The effect of geriatric intervention in frail older patients receiving chemotherapy for colorectal cancer: a randomised trial (GERICO)

Cecilia Margareta Lund, Kirsten Kjeldgaard Vistisen, Anne Pries Olsen, Pernille Bardal, Martin Schultz, Troels Gammeltoft Dolin, Finn Rønholt, Julia Sidenius Johansen, Dorte Lisbeth Nielsen, Cecilia Margareta Lund, Kirsten Kjeldgaard Vistisen, Anne Pries Olsen, Pernille Bardal, Martin Schultz, Troels Gammeltoft Dolin, Finn Rønholt, Julia Sidenius Johansen, Dorte Lisbeth Nielsen

Abstract

Background: Older patients with colorectal cancer (CRC) experience chemotherapy dose reductions or discontinuation. Comprehensive geriatric assessment (CGA) predicts survival and chemotherapy completion in patients with cancer, but the benefit of geriatric interventions remains unexplored.

Methods: The GERICO study is a randomised Phase 3 trial including patients ≥70 years receiving adjuvant or first-line palliative chemotherapy for CRC. Vulnerable patients (G8 questionnaire ≤14 points) were randomised 1:1 to CGA-based interventions or standard care, along with guideline-based chemotherapy. The primary outcome was chemotherapy completion without dose reductions or delays. Secondary outcomes were toxicity, survival and quality of life (QoL).

Results: Of 142 patients, 58% received adjuvant and 42% received first-line palliative chemotherapy. Interventions included medication changes (62%), nutritional therapy (51%) and physiotherapy (39%). More interventional patients completed scheduled chemotherapy compared with controls (45% vs. 28%, P = 0.0366). Severe toxicity occurred in 39% of controls and 28% of interventional patients (P = 0.156). QoL improved in interventional patients compared with controls with the decreased burden of illness (P = 0.048) and improved mobility (P = 0.008).

Conclusion: Geriatric interventions compared with standard care increased the number of older, vulnerable patients with CRC completing adjuvant chemotherapy, and may improve the burden of illness and mobility.

Trial registration: ClinicalTrials.gov ID: NCT02748811.

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1. Screening and inclusion in the…
Fig. 1. Screening and inclusion in the GERICO study.
Totally 484 patients were assessed and 153 patients were found eligeble for the study.
Fig. 2. Association between baseline characteristics and…
Fig. 2. Association between baseline characteristics and completion of planned chemotherapy.
CIRS Critical Illness Rating Scale, PS performance status.

References

    1. Mohile SG, Dale W, Somerfield MR, Schonberg MA, Boyd CM, Burhenn PS, et al. Practical assessment and management of vulnerabilities in older patients receiving chemotherapy: ASCO guideline for geriatric oncology. J. Clin. Oncol. 2018;36:2326–2347.
    1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J. Clin. 2020;70:7–30.
    1. Christensen K, Doblhammer G, Rau R, Vaupel JW. Ageing populations: the challenges ahead. Lancet. 2009;374:1196–1208.
    1. Papamichael D, Audisio RA, Glimelius B, de Gramont A, Glynne-Jones R, Haller D, et al. Treatment of colorectal cancer in older patients: International Society of Geriatric Oncology (SIOG) consensus recommendations 2013. Ann. Oncol. 2015;26:463–476.
    1. Hurria A, Togawa K, Mohile SG, Owusu C, Klepin HD, Gross CP, et al. Predicting chemotherapy toxicity in older adults with cancer: a prospective multicenter study. J. Clin. Oncol. 2011;29:3457–3465.
    1. Kordatou Z, Kountourakis P, Papamichael D. Treatment of older patients with colorectal cancer: a perspective review. Ther. Adv. Med. Oncol. 2014;6:128–140.
    1. Kim JH. Chemotherapy for colorectal cancer in the elderly. World J. Gastroenterol. 2015;21:5158–5166.
    1. Power DG, Lichtman SM. Chemotherapy for the elderly patient with colorectal cancer. Cancer J. 2010;16:241–252.
    1. Quaglia A, Tavilla A, Shack L, Brenner H, Janssen-Heijnen M, Allemani C, et al. The cancer survival gap between elderly and middle-aged patients in Europe is widening. Eur. J. Cancer. 2009;45:1006–1016.
    1. Winther SB, Baatrup G, Pfeiffer P, Qvortrup C. Trends in colorectal cancer in the elderly in Denmark, 1980-2012. Acta Oncol. 2016;55:29–39.
    1. Gill S, Loprinzi CL, Sargent DJ, Thome SD, Alberts SR, Haller DG, et al. Pooled analysis of fluorouracil-based adjuvant therapy for stage II and III colon cancer: who benefits and by how much? J. Clin. Oncol. 2004;22:1797–1806.
    1. Gray R, Barnwell J, McConkey C, Hills RK, Williams NS, Kerr DJ. Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomised study. Lancet. 2007;370:2020–2029.
    1. Twelves C, Wong A, Nowacki MP, Abt M, Burris H, 3rd, Carrato A, et al. Capecitabine as adjuvant treatment for stage III colon cancer. N. Engl. J. Med. 2005;352:2696–2704.
    1. Schmoll HJ, Twelves C, Sun W, O’Connell MJ, Cartwright T, McKenna E, et al. Effect of adjuvant capecitabine or fluorouracil, with or without oxaliplatin, on survival outcomes in stage III colon cancer and the effect of oxaliplatin on post-relapse survival: a pooled analysis of individual patient data from four randomised controlled trials. Lancet Oncol. 2014;15:1481–1492.
    1. Grothey A, Sobrero AF, Shields AF, Yoshino T, Paul J, Taieb J, et al. Duration of adjuvant chemotherapy for stage III colon cancer. N. Engl. J. Med. 2018;378:1177–1188.
    1. Petersen, S. H., Harling, H., Kirkeby, L. T., Wille-Jorgensen, P. & Mocellin, S. Postoperative adjuvant chemotherapy in rectal cancer operated for cure. Cochrane Database Syst. Rev. CD004078 (2012).
    1. Sargent DJ, Goldberg RM, Jacobson SD, Macdonald JS, Labianca R, Haller DG, et al. A pooled analysis of adjuvant chemotherapy for resected colon cancer in elderly patients. N. Engl. J. Med. 2001;345:1091–1097.
    1. Sanoff HK, Carpenter WR, Sturmer T, Goldberg RM, Martin CF, Fine JP, et al. Effect of adjuvant chemotherapy on survival of patients with stage III colon cancer diagnosed after age 75 years. J. Clin. Oncol. 2012;30:2624–2634.
    1. Hoeben KW, van Steenbergen LN, van de Wouw AJ, Rutten HJ, van Spronsen DJ, Janssen-Heijnen ML. Treatment and complications in elderly stage III colon cancer patients in the Netherlands. Ann. Oncol. 2013;24:974–979.
    1. Iwashyna TJ, Lamont EB. Effectiveness of adjuvant fluorouracil in clinical practice: a population-based cohort study of elderly patients with stage III colon cancer. J. Clin. Oncol. 2002;20:3992–3998.
    1. Sorbye H, Cvancarova M, Qvortrup C, Pfeiffer P, Glimelius B. Age-dependent improvement in median and long-term survival in unselected population-based Nordic registries of patients with synchronous metastatic colorectal cancer. Ann. Oncol. 2013;24:2354–2360.
    1. Wildiers H, Heeren P, Puts M, Topinkova E, Janssen-Heijnen ML, Extermann M, et al. International Society of Geriatric Oncology consensus on geriatric assessment in older patients with cancer. J. Clin. Oncol. 2014;32:2595–2603.
    1. Mohile SG, Velarde C, Hurria A, Magnuson A, Lowenstein L, Pandya C, et al. Geriatric assessment-guided care processes for older adults: a Delphi consensus of geriatric oncology experts. J. Natl Compr. Canc Netw. 2015;13:1120–1130.
    1. Ellis G, Whitehead MA, Robinson D, O’Neill D, Langhorne P. Comprehensive geriatric assessment for older adults admitted to hospital: meta-analysis of randomised controlled trials. BMJ. 2011;343:d6553.
    1. Extermann M, Hurria A. Comprehensive geriatric assessment for older patients with cancer. J. Clin. Oncol. 2007;25:1824–1831.
    1. Wildes TM, Ruwe AP, Fournier C, Gao F, Carson KR, Piccirillo JF, et al. Geriatric assessment is associated with completion of chemotherapy, toxicity, and survival in older adults with cancer. J. Geriatr. Oncol. 2013;4:227–234.
    1. Aparicio T, Jouve JL, Teillet L, Gargot D, Subtil F, Le Brun-Ly V, et al. Geriatric factors predict chemotherapy feasibility: ancillary results of FFCD 2001-02 phase III study in first-line chemotherapy for metastatic colorectal cancer in elderly patients. J. Clin. Oncol. 2013;31:1464–1470.
    1. 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.
    1. Ommundsen N, Wyller TB, Nesbakken A, Jordhoy MS, Bakka A, Skovlund E, et al. Frailty is an independent predictor of survival in older patients with colorectal cancer. Oncologist. 2014;19:1268–1275.
    1. Hamaker ME, Te Molder M, Thielen N, van Munster BC, Schiphorst AH, van Huis LH. The effect of a geriatric evaluation on treatment decisions and outcome for older cancer patients—a systematic review. J. Geriatr. Oncol. 2018;9:430–440.
    1. Decoster L, Van Puyvelde K, Mohile S, Wedding U, Basso U, Colloca G, et al. Screening tools for multidimensional health problems warranting a geriatric assessment in older cancer patients: an update on SIOG recommendations†. Ann. Oncol. 2015;26:288–300.
    1. van Walree IC, Scheepers E, van Huis-Tanja L, Emmelot-Vonk MH, Bellera C, Soubeyran P, et al. A systematic review on the association of the G8 with geriatric assessment, prognosis and course of treatment in older patients with cancer. J. Geriatr. Oncol. 2019;10:847–858.
    1. Leo S, Accettura C, Gnoni A, Licchetta A, Giampaglia M, Mauro A, et al. Systemic treatment of gastrointestinal cancer in elderly patients. J. Gastrointest. Cancer. 2013;44:22–32.
    1. Lund, C. M., Vistisen, K. K., Dehlendorff, C., Ronholt, F., Johansen, J. S. & Nielsen, D. L. The effect of geriatric intervention in frail elderly patients receiving chemotherapy for colorectal cancer: a randomized trial (GERICO). BMC Cancer17, 448 (2017).
    1. Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am. J. Clin. Oncol. 1982;5:649–655.
    1. Bellera CA, Rainfray M, Mathoulin-Pelissier S, Mertens C, Delva F, Fonck M, et al. Screening older cancer patients: first evaluation of the G-8 geriatric screening tool. Ann. Oncol. 2012;23:2166–2172.
    1. Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, Filiberti A, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J. Natl Cancer Inst. 1993;85:365–376.
    1. Wheelwright S, Darlington AS, Fitzsimmons D, Fayers P, Arraras JI, Bonnetain F, et al. International validation of the EORTC QLQ-ELD14 questionnaire for assessment of health-related quality of life elderly patients with cancer. Br. J. Cancer. 2013;109:852–858.
    1. RStudio Team, RStudio: Integrated Development for R. RStudio, Inc., Boston, MA. (2015).
    1. Lipsey MW, Wilson DB. The efficacy of psychological, educational, and behavioral treatment. Confirmation from meta-analysis. Am. Psychol. 1993;48:1181–1209.
    1. Martin L, Senesse P, Gioulbasanis I, Antoun S, Bozzetti F, Deans C, et al. Diagnostic criteria for the classification of cancer-associated weight loss. J. Clin. Oncol. 2015;33:90–99.
    1. Scher KS, Hurria A. Under-representation of older adults in cancer registration trials: known problem, little progress. J. Clin. Oncol. 2012;30:2036–2038.
    1. Kalsi T, Babic-Illman G, Ross PJ, Maisey NR, Hughes S, Fields P, et al. The impact of comprehensive geriatric assessment interventions on tolerance to chemotherapy in older people. Br. J. Cancer. 2015;112:1435–1444.
    1. Mohile, S. G., Refaat, M. M., Culakova, E., Xu, H., Loh, K. P., Magnuson, A. et al. A gertiatric assessment (GA) intervention to reduce treatment toxicity in older patients with advanced cancer: a University of Rochester Cancer Center NCI Community Pncology Research Program cluster randomized controlled trial (CRCT). 2020 ASCO Virtual Scientific Program (Abstract 12009) (2020).
    1. Li, D., Sun, C. L., Kim, H., Chung, V., Koczywas, M., Fakih, M. et al. Geriatric assessment-driven intervention (GAIN) on chemotherapy toxicity in older adults with cancer: a randomized controlled trial. 2020 ASCO Virtual Scientific Program (Abstract 12010) (2020).
    1. Crosby RD, Kolotkin RL, Williams GR. Defining clinically meaningful change in health-related quality of life. J. Clin. Epidemiol. 2003;56:395–407.
    1. Norman GR, Sloan JA, Wyrwich KW. Interpretation of changes in health-related quality of life: the remarkable universality of half a standard deviation. Med. Care. 2003;41:582–592.
    1. Snyder CF, Blackford AL, Sussman J, Bainbridge D, Howell D, Seow HY, et al. Identifying changes in scores on the EORTC-QLQ-C30 representing a change in patients’ supportive care needs. Qual. Life Res. 2015;24:1207–1216.
    1. Efficace F, Fayers P, Pusic A, Cemal Y, Yanagawa J, Jacobs M, et al. Quality of patient-reported outcome reporting across cancer randomized controlled trials according to the CONSORT patient-reported outcome extension: a pooled analysis of 557 trials. Cancer. 2015;121:3335–3342.
    1. Soo, W. K., King, M., Pope, A., Parente, P. & Darzins, P. Integrated geriatric assessment and treatment (INTEGERATE) in older people with cancer planned for systemic anticancer therapy. ASCO Virtuel Scientific Program (Abstract 12011) (2020).
    1. Lund CM, Vistisen KK, Dehlendorff C, Ronholt F, Johansen JS, Nielsen DL. Age-dependent differences in first-line chemotherapy in patients with metastatic colorectal cancer: the DISCO study. Acta Oncol. 2018;57:1445–1454.
    1. DuMontier C, Loh KP, Bain PA, Silliman RA, Hshieh T, Abel GA, et al. Defining undertreatment and overtreatment in older adults with cancer: a scoping literature review. J. Clin. Oncol. 2020;38:2558–2569.
    1. Dewys WD, Begg C, Lavin PT, Band PR, Bennett JM, Bertino JR, et al. Prognostic effect of weight loss prior to chemotherapy in cancer patients. Eastern Cooperative Oncology Group. Am. J. Med. 1980;69:491–497.
    1. Hamaker, M. E., Oosterlaan, F., van Huis, L. H., Thielen, N., Vondeling, A. & van den Bos, F. Nutritional status and interventions for patients with cancer—a systematic review. J. Geriatr. Oncol. 10.1016/j.jgo.2020.06.020 (2020).
    1. Wright AA, Cook CE, Baxter GD, Dockerty JD, Abbott JH. A comparison of 3 methodological approaches to defining major clinically important improvement of 4 performance measures in patients with hip osteoarthritis. J. Orthop. Sports Phys. Ther. 2011;41:319–327.
    1. Stout NL, Silver JK, Raj VS, Rowland J, Gerber L, Cheville A, et al. Toward a national initiative in cancer rehabilitation: recommendations from a subject matter expert group. Arch. Phys. Med. Rehabil. 2016;97:2006–2015.
    1. Freitas S, Simoes MR, Alves L, Santana I. The relevance of sociodemographic and health variables on MMSE normative data. Appl. Neuropsychol. Adult. 2015;22:311–319.
    1. Canoui-Poitrine F, Reinald N, Laurent M, Guery E, Caillet P, David JP, et al. Geriatric assessment findings independently associated with clinical depression in 1092 older patients with cancer: the ELCAPA cohort study. Psychooncology. 2016;25:104–111.

Source: PubMed

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