A mini geriatric assessment helps treatment decision in elderly patients with digestive cancer. A pilot study
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1 Critical Reviews in Oncology/Hematology 77 (2011) A mini geriatric assessment helps treatment decision in elderly patients with digestive cancer. A pilot study Thomas Aparicio a,c,, Laurence Girard b, Nadia Bouarioua a, Claire Patry b, Sylvie Legrain b, Jean Claude Soulé a a Service d Hépato-Gastroentérologie, Hôpital Bichat-Claude Bernard, APHP, 46 rue Henri Huchard, Paris, France b Service de Gériatrie, Hôpital Bichat-Claude Bernard, APHP, 46 rue Henri Huchard, Paris, France c Service de Gastroentérologie, Hôpital Avicenne, APHP, 125 rue de Stalingrad, Bobigny, France Accepted 6 January 2010 Contents 1. Introduction Patients and methods Results Patient s characteristics Mini geriatric assessment Comprehensive geriatric assessment Patient outcome Factors associated with full completion of therapeutic strategy Discussion Conflict of interest Reviewers References Biographies Abstract Comprehensive geriatric assessment (CGA) is advocate to improved care of elderly with cancer but is not available in every hospital within a short delay. Therefore, a tool allowing gastroenterologist to detect rapidly specific abnormalities in elderly is needed. Patients and methods: The aim of our pilot study was to evaluate feasibility of a mini geriatric assessment (MGA) to adapt the anticancer treatments. MGA was done by a gastroenterologist and was taken into account during the cancer multidisciplinary team meeting for making decision. Then, CGA was realised and suggested adaptation of care. Results: 21 patients over 75 years treated for different digestive cancers were enrolled. The treatments recommended by the cancer multidisciplinary team meeting after the GMA were: standard treatments in 9 (41%); modified in 10 (47%) and best supportive care in 2 (12%) patients. CGA led to an adaptation of the non-oncological treatment in 15 (72%) and of the social care in 8 (38%) patients, but never modified the oncological strategy. Conclusions: MGA could help gastroenterologists for adaptation of anticancer treatment. The characteristics of the patients that should subsequently have a geriatric follow-up remain to be defined Elsevier Ireland Ltd. All rights reserved. Keywords: Digestive tract; Cancer; Elderly; Prognostic factor; Geriatric assessment Corresponding author at: Service de Gastroentérologie, Hôpital Avicenne, APHP, 125 rue de Stalingrad, Bobigny, France. Tel.: ; fax: address: thomas.aparicio@avc.aphp.fr (T. Aparicio) /$ see front matter 2010 Elsevier Ireland Ltd. All rights reserved. doi: /j.critrevonc
2 64 T. Aparicio et al. / Critical Reviews in Oncology/Hematology 77 (2011) Introduction Most digestive tract cancer occur in elderly patients [1]. Until recently, elderly patients have been underrepresented in clinical trials [2]. Recent studies show that selected elderly patients can benefit from standard chemotherapy [3 6], and also from high-risk surgery such as hepatic or pancreatic resection [7 10]. Nevertheless, a large proportion of elderly patients do not receive the standard cancer treatments [11 13]. The reasons for therapeutic abstention are frequently unclear [13]. We can infer that numerous patients are inappropriately under treated [14]. Geriatricians have validated standardized tools to identify high-risk elderly patients. Comprehensive geriatric assessment (CGA) is a compilation of valid tools assessing cognitive function, psychological status, functional status, nutritional status, co-morbidities, and medication review. The use of CGA has shown its effectiveness to improve care of elderly patients [15 17]. CGA implicates a specialized and time-consuming geriatric consultation, which is not usually available within a short delay in every hospital. Recently shorter versions based on CGA had been proposed so as to allow oncologist to select patients for standard treatments [18 20]. The evaluation of a mini geriatric assessment (MGA) for digestive cancer before treatment decision had never been realised. We conducted a pilot study to evaluate the feasibility of MGA in gastroenterology consultation or during hospitalisation and its reliability with CGA. 2. Patients and methods A gastroenterologist performed MGA in consultation or during hospitalisation before the treatment decision for cancer cure was made, unless colic surgery had previously been planned. Patients self-evaluated their quality of life with a 10 cm scale. MGA includes 8 simplified modules evaluating cognitive status, psychological status, functional status, nutritional status, co-morbidities, medication review, social support and measuring hemoglobin level and creatinin clearance (Table 1). The modules performed in GMA derived from Balducci and Extermann [21]. MGA was considered during the cancer multidisciplinary team meeting before taking decision for treatment. After the therapeutic decision, CGA was realised during ambulatory hospitalisation in the geriatric department. The patient was evaluated with his caregiver as much as possible. CGA included the following tools: CIRS-G [22], ADL [23], IADL [24], MMSE [25], MNA[26], GDS [27], standing on one leg, number of falls in the 6 previous months, medication review and social support. The cuts-off for each module are presented in Table 2. The geriatrician then proposed adaptation of oncological treatment, nononcological treatment and/or social support. If a change in the oncological treatment was suggested the cancer multidisciplinary team had to reconsider the decision taken at the first meeting. The normality or abnormality of each module of MGA was compared to the score of the corresponding items of CGA to access the reliability of MGA to CGA. A second consultation with the geriatrician was proposed at 6 months to evaluate the recommended adaptation of treatment. If necessary the geriatrician recommended a specific geriatric follow-up. The patient follow-up was performed until death. 3. Results 3.1. Patient s characteristics Twenty-one consecutive patients over 75 years (11 men and 9 women) with digestive cancer were enrolled from May 2004 to November The median age was 80.5 (75 87) years. Primary cancers were colorectal [11], oesophagus [3], pancreas [3], biliary tract [2], small bowel [1] and anus [1]. Eleven patients had metastases at inclusion Mini geriatric assessment MGA was performed for each patient before cancer multidisciplinary team meetings. An abnormality was detected for at least one module of MGA in every patient. A median of 3 modules of the MGA was abnormal for the whole population. Nutritional status was most frequently altered followed by biology and co-morbidities (Table 3). The environment was the less frequently involved module but concerned more than 30% of the patients. The therapeutic strategies were then discussed during the cancer multidisciplinary team meeting. The recommended treatments were standard treatments in 9/21 (41%) of cases. In 10/21 (47%) patients, the recommended treatment was adapted from the standard treatment: chemotherapy dose reduction in 5 patients and rejection of surgery in 5 patients which received chemotherapy and/or radiotherapy. Moreover, solely best supportive care was proposed in 2 (12%) patients Comprehensive geriatric assessment CGA was performed for each patient with a median delay of 11 days [1 27] after the MGA. The abnormalities detected by CGA according to the threshold are presented in Table 3. The concordance between MGA and CGA was good for the assessment of cognitive function, psychological status and functional status. The concordance between the two evaluations was less accurate for nutritional status and comorbidity (Fig. 1). A severe undernutrition (MNA < 17) was present in 10% of the patients. CGA led to adaptation of the non-oncological treatment in 15/21 (72%) of the patients and changes in social care management for 8/21 (38%) of
3 T. Aparicio et al. / Critical Reviews in Oncology/Hematology 77 (2011) Table 1 Mini geriatric assessment, 8 simplified modules. Threshold used: (1) loss of more than 5% of weight and/or BMI < 23; (2) 7 medications or more; (3) Hb < 10 g/dl, clearance < 50 ml/min. patients. The cancer treatment strategy was never modified by CGA. The non-oncological treatment adaptation concerned comorbidity medications in 10 cases, psychotropic medication treatment in 5 cases, nutrition in 4 cases, anaemia in 3 cases, anticoagulation in 1 case and dementia in 1 case. The social care propositions were home caretaker in 4 cases, visiting nurse in 2 cases and institutionalization in 2 cases. A specific geriatric follow-up was recommended in 8 (38%) patients.
4 66 T. Aparicio et al. / Critical Reviews in Oncology/Hematology 77 (2011) Table 2 Threshold of the comprehensive geriatric assessment. Screening Test Threshold Mental status MMSE 24 Depression GDS simplified 1 Dependence ADL <6 IADL <100% of total applicable Nutrition MNA 23.5 Co-morbidities CIRS-G System 3 Polymedication Collected 1 anticoagulant or 2 cardiovascular or 2 psychotropic medication or 10 medications Environment Monopodal Social intervention support Story of fall Social service advice Biology Hemoglobin (<10 g/dl) Creatinin clearance (<50 ml/min) Table 3 Frequency of abnormality for the modules of MGA and CGA. MGA (%) CGA (%) Mental status 9/21 (43) 8/21 (38) Depression 9/21 (43) 9/21 (43) Dependence 10/21 (48) 7/21 (33) Nutrition 14/21 (67) 15/21 (71) Co-morbidities 13/21 (62) 11/21 (52) Polymedication 8/21 (38) 10/21 (48) Environment 7/21 (33) 7/21 (33) Biology 13/20 (65) 10/20 (50) MGA: mini geriatric assessment; CGA: comprehensive geriatric assessment Patient outcome The therapeutic strategies recommended by the cancer multidisciplinary team meeting were totally performed in 15/21 (72%) of patients. The reasons of non-implementation Fig. 1. Concordance between the MGA and the CGA. of the planned treatment were patient refusal in 4 cases and co-morbidity in 2 cases. Only 6 (29%) patients attended the geriatric follow-up consultation planned in the protocol. Among the 15 other, 6 (29%) patients died, 5 (24%) were unwilling to come, 2 were lost to follow-up and one patient was hospitalized for acute co-morbidity. Overall, the non-oncological treatment adaptations, recommended for 15 patients, were assessed in 10 cases (70%). They had been implemented in 9 (60%) cases, 1 patient having refused a psychotropic medication. In 5 cases the patient deceased. The social propositions for 8 patients were assessable in 5 cases (63%): they were achieved in 4 (50%) cases, one patient refused home caretaker. In 3 cases the patient deceased. The median survival was 9.5 months (1 47 months). At the end of follow-up all the patients had died. The death was related to the cancer in 20 (95%) cases Factors associated with full completion of therapeutic strategy Patient characteristics were analysed according to the full completion of the cancer treatment determined by the multidisciplinary team meeting (Table 4). The small number of the patient included did not allow a multivaried analysis. Nevertheless, the patients that did not complete the recom- Table 4 Patient s characteristics according the full completion of the cancer treatment. Patient s characteristic Full treatment completed n =15 Treatment not completed n =6 Medium age (extreme) 79 (75 87) 83 (78 85) Sex: men (%) 9 (60) 2 (33) Women (%) 6 (40) 4 (67) Metastases (%) 6 (40) 5 (83) WHO: 0 1 (%) 10 (67) 3 (50) 2 (%) 5 (33) 3 (50) Charlson: 0 1 (%) 6 (40) 3 (50) 2 (%) 9 (60) 3 (50) Quality of life (cm) Median number of abnormal 3 (1 7) 5 (3 6) a module of the MGA (extreme) Cancer treatment recommended Standard (%) 4 (27) 5 (83) Adapted (%) 11 (73) 1 (17) Median MMSE (extreme) 27 (18 30) 26.5 (19 30) GDS 1 (%) 7 (46) 3 (50) Median MNA (extreme) 20 (11 27) 20 (13 23) ADL < 6 (%) 2 (15) 4 (67) b IADL < 100% total applicable (%) 3 (23) 4 (67) Standing on one leg (%) 5 (38) 1 (17) Fall (%) 4 (30) 2 (33) a p = 0.01 (Student s test). b p = 0.04 (Fisher test).
5 T. Aparicio et al. / Critical Reviews in Oncology/Hematology 77 (2011) mended treatment appeared to be more vulnerable, having significantly more abnormal modules in the MGA and a worst ADL score. Interestingly, among these 6 patients, 5 have had a proposition of standard treatment. This suggests that the endurance of these patients was overestimated. 4. Discussion The adaptation of standard cancer treatment in elderly patients is a major challenge. A randomized study has showed that CGA improves prognosis of elderly patients with advanced cancer [28]. CGA has also allowed to identify preliminary depression and dependence as predictive factors of toxicity in elderly patients receiving chemotherapy for treatment of advanced ovarian cancer [29]. However if most studies in geriatric oncology have focused on identifying prognostic factors detected by CGA, they did not include an intervention in their design [30]. The lack of intervention studies limits conclusions about the value of CGA in oncology. The study included consecutive patients treated for digestive cancer in our institution, so selection bias was avoided. MGA detected most of the abnormalities found by the CGA and could allow gastroenterologist to a rapid adaptation of therapeutic strategy. Every patient had at least one abnormal module, so the presence of only one abnormality could not be used to select patient for CGA. Nutritional status was the most frequently altered module. It must be pointed out that nutritional status was recently identified as the main prognostic factor for death as detected by CGA in elderly patients treated with chemotherapy [31]. The impact of CGA on cancer treatment decision making has rarely been studied. In a recent study involving mostly breast cancer patients, CGA was followed by changes in the planned cancer treatment in 38% of the patients [32]. In Girre et al. s work, only body mass index and the absence of depressive symptoms were associated with a modification of the treatment plan. In our study there are numerous reasons for adapting anticancer treatment and the small sample size does not allow a statistical analysis. A severe undernourishment was described in 10% of our patients, which is comparable to the 15% observed in the study of Girre et al. In another pilot study performed on 15 breast cancer patients, extensive CGA influenced cancer treatment in 36% of the patients [33]. As in our study, social intervention was predominant to cancer treatment modification. These data suggest that a geriatric evaluation is necessary to adapt cancer treatment in a large number of cases. In our study, the cancer treatment recommended by the multidisciplinary team meeting was adapted from standard treatment in almost half of the cases. This adaptation was done after the MGA but before the CGA. This suggests that the MGA could help to adapt cancer treatment. However, our study could not assert the contribution of the MGA because this was only an observational pilot study. It must be pointed out that there is no randomized study in geriatric oncology demonstrating the value of MGA. The choice of the most suitable tools for MGA is still a matter for debate. Several scales similar to ours are currently used, from the work of Balducci and Extermann [21] and the Vulnerable Elders Survey-13 [19]. Two studies aiming to validate a MGA in cancer patients are ongoing in France (OLD study from GERCOR and ONCODAGE study from FNCLCC). A large French trial on metastatic colorectal in elderly patients will soon be completed and their accrual and preliminary results have been already presented [34]. The analysis of geriatric items collected in this study is planned. The validation of the most accurate tool is still necessary in large prospective trials. Nevertheless, MGA used in this study shows a good concordance with CGA. Multidimensional evaluation is necessary to detect vulnerability, it has been shown that solely scoring ADL and IADL is not enough [35]. Obviously, MGA could not be a substitute to CGA for specific geriatric decision making. The geriatrician modified non-oncological treatment for most of the patients. Some pathologies, such as anaemia and denutrition should be considered for treatment earlier by the gastroenterologist or oncologist to allow cancer treatment. Social care was modified in one-third of the patients after CGA, and can be an important factor for successful cancer treatment. On the other hand, the cancer treatment based on the GMA was never modified after CGA. This suggests that GMA performed before decision making for treatment helps to define the most accurate strategy. This two-step approach is recommended by the Society of Geriatric Oncology [36]. In our study, we had a high rate (72%) of achievement of the recommended cancer treatment, half of which had been adapted. Moreover, in 5 out of the 6 cases of treatment failure the treatment offered was the standard treatment. These six patients had a worst ADL score and more abnormal modules in the MGA than the other patients. This suggests that an adapted cancer treatment should be offered frailest patients. In our study, most of the patients died of cancer; this points out that digestive cancer even in elderly patients is generally the most severe disease and rules the prognosis. This should be taken into account when carefully discussing a treatment plan for every patient in multidisciplinary team meeting including geriatric evaluation. In summary, our study reveals that MGA is routinely feasible even in gastroenterologic consultation. MGA helps for cancer treatment decision and allows a majority of completed treatment. The characteristics of the patients that should have a specialized geriatric follow-up remain to be determined. Conflict of interest None of the authors had conflict of interest concerning this work.
6 68 T. Aparicio et al. / Critical Reviews in Oncology/Hematology 77 (2011) Reviewers Dr. Martine Extermann, H Lee Moffitt Cancer Center USF, Magnolia Drive, Tampa, FL 33612, United States. References [1] Vercelli M, Capocaccia R, Quaglia A, Casella C, Puppo A, Coebergh JW. Relative survival in elderly European cancer patients: evidence for health care inequalities. The EUROCARE Working Group. Crit Rev Oncol Hematol 2000;35: [2] Yee KW, Pater JL, Pho L, Zee B, Siu LL. Enrollment of older patients in cancer treatment trials in Canada: why is age a barrier? J Clin Oncol 2003;21: [3] Aparicio T, Desrame J, Lecomte T, et al. Oxaliplatin- or irinotecanbased chemotherapy for metastatic colorectal cancer in the elderly. Br J Cancer 2003;89: [4] Folprecht G, Cunningham D, Ross P, et al. Efficacy of 5-fluorouracilbased chemotherapy in elderly patients with metastatic colorectal cancer: a pooled analysis of clinical trials. Ann Oncol 2004;15: [5] Sargent DJ, Goldberg RM, Jacobson SD, et al. A pooled analysis of adjuvant chemotherapy for resected colon cancer in elderly patients. N Engl J Med 2001;345: [6] Tabah-Fisch I, Maindrault-Goebel F, Benavides M, Zaniboni A, Bigelow R, Bleiberg H. Oxaliplatin/5 FU/LV is feasible, safe and active in elderly colorectal cancer patients. Proc Am Soc Clin Oncol 2002;21:140a. [7] Fong Y, Blumgart LH, Fortner JG, Brennan MF. Pancreatic or liver resection for malignancy is safe and effective for the elderly. Ann Surg 1995;222: [8] Turrini O, Guiramand J, Moutardier V, et al. Major hepatectomy for metastasis of colorectal cancer improves survival in the elderly. Ann Chir 2005;130: [9] Brozzetti S, Mazzoni G, Miccini M, et al. Surgical treatment of pancreatic head carcinoma in elderly patients. Arch Surg 2006;141: [10] Minagawa M, Makuuchi M, Torzilli G, et al. Extension of the frontiers of surgical indications in the treatment of liver metastases from colorectal cancer: long-term results. Ann Surg 2000;231: [11] Aparicio T, Navazesh A, Boutron I, et al. Half of elderly patients routinely treated for colorectal cancer receive a sub-standard treatment. Crit Rev Oncol Hematol [12] Bouvier AM, Launoy G, Lepage C, Faivre J. Trends in the management and survival of digestive tract cancers among patients aged over 80 years. Aliment Pharmacol Ther 2005;22: [13] Mahoney T, Kuo YH, Topilow A, Davis JM. Stage III colon cancers: why adjuvant chemotherapy is not offered to elderly patients. Arch Surg 2000;135: [14] Aparicio T, Mitry E, Sa Cunha A, Girard L. Management of colorectal cancer of elderly patients. Gastroenterol Clin Biol 2005;29: [15] Cohen HJ, Feussner JR, Weinberger M, et al. A controlled trial of inpatient and outpatient geriatric evaluation and management. N Engl J Med 2002;346: [16] Stuck AE, Siu AL, Wieland GD, Adams J, Rubenstein LZ. Comprehensive geriatric assessment: a meta-analysis of controlled trials. 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J Am Geriatr Soc 2000;48: [29] Freyer G, Geay JF, Touzet S, et al. Comprehensive geriatric assessment predicts tolerance to chemotherapy and survival in elderly patients with advanced ovarian carcinoma: a GINECO study. Ann Oncol 2005;16: [30] Maas HA, Janssen-Heijnen ML, Olde Rikkert MG, Machteld Wymenga AN. Comprehensive geriatric assessment and its clinical impact in oncology. Eur J Cancer 2007;43: [31] Fonck M, Blanc-Bisson C, Mathoulin-Pelissier S, et al. Screening des patients âgés diagnostiqués pour un cancer et à risque de décès précoce. Résultats d une étude prospective multicentrique de 364 patients traités par chimiothérapie. Gastroenterol Clin Biol 2007;31 [HS II] Ref Type: Abstract. [32] Girre V, Falcou MC, Gisselbrecht M, et al. Does a geriatric oncology consultation modify the cancer treatment plan for elderly patients? J Gerontol A: Biol Sci Med Sci 2008;63: [33] Extermann M, Meyer J, McGinnis M, et al. A comprehensive geriatric intervention detects multiple problems in older breast cancer patients. Crit Rev Oncol Hematol 2004;49: [34] Mitry E, Phelip JM, Bonnetain F, et al. Phase III trial of chemotherapy with or without irinotecan in the front-line treatment of metastatic colorectal cancer in elderly patients (FFCD trial): results of a planned interim analysis. In: Proceedings of ASCO GI Cancer Symposium, A Ref Type: Abstract. [35] Retornaz F, Monette J, Batist G, et al. Usefulness of frailty markers in the assessment of the health and functional status of older cancer patients referred for chemotherapy: a pilot study. J Gerontol A: Biol Sci Med Sci 2008;63: [36] Extermann M, Aapro M, Bernabei R, et al. 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: Biographies Thomas Aparicio, M.D., Ph.D, is a member of the hepatogastroenterology team of Bichat Hospital in Paris and is now in charge of Digestive Oncology in Avicenne Hospital in Bobigny (France). His research focused on Digestive
7 T. Aparicio et al. / Critical Reviews in Oncology/Hematology 77 (2011) Oncology with a special interest on geriatric oncology. He is the secretary of the Scientific Council of the Fédération Francophone de Cancérologie Digestive (FFCD), member of the SIOG and belongs to the Organisation Committee of Echange et Pratique en Onco Gériatrie a French group focusing on geriatric oncology. Laurence Girard, M.D., is a member of the geriatric unit of Bichat Hospital in Paris (France). She is mainly involved in care of patients with cancer. Nadia Bouarioua, M.D., is a member of the hepatogastroenterology team of Bichat Hospital in Paris (France). She mainly managed the patients with digestive cancer. Claire Patry, M.D., is a member of the mobile team of the geriatric unit of Bichat Hospital in Paris (France). Sylvie Legrain, M.D., PhD., is professor of gerontology. She was head of the geriatric team at the time of study. She recently joined the geriatric unit of Bretonneau Hospital in Paris. Jean Claude Soulé, M.D., Ph.D., is professor of gastroenterology. He is head of the hepato-gastroenterology team of Bichat Hospital in Paris (France).
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