onc brain

Single-institution cohort from MD Anderson's INTERCEPT program, 2020-2024, N=110, with serial tumor-informed ctDNA during nonoperative management. Median follow-up 25 months (IQR 18-37).

Microsatellite stable stage I-III rectal adenocarcinoma achieving cCR or near-cCR after neoadjuvant therapy and managed nonoperatively. Median age 56; baseline cT3 in 72 and cT4 in 16; 69 received TNT, 41 CRT or chemotherapy alone.

Local regrowth and distant metastasis by longitudinal ctDNA status, by first post-NAT ctDNA (within 180 days), and per-sample accuracy for an event within ±90 days of each draw. Salvage-surgery pathology by ctDNA status at regrowth.

Twenty-three pts (21%) had local regrowth and 12 (11%) distant metastasis. Ever-positive ctDNA separated both curves (log rank p=0.0002 for regrowth, p<.0001 for metastasis). The per-sample table carries the operating characteristics.

Per-sample analysis pools 669 draws from 110 pts without accounting for repeated measures, so the confidence around 41% is softer than the denominator suggests. The first-post-NAT comparison rests on n=12 evaluable pts as reported in the source. No comparison against MRI or endoscopy, the tests ctDNA would have to beat.

The asymmetry between local (41%) and distant (74%) sensitivity is the informative result: intraluminal regrowth from a small residual burden sheds too little DNA to be caught reliably, while metastatic disease does. That biology argues for ctDNA as a distant-recurrence tool layered onto, not substituted for, luminal surveillance.

Retrospective single-center cohort; per-sample analysis treats 669 draws from 110 pts as independent. No head-to-head against MRI/endoscopy surveillance.

Post hoc intracranial analysis of the randomised DeLLphi-304 trial of second-line tarlatamab versus chemotherapy in SCLC. Two assessment frameworks: investigator RECIST in the ITT population and mRANO-BM by BICR in pts with baseline brain metastases. Data cutoff January 29, 2025; median follow-up 11.4 mo (tarlatamab) and 11.5 mo (chemotherapy).

ITT n=254 tarlatamab versus n=255 chemotherapy. The brain-metastasis cohort was n=67 versus n=56, defined as ≥1 brain metastasis at baseline per mRANO-BM by BICR plus ≥1 post-baseline scan. More than 70% had already received CNS-directed treatment, which is why the response categories were CR, non-CR/non-PD and PD rather than a conventional ORR.

This analysis reports time to CNS progression or death (CNS PFS) in the ITT population and in the brain-metastasis subset, plus best overall CNS response, CNS disease control rate, duration of CNS complete response and duration of CNS disease control. None of these was the trial's registered primary endpoint.

Both CNS PFS comparisons favor tarlatamab, and the effect is larger in the brain-metastasis subset (HR 0.40) than in the ITT population (HR 0.54). Intracranial complete response was 14.9% versus 5.4%, and CNS tumor shrinkage ≥30% occurred in 9/16 versus 5/13 pts with measurable lesions ≥10mm.

Brain metastases develop in the majority of SCLC pts, and second-line systemic options have historically been judged on extracranial disease with CNS control assumed to be the province of SRS, WBRT or prophylactic cranial irradiation. A bispecific T-cell engager showing an intracranial complete response rate of 14.9% is the notable part, because the working assumption for large-molecule agents has been limited intracranial penetration.

The ITT median CNS PFS was not estimable at 11.4 months of follow-up, so the ITT curve rests on the early portion of the data and the point estimate can still move. The two populations were also read with different tools and different models (stratified Cox for ITT, unstratified for the subset), so the ITT and subset HRs are not strictly comparable to each other.

The result establishes that intracranial disease does not progress faster under tarlatamab than under chemotherapy, and probably progresses more slowly. What it does not establish is whether that activity is sufficient to defer local therapy in a patient who would otherwise be referred for SRS, since the source reports no radiotherapy exposure data and no in-field versus out-of-field failure pattern.

Post hoc intracranial analysis of a randomised trial; CNS endpoints were not the registered primary, and the brain-met subset HR comes from an unstratified model.