Reaction on the Interpretation of the Hippocampus Avoidance Prophylactic Cranial Irradiation Trial in SCLC (NCT01780675)

We thank Mladkova et al.1Mladkova N. Lo S. Brown P.D. al.Hippocampal avoidance prophylactic cranial irradiation: interpreting the evidence.J Thorac Oncol. 2021; 16: e60-e63Scopus (1) Google Scholar for their important comments on our phase 3 randomized trial of irradiation (PCI) with or without hippocampus (HA) in SCLC (NCT01780675).2Belderbos J.S. De Ruysscher D.K. Jaeger K. al.Phase III (NCT01780675).J 840-849Abstract Full Text PDF PubMed Scopus (32) This trial, using aim to reduce incidence neurocognitive side effects PCI, could not detect a benefit. Remarks interpretation evidence and suggestions raised by authors are addressed subsequent texts.1.The power calculation In NCT01780675, we aimed 30% difference cognitive decline single prespecified hippocampal dependent test (power range: 82%–95%). may have been too ambitious this test, cannot rule out possible smaller differences. Our was powered 10% failure recently identified CC001 al.3Brown Gondi V. Pugh during whole-brain radiotherapy plus memantine patients brain metastases: NRG oncology CC001.J Clin 2020; 38: 1019-1029Crossref (229) metastases variety solid tumors receiving radiation therapy HA. used different end point, which defined as any six outcomes. Using point analytical approach data, observed an exploratory analysis significant (p = 0.0088) between study arms, only favoring standard treatment Considering small HA cost-effectiveness HA-PCI should be investigated.2.The correct absolute number failures. There 13 failures (28%) PCI arm 16 (29%) arm. Those percentages unfortunately swapped manuscript. The 95% confidence interval can explained fact that applied Yates’ continuity correction. missing values primary were expected at design stage. They imputed assumed related Comparison baseline characteristics assessable subset 102 did reveal differences arms. Reasons being points displayed consort diagram also do worrying patterns. reported deaths text (53 died arm) relates total number, beyond 24 months. addition, risk Figure 3A (32 alive takes into account censoring. (Fig. 1) reveals indeed 80 who received HA-PCI, 56 underwent testing 4 For breakdown, 10 died, four declined, had disease progression, other reasons. amount state (23 14 12 seven reasons) is breakdown all included trial. more details excluded from would help evaluate potential biases. think helpful. initial design, anticipated percentage available 4-month (estimated 40%). determined stage IV because death progressive disease. assumption made rather accurate; 101 168 equaling 60%.3.Use cause-specific Cox model agree competing debatable. purpose mimic Nevertheless, produce very pessimistic many reported. wondered whether rates per group change if standardized than raw scores used. recall Hopkins Verbal Learning Test—Revised months; least five considered failure. definition based reliable index criteria calculated scores. same holds true changes greater well. original approach, linear mixed models longitudinal profiles tests now checked score conclusion. case.4.The trials require central pretreatment post-treatment reviews define acceptable unacceptable deviations volumes planning. critical point. Contrary trials, include review delineation. organized dummy run train physicians trial.4Bartel F. van Herk M. Vrenken H. al.Inter-observer variation delineation irradiation... 2019; 21: 178-186Google results revealed observer acceptable, some observers delineating big. RTOG-atlas outlining protocol describes exclude fimbria, cases interobserver among participants.4Bartel Another part amygdala Therefore, these variations (localized posterior medial anterior border hippocampus) mainly enlarging area spare. affected metastases, but beneficial effect functioning Moreover, performed extensive quality assurance dose constraints HA-PCI5Candiff O, Belderbos J, Schagen S, al. Treatment planning OA profylactic multicenter (NCT01780675). Poster 49.01 presented 20th World Conference Lung Cancer, January 28–31, Singapore.Google Scholar; plans complied vast majority cases. 93% patients, constraint mean hippocampi achieved (≤8.5 Gy). plans, volume PTV 115% prescribed exceed 1%. remarks conclusion ongoing evaluating awaited. Jose Belderbos: Conceptualization, Investigation, Writing—original draft, Writing—reviewing editing. Dirk Ruysscher, Sanne B. Schagen: Katrien Jaeger, Friederike Koppe, Maarten Lambrecht, Yolande Lievens, Edith Dieleman, Jaap Jaspers, Jan Van Meerbeeck, Fred Ubbels, Magriet Kwint, Sabine Deprez, Michiel Ruiter: Reviewing. Marianne Kuenen: Project administration, Willem Boogerd: Karolina Sikorska: Data curation; Formal Harm Tinteren: analysis. Hippocampal Avoidance Prophylactic Cranial Irradiation: Interpreting EvidenceJournal Thoracic OncologyVol. 16Issue 8PreviewThe authors, al.,1 recent article entitled “Phase (NCT01780675),” congratulated completing study, focused yet under-researched (PCI). However, felt it issues concerns regarding Full-Text