC levels, subsets of peripheral naïve/memory T-cells and peripheral cell telomere length have been detected in elderly cancer patients and in age-matched controls.
A further critical issue of geriatric oncology is to uncover clinical problems that may impair the potential benefits and tolerability of anticancer treatments (Balducci, 2003; Extermann, 2003).
Recently, the International Society of Geriatric Oncology released a position paper where the obligatory integration of a comparable form of geriatric assessment is strongly recommended in future studies (Wildiers, 2013). The Multidimensional Prognostic Index (MPI) has been developed from a complete CGA and, differently from it, MPI may be administered and scored in a consistent manner. In order to answer this prioritary issue of geriatric oncology, the second project of this doctoral research program has been devoted to validate the MPI in patients with advanced cancer (Pilotto, 2008) to predict the 6 and 12-months overall mortality risk. In addition to estimate the tumor-independent survival, a CGA is essential when planning a cancer treatment as it uncovers medical conditions that may worsen the chemotherapy toxicity reported in clinical trials involving younger patients (Balducci, 2007). Despite there is strong evidence that any treatment decision in elderly cancer patients should be supported by a CGA, this is still performed in less than 10% of cancer centers because it is highly time-consuming. For this reason various author attempted to summarize the complete CGA in shorter versions. Among these screening tests, the Vulnerable Elders Survey (VES-13), a simple 13-item questionnaire has good sensitivity and acceptable specificity (Luciani, 2010) in comparison with a full CGA, but there is not consistent medical literature regarding its ability to predict chemotherapy toxicity. Therefore, the third chapter of the present Doctoral Research Program reports a joint analysis of 4 prospective studies that evaluated the accuracy of VES-13 in predicting the risk of high grade toxicity in elderly patients undergoing chemotherapy.
PATIENTS AND METHODS.
Immunesenescence and Cancer. Fifty-two elderly patients with breast or colorectal cancer 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 collected at the time of enrollment, prior to any oncological medical treatment (endocrine therapy, chemo- therapy, radiotherapy or immune therapy). Peripheral blood samples were studied for naïve and recent thymic emigrant (RTE) CD4+ and C8+ 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. In addition to descriptive analysis through Mann–Whitney U test and Student's t-test, correlations between age and TREC levels, or telomere length in both groups were analyzed with Pearson's χ2 test. TREC levels and telomere length were also analyzed as dichotomous variables (cut-off: ≤median) and Odd Ratios were estimated with a logistic regression model.
Validation of MPI in Cancer Patients. Patients aged 70 yrs and older with a recently-diagnosed metastatic or inoperable cancer were enrolled and received a complete CGA including functional state, comorbidity, cognitive and humoral state, nutritional state, risk of pressure scores, social aspect and medications. The MPI score was calculated for each patient from the results of the various tests (ADL, IADL, SPMSQ, CIRS-CI, MNA, ESS, number of drugs, and social conditions), as reported elsewhere by Pilotto et al (Pilotto, 2007).
Statistical Analysis. The associations between 6- or 12-months mortality and the MPI scores, was analyzed using a Cox’s proportional hazards regression model adjusted for age and gender. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated to estimate the strength of the associations. The discriminatory power of the mortality model at 6 and 12 months of follow-up was assessed by calculating the area under the ROC curves for the MPI (considered as a continuous variable) using logistic regression models.
VES-13 to predict chemotherapy toxicity. The study involved patients aged >70 years with a diagnosis of a solid or hematological tumor. All Patients were administered VES-13. For all patients number of medications, comorbidities, CIRS-G score and index, type of chemotherapy, line of treatment, MMSE and MNA scores were recorded. Grade 3-4 hematological and non hematological toxicities were avaibile for all patients. Regression analysis was performed.
RESULTS
Immunesenescence and Cancer. The 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.
Validation of MPI in Cancer Patients. A hundred and sixty patients entered the study. The MPI-related hazard ratios were higher at 6 months of follow-up than at 12 months, a high MPI being associated with a HR of 8.094 (95% CI 3.749-17.475, p<0.0001) at 6 months as opposed to 5.655 (95% CI 2.866-11.158, p<0.0001) at 12 months. When the MPI was considered as a continuous variable, any increase by 0.2 units (corresponding to the lower quartile) was associated with a 2.347-fold increase in the mortality risk (95% CI=1.838-2.997) at 6 months and a 2.051-fold increase (95% CI=1.662-2.531) at 12 months. The discriminatory power of the MPI’s predictive performance was statistically significant.
The age- and sex-adjusted area under the ROC curve for MPI score at 6 and 12 months of follow-up were 0.81 (95% CI, 0.74-0.88) and 0.78 (95% CI, 0.71-0.85), respectively.
VES-13 to predict chemotherapy toxicity. 648 patients aged ≥ 66 years old were included, mean age was 76.2 years (SD 4.5, 66 to 90), 336 (51.9%) were female. VES-13 identified 287 of the patients (44.3%) as vulnerable. Grade 3-4 hematological and non-hematological toxicities were more prevalent in the vulnerable subjects (35.2% vs 20.8%, p <0.0001, and 18.5% vs 10.8%, p = 0.0055). Vulnerable patients (OR) had a higher risk of hematological and non hematological toxicity with an OR 2.15, (95% CI 1.46-3.17; p<0.001) and 1.66 (95% CI 1.02-2.72; p = 0.043) respectively.
CONCLUSIONS
The study of Immunesenescence provided the first evidence that elderly cancer patients seemed to suffer from a more severe decline in thymic output and had a lower proportion of naïve CD8+ cells than age-matched controls. In addition, cancer patients had significantly shorter telomeres in their peripheral blood cells than age-matched non-cancer patients. This result suggests the unpublished hypothesis – which would need to be tested in a larger study - that elderly people with shorter telomeres are at higher risk of developing cancer. If confirmed, thymic output and telomere length could be widely used in elderly general population to easily identify subjects who run an higher risk of developing cancer and optimize the resources for screening procedures.
The second trial was the first to validate MPI in the oncological setting. The MPI retained in elderly patients with advanced cancer the same reliability and accuracy as reported in the original study by Pilotto et al. The results also suggested the possibility of creating a new, better-performing version of MPI by integrating it with the comorbidity severity index and the geriatric depression scale.
In the third study the patients identified as vulnerable by the VES-13 had a statistically significant higher risk of developing both hematological and non-hematological toxicity. These risk increases progressively with the aging of the population, particularly for haematological toxicity.
With the awareness that geriatric assessment of cancer patients cannot relies on a single test, future studies should be planned with the aim of prospectively identifying which is the most appropriate geriatric instrument for any single aspect of patient management (e.g. toxicity, overall survival, active life expectancy, or the quality of life) and clinical research

Abstract (italiano)

Nonostante i casi di neoplasie solide nell’anziano siano in aumento, da decenni gli anziani sono sistematicamente esclusi dagli studi clinici in oncologia e questo implica una notevole difficoltà per gli oncologi a trasferire ai pazienti ultrasettantenni i risultati delle ricerche terapeutiche oncologiche.
Solo una migliore conoscenza delle modificazioni fisiologiche e funzionali che si accompagnano all’invecchiamento consentirebbe di migliorare le strategie di trattamento dei pazienti anziani con tumore. In particolare, nonostante la tossicità ematologica rappresenti il principale ostacolo alla somministrazione di chemioterapia e l’età avanzata sia di per sé un fattore di rischio per l’oncogenesi, non esiste in letteratura alcuno studio che abbia affrontato l’immunosenescenza nel paziente oncologico anziano. Perciò, parte considerevole dell’attività di ricerca svolta nel presente programma di Dottorato è stata dedicata ad uno studio prospettico di ricerca translazionale che ha confrontato l’output timico (livelli di T-cell receptor rearrangement excision circle – TREC- e subset di cellule T naïve e memoria) e la lunghezza dei telomeri in sangue periferico in una coorte di pazienti ultrasettantenni con diagnosi di neoplasia mammaria o colorettale con quelli riportati in anziani di pari età senza anamnesi personale di neoplasia.
Un’altra criticità dell’Oncologia Geriatrica è quella di standardizzare la valutazione geriatrica multidimensionale (CGA), strumento fondamentale per identificare possibili ostacoli all’efficacia ed alla tollerabilità dei trattamenti oncologici, per poterla utilizzare negli studi clinici.
Per rispondere a tale richiesta il secondo progetto di questo programma di Dottorato è stato finalizzato a validare per la prima volta nel setting oncologico il Multidimensional Prognostic Index (MPI), uno strumento codificato che deriva dalla CGA tradizionale. Nell’ambito di uno studio di Ricerca Ministeriale Finalizzata è stata valutata la capacità del MPI di predire la mortalità a 6 e 12 mesi in una coorte di pazienti anziani con neoplasia solida avanzata.
Terza priorità dell’oncologia geriatrica è di diffondere maggiormente l’uso della valutazione geriatrica. Attualmente infatti meno del 10% dei centri oncologici applica la CGA, che richiede oltre 2 ore a paziente per la corretta esecuzione, mentre invece qualsiasi scelta terapeutica nel paziente anziano dovrebbe tenere conto di una CGA basale, anche allo scopo di identificare i pazienti a rischio di tossicità da chemioterapia. Per risolvere questa criticità negli ultimi anni sono stati introdotti dei test di screening fnializzati ad identificare i pazienti che meritano una valutazione geriatrica. Tra questi, la Vulnerable Elders Survey – 13 (VES-13) presenta una buona sensibilità e specificità rispetto alla CGA completa ma non era mai stata testata per predire la tossicità da chemioterapia. Pertanto, nel terzo studio riportato nella presente tesi sono stati analizzati i risultati di 4 studi prospettici che hanno valutato l’accuratezza della VES-13 nel predire il rischio di tossicità di alto grado in pazienti oncologici anziani in trattamento antiblatico.
PAZIENTI E METODI.
Immunesenescenza e Cancro. Cinquantadue pazienti con neoplasia mammaria o colorettale in stadio I-III e 39 controlli senza storia personale di tumore e di pari età sono stati arruolati nel presente studio e sottoposti inizialmente a CGA. Dopo la chirurgia e prima di iniziare qualsiasi trattamento medico adiuvante è stato prelevato sangue periferico per la determinazione citofluorimetrica di CD4+ and C8+ naïve e memoria e per la determinazione in real-time PCR dei livelli di TREC, della lunghezza dei telomeri nelle cellule periferiche e dell’attività telomerasica.
Validazione del MPI in pazienti oncologici. Pazienti ultrasettantenni e con recente diagnosi di neoplasia solida metastatica o inoperabile sono stati arruolati e sottoposti ad una CGA completa, comprendente lo stato funzionale, cognitive, umorale, le comorbidità, le medicazioni a domicilio, lo stato nutrizionale, il rischio di piaghe da decubito, gli aspetti sociali, da cui è stato calcolato il MPI come riportato da Pilotto et al (Pilotto, 2007). Per definire il valore prognostico di MPI sono stati utilizzati modelli di regressione Cox aggiustati per età e genere. Sono state inoltre calcolate le curve ROC attraverso modelli di regression logistica.
VES-13 e rischio di tossicità da chemioterapia. Quest’analisi combinata ha coinvolto pazienti ultrasettantenni con diagnosi di neoplasia solida o ematologica. Tutti i pazienti hanno compilato il questionario VES-13. Sono stati riportati infine I dati relative al tipo di chemioterapia ricevuta, la linea di trattamento, la tossicità ematologica e non ematologica di grado 3-4 secondo I common toxicity criteria for adverse events (CTCAE). A questi dati è stata applicata un’analisi di regressione.
RISULTATI
Immunosenescenza e Cancro. La percentuale di cellule CD8+ naïve, CD8+ RTE ed i livelli di TREC sono risultati significativamente più bassi nei pazienti oncologici rispetto ai controlli (p = 0.003, p = 0.004, p = 0.031, rispettivamente). La lunghezza dei telomeri nelle cellule di sangue periferico era significativamente inferiore nei pazienti oncologici rispetto ai controlli (p = 0.046) e non correlava con l’età, come avveniva invece nei controlli (r = −0.354, p = 0.031). Il profilo con telomero corto (inferiori alla mediana) e bassi livelli di TREC (inferiori alla mediana) era significativamente associato con la diagnosi di neoplasia (OR = 3.68 [95% CI 1.22–11.11]; p = 0.021) mentre non vi era alcuna correlazione tra l’esito della CGA ed il punteggio MPI da un lato ed i marcatori di immunosenescenza dall’altro in entrambi i gruppi.
Validazione del MPI in pazienti oncologici. Lo studio ha coinvolto 160 pazienti. Gli hazard ratio correlati a MPI sfavorevole sono risultati significativamente più alti per la mortalità a 6 mesi rispetto a 12 mesi, più precisamente 8.094 (95% CI 3.749-17.475, p<0.0001) a 6 mesi e 5.655 (95% CI 2.866-11.158, p<0.0001) a 12 mesi. Quando MPI è stato valutato come una variabile continua, ogni incremento di 0.2 unità era associato ad un aumento di 2.347-volte del rischio di mortalità (95% CI=1.838-2.997) a 6 mesi e 2.051-volte (95% CI=1.662-2.531) a 12 mesi. Il valore prognostico di MPI è risultato statisticamente significativo. L’area delle curve ROC a 6 e 12 mesi, aggiustate per genere ed età era 0.81 (95% CI, 0.74-0.88) e 0.78 (95% CI, 0.71-0.85), rispettivamente.
VES-13 e rischio di tossicità da chemioterapia. Seicentoquarantotto pazienti di età ≥ 66 anni sono stati considerati nella presente analisi. Attraverso la VES-13 sono stati identificati 287 pazienti vulnerabili. Gli eventi di tossicità ematologica e non ematologica di grado 3-4 sono risultati prevalenti nei soggetti vulnerabili (35.2% vs 20.8%, p <0.0001, e 18.5% vs 10.8%, p = 0.0055). Gli odd ratios per la tossicità ematologica e non ematologica nei pazienti vulnerabili sono risultati pari a 2.15, (95% CI 1.46-3.17; p<0.001) e 1.66 (95% CI 1.02-2.72; p = 0.043) rispettivamente.
CONCLUSIONI
Lo studio sull’immunosenescenza e cancro ha fornito la prima evidenza che i pazienti anziani oncologici, rispetto ai controlli sani, presentano una severa riduzione dell’output timico e della lunghezza dei telomeri in cellule di sangue periferico. Tali risultati suggeriscono l’ipotesi che i soggetti anziani con sistema immunitario senescente e telomeri più corti abbiano un rischio più alto di sviluppare neoplasie. Se tale associazione fosse confermata in una popolazione più ampia, i marcatori di immunosenescenza potrebbero essere impiegati per identificare gli anziani a rischio più elevato di neoplasia, sui quali concentrare le risorse per la diagnosi precoce.
Il secondo studio riportato è stato il primo a dimostrare che nei pazienti oncologici MPI mantiene il suo valore prognostico, con la stessa affidabilità ed accuratezza riportate nello studio originale di Pilotto et al. I risultati dello studio suggeriscono infine la possibilità di migliorare le prestazioni di MPI in oncologia integrandolo con l’indice di comorbidità e lo stato umorale.
Il terzo studio ha dimostrato che i pazienti giudicati vulnerabili alla VES-13 hanno un rischio significativamente più alto di sviluppare tossicità ematologica e non ematologica di alto grado. Tale rischio aumenta progressivamente con l’età, soprattutto per la tossicità eamtologica.
Con la consapevolezza che la valutazione geriatrica del paziente oncologico anziano non può essere esaustivamente svolta con un unico test, ulteriori studi dovranno essere condotti per identificare i test più appropriati per altri aspetti rilevanti per la gestione del paziente con neoplasia, ovvero la l’aspettativa di vita tumore-indipendente e la qualità di vita. Parallelamente vi è la necessità di studiare il processo di invecchiamento nell’anziano oncologico per identificare dei marcatori molecolari di età biologica, che guidino in maniera oggettiva la scelta terapeutica in questa popolazione

Statistiche Download - Aggiungi a RefWorks
Tipo di EPrint:Tesi di dottorato
Relatore:Manzato, Enzo
Dottorato (corsi e scuole):Ciclo 27 > scuole 27 > SCIENZE MEDICHE, CLINICHE E SPERIMENTALI > SCIENZE GERIATRICHE ED EMATOLOGICHE
Data di deposito della tesi:28 Gennaio 2015
Anno di Pubblicazione:28 Gennaio 2015
Parole chiave (italiano / inglese):Senescenza, oncogenesi, rischio, mortalità, tossicità; ageing, cancer, risk, mortality, toxicity
Settori scientifico-disciplinari MIUR:Area 06 - Scienze mediche > MED/06 Oncologia medica
Struttura di riferimento:Dipartimenti > Dipartimento di Scienze Cardiologiche, Toraciche e Vascolari
Codice ID:7671
Depositato il:09 Nov 2015 11:36
Simple Metadata
Full Metadata
EndNote Format

Bibliografia

I riferimenti della bibliografia possono essere cercati con Cerca la citazione di AIRE, copiando il titolo dell'articolo (o del libro) e la rivista (se presente) nei campi appositi di "Cerca la Citazione di AIRE".
Le url contenute in alcuni riferimenti sono raggiungibili cliccando sul link alla fine della citazione (Vai!) e tramite Google (Ricerca con Google). Il risultato dipende dalla formattazione della citazione.

American Cancer Society. Cancer Facts & Figures. Atlanta: American Cancer Society 2012; 1-65. Cerca con Google

Aviv A. Telomeres and human somatic fitness. J Gerontol A Biol Med Sci 2006; 61: 871-873. Cerca con Google

Baird DM. Telomeres. Exp Gerontol 2006; 41: 1223-1227. Cerca con Google

Balducci L, Colloca G, Cesari M, Gambassi G. Assessment and treatment of elderly patients with cancer. Surg Oncol 2010; 19: 117-123. Cerca con Google

Balducci L, Santa G. Cancer in the frail patient. Hematol Oncol Clin North Am 2000;14: 235-251. Cerca con Google

Balducci L. Aging, frailty and chemotherapy. Cancer Control 2007; Jan:14(1), 7-12. Cerca con Google

Balducci L. New paradigms for treating elderly patients with cancer: the Comprehensive Geriatric Assessment and Guidelines for Supportive Care. The Journal of Supportive Oncology 2003; 1: 30-37. Cerca con Google

Barone L, Milosavljevic M, Gazibarich B. Assessing the older person: is the MNA a more appropriate nutritional assessment tool than the SGA? J Nutr Health Aging 2003; 7: 13-17. Cerca con Google

Basso U, Falci C, Brunello A, Zafferri V, Fiducia P, Sergi S, et al. Prognostic value of multidimensional geriatric assessment (MGA) on survival of a prospective cohort of 880 elderly cancer patients (ECP). J Clin Oncol 2011; 29: suppl, abstr 9065. Cerca con Google

Basso U, Monfardini S. Multidimensional geriatric evaluation in elderly cancer patients: a practical approach. Eur J Cancer Care 2004;13: 424-433. Cerca con Google

Basso U, Tonti S, Bassi C, Brunello A, Pasetto LM, Scaglione D, et al. Management of frail and not-frail elderly cancer patients in a hospital-based geriatric oncology program. Oncology Hematology 2007; 66:163-170. Cerca con Google

Berzins SP, Boyd RL, Miller JF. The role of the thymus and recent thymic migrants in the maintenance of the adult peripheral lymphocyte pool. J Exp Med 1998; 187: 1839-1848. Cerca con Google

Biganzoli L, Boni L, Becheri D et al. Evaluation of the cardiovascular health study (CHS) instrument and the Vulnerable Elders Survey-13 (VES-13) in elderly cancer patients. Are we still missing the right screening tool? Ann Oncol 2013; 24: 494-500. Cerca con Google

Bisoffi M, Heaphy CM, Griffith JK. Telomeres: Prognostic markers for solid tumors. Int J Cancer 2006; 119: 2255-2260 Cerca con Google

Blackburn EH, Greider CW, Szostak JW. Telomeres and telomerase: the path from maize, Tetrahynema and yeast to human cancer and aging. Nature Med 2006; 12: 1133-1138 Cerca con Google

Blasco MA. Telomeres and human disease: ageing, cancer and beyond. Nat Rev Genet 2005; 6: 611-622. Cerca con Google

Bleda MJ, Bolibar I, Pares R, Salva A. Reliability of the mini nutritional assessment (MNA) in institutionalized elderly people. J Nutr Health Aging 2002; 6: 134-137. Cerca con Google

Bliss MR, McLaren R, Exton Smith AN. Mattresses for preventing pressure sores in geriatric patients. Mon Bull Minist Health Public Health Lab Serv 1966. Cerca con Google

Bojesen SE, Pooley KA, Johnatty SE, et al. Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer. Nat Genet. 2013; 45: 371-384. Cerca con Google

Bouchardy C, Rapiti E, Fioretta G, Laissue P, Neyroud-Caspar I, Schäfer P, Kurtz J, Sappino AP, Vlastos G. Undertreatment strongly decreases prognosis of breast cancer in elderly women. J Clin Oncol 2003; 21: 3580-3587. Cerca con Google

Browe RH. On the use of a pilot sample for sample size determination. Stat med 1995; 14: 1933-1940. Cerca con Google

Castagneto B, Di Pietrantonj C, Stevani I et al. The importance of negative predictive value (NPV) of vulnerable elderly survey (VES 13) as a pre-screening test in older patients with cancer. Med Oncol 2013; 30: 708. Cerca con Google

Chen CCH, Kenefick AL, Tang ST, McCorkle R. Utilization of comprehensive geriatric assessment in cancer patients. Critical Rewiews in Oncology Haematology 2007; 49: 53-67. Cerca con Google

Collerton J, Martin-Ruiz C, Davies K, Hilkens CM, Isaacs J, Kolenda C, Parker C, Dunn M, Catt M, Jagger C, von Zglinicki T, Kirkwood TB. Frailty and the role of inflammation, immunosenescence and cellular ageing in the very old: cross-sectional findings from the Newcastle 85+ Study. Mech Ageing Dev 2012; 133: 456-466. Cerca con Google

Conwell Y, Forbes NT, Cox C, Caine ED. Validation of a measure of physical illness burden at autopsy: the cumulative illness rating scale. J Am Geriatr Soc 1993; 41: 38-41. Cerca con Google

Cudennec T, Gendry T, Labrune S, Giraud V, Moulias S. Use of a simplified geriatric evaluation in thoracic oncology. Lung Cancer 2009; 3329. Cerca con Google

Dale DC. Poor prognosis in elderly patients with cancer: the role of bias and undertreatment. J Support Oncol 2003; 1: 11-17 (4 Suppl 2). Cerca con Google

De Groot LC, Beck AM, Schroll M, et al. Evaluating your Nutritional Health Checklist and the Mini Nutritional Assessment as tools to identify nutritional problems in elderly Europeans. Eur J Clin Nutr 1998; 52: 877-883. Cerca con Google

De Rossi A, Walker AS, Klein N, De Forni D, King D, Gibb DM. For the Paediatric European Network for treatment of AIDS. Increased thymic output after initiation of antiretroviral therapy in HIV-1-infected children in the PENTA 5 trial. J Infect Dis 2002; 186: 312-320 . Cerca con Google

Dolcetti R, De Rossi A. Telomere/telomerase interplay in virus-driven and virus-independent lymphomagenesis: pathogenic and clinical implications. Med Res Rev 2012; 32: 233-253. Cerca con Google

Douek DC, McFarland RD, Keiser PH, Gage EA, Massey JM, Haynes BF, Polis MA, Haase AT, Feinberg MB, Sullivan JL, Jamieson BD, Zack JA, Picker LJ, Koup RA. Changes in thymic function with age and during the treatment of HIV infection. Nature 1998; 396: 690-695. Cerca con Google

DuBois D, DuBois EF. A formula to estimate the approximate surface area if height and weight be known. Arch Int Med 1916; 17: 863-71. Cerca con Google

Extermann M, Aapro M, Bernabei R, Cohen HJ, Droz JP, Lichtman S, et al. Task Force on CGA of the International Society of Geriatric Oncology. 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; Sep, 55(3): 241-52. Review. Cerca con Google

Extermann M, Boler I, Reich RR et al. Predicting the risk of chemotherapy toxicity in older patients: the Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH) score. Cancer 2012; 118: 3377-3386. Cerca con Google

Extermann M, Bonetti M, Sledge GW et al. MAX2--a convenient index to estimate the average per patient risk for chemotherapy toxicity; validation in ECOG trials. Eur J Cancer 2004; 40: 1193-1198. Cerca con Google

Extermann M, Chen H, Cantor AB et al. Predictors of tolerance to chemotherapy in older cancer patients: a prospective pilot study. Eur J Cancer 2002; 38: 1466-1473. Cerca con Google

Extermann M, Hurria A. Comprehensive geriatric assessment for older patients with cancer. J Clin Oncol 2007; 25: 1824-1831. Cerca con Google

Extermann M, Meyer J, McGinnis M, Crocker TT, Corcoran MB, Yoder J, et al. A comprehensive geriatric intervention detects multiple problems in older breast cancer patients. Oncology Hematology 2004; 49: 69-75. Cerca con Google

Extermann M, Overcash J, Lyman GH et al. Comorbidity and functional status are independent in older cancer patients. J Clin Oncol 1998; 16: 1582-1587. Cerca con Google

Extermann M. Studies of comprehensive geriatric assessment in patients with cancer. Cancer Control 2003; 10: 463-469. Cerca con Google

Falandry C, Brain E, Bonnefoy M et al. Impact of geriatric risk factors on pegylated liposomal doxorubicin tolerance and efficacy in elderly metastatic breast cancer patients: Final results of the DOGMES multicentre GINECO trial. Eur J Cancer 2013; 49: 2806-2814. Cerca con Google

Falci C, Fiduccia P, Brunello A, Baretta Z, Solda C, Lamberti E, Bozza F, Capovilla E, Jirillo A, Monfardini S. Is vulnerable elders survey 13 (VES-13) a sensitive and specific screening tool for identifying vulnerable/frail elderly cancer patients compared to full comprehensive geriatric assessment (CGA)? Crit Rev Oncol Hematol 2009; 72 (suppl 1): S19-S20. Cerca con Google

Falci C, Brunello A, Monfardini S. Detecting functional impairment in older patients with cancer: Is vulnerable elders survey-13 the right prescreening tool? An open question. J Clin Oncol 2010; 28: e665-e666. Cerca con Google

Falci C, Brunello A, Monfardini S. Reply to MJ Molina-Garrido et al. Journal of Clinical Oncology 2011; 3202. Cerca con Google

Ferrucci L, Marchionni N. Linee guida sull’utilizzazione della valutazione multidimensionale per l’anziano fragile nella rete dei servizi. G Geront 2001; 49: 1-73. Cerca con Google

Folstein M, Folstein S, McHugh PR. Mini-Mental State: a practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research 1975; 12: 189-198. Cerca con Google

Franken B, de Groot MR, Mastboom WJ, Vermes I, van der Palen J, Tibbe AG, Terstappen LW. Circulating tumor cells, disease recurrence and survival in newly diagnosed breast cancer. Breast Cancer Res 2012; 14: R133. Cerca con Google

Freguja R, Gianesin K, Mosconi I, Zanchetta M, Carmona F, Rampon O, Giaquinto C, De Rossi A. Regulatory T cells and chronic immune activation in human immunodeficiency virus 1 (HIV-1)-infected children. Clin Exp Immunol 2011; 164: 373-380. Cerca con Google

Frese T, Deutsch T, Keyser M, Sandholzer H. In Home preventive comprehensive geriatric assessment (CGA) reduce mortality- A randomized controlled trial. Arch Gerontol Geriatr 2012; 13-26. Cerca con Google

Fries JF. Measuring and monitoring success in compressing morbidity. Ann Intern Med 2003. 139: 455-459. Cerca con Google

Garcia-Aranda C, de Juan C, Diaz-Lopez A, Sanchez-Pernaute A, Torres AJ, Diaz-Rubio E, Balibrea JL, Benito M, Iniesta P. Correlations of telomere length, telomerase activity, and telomeric-repeat binding factor 1 expression in colorectal carcinoma. Cancer 2006; 106: 541-551. Cerca con Google

Gerber V, Krieg MA, Cornuz J et al. Nutritional status using the Mini Nutritional Assessment questionnaire and its relationship with bone quality in a population of institutionalized elderly women. J Nutr Health Aging 2003; 7: 140-145. Cerca con Google

Giantin V, Valentini E, Iasevoli M, Falci C, Siviero P, De Luca E, Maggi S, Martella B, Orrù G, Crepaldi G, Monfardini S, Terranova O, Manzato E. Does the Multidimensional prognostic Index (MPI) based on a Comprehensive Geriatric assessment (CGA) predict mortality in cancer patients? Results of a prospective observational trial. J Geriatr Oncol 2013; 4: 208-217. Cerca con Google

Guigoz Y, Vellas B. The Mini Nutritional Assessment (MNA) for grading the nutritional state of elderly patients. Presentation of the MNA, history and validation. Nestle Nutr Workshop Ser Clin Perform Programm 1999; 1: 3-11. Cerca con Google

Guigoz Y, Vellas B. The Mini Nutritional Assessment (MNA) for grading the nutritional state of elderly patients. Presentation of the MNA, history and validation. Nestle Nutr Workshop Ser Clin Perform Programme 1999; 1: 3-11. Cerca con Google

Hueman MT, Stojadinovic A, Storrer CE, Dehqanzada ZA, Gurney JM, Shriver CD, Ponniah S, Peoples GE. Analysis of naïve and memory CD4 and CD8 T cell populations in breast cancer patients receiving a HER2/neu peptide (E75) and GM-CSF vaccine. Cancer Immunol Immunother 2007; 56: 135-146. Cerca con Google

Hurria A, Browner IS, Cohen HJ, Denlinger CS, deShazo M, Extermann M, Ganti AK, Holland JC, Holmes HM, Karlekar MB, Keating NL, McKoy J, Medeiros BC, Mrozek E, O'Connor T, Petersdorf SH, Rugo HS, Silliman RA, Tew WP, Walter LC, Weir AB 3rd, Wildes T. Senior adult oncology. J Natl Compr Canc Netw 2012; 10: 162-209. Cerca con Google

Hurria A, Togawa K, Mohile SG et al. Predicting chemotherapy toxicity in older adults with cancer: a prospective multicenter study. J Clin Oncol 2011; 29: 3457-3465. Cerca con Google

Hurria A. Embracing the complexity of comorbidity. J Clin Onco 2011; 10: 29(32),4217-8. Cerca con Google

Junge S, Kloeckener-Gruissem B, Zufferey R, Keisker A, Salgo B, Fauchere JC, Scherer F, Shalaby T, Grotzer M, Siler U, Seger R, Güngör T. Correlation between recent thymic emigrants and CD31+ (PECAM-1) CD4+ T cells in normal individuals during aging and in lymphopenic children. 2007; Eur J Immunol 37: 3270-3280. Cerca con Google

Katz S, Downs TD, Cash HR, Grotz HR. Progress in development of the index of ADL. Gerontologist 1970; 10: 20-30. Cerca con Google

Kimmig S, Przybylski GK, Schmidt CA, Laurisch K, Möwes B, Radbruch A, Thiel A. Two subsets of naive T helper cells with distinct T cell receptor excision circle content in human adult peripheral blood. J Exp Med 2002; 195: 789-794. Cerca con Google

Klebanoff CA, Gattinoni L, Restifo NP. CD8+ T-cell memory in tumor immunology and immunotherapy. Immunol Rev 2006; 211: 214-224. Cerca con Google

Kroenke CH, Kubzansky LD, Schernhammer ES, et al. Social networks, social support, and survival after breast cancer diagnosis. J Clin Oncol 2006; 24: 1105-1111. Cerca con Google

Kuss I, Schaefera C, Godfreya TE, Ferris RL, Harris JM, Gooding W, Whiteside TL. Recent thymic emigrants and subsets of naive and memory T cells in the circulation of patients with head and neck cancer. Clin Immunol 2005; 116: 27-36. Cerca con Google

Lan Q, Cawthon R, Gao Y, Hu W, Hosgood HD 3rd, Barone-Adesi F, Ji BT, Bassig B, Chow WH, Shu X, Cai Q, Xiang Y, Berndt S, Kim C, Chanock S, Zheng W, Rothman N. Telomere Length in Peripheral White Blood Cells Is Associated with Risk of Lung Cancer and the rs2736100 (CLPTM1L-TERT) Polymorphism in a Prospective Cohort Study among Women in China. PLoS One 2013; 8-18. Cerca con Google

Lawton MP, Brody EM. Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist 1969; 9: 179-186. Cerca con Google

Luciani A, Ascione G, Bertuzzi C et al. Detecting disabilities in older patients with cancer: comparison between comprehensive geriatric assessment and vulnerable elders survey-13. J Clin Oncol 2010; 28: 2046-2050. Cerca con Google

Luciani A, Jacobsen P.B.; Extermann, M; Foa, P; Marussi, D; Ferrari, D; Morabito, A; Overcash, J.A.; Balducci, L. The impact of fatigue and anemia on functional status in older cancer patients treated with chemotherapy. Journal of Geriatric Oncology 2012; 3-11. Cerca con Google

Marenco D, Marinello R, Berruti R, Gaspari F, Stasi MF, Rosato R, et al. Multidimensional geriatric assessment in treatment decisions in elderly cancer patients: 6-year experience in an outpatient geriatric oncology service. Oncology Hematology 2008; 68: 157-164. Cerca con Google

Miller MD, Paradis CF, Houck PR et al. Rating chronic medical illness burden in geropsychiatric practice and research: application of the Cumulative Illness Rating Scale. Psychiatry Res 1992; 41: 237-248. Cerca con Google

Min LC, Elliott MN, Wenger NS, Saliba D. Higher vulnerable elders survey scores predict death and functional decline in vulnerable older people. J Am Geriatr Soc 2006; 54: 507-511. Cerca con Google

Mitchell WA, Lang PO, Aspinall R. Tracing thymic output in older individuals. Clin Exp Immunol 2010; 161: 497-503. Cerca con Google

Mohile SG, Bylow K, Dale W et al. A pilot study of the vulnerable elders survey-13 compared with the comprehensive geriatric assessment for identifying disability in older patients with prostate cancer who receive androgen ablation. Cancer 2007; 109: 802-810. Cerca con Google

Molina-Garrido MJ, Guillen-Ponce C. Comparison of two frailty screening tools in older women with early breast cancer. Crit Rev Oncol Hematol 2011; 79: 51-64. Cerca con Google

Monfardini S, Ferrucci L, Fratino L et al. Validation of a multidimensional evaluation scale for use in elderly cancer patients. Cancer 1996; 77: 395-401. Cerca con Google

Monfardini S, Giordano G, Sandri R, Gnocchi PL, Galetti G. Ringing geriatrics into oncology or also oncology into geriatrics? Ann Oncol. Mar 2012; 23(3): 801. Cerca con Google

Muss HB, Berry DA, Cirrincione C, Budman DR, Henderson IC, Citron ML, Norton L, Winer EP, Hudis CA. Toxicity of older and younger patients treated with adjuvant chemotherapy for node-positive breast cancer: the Cancer and Leukemia Group B Experience. J Clin Oncol 2007; 25: 3699-3704. Cerca con Google

Nasi M, Troiano L, Lugli E, Pinti M, Ferraresi R, Monterastelli E, Mussi C, Salvioli G, Franceschi C, Cossarizza A. Thymic output and functionality of the IL-7/IL-7 receptor system in centenarians: implications for the neolymphogenesis at the limit of human life. Aging Cell 2006; 5: 167-175. Cerca con Google

National Institutes of Health Consensus Development Conference Statement: geriatric assessment methods for clinical decision-making. J Am Geriatr Soc 1988; 36: 342-347. Cerca con Google

Naylor K, Li G, Vallejo AN, Lee WW, Koetz K, Bryl E, Witkowski J, Fulbright J, Weyand CM, Goronzy JJ. The influence of age on T cell generation and TCR diversity. J Immunol 2005; 174: 7446-7452. Cerca con Google

Novak M, Guest C. Application of a multidimensional caregiver burden inventory. Gerontologist 1989; 29: 798-803. Cerca con Google

Overcash J, Overcash JA, Beckstead J, Moody L, Extermann M, Cobb S. The abbreviated comprehensive geriatric assessment (aCGA) for use in the older cancer patient as a prescreen: scoring and interpretation. Crit Rev Oncol Hematol 2006; Sep;59(3):205-10. Cerca con Google

Owusu C, Koroukian SM, Schluchter M et al. Screening older cancer patients for a Comprehensive Geriatric Assessment: A comparison of three instruments. J Geriatr Oncol 2011; 2: 121-129. Cerca con Google

Pfeiffer E. A short portable mental status questionnaire for the assessment of organic brain deficit in elderly patients. J Am Geriatr Soc 1975; 23: 433-441. Cerca con Google

Pilotto A, Addante F, Ferrucci L, Leandro G, D’Onofrio G, Corridore M, et al. The multidimensional prognostic index predicts short- and long-term mortality in hospitalized geriatric patients with pneumonia. J Gerontol A Biol Sci Med Sci 2009; 1-5. Cerca con Google

Pilotto A, Addante F, Franceschi M, Leandro G, Rengo G, D'Ambrosio P, et al. Multidimensional Prognostic Index based on a comprehensive geriatric assessment predicts short-term mortality in older patients with heart failure. Circ Heart Fail 2010; 3(1): 14-20. Cerca con Google

Pilotto A, Ferrucci L, Franceschi M, D’Ambrosio LP, Scancelli C, Cascavilla L, et al. Development and validation of a multidimensional prognostic index for one-year mortality from comprehensive geriatric assessment in hospitalizad older patients. Rejuvenation Res 2008; 11(1): 151-161. Cerca con Google

Pilotto A, Ferrucci L, Scarcelli C, Niro V, Di Mario F, Seripa D, et al. Usefulness of the comprehensive geriatric assessment in older patients with upper gastrointestinal bleeding: a two-year follow-up study. Dig Dis 2007; 25: 124-128. Cerca con Google

Pilotto A, Franceschi M, Ferrucci L. Il multidimensional prognostic index (MPI) per la valutazione dell’anziano fragile ospedalizzato. G Gerontol 2007; 55: 7-10. Cerca con Google

Pilotto A, Franceschi M, Vitale DF, Zaninelli A, Casotti G, Rengo F. Upper gastrointestinal symptoms, users of non-selective NSAIDs or coxibs. In: Behalf of FIRI (Fondazione Italiana Ricerca sull’Invecchiamento) and the SOFIA Investigators. Aliment Pharmacol Ther Publ 1995; 22: 147-49. Cerca con Google

Pilotto A, Sancarlo D, Panza F, Paris F, D'Onofrio G, Cascavilla L, et al. The Multidimensional Prognostic Index (MPI), based on a comprehensive geriatric assessment predicts short- and long-term mortality in hospitalized older patients with dementia. J Alzheimers Dis 2009; 18(1):191-9. Cerca con Google

Pilotto A, Scarcelli C, D’Ambrosio LP, Cascavilla L, Longo MG, Greco A, et al. All patients refined diagnosis related groups (APR-DRG): a new administrative tool for identifying elderly patients at risk of high resource consumption. J Am Geriatr 2005; 53: 167-168. Cerca con Google

Pilotto A. Comprehensive geriatric assessment in the older patient with metabolic syndrome. Adv Gerontol 2007; 25: 124-8. Cerca con Google

Poschke I, De Boniface J, Mao Y, Kiessling R. Tumor-induced changes in the phenotype of blood-derived and tumor-associated T cells of early stage breast cancer patients. Int J Cancer 2012; 131: 1611-1620. Cerca con Google

Pottel L BT, Pottel H, Goethals L, Van Den Noortgate N, Duprez F, De Neve W, Rottey S, Geldhof K, Van Eygen K, Kargar-Samani K, Ghekiere V, Cornelis F, Mohile S, Debruyne PR. Determination of an adequate screening tool for the identification of vulnerable elderly head and neck cancer patients treated with radio(chemo)therapy. . J Geriatr Oncol 2012; 3: 24-32. Cerca con Google

Rampazzo E, Bertorelle R, Serra L, Terrin L, Candiotto C, Pucciarelli S, Del Bianco P, Nitti D, De Rossi A. Relationship between telomere shortening, genetic instability and site of tumour origin in colorectal cancers. Br J Cancer 2010; 102: 1300-1305. Cerca con Google

Rampazzo E, Bonaldi L, Trentin L, Visco C, Keppel S, Giunco S, Frezzato F, Facco M, Novella E, Giaretta I, Del Bianco P, Semenzato G, De Rossi A. Telomere length and telomerase levels delineate subgroups of B-cell chronic lymphocytic leukemia with different biological characteristics and clinical outcomes. Haematologica 2012; 97: 56-63. Cerca con Google

Repetto L, Fratino L, Audisio RA et al. Comprehensive geriatric assessment adds information to Eastern Cooperative Oncology Group performance status in elderly cancer patients: an Italian Group for Geriatric Oncology Study. J Clin Oncol 2002; 20: 494-502. Cerca con Google

Reuben DB, Rubenstein LV, Hirsch SH, et al. Value of functional status as a predictor of mortality: results of a prospective study. Am J Med 1992; 93: 663-669. Cerca con Google

Ritter PL, Gonzales VM, Laurent DD, Lorig KR. Measurement of pain using the visual numeric scale. The Journal of Rheumatology 2006; 33:3-7. Cerca con Google

Rodin MB, Mohile SG. A practical approach to geriatric assessment in oncology. J Clin Oncol 2007; 25: 1936-1944. Cerca con Google

Rubenstein LZ, Josephson KR, Wieland GD et al. Effectiveness of a geriatric evaluation unit. A randomized clinical trial. N Engl J Med 1984; 311: 1664-1670. Cerca con Google

Rubenstein LZ. Comprehensive geriatric assessment: from miracle to reality. Journal of Gerontology: Medical Sciences 2004; 59A(5): 473-477. Cerca con Google

Saliba D, Elliott M, Rubenstein LZ et al. The Vulnerable Elders Survey: a tool for identifying vulnerable older people in the community. J Am Geriatr Soc 2001; 49: 1691-1699. Cerca con Google

Scher KS, Hurria A. Under-representation of older adults in cancer registration trials: known problem, little progress. J Clin Oncol 2012; 10: 30(17), 2036-8. Cerca con Google

Shimada R, Iinuma H, Akahane T, Horiuchi A, Watanabe T. Prognostic significance of CTCs and CSCs of tumor drainage vein blood in Dukes' stage B and C colorectal cancer patients. Oncol Rep 2012; 27: 947-953. Cerca con Google

Siegel R, Naishadham D, Jemal A. Cancer Statistics. CA Cancer J Clin 2012; 62:10-29. Cerca con Google

Steenstrup T, Hjelmborg JV, Mortensen LH, Kimura M, Christensen K, Aviv A. Leukocyte telomere dynamics in the elderly. Eur J Epidemiol 2013; 28: 181-187. Cerca con Google

Stokoe JM PJ, SinhaR, Ring A. G8 and VES-13 scores predict chemotherapy toxicity in older patients with cancer. J Geriatr Oncol 2012; 3: S81. Cerca con Google

Surbone A, Kagawa-Singer M, Terret C, Baider L. The illness trajectory of elderly cancer patients across cultures: SIOG position paper. Annals of Oncology 2007; 18: 633–638. Cerca con Google

Svenson U, Nordfjall K, Stegmaryr B, Manjer J, Nilsson P, Tavelin B, Henriksson R, Lenner P, Roos G. Breast cancer survival is associated with telomere length in peripheral blood cells. Cancer Res 2008; 68: 3618-3623. Cerca con Google

Takahashi PY, Cha SS, Kiemele LJ. Six-month mortality risks in long-term care residents with chronic ulcers. Int Wound J 2008; 5(5): 625-631. Cerca con Google

Wedding U, Roehrig B, Klippstein A, et al. Comorbidity in patients with cancer: prevalence and severity measured by cumulative illness rating scale. Critical Reviews in Oncology Haematology 2007; 61(3): 269-76. Cerca con Google

Wildiers H, Mauer M, Pallis A, Hurria A, Mohile SG, Luciani A, Curigliano G, Extermann M, Lichtman SM, Ballman K, Cohen HJ, Muss H, Wedding U. End points and trial design in geriatric oncology research: a joint European organisation for research and treatment of cancer-Alliance for Clinical Trials in Oncology--International Society Of Geriatric Oncology position article. J Clin Oncol. 2013; Oct 10; 31(29): 3711-8. Cerca con Google

Woo J, Tang NLS, Suen E, Leung JC, Leung PC. Telomeres and frailty. Mech Ageing Dev 2008; 129: 642-648. Cerca con Google

Yesavage JA, Brink TL, Rose TL, Lum O, Huang V, Adey M, Leirer VO. Development and validation of geriatric depression screening: a preliminary report. J Psychiatr Res 1982-1983; 17: 37-49. Cerca con Google

Yesavage JA, Rose TL, Lum O, Huang V. Development and validation of geriatric depression screening: a preliminary report. J Psychiatr Res 1983; 17:37. Cerca con Google

Yourman LC. Prognostic indices for older adults. A systematic review. JAMA 2012; 11: 307, 182-192. Cerca con Google

Zagonel V, Fratino L, Piselli P, et al. The comprehensive geriatric assessment (CGA) predicts mortality among elderly cancer patients (ECP). Proc Ann Meet Am Soc Clin Oncol 2002; 21: 145. Cerca con Google

Zhang L, Lewin SR, Markowitz M, Lin HH, Skulsky E, Karanicolas R, He Y, Jin X, Tuttleton S, Vesanen M, Spiegel H, Kost R, van Lunzen J, Stellbrink HJ, Wolinsky S, Borkowsky W, Palumbo P, Kostrikis LG, Ho DD. Measuring recent thymic emigrants in blood of normal and HIV-1-infected individuals before and after effective therapy. J Exp Med 1999; 190: 725-732. Cerca con Google

http://www.nccn.org/professionals/physician gls/PDF/senior.pdf. Vai! Cerca con Google

Download statistics

Solo per lo Staff dell Archivio: Modifica questo record