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CTCAE version 6.0 is the sixth major release of the National Cancer Institute’s Common Terminology Criteria for Adverse Events. It changes how some adverse events are graded, most visibly neutropenia, so the same laboratory value can receive a lower grade than it did under version 5.0. Which version a study must use depends on the sponsor; for NCI CTEP and DCP studies it depends on when the study’s Rave build begins. For a plain definition of the scale itself, see the CTCAE dictionary entry; this guide covers the version 6.0 change and what it means for study data.
Definition: what CTCAE v6.0 is
CTCAE is a standard vocabulary and five-point severity scale for adverse events (AEs) in cancer trials: Grade 1 mild, Grade 2 moderate, Grade 3 severe or medically significant, Grade 4 life-threatening, Grade 5 death related to the AE. Version 6.0 was developed through an inter-agency collaboration of NCI’s Division of Cancer Treatment and Diagnosis (DCTD), NCI’s Division of Cancer Prevention and the FDA. NCI describes three problems it was designed to address: grading AEs in patients whose baseline laboratory values are already abnormal, characterising AEs associated with immunotherapeutics, and refining how cardiac-related AEs are categorised.
What changed from v5.0: the grade-threshold rule
For a laboratory-based term such as neutrophil count decreased, the “formula” is a ladder of cut-points: a measured value receives the grade whose band it falls in. Version 6.0 moved the neutrophil ladder. According to a peer-reviewed commentary by Merz (HemaSphere, 2025), the former Grade 1 band (lower limit of normal to 1500/µL) no longer exists, and Grade 4 now begins below 100/µL rather than below 500/µL. The commentary adds that this criterion had not changed in earlier versions and that the rationale for the change is not given in the criteria; the author suggests the likely reasons are people with the Duffy-null variant, who have lower normal counts, and newer drugs that lower neutrophils with a comparatively low rate of febrile neutropenia.
Neutrophil count decreased: v5.0 versus v6.0
Absolute neutrophil count (ANC) in cells per microlitre. A range such as “<1500 to 1000” is read as less than 1500 down to and including 1000.
| Grade | CTCAE v5.0 | CTCAE v6.0 |
|---|---|---|
| 1 | <LLN to 1500 | <1500 to 1000 |
| 2 | <1500 to 1000 | <1000 to 500 |
| 3 | <1000 to 500 | <500 to 100 |
| 4 | <500 | <100 |
Source: values as tabulated in Merz (2025). NCI’s v6.0 quick-reference file is the authority for every other term.
Worked example: regrading the same counts
The ten nadir ANC values below are hypothetical numbers chosen to show the arithmetic; they are not trial data. Each value is graded by applying each ladder.
| Patient | Nadir ANC (/µL) | v5.0 grade | v6.0 grade |
|---|---|---|---|
| 1 | 1450 | 2 | 1 |
| 2 | 1200 | 2 | 1 |
| 3 | 950 | 3 | 2 |
| 4 | 800 | 3 | 2 |
| 5 | 640 | 3 | 2 |
| 6 | 480 | 4 | 3 |
| 7 | 350 | 4 | 3 |
| 8 | 220 | 4 | 3 |
| 9 | 120 | 4 | 3 |
| 10 | 60 | 4 | 4 |
Grade 3 or higher under v5.0: patients 3 to 10, which is 8 of 10 = 80%. Grade 4 under v5.0: patients 6 to 10, 5 of 10 = 50%. Under v6.0, Grade 3 or higher is patients 6 to 10, 5 of 10 = 50%, and Grade 4 is patient 10 alone, 1 of 10 = 10%. Nothing about the patients changed; only the ladder did. A rate of Grade 3 or higher neutropenia from a v5.0 study and one from a v6.0 study therefore do not mean the same thing.
Interpretation: reading the shift
| If you see | It means |
|---|---|
| The same ANC graded lower under v6.0 | The change is in the scale, not in the patient. Compare grades only within one version. |
| Grade 1 neutropenia in a v6.0 dataset | The count is below 1500/µL but not below 1000/µL; the old “LLN to 1500” band has no equivalent. |
| Grade 4 in a v6.0 dataset | ANC below 100/µL, a stricter threshold than the v5.0 value of below 500/µL. |
| A protocol rule keyed to “Grade 3 or higher” neutropenia | Under v6.0 it is met only at a lower count (below 500/µL instead of below 1000/µL), so confirm which version the rule was written against. |
Which studies must use v6.0
NCI’s CTCAE v6.0 Implementation FAQs (dated 9 September 2025) set the rules by study type.
| Study type | What the FAQ says |
|---|---|
| Any study other than NCI CTEP or DCP NCORP studies | v6.0 is ready for immediate use; ask your sponsor. |
| NCI CTEP/DCP studies already running on v5.0 | Continue to report in v5.0 for the life of the study; data conversion is not required. CDUS, DMU and CTEP-AERS reporting stays on v5.0. |
| New NCI CTEP/DCP studies | v6.0 is required for all new studies whose Rave study build begins after the CTCAE v6.0 Rave ALS (ALS 7.2) is released, regardless of IND status. The FAQ described the ALS 7.2 release as tentatively scheduled for July 2026 and subject to further delay. |
Assumptions and common mistakes
- Hand-converting grades. Do not re-derive grades from memory. NCI created a mapping resource that aligns every v5.0 term and grade combination to v6.0; use it when consolidating versions.
- Mixing versions in one table. Pooling v5.0 and v6.0 grades without mapping produces rates that mean different things.
- Applying the CTEP/DCP rule to other sponsors. The rule above is NCI’s for its own studies; for any other study, follow the protocol.
- Misreading boundary values. An ANC of exactly 1000 is v5.0 Grade 2 and v6.0 Grade 1; exactly 500 is Grade 3 and Grade 2; exactly 100 is Grade 4 and Grade 3.
Operational suggestions, which are practice advice and not NCI requirements: state the CTCAE version in the protocol and the statistical analysis plan, make sure the CRF and database version match, and flag any dose-modification or stopping rules that use grade cut-points. For how graded events feed safety reporting, see pharmacovigilance in clinical research, MedDRA coding for trial safety data, adverse event reporting to the IRB and CDISC standards for submissions.
How to report it (APA example)
In the methods: “Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 6.0.” In the reference list, for the NCI implementation FAQ:
National Cancer Institute, Division of Cancer Treatment and Diagnosis. (2025, September 9). CTCAE v6.0 implementation FAQs. https://dctd.cancer.gov/research/ctep-trials/for-sites/adverse-events/ctcae-v6-faq.pdf
How to calculate it in Excel, R or Python
Each snippet assigns a v6.0 neutrophil grade from ANC in cells per microlitre (0 means below Grade 1). For v5.0, use the thresholds 500, 1000 and 1500, and assign Grade 1 only to values below the lower limit of normal.
Excel (ANC in A2):
=IF(A2<100,4,IF(A2<500,3,IF(A2<1000,2,IF(A2<1500,1,0))))R:
grade_v6 <- function(anc) ifelse(anc < 100, 4, ifelse(anc < 500, 3, ifelse(anc < 1000, 2, ifelse(anc < 1500, 1, 0))))
grade_v6(c(1450, 800, 60)) # 1 2 4Python:
def grade_v6(anc):
return 4 if anc < 100 else 3 if anc < 500 else 2 if anc < 1000 else 1 if anc < 1500 else 0
[grade_v6(x) for x in (1450, 800, 60)] # [1, 2, 4]FAQ
Is CTCAE v6.0 final?
Yes. The NCI FAQ states that no further changes are planned and that the release version is the final version of CTCAE v6.0. Comments go to the NCI CTCAE help address ([email protected]) and are discussed at the v7.0 update.
Is there a CTCAE version 7?
Not yet. NCI expects CTCAE v7.0 to be developed and released between 2027 and 2030.
Can I use v6.0 on my non-CTEP trial?
According to the NCI FAQ, v6.0 is ready for immediate use for any study except NCI CTEP or DCP NCORP studies; confirm with your sponsor.
Do I have to convert v5.0 data to v6.0?
NCI CTEP/DCP studies on v5.0 do not have to convert. For other consolidation needs, NCI’s mapping resource aligns every v5.0 term and grade combination to v6.0.
Sources
- National Cancer Institute, DCTD. “CTCAE updated version 6.” https://dctd.cancer.gov/about/news-events/news/2026-news/ctcae-updated-version-6 (checked 29 October 2026).
- National Cancer Institute. “CTCAE v6.0 Implementation FAQs,” 9 September 2025. https://dctd.cancer.gov/research/ctep-trials/for-sites/adverse-events/ctcae-v6-faq.pdf (checked 29 October 2026).
- Merz LE. “A paradigm shift in neutrophil adverse event grading: Why now?” HemaSphere 2025;9(10):e70242. https://pmc.ncbi.nlm.nih.gov/articles/PMC12558435/ (checked 29 October 2026).
