Rapport intermédiaire 2017-2018 Dominique BRON Impact Facteurs Neuropsychologiques
Projet mené à l’Institut J. Bordet sous la direction du Pr D. Bron (2018)
Rapport intermédiaire de l’avancement du projet « Impact des facteurs neuropsychologiques et biologiques
sur l’adhérence des prescriptions médicales par les patients âgés porteurs d'une hémopathie maligne »
Directeur du projet : Professeur Dominique BRON
Durée du projet : 2 ans
Neuropsychologue : Stéphanie Dubruille
Pour rappel les objectifs du projet
1) Evaluer l’impact et les liens des facteurs neuropsychologiques et biologiques du patient âgé sur l’adhérence aux traitements hématologiques.
2) Evaluer l’impact des facteurs neuropsychologiques, biologiques et l’adhérence aux traitements hématologiques sur la toxicité induite par le traitement et la survie.
3) Valider l’outil innovant de dépistage de la fragilité sur une plus grande cohorte de patients âgés.
Avancement du projet
Depuis le 1 novembre 2017 (date du début du finacement du projet), nous avons pu évaluer 10 nouveaux patients âgés débutant une chimiothérapie orale et 30 nouveaux patients âgés débutant un nouveau traitement hématologique, afin de répondre respectivement à l’objectif primaire ainsi que secondaire et tertiaire. Le recrutement des patiens âgés porteurs d’une hémopathie maligne se déroule comme prévu.
Concernant, plus précisement l’objectif tertiaire, un article scientifique validant notre nouveau « frailty scoring » devrait sous peu être soumis à un journal scientifique de renom (cfr : Annexe 1 & 2).
Une revue de la littérature concernant les facteurs de fragilité chez la personne âgée souffrant d’une hémopathie maligne a été soumise au Belgian Journal of Hematology (cfr : Annexe 3).
Stéphanie Dubruille, la neuropsychologue, en charge du projet a soumis de nombreux abstracts et a participé à de nombreux congrès afin d’apporter de la visibilté au projet (cfr : Annexe 4).
L’année à venir, se concentrera principalement sur le recrutement des patients âgés débutant une chimiothérapie orale afin de répondre à l’objectif primaire et secondaire, à la soumission d’articles et d’abstracts scientifiques ainsi qu’à la participation à des congrès internationaux.
Depuis le 1 novembre 2017 (date du début du finacement du projet), nous avons pu évaluer 10 nouveaux patients âgés débutant une chimiothérapie orale et 30 nouveaux patients âgés débutant un nouveau traitement hématologique, afin de répondre respectivement à l’objectif primaire ainsi que secondaire et tertiaire. Le recrutement des patiens âgés porteurs d’une hémopathie maligne se déroule comme prévu.
Concernant, plus précisement l’objectif tertiaire, un article scientifique validant notre nouveau « frailty scoring » devrait sous peu être soumis à un journal scientifique de renom (cfr : Annexe 1 & 2).
Une revue de la littérature concernant les facteurs de fragilité chez la personne âgée souffrant d’une hémopathie maligne a été soumise au Belgian Journal of Hematology (cfr : Annexe 3).
Stéphanie Dubruille, la neuropsychologue, en charge du projet a soumis de nombreux abstracts et a participé à de nombreux congrès afin d’apporter de la visibilté au projet (cfr : Annexe 4).
L’année à venir, se concentrera principalement sur le recrutement des patients âgés débutant une chimiothérapie orale afin de répondre à l’objectif primaire et secondaire, à la soumission d’articles et d’abstracts scientifiques ainsi qu’à la participation à des congrès internationaux.
Annexe 1
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Annexe 2
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Clinical and Biologic Correlates of Frailty in Older patients with malignant hemopathies
S. Dubruille Ph.D1, V. Thibaud M.D1, T. Pepersack M.D, Ph.D2, D. Bron M.D, Ph.D1
1: Department of Hematology, Institut Jules Bordet, ULB, Brussels, Belgium
2: Onco-geriatrics Unit, Institut Jules Bordet, ULB, Brussels, Belgium
Summary
Frailty assessment in older patients with malignant hemopathies is very useful in order to improve care and treatment options. However, some lacks of data exist regarding the unsuspected frail population in presumed “clinically fit” patients who should not benefit from chemotherapy. In this article, we review current data regarding prognostic factors and frailty scoring in older patients with malignant hemopathies. Prospective trials are needed to build a new frailty scoring to assess the unsuspected frail population in “clinically fit” patients including specifically assessment of cognitive impairment.
Keywords
Older patients, cancer, frailty, geriatric assessment
Key messages for clinical practice
Article
Frailty is a vulnerable state that arises from “decreased reserves in multiple organ systems, which are initiated by disease, lack of activity, inadequate nutritional intake, stress, and/or the physiologic changes of aging” (1,2).
Although chronological age, comorbidity, and performance status are relatively easy to assess, they have only limited utility in capturing the heterogeneity of older patients with malignant hemopathies (3).
The goal of a frailty screening is to estimate a patient’s physiological age when considering treatment options and goals of care (4). Such assessment includes several domains such as comorbidity, psychological health, current quality of life, medication burden, physical health, cognitive function, and social support (4).
In gerontology, two approaches are opposed when we are talking about frailty, the approach of Linda Fried (the physical model) and the approach of Kenneth Rockwood (the multi-domain model). The Fried’s phenotype model is focus principally on physical performance (5). The Rockwood model alternatively assesses frailty as the cumulative effect of “deficits” (6). For geriatricians, there are three categories of older patients: patients clearly fit, patients vulnerable and patients clearly frail. Nevertheless, screening is best captured through in-person functional examination, known as Comprehensive Geriatric Assessment (CGA) (4).
Growing evidence suggests that a CGA in older patients with malignant hemopathies helps hematologists to detect “vulnerabilities” leading to useful interventions but CGA is less useful to identify patients for whom chemotherapy should be avoided or reduced as it could negatively impact functionality, quality of life, treatment-related toxicity or survival (7,3). Moreover, the CGA is time consuming, expensive, complex, not reproducible and not helpful for an individual patient with a specific treatment (8).
To overcome these difficulties, the G8 screening test was developed by Soubeyran and colleagues (9) to identify vulnerable patients who might benefit from a full CGA and adapted interventions. In a systematic review of a mixed population of oncological patients, G8 showed a good sensitivity (87%) in detecting geriatric impairments in multiple domains, in fact, most of these patients were identified as having geriatric impairments (10).
However, regarding hematological patients and in particularly in “clinically fit” (meaning not exhibiting geriatric syndromes, irreversible comorbidities and/or significantly impaired function, and thus able to receive chemotherapy (“patient clearly not frail”)), we found in our previous study that the G8 score does not help selecting patients for CGA and that the G8 and CGA total scores do not predict overall survival. Only the presence of cognitive impairment (CI), in addition to the age and disease itself, appears to be powerful prognostic factors (11).
Regarding these results, it seems useful to make a review of the prognostic factors in the CGA and the frailty assessment in older patient with malignant hemopathies. In the literature, a recent review found in 55% of the studies a correlation between instrumental activities and survival, 67% a correlation between nutritional status and survival, 83% a correlation between CI and survival, and 100% between physical capacity and survival. Comorbidity, physical capacity and nutritional status retained their significance even in multivariate analyses in 50%, 75%, and 67% of analyses respectively (3). Table 1 shows factors in the CGA correlated with survival in older patients with malignant hemopathies.
S. Dubruille Ph.D1, V. Thibaud M.D1, T. Pepersack M.D, Ph.D2, D. Bron M.D, Ph.D1
1: Department of Hematology, Institut Jules Bordet, ULB, Brussels, Belgium
2: Onco-geriatrics Unit, Institut Jules Bordet, ULB, Brussels, Belgium
Summary
Frailty assessment in older patients with malignant hemopathies is very useful in order to improve care and treatment options. However, some lacks of data exist regarding the unsuspected frail population in presumed “clinically fit” patients who should not benefit from chemotherapy. In this article, we review current data regarding prognostic factors and frailty scoring in older patients with malignant hemopathies. Prospective trials are needed to build a new frailty scoring to assess the unsuspected frail population in “clinically fit” patients including specifically assessment of cognitive impairment.
Keywords
Older patients, cancer, frailty, geriatric assessment
Key messages for clinical practice
- Importance of frailty factors to help the clinician to predict outcome and to improve care
- Need to build a new frailty score to detect unsuspected frailty in presumed “clinically fit” patients
- Need to inform health care professionals about the importance of cognitive impairment
Article
Frailty is a vulnerable state that arises from “decreased reserves in multiple organ systems, which are initiated by disease, lack of activity, inadequate nutritional intake, stress, and/or the physiologic changes of aging” (1,2).
Although chronological age, comorbidity, and performance status are relatively easy to assess, they have only limited utility in capturing the heterogeneity of older patients with malignant hemopathies (3).
The goal of a frailty screening is to estimate a patient’s physiological age when considering treatment options and goals of care (4). Such assessment includes several domains such as comorbidity, psychological health, current quality of life, medication burden, physical health, cognitive function, and social support (4).
In gerontology, two approaches are opposed when we are talking about frailty, the approach of Linda Fried (the physical model) and the approach of Kenneth Rockwood (the multi-domain model). The Fried’s phenotype model is focus principally on physical performance (5). The Rockwood model alternatively assesses frailty as the cumulative effect of “deficits” (6). For geriatricians, there are three categories of older patients: patients clearly fit, patients vulnerable and patients clearly frail. Nevertheless, screening is best captured through in-person functional examination, known as Comprehensive Geriatric Assessment (CGA) (4).
Growing evidence suggests that a CGA in older patients with malignant hemopathies helps hematologists to detect “vulnerabilities” leading to useful interventions but CGA is less useful to identify patients for whom chemotherapy should be avoided or reduced as it could negatively impact functionality, quality of life, treatment-related toxicity or survival (7,3). Moreover, the CGA is time consuming, expensive, complex, not reproducible and not helpful for an individual patient with a specific treatment (8).
To overcome these difficulties, the G8 screening test was developed by Soubeyran and colleagues (9) to identify vulnerable patients who might benefit from a full CGA and adapted interventions. In a systematic review of a mixed population of oncological patients, G8 showed a good sensitivity (87%) in detecting geriatric impairments in multiple domains, in fact, most of these patients were identified as having geriatric impairments (10).
However, regarding hematological patients and in particularly in “clinically fit” (meaning not exhibiting geriatric syndromes, irreversible comorbidities and/or significantly impaired function, and thus able to receive chemotherapy (“patient clearly not frail”)), we found in our previous study that the G8 score does not help selecting patients for CGA and that the G8 and CGA total scores do not predict overall survival. Only the presence of cognitive impairment (CI), in addition to the age and disease itself, appears to be powerful prognostic factors (11).
Regarding these results, it seems useful to make a review of the prognostic factors in the CGA and the frailty assessment in older patient with malignant hemopathies. In the literature, a recent review found in 55% of the studies a correlation between instrumental activities and survival, 67% a correlation between nutritional status and survival, 83% a correlation between CI and survival, and 100% between physical capacity and survival. Comorbidity, physical capacity and nutritional status retained their significance even in multivariate analyses in 50%, 75%, and 67% of analyses respectively (3). Table 1 shows factors in the CGA correlated with survival in older patients with malignant hemopathies.
Disease-specific screening in terms of frailty has not yet been developed expected for myeloma where a real validated frailty scoring has been published (21). Nevertheless, as seen in the Table 2 several tools and scores can be useful to screen for frailty in hematology practice. These tools are unmet needs for geriatricians and oncologists.
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Regarding the literature and our personal data, we observed, in addition to well-known prognostic factors, the major impact of CI in older patients with malignant hemopathies. These results could be easily explained. First, older patients with CI are less compliant to the treatment (24). Second, CI in older patients are often associated with late-life depression (25) which is correlated with a poorer survival in older cancer patients (26). Third, older people with CI are more frequently isolated (27), and turn away persons who want to help, to avoid facing their difficulties (28). Finally, it is increasingly reported that chemotherapeutic agents can worsen the patient’s cognitive status (29). Thus, it is likely that patients with CI at the start of a chemotherapy are more vulnerable, and that their vulnerability is worsened by chemotherapeutic agents (30).
Prospective trials are needed to build a reliable frailty score able to identify the unsuspected frail population in “clinically fit” patients who should not benefit from chemotherapy. This new frailty scoring should obviously include assessment of physical function, cognitive function and comorbidity (4).
CONCLUSIONS
Frailty assessment is useful to predict a poor outcome and to build adaptive interventions in older patients with malignant hemopathies. However, we are still lacking a specific screening tool able to detect unsuspected frail population in “clinically fit” patients who should not benefit from chemotherapy. Prospective trials are urgently needed to build and validate a new frailty scoring including specifically assessment of cognitive impairment to assess this specific highly vulnerable population.
Disclosure: The authors indicate have nothing to disclose no conflicts of interest.
Acknowledgment: We would like to thank the Yvonne Boël Foundation for its support to Ms Stéphanie Dubruille, neuropsychologist, in charge of the project “Biomarkers and frailty of older cancer patients”
Bibliography
1. Ahmed N, Mandel R, Fain MJ. Frailty: an emerging geriatric syndrome. Am J Med. 2007;120(9):748-753.
2. Fried LP, Ferrucci L, Darer J, Williamson JD, Anderson G. Untangling the concepts of disability, frailty, and comorbidity: implications for improved targeting and care. J Gerontol A Biol Sci Med Sci. 2004;59(3):255-263.
3. Hamaker ME, Prins MC, Stauder R. The relevance of a geriatric assessment for elderly patients with a haematological malignancy–a systematic review. Leuk. Res. 2014;38(3):275–283.
4. Abel GA and Klepin HD. Frailty and the management of hematologic malignancies. Blood. 2018;131(5):515-524.
5. Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, Seeman T, Tracy R, Kop WJ, Burke G, McBurnie MA. Cardiovascular Health Study Collaborative Research Group. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56(3):M146-M156.
6. Rockwood K, Mitnitski A. Frailty in relation to the accumulation of deficits. J Gerontol A Biol Sci Med Sci. 2007;62(7):722-727.
7. Extermann M, Aapro M, Bernabei R, Cohen HJ, Droz JP, Lichtman S, Mor V, Monfardini S, Repetto L, Sørbye L, Topinkova E; 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;55(3):241–252.
8. Extermann M, Meyer J, McGinnis M, Crocker TT, Corcoran MB, Yoder J, Haley WE, Chen H, Boulware D, Balducci L. A comprehensive geriatric intervention detects multiple problems in older breast cancer patients. Crit Rev Oncol Hematol. 2004;49(1):69–75.
9. Soubeyran P, Bellera C, Goyard J, Heitz D, Curé H, Rousselot H, Albrand G, Servent V, Jean OS, van Praagh I, Kurtz JE, Périn S, Verhaeghe JL1, Terret C, Desauw C, Girre V, Mertens C, Mathoulin-Pélissier S, Rainfray M. Screening for vulnerability in older cancer patients: the ONCODAGE Prospective Multicenter Cohort Study. PLoS One. 2014;11;9(12):e115060.
10. Hamaker ME, Jonker JM, de Rooij SE, Vos AG, Smorenburg CH, van Munster BC. Frailty screening methods for predicting outcome of a comprehensive geriatric assessment in elderly patients with cancer: a systematic review. Lancet Oncol. 2012;13(10):e437–e444.
11. Dubruille S, Libert Y, Roos M, et al. Identification of clinical parameters predictive of one-year survival using two geriatric tools in clinically fit older patients with haematological malignancies: major impact of cognition. J Geriatr Oncol. 2015;6:362-369.
12. Sherman AE, Motyckova G, Fega KR, Deangelo DJ, Abel GA, Steensma D, Wadleigh M, Stone RM, Driver JA. Geriatric assessment in older patients with acute myeloid leukemia: a retrospective study of associated treatment and outcomes. Leuk Res. 2013;37(9):998-1003.
13. Klepin HD, Geiger AM, Tooze JA, Kritchevsky SB, Williamson JD, Pardee TS, Ellis LR, Powell BL. Geriatric assessment predicts survival for older adults receiving induction chemotherapy for acute myelogenous leukemia. Blood 2013;121(21):4287–4294.
14. Fega KR, Abel GA, Motyckova G, Sherman AE, DeAngelo DJ, Steensma DP, Galinsky I, Wadleigh M, Stone RM, Driver JA. Nonhematologic predictors of mortality improve the prognostic value of the international prognostic scoring system for MDS in older adults. J Geriatr Oncol. 2015;6(4):288-298.
15. Deschler B, Ihorst G, Platzbecker U, Germing U, März E, de Figuerido M, Fritzsche K, Haas P, Salih HR, Giagounidis A, Selleslag D, Labar B, de Witte T, Wijermans P, Lübbert M. Parameters detected by geriatric and quality of life assessment in 195 older patients with myelodysplastic syndromes and acute myeloid leukemia are highly predictive for outcome. Haematologica. 2013;98(2):208-216.
16. Winkelmann N, Petersen I, Kiehntopf M, Fricke HJ, Hochhaus A, Wedding U. Results of comprehensive geriatric assessment effect survival in patients with malignant lymphoma. J Cancer Res Clin Oncol. 2011;137(4):733-738.
17. Goede V, Bahlo J, Chataline V, et al. Evaluation of geriatric assessment in patients with chronic lymphocytic leukemia: Results of the CLL9 trial of the German CLL study group. Leuk Lymphoma. 2016;57(4):789-796.
18. Engelhardt M, Dold SM, Ihorst G, Eichhorst B, Dürig J, Stilgenbauer S, Kolb G, Honecker F, Wedding U, Hallek M. Geriatric assessment in multiple myeloma patients: validation of the International Myeloma Working Group (IMWG) score and comparison with other common comorbidity scores. Haematologica. 2016;101(9):1110-1119.
19. Rao AV. Fitness in the elderly: how to make decisions regarding acute myeloid leukemia induction. Hematology Am Soc Hematol Educ Program. 2016;(1):339-347.
20. Tucci A, Martelli M, Rigacci L, Riccomagno P, Cabras MG, Salvi F, Stelitano C, Fabbri A, Storti S, Fogazzi S, Mancuso S, Brugiatelli M, Fama A, Paesano P, Puccini B, Bottelli C, Dalceggio D, Bertagna F, Rossi G, Spina M; Italian Lymphoma Foundation (FIL). Comprehensive geriatric assessment is an essential tool to support treatment decisions in elderly patients with diffuse large B-cell lymphoma: a prospective multicenter evaluation in 173 patients by the Lymphoma Italian Foundation (FIL). Leuk Lymphoma. 2015; 56(4):921-926.
21. Engelhardt M, Domm AS, Dold SM, Ihorst G, Reinhardt H, Zober A, Hieke S, Baayen C, Müller SJ, Einsele H, Sonneveld P, Landgren O, Schumacher M, Wäsch R. A concise revised Myeloma Comorbidity Index as a valid prognostic instrument in a large cohort of 801 multiple myeloma. Haematologica. 2017;102(5):910-921.
22. Guerard EJ, Deal AM, Chang Y, Williams GR, Nyrop KA, Pergolotti M, Muss HB, Sanoff HK, Lund JL. Frailty Index Developed From a Cancer-Specific Geriatric Assessment and the Association With Mortality Among Older Adults With Cancer. J Natl Compr Canc Netw. 2017;15(7):894-902.
23. Takahashi M, Takahashi M, Komine K, Yamada H, Kasahara Y, Chikamatsu S, Okita A, Ito S, Ouchi K, Okada Y, Imai H, Saijo K, Shirota H, Takahashi S, Mori T, Shimodaira H, Ishioka C. The G8 screening tool enhances prognostic value to ECOG performance status in elderly cancer patients: A retrospective, single institutional study. PLoS One. 2017;12(6):e0179694.
24. Granjon C, Beyens MN, Frederico D, Blanc P, Gonthier R. Is there a risk of drug accidents in elderly subjects with cognitive disorders? A study of 82 demented institutionalized patients. NPG 2006;6(35):21–28.
25. Li W, Muftuler LT, Chen G, Ward BD, Budde MD, Jones JL, Franczak MB, Antuono PG, Li SJ, Goveas JS. Effects of the coexistence of late-life depression and mild cognitive impairment on white matter microstructure. J. Neurol Sci. 2014;338(1-2):46–56.
26. Wagner DC, Short JL. Longitudinal predictors of self-rated health and mortality in older adults. Prev Chronic Dis. 2014;11 E93.
27. Amieva H, Stoykova R, Matharan F, Helmer C, Antonucci TC, Dartigues JF. What aspects of social network are protective for dementia? Not the quantity but the quality of social interactions is protective up to 15 years later. Psychosom Med. 2010;72(9):905–911.
28. Dubruille S, Libert Y, Merckaert I, Reynaert C, Vandenbossche S, Roos M, Bron D, Razavi D. The prevalence and implications of elderly inpatients' desire for a formal psychological help at the start of cancer treatment. Psychooncology. 2015;24:294-301.
29. Schagen SB, van Dam FS, Muller MJ, Boogerd W, Lindeboom J, Bruning PF. Cognitive deficits after postoperative adjuvant chemotherapy for breast carcinoma. Cancer 1999;85(3):640–650.
30. Mandelblatt JS, Stern RA, Luta G, McGuckin M, Clapp JD, Hurria A, Jacobsen PB, Faul LA, Isaacs C, Denduluri N, Gavett B, Traina TA, Johnson P, Silliman RA, Turner RS, Howard D, Van Meter JW, Saykin A, Ahles T. Cognitive impairment in older patients with breast cancer before systemic therapy: is there an interaction between cancer and comorbidity? J Clin Oncol. 2014;32(18):1909–1918.
Abstract (2017-2018)
DUBRUILLE S, KENIS C, LIBERT Y, DELFORGE M, ALEXIS RUIZ J, ROOS M, COLLARD A, MEULEMAN N, MAEREVOET M, RAVAZI D, WILDIERS H, BRON D.
A new frailty scoring in "clinically fit” older patients with malignant hemopathies admitted to receive chemotherapy.
Accepted for an oral presentation at 32th General Annual Meeting of the Belgian Hematological Society. Dolce la Hulpe, February 2017
DUBRUILLE S, KENIS C, LIBERT Y, DELFORGE M, DAL LAGO L, ROOS M, BORGHGRAEF C, SALAROLI A, MEULEMAN N, MAEREVOET M, RAVAZI D, WILDIERS H, BRON D. Major impact of Mild Cognitive Impairment (MCI) and inflammatory status in older patients receiving chemotherapy for hematological malignancies. Accepted for on oral at 17th International Society of Geriatric Oncology Presented at 32th General Annual Meeting of the Belgian Hematological Society. Warszawa, November 2017
DUBRUILLE S, KENIS C, LIBERT Y, DELFORGE M, DAL LAGO L, ROOS M, BORGHGRAEF C, SALAROLI A, MEULEMAN N, MAEREVOET M, RAVAZI D, WILDIERS H, BRON D. A simple frailty score to identity patients with malignant hemopathies who don’t benefit from standard dose chemotherapy.
Accepted for a poster presentation at 33th General Annual Meeting of the Belgian Hematological Society. Dolce la Hulpe, February 2018
DUBRUILLE S, KENIS C, LIBERT Y, DELFORGE M, DAL LAGO L, ROOS M, BORGHGRAEF C, PEPERSACK T, MEULEMAN N, MAEREVOET M, RAVAZI D, WILDIERS H, BRON D. How to identify patients with malignant hemopathies who don’t benefit from standard dose chemotherapy.
Accepted for a poster presentation at 23th General Annual Meeting of the European Hematology Association. Stockholm, June 2018
DUBRUILLE S, BORGHGRAEF C, BRON D. Practical aspects of managing patients with cognitive impairment.
Accepted for an oral presentation at the General Annual Meeting of MASCC/ISOO. Vienna, June 2018
Présentation orale (2017-2018)
DUBRUILLE S.
A new frailty scoring in "clinically fit” older patients with malignant hemopathies admitted to receive chemotherapy.
Presented at 32th General Annual Meeting of the Belgian Hematological Society. Dolce la Hulpe, February 2017
DUBRUILLE S.
Major impact of Mild Cognitive Impairment (MCI) and inflammatory status in older patients receiving chemotherapy for hematological malignancies.
Presented at 17th International Society of Geriatric Oncology Presented at 32th General Annual Meeting of the Belgian Hematological Society. Warszawa, November 2017
DUBRUILLE S.
Practical aspects of managing patients with cognitive impairment.
Accepted at the General Annual Meeting of MASCC/ISOO. Vienna, June 2018
Prospective trials are needed to build a reliable frailty score able to identify the unsuspected frail population in “clinically fit” patients who should not benefit from chemotherapy. This new frailty scoring should obviously include assessment of physical function, cognitive function and comorbidity (4).
CONCLUSIONS
Frailty assessment is useful to predict a poor outcome and to build adaptive interventions in older patients with malignant hemopathies. However, we are still lacking a specific screening tool able to detect unsuspected frail population in “clinically fit” patients who should not benefit from chemotherapy. Prospective trials are urgently needed to build and validate a new frailty scoring including specifically assessment of cognitive impairment to assess this specific highly vulnerable population.
Disclosure: The authors indicate have nothing to disclose no conflicts of interest.
Acknowledgment: We would like to thank the Yvonne Boël Foundation for its support to Ms Stéphanie Dubruille, neuropsychologist, in charge of the project “Biomarkers and frailty of older cancer patients”
Bibliography
1. Ahmed N, Mandel R, Fain MJ. Frailty: an emerging geriatric syndrome. Am J Med. 2007;120(9):748-753.
2. Fried LP, Ferrucci L, Darer J, Williamson JD, Anderson G. Untangling the concepts of disability, frailty, and comorbidity: implications for improved targeting and care. J Gerontol A Biol Sci Med Sci. 2004;59(3):255-263.
3. Hamaker ME, Prins MC, Stauder R. The relevance of a geriatric assessment for elderly patients with a haematological malignancy–a systematic review. Leuk. Res. 2014;38(3):275–283.
4. Abel GA and Klepin HD. Frailty and the management of hematologic malignancies. Blood. 2018;131(5):515-524.
5. Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, Seeman T, Tracy R, Kop WJ, Burke G, McBurnie MA. Cardiovascular Health Study Collaborative Research Group. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56(3):M146-M156.
6. Rockwood K, Mitnitski A. Frailty in relation to the accumulation of deficits. J Gerontol A Biol Sci Med Sci. 2007;62(7):722-727.
7. Extermann M, Aapro M, Bernabei R, Cohen HJ, Droz JP, Lichtman S, Mor V, Monfardini S, Repetto L, Sørbye L, Topinkova E; 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;55(3):241–252.
8. Extermann M, Meyer J, McGinnis M, Crocker TT, Corcoran MB, Yoder J, Haley WE, Chen H, Boulware D, Balducci L. A comprehensive geriatric intervention detects multiple problems in older breast cancer patients. Crit Rev Oncol Hematol. 2004;49(1):69–75.
9. Soubeyran P, Bellera C, Goyard J, Heitz D, Curé H, Rousselot H, Albrand G, Servent V, Jean OS, van Praagh I, Kurtz JE, Périn S, Verhaeghe JL1, Terret C, Desauw C, Girre V, Mertens C, Mathoulin-Pélissier S, Rainfray M. Screening for vulnerability in older cancer patients: the ONCODAGE Prospective Multicenter Cohort Study. PLoS One. 2014;11;9(12):e115060.
10. Hamaker ME, Jonker JM, de Rooij SE, Vos AG, Smorenburg CH, van Munster BC. Frailty screening methods for predicting outcome of a comprehensive geriatric assessment in elderly patients with cancer: a systematic review. Lancet Oncol. 2012;13(10):e437–e444.
11. Dubruille S, Libert Y, Roos M, et al. Identification of clinical parameters predictive of one-year survival using two geriatric tools in clinically fit older patients with haematological malignancies: major impact of cognition. J Geriatr Oncol. 2015;6:362-369.
12. Sherman AE, Motyckova G, Fega KR, Deangelo DJ, Abel GA, Steensma D, Wadleigh M, Stone RM, Driver JA. Geriatric assessment in older patients with acute myeloid leukemia: a retrospective study of associated treatment and outcomes. Leuk Res. 2013;37(9):998-1003.
13. Klepin HD, Geiger AM, Tooze JA, Kritchevsky SB, Williamson JD, Pardee TS, Ellis LR, Powell BL. Geriatric assessment predicts survival for older adults receiving induction chemotherapy for acute myelogenous leukemia. Blood 2013;121(21):4287–4294.
14. Fega KR, Abel GA, Motyckova G, Sherman AE, DeAngelo DJ, Steensma DP, Galinsky I, Wadleigh M, Stone RM, Driver JA. Nonhematologic predictors of mortality improve the prognostic value of the international prognostic scoring system for MDS in older adults. J Geriatr Oncol. 2015;6(4):288-298.
15. Deschler B, Ihorst G, Platzbecker U, Germing U, März E, de Figuerido M, Fritzsche K, Haas P, Salih HR, Giagounidis A, Selleslag D, Labar B, de Witte T, Wijermans P, Lübbert M. Parameters detected by geriatric and quality of life assessment in 195 older patients with myelodysplastic syndromes and acute myeloid leukemia are highly predictive for outcome. Haematologica. 2013;98(2):208-216.
16. Winkelmann N, Petersen I, Kiehntopf M, Fricke HJ, Hochhaus A, Wedding U. Results of comprehensive geriatric assessment effect survival in patients with malignant lymphoma. J Cancer Res Clin Oncol. 2011;137(4):733-738.
17. Goede V, Bahlo J, Chataline V, et al. Evaluation of geriatric assessment in patients with chronic lymphocytic leukemia: Results of the CLL9 trial of the German CLL study group. Leuk Lymphoma. 2016;57(4):789-796.
18. Engelhardt M, Dold SM, Ihorst G, Eichhorst B, Dürig J, Stilgenbauer S, Kolb G, Honecker F, Wedding U, Hallek M. Geriatric assessment in multiple myeloma patients: validation of the International Myeloma Working Group (IMWG) score and comparison with other common comorbidity scores. Haematologica. 2016;101(9):1110-1119.
19. Rao AV. Fitness in the elderly: how to make decisions regarding acute myeloid leukemia induction. Hematology Am Soc Hematol Educ Program. 2016;(1):339-347.
20. Tucci A, Martelli M, Rigacci L, Riccomagno P, Cabras MG, Salvi F, Stelitano C, Fabbri A, Storti S, Fogazzi S, Mancuso S, Brugiatelli M, Fama A, Paesano P, Puccini B, Bottelli C, Dalceggio D, Bertagna F, Rossi G, Spina M; Italian Lymphoma Foundation (FIL). Comprehensive geriatric assessment is an essential tool to support treatment decisions in elderly patients with diffuse large B-cell lymphoma: a prospective multicenter evaluation in 173 patients by the Lymphoma Italian Foundation (FIL). Leuk Lymphoma. 2015; 56(4):921-926.
21. Engelhardt M, Domm AS, Dold SM, Ihorst G, Reinhardt H, Zober A, Hieke S, Baayen C, Müller SJ, Einsele H, Sonneveld P, Landgren O, Schumacher M, Wäsch R. A concise revised Myeloma Comorbidity Index as a valid prognostic instrument in a large cohort of 801 multiple myeloma. Haematologica. 2017;102(5):910-921.
22. Guerard EJ, Deal AM, Chang Y, Williams GR, Nyrop KA, Pergolotti M, Muss HB, Sanoff HK, Lund JL. Frailty Index Developed From a Cancer-Specific Geriatric Assessment and the Association With Mortality Among Older Adults With Cancer. J Natl Compr Canc Netw. 2017;15(7):894-902.
23. Takahashi M, Takahashi M, Komine K, Yamada H, Kasahara Y, Chikamatsu S, Okita A, Ito S, Ouchi K, Okada Y, Imai H, Saijo K, Shirota H, Takahashi S, Mori T, Shimodaira H, Ishioka C. The G8 screening tool enhances prognostic value to ECOG performance status in elderly cancer patients: A retrospective, single institutional study. PLoS One. 2017;12(6):e0179694.
24. Granjon C, Beyens MN, Frederico D, Blanc P, Gonthier R. Is there a risk of drug accidents in elderly subjects with cognitive disorders? A study of 82 demented institutionalized patients. NPG 2006;6(35):21–28.
25. Li W, Muftuler LT, Chen G, Ward BD, Budde MD, Jones JL, Franczak MB, Antuono PG, Li SJ, Goveas JS. Effects of the coexistence of late-life depression and mild cognitive impairment on white matter microstructure. J. Neurol Sci. 2014;338(1-2):46–56.
26. Wagner DC, Short JL. Longitudinal predictors of self-rated health and mortality in older adults. Prev Chronic Dis. 2014;11 E93.
27. Amieva H, Stoykova R, Matharan F, Helmer C, Antonucci TC, Dartigues JF. What aspects of social network are protective for dementia? Not the quantity but the quality of social interactions is protective up to 15 years later. Psychosom Med. 2010;72(9):905–911.
28. Dubruille S, Libert Y, Merckaert I, Reynaert C, Vandenbossche S, Roos M, Bron D, Razavi D. The prevalence and implications of elderly inpatients' desire for a formal psychological help at the start of cancer treatment. Psychooncology. 2015;24:294-301.
29. Schagen SB, van Dam FS, Muller MJ, Boogerd W, Lindeboom J, Bruning PF. Cognitive deficits after postoperative adjuvant chemotherapy for breast carcinoma. Cancer 1999;85(3):640–650.
30. Mandelblatt JS, Stern RA, Luta G, McGuckin M, Clapp JD, Hurria A, Jacobsen PB, Faul LA, Isaacs C, Denduluri N, Gavett B, Traina TA, Johnson P, Silliman RA, Turner RS, Howard D, Van Meter JW, Saykin A, Ahles T. Cognitive impairment in older patients with breast cancer before systemic therapy: is there an interaction between cancer and comorbidity? J Clin Oncol. 2014;32(18):1909–1918.
Abstract (2017-2018)
DUBRUILLE S, KENIS C, LIBERT Y, DELFORGE M, ALEXIS RUIZ J, ROOS M, COLLARD A, MEULEMAN N, MAEREVOET M, RAVAZI D, WILDIERS H, BRON D.
A new frailty scoring in "clinically fit” older patients with malignant hemopathies admitted to receive chemotherapy.
Accepted for an oral presentation at 32th General Annual Meeting of the Belgian Hematological Society. Dolce la Hulpe, February 2017
DUBRUILLE S, KENIS C, LIBERT Y, DELFORGE M, DAL LAGO L, ROOS M, BORGHGRAEF C, SALAROLI A, MEULEMAN N, MAEREVOET M, RAVAZI D, WILDIERS H, BRON D. Major impact of Mild Cognitive Impairment (MCI) and inflammatory status in older patients receiving chemotherapy for hematological malignancies. Accepted for on oral at 17th International Society of Geriatric Oncology Presented at 32th General Annual Meeting of the Belgian Hematological Society. Warszawa, November 2017
DUBRUILLE S, KENIS C, LIBERT Y, DELFORGE M, DAL LAGO L, ROOS M, BORGHGRAEF C, SALAROLI A, MEULEMAN N, MAEREVOET M, RAVAZI D, WILDIERS H, BRON D. A simple frailty score to identity patients with malignant hemopathies who don’t benefit from standard dose chemotherapy.
Accepted for a poster presentation at 33th General Annual Meeting of the Belgian Hematological Society. Dolce la Hulpe, February 2018
DUBRUILLE S, KENIS C, LIBERT Y, DELFORGE M, DAL LAGO L, ROOS M, BORGHGRAEF C, PEPERSACK T, MEULEMAN N, MAEREVOET M, RAVAZI D, WILDIERS H, BRON D. How to identify patients with malignant hemopathies who don’t benefit from standard dose chemotherapy.
Accepted for a poster presentation at 23th General Annual Meeting of the European Hematology Association. Stockholm, June 2018
DUBRUILLE S, BORGHGRAEF C, BRON D. Practical aspects of managing patients with cognitive impairment.
Accepted for an oral presentation at the General Annual Meeting of MASCC/ISOO. Vienna, June 2018
Présentation orale (2017-2018)
DUBRUILLE S.
A new frailty scoring in "clinically fit” older patients with malignant hemopathies admitted to receive chemotherapy.
Presented at 32th General Annual Meeting of the Belgian Hematological Society. Dolce la Hulpe, February 2017
DUBRUILLE S.
Major impact of Mild Cognitive Impairment (MCI) and inflammatory status in older patients receiving chemotherapy for hematological malignancies.
Presented at 17th International Society of Geriatric Oncology Presented at 32th General Annual Meeting of the Belgian Hematological Society. Warszawa, November 2017
DUBRUILLE S.
Practical aspects of managing patients with cognitive impairment.
Accepted at the General Annual Meeting of MASCC/ISOO. Vienna, June 2018
