Ambulatory Toxicity Management (AToM) in patients receiving adjuvant or neo-adjuvant chemotherapy for early stage breast cancer - a pragmatic cluster randomized trial protocol

Monika K Krzyzanowska, Jim A Julian, Melanie Powis, Doris Howell, Craig C Earle, Katherine A Enright, Nicole Mittmann, Maureen E Trudeau, Eva Grunfeld, Monika K Krzyzanowska, Jim A Julian, Melanie Powis, Doris Howell, Craig C Earle, Katherine A Enright, Nicole Mittmann, Maureen E Trudeau, Eva Grunfeld

Abstract

Background: Population-based studies suggest that emergency department visits and hospitalizations are common among patients receiving chemotherapy and that rates in routine practice are higher than expected from clinical trials. Chemotherapy-related toxicities are often predictable and, consequently, acute care visits may be preventable with adequate treatment planning and support between visits to the cancer centre. We will evaluate the impact of proactive telephone-based toxicity management on emergency department visits and hospitalizations in women with early stage breast cancer receiving chemotherapy.

Methods: In this pragmatic covariate constraint-based cluster randomized trial, 20 centres in Ontario, Canada are randomly allocated to either proactive telephone toxicity management (intervention) or routine care (control). The primary outcome is the cluster-level mean number of ED + H visits per patient evaluated using Ontario administrative healthcare data. Participants are all patients with early stage (I-III) breast cancer commencing adjuvant or neo-adjuvant chemotherapy at participating institutions during the intervention period. At least 25 patients at each centre participate in a patient reported outcomes sub-study involving the collection of standardized questionnaires to measure: severity of treatment toxicities, self-care, self-efficacy, quality of life, and coordination of care. Patients participating in the patient reported outcomes (PRO) sub-study are asked to provide written consent to link their PRO data to administrative data. Unit costs will be applied to each per person resource utilized, and a total cost per population and patient will be generated. An incremental cost-effectiveness analysis will be undertaken to compare the incremental costs and outcomes between the intervention and control groups from the health system perspective.

Discussion: This study evaluates the effectiveness of a proactive toxicity management intervention in a routine care setting. The use of administrative healthcare data to evaluate the primary outcome enables an evaluation in a real world setting and at a much larger scale than previous studies.

Trial registration: Clinicaltrials.gov , NCT02485678. Registered 30 June 2015.

Keywords: Breast cancer; Chemotherapy toxicity; Quality improvement; Symptom management; Telephone case management.

Conflict of interest statement

Authors CCE and EG hold appointments at the Ontario Institute for Cancer Research (OICR) Health Services Research Program. All other authors have no competing interests to declare.

Figures

Fig. 1
Fig. 1
Schema for main study and patient reported outcomes (PRO) sub-study: A Pragmatic Cluster Randomized Trial of Ambulatory Toxicity Management in Patients Receiving Adjuvant or Neo-adjuvant Chemotherapy for Early Stage Breast Cancer (AToM)
Fig. 2
Fig. 2
Overview of procedures for main study and patient reported outcomes (PRO) sub-study

References

    1. Cancer Quality Council of Ontario. Cancer System Quality Index (CSQI). 2017. . Accessed on 23 Feb 2018.
    1. Enright K, Grunfeld E, Yun L, Moineddin R, Ghannam M, Dent S, et al. Population-based assessment of emergency room visits and hospitalizations among women receiving adjuvant chemotherapy for early breast cancer. J Oncol Pract. 2015;11(2):126–132. doi: 10.1200/JOP.2014.001073.
    1. Lee L, Crump M, Khor S, Hoch JS, Luo J, Bremner K, et al. Impact of rituximab on treatment outcomes of patients with diffuse large b-cell lymphoma: a population-based analysis. Br J Haematol. 2012;158(4):481–488. doi: 10.1111/j.1365-2141.2012.09177.x.
    1. Barcenas CH, Niu J, Zhang N, Zhang Y, Buchholz TA, Elting LS, et al. Risk of hospitalization according to chemotherapy regimen in early-stage breast cancer. J Clin Oncol. 2014;32(19):2010–2017. doi: 10.1200/JCO.2013.49.3676.
    1. Prince RM, Atenafu EG, Krzyzanowska MK. Hospitalizations during systemic therapy for metastatic lung cancer: a systematic review of real world vs clinical trial outcomes. JAMA Oncol. 2015;1(9):1333–1339. doi: 10.1001/jamaoncol.2015.3440.
    1. Prince Rebecca M., Powis Melanie, Zer Alona, Atenafu Eshetu G., Krzyzanowska Monika K. Hospitalisations and emergency department visits in cancer patients receiving systemic therapy: Systematic review and meta-analysis. European Journal of Cancer Care. 2018;28(1):e12909. doi: 10.1111/ecc.12909.
    1. Kearney N, Miller M, Maguire R, Dolan S, MacDonald R, McLeod J, et al. WISECARE+: results of a European study of a nursing intervention for the management of chemotherapy-related symptoms. Eur J Oncol Nurs. 2008;12(5):443–448. doi: 10.1016/j.ejon.2008.07.005.
    1. Kearney N, McCann L, Norrie J, Taylor L, Gray P, McGee-Lennon M, et al. Evaluation of a mobile phone-based, advanced symptom management system (ASyMS) in the management of chemotherapy-related toxicity. Support Care Cancer. 2008;17(4):437–444. doi: 10.1007/s00520-008-0515-0.
    1. Mooney KH, Beck SL, Friedman RH, Farzanfar R. Telephone-linked care for cancer symptom monitoring: a pilot study. Cancer Pract. 2002;10(3):147–154. doi: 10.1046/j.1523-5394.2002.103006.x.
    1. Mooney KH, Beck SL, Friedman RH, Farzanfar R, Wong B. Automated monitoring of symptoms during ambulatory chemotherapy and oncology providers' use of the information: a randomized controlled clinical trial. Support Care Cancer. 2014;22(9):2343–2350. doi: 10.1007/s00520-014-2216-1.
    1. Decker V, Spoelstra S, Miezio E, You M, Given B, Given CW. A pilot study of an automated voice response system and nursing intervention to monitor adherence to oral chemotherapy agents. Cancer Nurs. 2009;32(6):E20–E29. doi: 10.1097/NCC.0b013e3181b31114.
    1. Basch E, Deal AM, Dueck AC, Scher HI, Kris MG, Hudis C, Schrag D. Overall survival results of a trial assessing patient-reported outcomes for symptom monitoring during routine Cancer treatment. JAMA. 2017;318(2):197–198. doi: 10.1001/jama.2017.7156.
    1. Krzyzanowska MK, McKay C, Han H, Eberg M, Gandhi S, Laferriere NB, et al. Ambulatory toxicity management (AToM) pilot: results of a pilot study of a pro-active, telephone-based intervention to improve toxicity management during chemotherapy for breast cancer. Pilot Feasibility Stud. 2019;5:39. doi: 10.1186/s40814-019-0404-y.
    1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108. doi: 10.3322/caac.21262.
    1. American Cancer Society [Internet]. Cancer Facts and Figures; 2017. [cited 27 February 2018]. Available from: .
    1. Carlson RW, Brown E, Burstein HJ, Gradishar WJ, Hudis CA, Loprinzi C, et al. NCCN task force report: adjuvant therapy for breast Cancer. J Natl Compr Cancer Netw. 2006;4(Suppl 1):S1–26.
    1. Goldhirsch A, Wood WC, Gelber RD, Coates AS, Thürlimann B, Senn HJ. 10th St. Gallen conference. Progress and promise: Highlights of the international expert consensus on the primary therapy of early breast cancer 2007. Ann Oncol. 2007;18(7):1133–1144. doi: 10.1093/annonc/mdm271.
    1. Cancer Care Ontario [Internet]. Toronto: Adjuvant Systemic Therapy for Node Negative Breast Cancer. Practice Guideline Report #1–8. [cited 27 February 2018]. Accessed from: .
    1. Early Breast Cancer Trialist's Collaborative Group Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;365(9472):1687–1717. doi: 10.1016/S0140-6736(05)66544-0.
    1. Clarke EA, Marrett LD, Kreiger N. Cancer registration in Ontario: a computer approach. IARC Sci Publ. 1991;95:246–257.
    1. Moulton LH. Covariate-based constrained randomization of group-randomized trials. Clin Trials. 2004;1(3):297–305. doi: 10.1191/1740774504cn024oa.
    1. Sismanidis C, Moulton LH, Ayles H, Fielding K, Schaap A, Beyers N, et al. Restricted randomization of ZAMSTAR: a 2 x 2 factorial cluster randomized trial. Clin Trials. 2008;5(4):316–327. doi: 10.1177/1740774508094747.
    1. Shapiro CL, Recht A. Side effects of adjuvant treatment of breast cancer. N Engl J Med. 2001;344(26):1997–2008. doi: 10.1056/NEJM200106283442607.
    1. Jones S, Holmes FA, O'Shaughnessy J, Blum JL, Vukelja SJ, McIntyre KJ, et al. Docetaxel with cyclophosphamide is associated with an overall survival benefit compared with doxorubicin and cyclophosphamide: 7-year follow-up of US oncology research trial 9735. J Clin Oncol. 2009;27(8):1177–1183. doi: 10.1200/JCO.2008.18.4028.
    1. Roché H, Fumoleau P, Spielmann M, Canon JL, Delozier T, Serin D, et al. Sequential adjuvant epirubicin-based and docetaxel chemotherapy for node-positive breast cancer patients: the FNCLCC PACS 01 trial. J Clin Oncol. 2006;24(36):5664–5671. doi: 10.1200/JCO.2006.07.3916.
    1. Basch E., Reeve B. B., Mitchell S. A., Clauser S. B., Minasian L. M., Dueck A. C., Mendoza T. R., Hay J., Atkinson T. M., Abernethy A. P., Bruner D. W., Cleeland C. S., Sloan J. A., Chilukuri R., Baumgartner P., Denicoff A., St. Germain D., O'Mara A. M., Chen A., Kelaghan J., Bennett A. V., Sit L., Rogak L., Barz A., Paul D. B., Schrag D. Development of the National Cancer Institute's Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) JNCI Journal of the National Cancer Institute. 2014;106(9):dju244–dju244. doi: 10.1093/jnci/dju244.
    1. Bennett AV, Dueck AC, Mitchell SA, Mendoza TR, Reeve BB, Atkinson TM, et al. Mode equivalence and acceptability of tablet computer-, interactive voice response system-, and paper-based administration of the U.S. National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Health Qual Life Outcomes. 2016;14:24. doi: 10.1186/s12955-016-0426-6.
    1. Bruera E, Kuehn N, Miller MJ, Selmser P, Macmillan K. The Edmonton symptom assessment system (ESAS): a simple method for the assessment of palliative care patients. J Palliat Care. 1991;7(2):6–9. doi: 10.1177/082585979100700202.
    1. The EuroQol Group EuroQol-a new facility for the measurement of health-related quality of life. Health Policy. 1990;16(3):199–208. doi: 10.1016/0168-8510(90)90421-9.
    1. Smith AB, Rush R, Wright P. Validation of an item bank for detecting and assessing psychological distress in cancer patients. Psychooncology. 2009;18:195–199. doi: 10.1002/pon.1423.
    1. Lowe B, Decker O, Muller S, Brahler E, Schellberg D, Herzog W, Herzberg PY. Validation and standardization of the generalized anxiety disorder screener (GAD-7) in the general population. Med Care. 2008;46(3):266–274. doi: 10.1097/MLR.0b013e318160d093.
    1. Brady MJ, Cella DF, Mo F, Bonomi AE, Tulsky DS, Lloyd SR, et al. Reliability and validity of the functional assessment of Cancer therapy-breast quality-of-life instrument. J Clin Oncol. 1997;15(3):974–986. doi: 10.1200/JCO.1997.15.3.974.
    1. National Research Corporation, Ontario Hospital Association N.R.C . Development and Validation of the Picker Ambulatory Oncology Survey Instrument in Canada. Lincoln, NE: National Research Corporation; 2003.
    1. Husain A, Barbera L, Howell D, Moineddin R, Bezjak A, Sussman J. Advanced lung Cancer patients’ experience with continuity of care and supportive care needs. Support Care Cancer. 2013;21(5):1351–1358. doi: 10.1007/s00520-012-1673-7.
    1. Coolbrandt A, Van den Heede K, Jans E, Laenen A, Verslype C, Wildiers H, Milisen K. The Leuven questionnaire on patient knowledge of chemotherapy (L-PaKC): instrument development and psychometric evaluation. Eur J Oncol Nurs. 2013;17:465–473. doi: 10.1016/j.ejon.2012.10.012.
    1. Carroll C, Patterson M, Wood S, Booth A, Rick J, Balain S. A conceptual framework for implementation fidelity. Implement Sci. 2007;2:40. doi: 10.1186/1748-5908-2-40.
    1. Kim SY, Miller FG. Informed consent for pragmatic trials-the integrated consent model. N Engl J Med. 2014;370(8):769–772. doi: 10.1056/NEJMhle1312508.
    1. Damschroder LJ, Aron DC, Keith RE, Kirsh SR, Alexander JA, Lowery JC. Fostering implementation of health services research findings into practice: a consolidated framework for advancing implementation science. Implement Sci. 2009;4:50. doi: 10.1186/1748-5908-4-50.
    1. Warrington L, Absolom K, Conner M, Kellar I, Clayton B, Ayres M, Velikova G. Electronic Systems for Patients to report and manage side effects of Cancer treatment: systematic review. J Med Internet Res. 2019;21(1):e10875. doi: 10.2196/10875.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe