Shelli R Kesler1, Douglas W Blayney2. 1. Department of Neuro-oncology, University of Texas MD Anderson Cancer Center, Houston. 2. Division of Medical Oncology, Stanford University School of Medicine, Stanford, California.
Abstract
IMPORTANCE: Chemotherapy exposure is a known risk factor for cancer-related cognitive impairments. Anthracycline-based regimens are commonly used chemotherapies that have been shown to be associated with cognitive impairment and brain changes in clinical studies. OBJECTIVE: To directly compare the effects of anthracycline and nonanthracycline regimens on cognitive status and functional brain connectivity. DESIGN, SETTING, AND PARTICIPANTS: In this observational study, we retrospectively examined cognitive and resting state functional magnetic resonance imaging data acquired from 62 primary breast cancer survivors (mean [SD] age, 54.7 [8.5] years) who were more than 2 years off-therapy, on average. Twenty of these women received anthracycline-based chemotherapy as part of their primary treatment, 19 received nonanthracycline regimens, and 23 did not receive any chemotherapy. Participants were enrolled at a single academic institution (Stanford University) from 2008 to 2014, and the study analyses were performed at this time. MAIN OUTCOMES AND MEASURES: Cognitive status was measured using standardized neuropsychological tests, and functional brain connectivity was evaluated using resting state functional magnetic resonance imaging with a focus on the brain's default mode network. RESULTS: The anthracycline group demonstrated significantly lower verbal memory performance including immediate recall (F = 3.73; P = .03) and delayed recall (F = 11.11; P < .001) as well as lower left precuneus connectivity (F = 7.48; P = .001) compared with the other 2 groups. Patient-reported outcomes related to cognitive dysfunction (F = 7.27; P = .002) and psychological distress (F = 5.64; P = .006) were similarly elevated in both chemotherapy groups compared with the non-chemotherapy-treated controls. CONCLUSIONS AND RELEVANCE: These results suggest that anthracyclines may have greater negative effects than nonanthracycline regimens on particular cognitive domains and brain network connections. Both anthracycline and nonanthracycline regimens may have nonspecific effects on other cognitive domains as well as certain patient reported outcomes. Further research is needed to identify potential methods for protecting the brain against the effects of various chemotherapeutic agents.
IMPORTANCE: Chemotherapy exposure is a known risk factor for cancer-related cognitive impairments. Anthracycline-based regimens are commonly used chemotherapies that have been shown to be associated with cognitive impairment and brain changes in clinical studies. OBJECTIVE: To directly compare the effects of anthracycline and nonanthracycline regimens on cognitive status and functional brain connectivity. DESIGN, SETTING, AND PARTICIPANTS: In this observational study, we retrospectively examined cognitive and resting state functional magnetic resonance imaging data acquired from 62 primary breast cancer survivors (mean [SD] age, 54.7 [8.5] years) who were more than 2 years off-therapy, on average. Twenty of these women received anthracycline-based chemotherapy as part of their primary treatment, 19 received nonanthracycline regimens, and 23 did not receive any chemotherapy. Participants were enrolled at a single academic institution (Stanford University) from 2008 to 2014, and the study analyses were performed at this time. MAIN OUTCOMES AND MEASURES: Cognitive status was measured using standardized neuropsychological tests, and functional brain connectivity was evaluated using resting state functional magnetic resonance imaging with a focus on the brain's default mode network. RESULTS: The anthracycline group demonstrated significantly lower verbal memory performance including immediate recall (F = 3.73; P = .03) and delayed recall (F = 11.11; P < .001) as well as lower left precuneus connectivity (F = 7.48; P = .001) compared with the other 2 groups. Patient-reported outcomes related to cognitive dysfunction (F = 7.27; P = .002) and psychological distress (F = 5.64; P = .006) were similarly elevated in both chemotherapy groups compared with the non-chemotherapy-treated controls. CONCLUSIONS AND RELEVANCE: These results suggest that anthracyclines may have greater negative effects than nonanthracycline regimens on particular cognitive domains and brain network connections. Both anthracycline and nonanthracycline regimens may have nonspecific effects on other cognitive domains as well as certain patient reported outcomes. Further research is needed to identify potential methods for protecting the brain against the effects of various chemotherapeutic agents.
Authors: Hanna K Sanoff; Allison M Deal; Janakiraman Krishnamurthy; Chad Torrice; Patrick Dillon; Jessica Sorrentino; Joseph G Ibrahim; Trevor A Jolly; Grant Williams; Lisa A Carey; Amy Drobish; Brittaney-Belle Gordon; Shani Alston; Arti Hurria; Karin Kleinhans; K Lenhard Rudolph; Norman E Sharpless; Hyman B Muss Journal: J Natl Cancer Inst Date: 2014-03-28 Impact factor: 13.506
Authors: Shelli R Kesler; Meike Gugel; Mika Pritchard-Berman; Clement Lee; Emily Kutner; S M Hadi Hosseini; Gary Dahl; Norman Lacayo Journal: Pediatr Blood Cancer Date: 2014-03-12 Impact factor: 3.167
Authors: C Rousselle; M Smirnova; P Clair; J M Lefauconnier; A Chavanieu; B Calas; J M Scherrmann; J Temsamani Journal: J Pharmacol Exp Ther Date: 2001-01 Impact factor: 4.030
Authors: Jay F Piccirillo; Frances Mei Hardin; Joyce Nicklaus; Dorina Kallogjeri; Michael Wilson; Cynthia X Ma; Rebecca S Coalson; Joshua Shimony; Bradley L Schlaggar Journal: Oncology Date: 2015-02-07 Impact factor: 2.935
Authors: M Lange; F Joly; J Vardy; T Ahles; M Dubois; L Tron; G Winocur; M B De Ruiter; H Castel Journal: Ann Oncol Date: 2019-12-01 Impact factor: 32.976
Authors: Debra E Lyon; Ronald Cohen; Huaihou Chen; Debra L Kelly; Angela Starkweather; Hyo-Chol Ahn; Colleen K Jackson-Cook Journal: J Cancer Res Clin Oncol Date: 2016-04-21 Impact factor: 4.553
Authors: Tara M Brinkman; Chenghong Li; Kathryn Vannatta; Jordan G Marchak; Jin-Shei Lai; Pinki K Prasad; Cara Kimberg; Stefanie Vuotto; Chongzhi Di; Deokumar Srivastava; Leslie L Robison; Gregory T Armstrong; Kevin R Krull Journal: J Clin Oncol Date: 2016-07-18 Impact factor: 44.544
Authors: Gabriel S Chiu; Magdalena A Maj; Sahar Rizvi; Robert Dantzer; Elisabeth G Vichaya; Geoffroy Laumet; Annemieke Kavelaars; Cobi J Heijnen Journal: Cancer Res Date: 2016-11-22 Impact factor: 12.701
Authors: Jose F Moruno-Manchon; Ndidi-Ese Uzor; Shelli R Kesler; Jeffrey S Wefel; Debra M Townley; Archana Sidalaghatta Nagaraja; Sunila Pradeep; Lingegowda S Mangala; Anil K Sood; Andrey S Tsvetkov Journal: Mol Cell Neurosci Date: 2017-11-24 Impact factor: 4.314
Authors: Bihong T Chen; Ningrong Ye; Chi Wah Wong; Sunita K Patel; Taihao Jin; Can-Lan Sun; Russell C Rockne; Heeyoung Kim; James C Root; Andrew J Saykin; Tim A Ahles; Andrei I Holodny; Neal Prakash; Joanne Mortimer; Mina S Sedrak; James Waisman; Yuan Yuan; Daneng Li; Jessica Vazquez; Vani Katheria; William Dale Journal: J Geriatr Oncol Date: 2019-11-02 Impact factor: 3.599