PMID- 37801678 OWN - NLM STAT- MEDLINE DCOM- 20240119 LR - 20240201 IS - 1527-7755 (Electronic) IS - 0732-183X (Print) IS - 0732-183X (Linking) VI - 42 IP - 3 DP - 2024 Jan 20 TI - Importance of Low- and Moderate-Grade Adverse Events in Patients' Treatment Experience and Treatment Discontinuation: An Analysis of the E1912 Trial. PG - 266-272 LID - 10.1200/JCO.23.00377 [doi] AB - PURPOSE: Despite defined grades of 1 to 5 for adverse events (AEs) on the basis of Common Terminology Criteria for Adverse Events criteria, mild (G1) and moderate (G2) AEs are often not reported in phase III trials. This under-reporting may inhibit our ability to understand patient toxicity burden. We analyze the relationship between the grades of AEs experienced with patient side-effect bother and treatment discontinuation. METHODS: We analyzed a phase III Eastern Cooperative Oncology Group-American College of Radiology Imaging Network trial with comprehensive AE data. The Likert response Functional Assessment of Cancer Therapy-GP5 item, "I am bothered by side effects of treatment" was used to define side-effect bother. Bayesian mixed models were used to assess the impact of G1 and G2 AE counts on patient side-effect bother and treatment discontinuation. AEs were further analyzed on the basis of symptomatology (symptomatic or asymptomatic). The results are given as odds ratios (ORs) and 95% credible interval (CrI). RESULTS: Each additional G1 and G2 AEs experienced during a treatment cycle increased the odds of increased self-reported patient side-effect bother by 13% (95% CrI, 1.06 to 1.21) and 35% (95% CrI, 1.19 to 1.54), respectively. Furthermore, only AEs defined as symptomatic were associated with increased side-effect bother, with asymptomatic AEs showing no association regardless of grade. Count of G2 AEs increased the odds of treatment discontinuation by 59% (95% CrI, 1.32 to 1.95), with symptomatic G2 AEs showing a stronger association (OR, 1.75; 95% CrI, 1.28 to 2.39) relative to asymptomatic G2 AEs (OR, 1.45; 95% CrI, 1.12 to 1.89). CONCLUSION: Low- and moderate-grade AEs are related to increased odds of increased patient side-effect bother and treatment discontinuation, with symptomatic AEs demonstrating greater magnitude of association than asymptomatic. Our findings suggest that limiting AE capture to grade 3+ misses important contributors to treatment side-effect bother and discontinuation. FAU - O'Connell, Nathaniel S AU - O'Connell NS AUID- ORCID: 0000-0002-3827-5152 AD - Wake Forest University School of Medicine, Winston-Salem, NC. FAU - Zhao, Fengmin AU - Zhao F AD - Dana Farber Cancer Institute, ECOG-ACRIN Biostatistics Center, Boston, MA. FAU - Lee, Ju-Whei AU - Lee JW AUID- ORCID: 0000-0003-2068-8511 AD - Dana Farber Cancer Institute, ECOG-ACRIN Biostatistics Center, Boston, MA. FAU - Ip, Edward H AU - Ip EH AUID- ORCID: 0000-0002-4811-4205 AD - Wake Forest University School of Medicine, Winston-Salem, NC. FAU - Peipert, John Devin AU - Peipert JD AUID- ORCID: 0000-0001-5762-7881 AD - Northwestern University Feinberg School of Medicine, Chicago, IL. FAU - Graham, Noah AU - Graham N AD - Dana Farber Cancer Institute, ECOG-ACRIN Biostatistics Center, Boston, MA. FAU - Smith, Mary Lou AU - Smith ML AD - Research Advocacy Network, Chicago, IL. FAU - Gareen, Ilana F AU - Gareen IF AUID- ORCID: 0000-0002-0457-5595 AD - Department of Epidemiology and the Center for Statistical Sciences, Brown University School of Public Health, Providence, RI. FAU - Carlos, Ruth C AU - Carlos RC AUID- ORCID: 0000-0001-7055-7662 AD - University of Michigan Comprehensive Cancer Center, Ann Arbor, MI. FAU - Obeng-Gyasi, Samilia AU - Obeng-Gyasi S AUID- ORCID: 0000-0002-5330-7247 AD - The Ohio State University, Columbus, OH. FAU - Sparano, Joseph A AU - Sparano JA AUID- ORCID: 0000-0002-9031-2010 AD - Icahn School of Medicine at Mount Sinai, Tisch Cancer Institute, New York, NY. FAU - Shanafelt, Tait D AU - Shanafelt TD AUID- ORCID: 0000-0002-7106-5202 AD - Stanford Center Institute Palo Alto, Stanford, CA. FAU - Thomas, Mary L AU - Thomas ML AD - VA Palo Alto Health Care System, Palo Alto, CA. FAU - Cella, David AU - Cella D AUID- ORCID: 0000-0002-9881-4541 AD - Northwestern University Feinberg School of Medicine, Chicago, IL. FAU - Wagner, Lynne I AU - Wagner LI AUID- ORCID: 0000-0001-9685-4796 AD - Wake Forest University School of Medicine, Winston-Salem, NC. FAU - Gray, Robert AU - Gray R AUID- ORCID: 0000-0002-5724-4917 AD - Dana Farber Cancer Institute, ECOG-ACRIN Biostatistics Center, Boston, MA. LA - eng SI - ClinicalTrials.gov/NCT02048813 GR - U01 CA233169/CA/NCI NIH HHS/United States GR - UG1 CA233160/CA/NCI NIH HHS/United States PT - Journal Article DEP - 20231006 PL - United States TA - J Clin Oncol JT - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JID - 8309333 SB - IM CIN - doi: 10.1200/JCO.23.01976 MH - Humans MH - *Bayes Theorem MH - Self Report PMC - PMC10824381 COIS- The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center. Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments). EDAT- 2023/10/06 18:41 MHDA- 2024/01/19 06:43 PMCR- 2025/01/20 CRDT- 2023/10/06 16:03 PHST- 2025/01/20 00:00 [pmc-release] PHST- 2024/01/19 06:43 [medline] PHST- 2023/10/06 18:41 [pubmed] PHST- 2023/10/06 16:03 [entrez] AID - JCO.23.00377 [pii] AID - 10.1200/JCO.23.00377 [doi] PST - ppublish SO - J Clin Oncol. 2024 Jan 20;42(3):266-272. doi: 10.1200/JCO.23.00377. Epub 2023 Oct 6.