{"doi":"10.1200/jco.24.00518","title":"Reply to S. Zhang et al and S. Selukar","abstract":"We thank each of the letter writers for the enthusiasm and engagement with our published work on low-grade adverse events.Drs. Zhang and Li point out that duration of toxicity cannot be determined easily in the framework for which AEs are generally collected in cancer trials, and that chronicity inherently matters when assessing low-and moderate-grade AEs.They outline the following example: when experienced acutely, grade 1 and 2 diarrhea may be tolerable, but when experienced chronically -say, over multiple cycles of treatment -it may be intolerable.We agree with this sentiment completely, and in fact included this as a limitation in our discussion in our original paper (paragraph 5 of discussion).Chronicity certainly matters, and we think it is reasonable to assume that patients experiencing the cumulative effect of low-and moderate-grade AEs over several cycles of treatment experience a higher toxicity burden than patients who experience the same AEs acutely.We feel it's reasonable to hypothesize that such patients carry a higher risk of treatment discontinuation.However, in our consideration of this, we have found accounting for this cumulative toxicity burden effect is not straightforward.The primary question is, \"How do we best account for the","journal":"Journal of Clinical Oncology","year":2024,"id":496989,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9619,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":562898,"name":"Nathaniel S. O’Connell","orcid":"0000-0002-3827-5152","position":0,"is_corresponding":true}],"reference_count":5,"raw_metadata":null,"created_at":"2026-07-19T02:09:30.779495Z","pmid":"38657186","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}