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Thibaud, V.; Thibaud, V.; Billy, C.; Prud'homm, J.; , . Geriatric Assessment-Driven Interventions in Older Adults with Cancer. Encyclopedia. Available online: https://encyclopedia.pub/entry/21371 (accessed on 20 June 2024).
Thibaud V, Thibaud V, Billy C, Prud'homm J,  . Geriatric Assessment-Driven Interventions in Older Adults with Cancer. Encyclopedia. Available at: https://encyclopedia.pub/entry/21371. Accessed June 20, 2024.
Thibaud, Vincent, Vincent Thibaud, Claire Billy, Joaquim Prud'homm,  . "Geriatric Assessment-Driven Interventions in Older Adults with Cancer" Encyclopedia, https://encyclopedia.pub/entry/21371 (accessed June 20, 2024).
Thibaud, V., Thibaud, V., Billy, C., Prud'homm, J., & , . (2022, April 05). Geriatric Assessment-Driven Interventions in Older Adults with Cancer. In Encyclopedia. https://encyclopedia.pub/entry/21371
Thibaud, Vincent, et al. "Geriatric Assessment-Driven Interventions in Older Adults with Cancer." Encyclopedia. Web. 05 April, 2022.
Geriatric Assessment-Driven Interventions in Older Adults with Cancer
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Comprehensive geriatric assessment is defined as a multi-dimensional, multi-disciplinary diagnostic and therapeutic process that is conducted to determine the medical, mental, and functional problems that older people with frailty have so that a coordinated and integrated plan for treatment and follow-up can be developed. Progress has been made in the definition of the best way to detect problems, but the benefits are mostly based on prognosis stratification and on the adaptation of cancer treatment.

CGA comprehensive geriatric assessment cancer malignant hemopathies older patients

1. Introduction

In the past century, life expectancy in developed countries has substantially increased. The world population is aging, and it is expected that the number of people over 80 years of age will more than double in Europe before the end of the 21st century, from 26.8 million (5.8%) in 2019 to 60.8 million (14.6%) in 2100 [1]. As the incidence of cancer and malignant hemopathies increases with age (approximately 70% of patients with cancer are aged 65 years and older [2]), recommendations for the optimal management of these diseases in the older population are urgently needed. There is a consensus, based on original studies and meta-analyses, that the use of Comprehensive Geriatrics Assessment (CGA) is good clinical practice for most older patients with solid tumors or hematological malignancies, and its implementation is recommended by all major Clinical and Geriatric Oncology Societies [2]. CGA is defined as a multi-dimensional, multi-disciplinary diagnostic and therapeutic process that is conducted to determine the medical, mental, and functional problems that older people with frailty have so that a coordinated and integrated plan for treatment and follow-up can be developed [3]. Thus, to be complete, a CGA must include a geriatric assessment and an intervention plan. In addition, in 2014, the International Society of Geriatric Oncology (SIOG) consensus recommended that the following domains be assessed in a CGA: functional status, comorbidity, cognition, mental health status, fatigue, social status and support, nutrition, and the presence of geriatric syndromes [4].
The CGA was initially used in oncology to distinguish fit, vulnerable, and frail patients [5]. High-quality studies have been published that support the use of CGA in the identification of geriatric syndromes and the prediction of mortality and chemotherapy toxicity. However, these studies generally limit the CGA process to the assessment component, which is mainly tool-based (e.g., cognitive scores, nutritional screening tools, and comorbidity scores) [6][7], and use the scores to adapt the treatment plan. Using the Delphi approach, experts proposed recommendations for implementing CGA-guided care processes [8], but these recommendations were mainly based on the extrapolation of results obtained in a non-cancer population [2]. Previous meta-analyses and review articles focused on the prognostic and predictive value of the CGA in assessing overall survival and adverse outcome rates, and CGA is currently used to prevent over- and under-treatment [9]. It also informs shared decision-making conversations [10], but no clear impact on mortality rates has been demonstrated [11].

2. Geriatric Assessment-Driven Interventions in Older Adults with Cancer

The implementation of a CGA in clinical practice and the number of publications on this subject has greatly increased during the last few decades. As “usual care” evolves with new evidence, the researchers limited the researchers research to research published since 2010 to limit heterogeneity in control groups. the researchers chose to develop research algorithms for the researchers narrative review, even though algorithms are not commonly used in narrative reviews, to ensure the better objectivity of the researchers work. In the researchers research algorithm, the researchers required the presence of the term “geriatric assessment”. This means that the researchers did not consider mono-domain interventions in the absence of an initial global geriatric assessment in order to avoid confusing results. This choice may have led us to reject potentially relevant articles, such as the study by Gilbert et al., which showed that perioperative nutritional management overseen by a geriatrician and a dietician (without a CGA) improves adherence to international guidelines for older patients scheduled for colorectal cancer surgery, with no significant impact on adverse events [12]. A study by Ommundsen et al., which was a monocentric trial regarding preoperative geriatric assessment and global intervention, was also not selected, as no specific geriatric domains were cited in the title and abstract [13]. Geriatric intervention failed to reduce grade II–V complications in frail, older patients scheduled for colorectal cancer surgery. This may be linked with the absence of teamwork, with a unique “medical doctor specializing in geriatric medicine” who carried out one session evaluation and intervention based on comorbidity management, a drugs review, and recommendations to prevent delirium and malnutrition. the researchers focused on patients over 65 years old, even though 60-year-old patients are sometimes considered as “older patients” in the oncology literature [14]. As shown here, the specific impacts of CGA-based interventions on cancer patients have not yet been demonstrated, although some studies have shown positive results for older people in geriatric care settings. Therefore, the use of the CGA in a different population may be questionable. Symptoms such as fatigue, weight loss, or depression may be associated with various physiopathological processes and prognoses, and thus require different interventions according to age, comorbidities, and frailty. Some domains assessed in the CGA are more commonly used to select patients and adapt treatment than to develop interventions. For instance, the efficacity of interventions dedicated to cognitive impairment or fatigue are more difficult to achieve than those concerning other CGA domains, as shown in the researchers results. Nevertheless, the efficacities of intervention protocols such as the HELP program in the prevention of delirium in hospitalized older patients have been demonstrated [15]. Therefore, interventional studies remain necessary so that their impact on older patients with cancer and on a treatment’s cognitive toxicity or chemo brain can be evaluated. Other interventions could be designed to reduce adverse events and optimize the adherence of patients with cognitive impairment (e.g., optimizing home intervention professionals, organizing relief periods to prevent helpers’ exhaustion, daily or multi-daily home nurses’ interventions, home calls, and electronic, customized devices to help individuals to remember to take drugs and evaluate the observance (e.g., a communicating pill box)).
Multi-domain interventions seem promising, especially when they are based on global assessments. Three recent, good-quality clinical trials assessed multi-domain interventions on chemotherapy toxicity: GAIN [16], GERICO [17], and GAP70+ [18]. GAIN was the most convincing trial, with a CGA-based intervention characterized by predetermined assessment thresholds. A multi-disciplinary team trained in geriatrics, which included a geriatric nurse practitioner in charge of follow-ups, delivered it. Here was strongly focused on the management section of the CGA. In the control group, the oncologist had access to the results of the CGA (as in the intervention arm) but implemented fewer interventions (12.5% of identified interventions were implemented, versus 76.8% in the intervention arm). 
As shown in Table 1, both the intervention and control groups were quite different in these three trials. The intervention was either delivered by a team (GAIN), a geriatrician alone (GERICO), or an oncologist informed by recommendations derived from the CGA (GAP70+). The control groups were also different, with no CGA in the GERICO trial and a complete CGA sent to the oncologist in the GAIN trial. So, the control group in the GAIN trial seemed similar to the intervention group in the GAP70+ trial. The authors tried to base the interventions on guides [18] or thresholds [16], but standardization seemed difficult to implement considering the lack of evidence for each domain. The ongoing study “PREPARE”, which aims to evaluate, in a randomized controlled trial, the impact of CGA intervention programs in older adults with cancer, addressed this issue with a geriatric care protocol written by an independent committee and a mandatory centralized nurses’ training program to standardize intervention programs [19].
Table 1. Comparison of the three randomized trials on global CGA-based interventions.
References Population (Age, Type of Cancer) Number of Patients Type of Study CGA Intervention Results
Primary
Outcome
Secondary
Outcomes
Li et al. [16]
GAIN
65+, solid cancer 613 RCT
Single-center
Intervention and referrals,
based on predetermined thresholds, delivered by a multi-disciplinary team
(oncologist, nurse practitioner, social worker,
physical/occupation therapist, nutritionist, and pharmacist)
Follow-up by the geriatric nurse practitioner
Control group: CGA is sent to the oncologist
AE grade 3–5: reduction in CGA group of 10.1% (95% CI 1.5–18.2; p = 0.02) More completion of chemotherapy treatment plan in the CGA group: 28.4% vs. 13.3%, p < 0.01
Lund et al. [17]
GERICO
70+, colorectal cancer 142 RCT
Single-center
Intervention and referrals,
tailored by a geriatrician
Follow-up after two months or more frequently
Control group: no CGA is performed;
no change in chemotherapy treatment
Completion of chemotherapy treatment plan: 45% vs. 28%, p = 0.00366. Less AE grade 3–5 in the CGA group: 28% vs. 39%, p = 0.156
Mohile et al. [18]
GAP70+
70+, incurable solid tumors or lymphoma 718 Cluster-randomized trial Geriatric assessment summary
and management recommendations
(including dose reduction)
sent to the oncologist
Control group: oncologists received alerts
for impaired depression or cognitive score
Relative risk of AE grade 3–5 in CGA group of 0.74 (95% CI 0.64–0.86; p = 0.0001)  
the researchers note that some endpoints are “oncologic” (e.g., treatment completion, toxicity, and recurrence time) and others are “geriatric” (e.g., functional or nutritional status and deprescription). The CGA can be used to tailor interventions, but its components are sometimes valuable endpoints (e.g., functional or cognitive status). the researchers believe that global endpoints, including the impact of interventions on cancer evolution or patient-centered goals, should be preferred. Overall mortality rates, quality of life, or time spent in hospitals seem interesting outcomes. Concerning ongoing studies, the authors of the PREPARE study [19] choose a co-primary endpoint encompassing overall survival rates and health-related quality of life, whereas Røyset et al. preferred physical function, with quality of life as a secondary objective [20].
These points underline the issues that can arise when designing CGA-based intervention trials. Older patients with cancer usually present several altered domains, limiting the clinical impact of monodomain compared to multi-domain interventions. Monodomain interventions do not seem to be efficient enough, unless the population is highly selected, which decreases the external validity. In this context, two ongoing randomized controlled trials opted for a selected population of patients with colorectal cancer to evaluate a monodomain intervention for patients addressed for surgery [14] or a multi-domain intervention for patients addressed for radiotherapy [20].
The management section of a CGA is a complex intervention that cannot be completely standardized, unlike the assessment section. Randomized controlled trials have been designed to evaluate new drugs, but they may not be the best way to evaluate complex interventions that are highly variable in clinical settings, depending on the provider and the context [21]. The researchers chose to include observational studies that are frequently more important sources of knowledge in gerontology than randomized controlled trials. Randomization, if chosen, should be clustered as much as possible to avoid contamination bias. Researchers may thus have to make compromises between internal and external validity. Internal validity refers to the reliability of the results and requires a strong standardization of interventions, as well as so-called “usual care”. External validity refers to the generalizability of results and implies flexible real-life practices and the accurate description of contexts [22]. Stepped wedge trial designs seem promising to achieve both internal and external validity. This design allows for the progressive implementation of innovation in different settings, together with its evaluation [23], whereas randomization can be ethically questionable, as the comprehensive geriatric assessment is currently largely recommended. This ethical concern could lead to a recruitment bias in randomized trials if clinicians have access to the CGA outside clinical trials and prefer not to randomize the frailest patients. Stepped wedge trials remain difficult to implement and costly, as they require the collaboration of multiple centers of inclusion. However, it is not impossible in the geriatric field, as demonstrated in the study by Gilbert et al. [12].

References

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  2. Mohile, S.G.; Dale, W.; Somerfield, M.R.; Hurria, A. Practical Assessment and Management of Vulnerabilities in Older Patients Receiving Chemotherapy: ASCO Guideline for Geriatric Oncology Summary. J. Oncol. Pract. 2018, 14, 442–446.
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  4. Wildiers, H.; Heeren, P.; Puts, M.; Topinkova, E.; Janssen-Heijnen, M.L.G.; Extermann, M.; Falandry, C.; Artz, A.; Brain, E.; Colloca, G.; et al. International Society of Geriatric Oncology Consensus on Geriatric Assessment in Older Patients With Cancer. J. Clin. Oncol. 2014, 32, 2595–2603.
  5. Balducci, L.; Extermann, M. Management of Cancer in the Older Person: A Practical Approach. The Oncol. 2000, 5, 224–237.
  6. Extermann, M.; Boler, I.; Reich, R.R.; Lyman, G.H.; Brown, R.H.; DeFelice, J.; Levine, R.M.; Lubiner, E.T.; Reyes, P.; Schreiber, F.J.; et al. Predicting the Risk of Chemotherapy Toxicity in Older Patients: The Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH) Score: CRASH Score. Cancer 2012, 118, 3377–3386.
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  9. Rostoft, S.; O’Donovan, A.; Soubeyran, P.; Alibhai, S.M.H.; Hamaker, M.E. Geriatric Assessment and Management in Cancer. J. Clin. Oncol. 2021, 39, 2058–2067.
  10. Mohile, S.G.; Epstein, R.M.; Hurria, A.; Heckler, C.E.; Canin, B.; Culakova, E.; Duberstein, P.; Gilmore, N.; Xu, H.; Plumb, S.; et al. Communication With Older Patients With Cancer Using Geriatric Assessment: A Cluster-Randomized Clinical Trial From the National Cancer Institute Community Oncology Research Program. JAMA Oncol. 2020, 6, 196–204.
  11. Li, D.; Soto-Perez-de-Celis, E.; Hurria, A. Geriatric Assessment and Tools for Predicting Treatment Toxicity in Older Adults With Cancer. Cancer J. 2017, 23, 206–210.
  12. Gilbert, T.; Bernard, L.; Alexandre, M.; Bin-Dorel, S.; Villeneuve, L.; Decullier, E.; Bonnefoy, M.; ANC Working Group. Impact of a Geriatric Intervention to Improve Screening and Management of Undernutrition in Older Patients Undergoing Surgery for Colorectal Cancer: Results of the ANC Stepped-Wedge Trial. Nutrients 2021, 13, 2347.
  13. Ommundsen, N.; Wyller, T.B.; Nesbakken, A.; Bakka, A.O.; Jordhøy, M.S.; Skovlund, E.; Rostoft, S. Preoperative Geriatric Assessment and Tailored Interventions in Frail Older Patients with Colorectal Cancer: A Randomized Controlled Trial. Color. Dis. 2018, 20, 16–25.
  14. Berkel, A.E.M.; Bongers, B.C.; van Kamp, M.-J.S.; Kotte, H.; Weltevreden, P.; de Jongh, F.H.C.; Eijsvogel, M.M.M.; Wymenga, A.N.M.; Bigirwamungu-Bargeman, M.; van der Palen, J.; et al. The Effects of Prehabilitation versus Usual Care to Reduce Postoperative Complications in High-Risk Patients with Colorectal Cancer or Dysplasia Scheduled for Elective Colorectal Resection: Study Protocol of a Randomized Controlled Trial. BMC Gastroenterol. 2018, 18, 29.
  15. Inouye, S.K.; Bogardus, S.T.; Charpentier, P.A.; Leo-Summers, L.; Acampora, D.; Holford, T.R.; Cooney, L.M. A Multicomponent Intervention to Prevent Delirium in Hospitalized Older Patients. N. Engl. J. Med. 1999, 340, 669–676.
  16. Li, D.; Sun, C.-L.; Kim, H.; Soto-Perez-de-Celis, E.; Chung, V.; Koczywas, M.; Fakih, M.; Chao, J.; Cabrera Chien, L.; Charles, K.; et al. Geriatric Assessment–Driven Intervention (GAIN) on Chemotherapy-Related Toxic Effects in Older Adults With Cancer: A Randomized Clinical Trial. JAMA Oncol. 2021, 7, e214158.
  17. Lund, C.M.; Vistisen, K.K.; Olsen, A.P.; Bardal, P.; Schultz, M.; Dolin, T.G.; Rønholt, F.; Johansen, J.S.; Nielsen, D.L. The Effect of Geriatric Intervention in Frail Older Patients Receiving Chemotherapy for Colorectal Cancer: A Randomised Trial (GERICO). Br. J. Cancer 2021, 124, 1949–1958.
  18. Mohile, S.G.; Mohamed, M.R.; Xu, H.; Culakova, E.; Loh, K.P.; Magnuson, A.; Flannery, M.A.; Obrecht, S.; Gilmore, N.; Ramsdale, E.; et al. Evaluation of Geriatric Assessment and Management on the Toxic Effects of Cancer Treatment (GAP70+): A Cluster-Randomised Study. Lancet 2021, 398, 1894–1904.
  19. Soubeyran, P.; Terret, C.; Bellera, C.; Bonnetain, F.; Jean, O.S.; Galvin, A.; Chakiba, C.; Zwolakowski, M.-D.; Mathoulin-Pélissier, S.; Rainfray, M. Role of Geriatric Intervention in the Treatment of Older Patients with Cancer: Rationale and Design of a Phase III Multicenter Trial. BMC Cancer 2016, 16, 932.
  20. Røyset, I.; Saltvedt, I.; Rostoft, S.; Grønberg, B.H.; Kirkevold, Ø.; Oldervoll, L.; Bye, A.; Benth, J.Š.; Bergh, S.; Melby, L.; et al. Geriatric Assessment with Management for Older Patients with Cancer Receiving Radiotherapy. Protocol of a Norwegian Cluster-Randomised Controlled Pilot Study. J. Geriatr. Oncol. 2021, S1879406821002472.
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  23. Brown, C.A.; Lilford, R.J. The Stepped Wedge Trial Design: A Systematic Review. BMC Med. Res. Methodol. 2006, 6, 54.
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