Phase 1
F-SHARP
ForIntraprostatic radiorecurrence after definitive RT for localized prostate cancer
TL;DRNo acute G3+ toxicity and 3-yr bPFS 62.7% after dose-escalated focal salvage HDR (up to 30 Gy/1-2 fx) for intraprostatic radiorecurrence, N=62.
The single-fraction arm (24 pts) matched two fractions on every endpoint (all P > .05), making a one-visit focal salvage HDR schedule a real option. The GC tail is the second read: all 4 pts with score >0.85 recurred locally and distantly, so focal-only salvage looks like the wrong tool for them.
In intraprostatic radiorecurrence after definitive RT, this supports focal salvage HDR (up to 30 Gy in 1-2 fractions) as a low-toxicity local option; it does not settle management for the GC score >0.85 pt, where focal salvage alone failed in all 4. The longer read
Single-fraction focal salvage HDR (24 pts) performed no differently from two fractions (all P > .05), with no acute G3 toxicity at up to 30 Gy. The GC tail flags who focal salvage fails: all 4 pts with score >0.85 recurred locally and distantly, arguing against focal-only treatment in that group.
12 details
Multi-institutional phase I/II, single-arm, N = 62. Median follow-up 39.4 mo.
Intraprostatic radiorecurrence (IPR) after any form of RT for localized prostate cancer. GC results available in 31 pts.
Dose-escalated focal salvage HDR, up to 30 Gy in 1-2 fractions. 24 pts received one fraction and 38 received two.
Primary: acute RT-related G3+ GU and GI toxicity (CTCAE v4.03). Secondary: all-grade toxicity, QoL (EPIC-26, IPSS), bPFS, rPFS, LRFS, MFS and survival.
No acute G3 toxicity. Late G3 toxicity in 2 pts (3.2%); QoL changes did not meet MCID criteria.
Prospective salvage brachytherapy data after EBRT are sparse, with RTOG 0526 testing whole-gland salvage LDR in this setting. F-SHARP adds a focal, dose-escalated HDR approach and a genomic risk layer that prior salvage series lacked.
The GC analysis is restricted to 31 of 62 pts and the >0.85 cutpoint rests on n = 4, so it is a descriptive tail, not a validated threshold. The 1 vs 2 fraction comparison was not randomized and is underpowered for equivalence.
Toxicity is the settled part: focal dose escalation to 30 Gy in the re-irradiated gland produced no acute G3 events. Durability is the open part, since bPFS at 3 yr is 62.7% and the efficacy endpoints carry no comparator.
| Endpoint | 3-yr rate |
|---|---|
| bPFS | 62.7% |
| rPFS | 67.5% |
| LRFS | 73.0% |
| MFS | 85.9% |
Single-arm phase I/II, N=62, toxicity primary objective; efficacy endpoints secondary and uncontrolled. GC signal from half the cohort.
- Focal vs whole-gland salvage brachytherapy for intraprostatic radiorecurrence
- Does GC-guided intensification improve outcomes in high-score pts?
- Is single-fraction focal salvage HDR equivalent to two fractions?
📚 Sources · 📄 1 paper
Abstract
MIRACLE-2
For1L MSS rectal cancer ≤10 cm from AV, synchronous unresectable mets
TL;DRORR 68.0%, mOS 23.2 mo, 18% NED with HFRT/SBRT then chemo-biologic + tislelizumab in 1L MSS rectal cancer with synchronous unresectable mets.
HFRT went to the primary and HFRT or SBRT to metastases before PD-1, but no dose, fractionation or target volume is reported, so the RT component cannot be reproduced. G3/4 lymphopenia 36.7% (all-grade 95.9%) is worth weighing when multisite RT precedes PD-1 blockade. Upfront RT to all sites in MSS disease stays investigational.
Every pt got HFRT to the primary and HFRT or SBRT to metastases before PD-1, but no dose, fractionation or target volume is reported, so the RT schedule cannot be reproduced. G3/4 lymphopenia 36.7% is worth weighing when multisite RT precedes PD-1 blockade.
The backbone was RAS/BRAF-selected: FOLFOX-bevacizumab for mutant, FOLFIRI-cetuximab for wild-type, each with tislelizumab. Short durability (mPFS 9.3 mo, 1-yr DOR rate 20%) tempers the claim that adding RT and PD-1 overcomes MSS immune resistance, and first-line regimen choice is unchanged.
| Best overall response | n (%) | 95% CI |
|---|---|---|
| CR | 1 (2.0%) | n/a |
| PR | 33 (66.0%) | n/a |
| SD | 10 (20.0%) | n/a |
| PD | 6 (12.0%) | n/a |
| ORR | 34 (68.0%) | 53.6%-80.0% |
| DCR | 44 (88.0%) | 76.0%-95.2% |
| ETS rate | 38 (76.0%) | 62.4%-86.8% |
10 details 1 trial watching
Prospective, single-arm, phase I. Efficacy data for N=50 as of December 31, 2025; median follow-up 19.9 mo (95% CI 16.4-23.4). Reassessment every 8 weeks.
MSS rectal cancer, primary ≤10 cm from anal verge on MRI, with synchronous unresectable metastases, first-line. 76.0% male, median age 57 (range 30-73); liver mets 52.0%, lung 8.0%, both 40.0%; RAS/BRAF mutant 56.0%.
HFRT to the primary and HFRT or SBRT to metastases, delivered before systemic therapy. Dose, fractionation and target volumes not reported in source.
RAS/BRAF-mutant: FOLFOX-bevacizumab-tislelizumab; wild-type: FOLFIRI-cetuximab-tislelizumab, tislelizumab 200mg Q2W per flowchart. Median 8 courses (range 3-12). Resectable disease went to primary resection plus metastasectomy/local ablation; watch-and-wait considered for primary cCR when the sphincter could not be preserved.
Primary: ETS rate (≥20% target lesion reduction at 8 wks after systemic start). Secondary: DCR, DOR, OS, PFS, safety.
18% (9/50) reached NED; how many got there via resection, ablation or watch-and-wait is not reported.
| Endpoint | Median (95% CI) | 1-yr rate |
|---|---|---|
| PFS | 9.3 mo (7.1-11.5) | 33.4% |
| OS | 23.2 mo (15.1-31.3) | 93.3% |
| DOR (34 CR/PR) | 8.0 mo (5.2-10.8) | 20% |
No grade 5 TRAEs. G3/4: lymphopenia 36.7%, neutropenia 26.5%, leukopenia 20.4%. All-grade lymphopenia 95.9%, anemia 91.8%.
PD-1 benefit in mCRC rests on MSI-H/dMMR disease (KEYNOTE-177), not MSS. This single arm cannot show RT converts MSS IO resistance, because the doublet plus bevacizumab or cetuximab backbone is itself active first-line.
Median OS 23.2 mo carries a wide CI (15.1-31.3) at 19.9 mo median follow-up. Primary endpoint ETS is an 8-week shrinkage measure, not a durable outcome.
High early shrinkage (ETS 76.0%, ORR 68.0%) sits against short durability (1-yr PFS 33.4%, 1-yr DOR rate 20%), so durable immune conversion is not yet shown. The testable claim, that RT to all disease sites sensitizes MSS tumors to PD-1 blockade, needs a randomised design and biomarker selection, which the authors flag as a priority.
Single-arm phase I, N=50, surrogate primary (ETS); no RT-free or IO-free control, so neither RT nor tislelizumab contribution is isolated.
- RT contribution vs systemic therapy + PD-1 alone in MSS rectal cancer
- Predictive biomarkers for RT + PD-1 response in MSS disease n=497 · primary completion 2028-10 · ctDNA methylation response tracking, RT ± PD-1 in mCRC
- Optimal RT dose/fractionation to prime PD-1 response
📚 Sources · 🐦 1 tweet
MIRACLE-2: RT to primary/mets -> chemo + tislelizumab in MSS unresectable met rectal ca (N=50): 68% ORR & median OS 23 mo.
— Dr. Nina Niu Sanford (@NiuSanford) May 31, 2026
Early, single-arm data, but ~1 in 5 pts reached NED.
Suggests RT + systemic + PD1 blockade could overcome immune resistance in MSS mCRC. #ASCO26 @OncoAlert pic.twitter.com/sjnUW8x7f3