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ASCO Annual Meeting 2026

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Confirmatory

MROQC ADT Practice Patterns

ForHigh-risk M0/N0-1 prostate on definitive RT, GG4-5 predominant

TL;DRGuideline-concordant ADT (≥18mo) recommended in 67.0% of high-risk pts on definitive RT; ARPI intensification just 23.2% of STAMPEDE-eligible.

Why it mattersRadiation oncology

The RT prescriber's read is the adoption gap, not a treatment effect: even in a quality consortium, only 67.0% of high-risk pts on definitive RT are recommended ≥18mo ADT, and just 23.2% of STAMPEDE-eligible get ARPI intensification. Facility-level variability persists on multivariable analysis (P<.0001), so where a man is treated, not only his risk, sets his ADT. Prompts an audit of your own duration and intensification practice.

8 details

Prospective practice-pattern study within the Michigan Radiation Oncology Quality Consortium (MROQC), a statewide RT registry. 553 pts across 26 centers, Jun 2020–Nov 2024. Facility modeled as a random intercept (mixed-effects).

Intact, high-risk M0/N0-1 prostate cancer on definitive RT. GG4-5 75.0%, PSA ≥20 40.0%, cN1 19.9%, cT3/4 13.3%. 27.9% met STAMPEDE M0 intensification criteria.

Primary: intended guideline-concordant ADT (≥18mo). Also assessed: ARPI adoption before vs after STAMPEDE M0 publication, facility-level variability, and multivariable predictors of concordance.

91.3% recommended any ADT, 67.0% guideline-concordant. ARPI intensification among STAMPEDE-eligible rose 0%23.2% post-publication. Facility variability persisted on MVA (P<.0001).

FactorOR (GC-ADT)95% CI
cN12.941.44-5.99
GG46.232.85-13.62
GG59.454.46-20.06
PSA ≥403.641.22-10.87

Benchmarks real practice against the 2022 AUA/ASTRO guideline (18-36mo ADT) and STAMPEDE M0 (ARPI for high-burden high-risk). Documents a persistent adoption gap, not a treatment effect.

high-risk M0/N0-1 prostate treated with definitive RT within a quality consortium
Does not represent low/intermediate-risk disease, national non-consortium practice, or delivered (vs intended) treatment.

Captures intended ADT duration and recommendations, not delivered therapy or adherence. Single-state consortium limits generalizability, and there is no efficacy or outcome endpoint.

Descriptive practice-pattern audit (no efficacy endpoint); reinforces AUA/ASTRO ADT guideline and STAMPEDE M0 as benchmark, documenting under-adoption rather than testing a new effect.

In high-risk men (GG4-5, cN1, PSA ≥40, or ≥2 STAMPEDE factors) starting definitive RT, this supports benchmarking ADT to ≥18mo and weighing ARPI intensification when STAMPEDE-eligible; it does not extend to low/intermediate-risk disease or ADT-omission decisions.

  • Does intended guideline-concordant ADT translate to delivered treatment and adherence?
  • What interventions reduce facility-level variability in ADT recommendations?
  • Do Michigan consortium patterns generalize to national practice?
📚 Sources · 📄 1 paper
📄 PAPER Dykstra, Michael P.; Regan, Samuel N.; Yin, Huiying (Maggie) et al. · JCO Oncology Practice (2025-09)
Androgen Deprivation Therapy Practice Patterns in High-Risk Prostate Cancer Treated With Definitive Radiotherapy: Prospective Results From a Statewide Quality Consortium
Abstract
PURPOSE The 2022 AUA/ASTRO guidelines recommend 18-36 months of androgen deprivation therapy (ADT) with definitive radiotherapy for localized, high-risk prostate cancer. The STAMPEDE M0 trial supports intensification with androgen receptor pathway inhibitors (ARPIs) for patients with ≥2 cT3/T4, Grade Group [GG] 4-5, prostate-specific antigen (PSA) ≥40 ng/mL, or cN1. Given advances in imaging, risk stratification, and treatment delivery, we characterized contemporary practice patterns using prospective data from the Michigan Radiation Oncology Quality Consortium (MROQC). METHODS Patients enrolled in MROQC with intact, high-risk M0/N0-1 prostate cancer were included. Clinical information, including intended ADT duration and ARPI use, was prospectively collected. The primary outcome was intended guideline-concordant ADT (GC-ADT, ≥18 months). Multivariable analyses (MVA) assessed associations between clinical factors and GC-ADT recommendations. We compared the adoption of ARPI with standard therapies before and after the publication of STAMPEDE M0. Facility-level variability was evaluated using a mixed-effects model, with the treatment site as a random intercept. RESULTS Between June 2020 and November 2024, 553 patients across 26 centers were included: cT3/4 (13.3%), cN1 (19.9%), GG 4-5 (75.0%), and PSA ≥20 ng/mL (40.0%). Overall, 91.3% were recommended ADT, with 67.0% being guideline-concordant. On MVA, GC-ADT was significantly associated with cN1 (odds ratio [OR], 2.94 [95% CI, 1.44 to 5.99]), GG (GG4 OR, 6.23 [95% CI, 2.85 to 13.62]; GG5 OR, 9.45 [95% CI, 4.46 to 20.06]), and PSA ≥40 (OR, 3.64 [95% CI, 1.22–10.87]). Facility-level variability persisted in the MVA ( P &lt; .0001). Among the 27.9% who met meeting STAMPEDE criteria, ARPI recommendations increased from 0% prepublication to 23.2% afterward. CONCLUSION Within a statewide quality consortium, guideline-concordant ADT recommendations occurred in two thirds of patients, with ARPI intensification in under 25% among STAMPEDE-eligible patients. These findings highlight the need for individualized ADT strategies and collaborative efforts to standardize high-quality care.
Confirmatory

AREST

ForAdequately resected pT1-2N0 oral SCC with ≥1 intermediate-risk feature

Loco-regional recurrence-free survival local control

HR 0.52

3-yr LRFS 89.2% vs 80.9%, 95% CI 0.30-0.91, p=0.02 (ITT)

TL;DR3-yr LRFS 89.2% vs 80.9%, HR 0.52 (0.30-0.91) p=0.02 favoring adjuvant RT in resected intermediate-risk pT1-2N0 oral SCC; no OS/DFS gain.

Why it mattersRadiation oncology

The move is observe-vs-treat in adequately resected pT1-2N0 OSCC with one adverse feature: 60Gy/30fx to tumor bed plus at-risk neck cut 3-yr loco-regional failure (HR 0.52), strongest in oral tongue over buccal mucosa (exploratory). The gain is loco-regional only, so weigh it against RT morbidity when baseline LRR risk is low.

AREST
Arm3-yr LRFSHR (95% CI)p
Adjuvant RT89.2% (84.3-93.3)0.52 (0.30-0.91)0.02
Observation80.9% (74.6-86.1)ref
8 details 2 trials watching

Phase 3, open-label, multicenter RCT (India); 1:1 to adjuvant RT vs observation, N=392 (191 RT, 201 observation), stratified by subsite, PNI/LVE, differentiation. Median follow-up 47.2 months.

pT1-2 pN0 OSCC with ≥1 intermediate-risk feature (DOI 5-10mm, PNI, LVE, or poor differentiation), after adequate surgery: margins ≥5mm and ipsilateral level I-III neck dissection with ≥16 nodes.

60Gy in 30 fractions over 6 weeks to the resected tumor bed and at-risk neck nodal region.

Primary: 3-yr loco-regional recurrence-free survival (LRFS), KM with log-rank. Secondary: DFS, OS, and cumulative incidence of loco-regional failure (competing-risk).

Per-protocol LRFS 91.1% vs 80.9%, HR 0.43 (0.23-0.80), p=0.01. DFS and OS not significantly different between arms.

AnalysisAdjuvant RTObservationHR (95% CI), p
ITT10.6% (6.1-15.1)18.9% (13.3-24.6)0.52 (0.30-0.91), p=0.021
Per-protocol8.7% (4.3-13.1)18.9% (13.3-24.6)0.43 (0.23-0.79), p=0.007

Prior evidence for adjuvant RT in this pN0 intermediate-risk setting was retrospective (per the abstract); AREST is the first randomized confirmation.

adequately resected pT1-2 pN0 oral SCC (margins ≥5mm, ≥16-node neck dissection) with one intermediate-risk feature
Does not represent node-positive disease, positive/close margins, or inadequately staged necks.

Open-label, abstract-only; benefit is loco-regional control only, no OS/DFS at 47.2-mo median. Observation LRFS (80.9%) exceeded the 70% powering assumption, so the absolute LRFS gain is modest.

First randomized backing for the guideline-listed retrospective signal that RT cuts LRR in adverse-feature pN0 OSCC; loco-regional benefit only, no OS/DFS, open-label abstract.

In an adequately resected pT1-2N0 oral tongue SCC with a single intermediate-risk feature, this supports adjuvant RT for loco-regional control but not survival, and it does not extend to buccal mucosa (weaker signal) or node-positive disease.

📚 Sources · 🐦 1 tweet · 📄 1 paper
📄 PAPER Nair, Sudhir Vasudevan; Gupta, Tejpal; Rane, Swapnil Ulhas et al. · Journal of Clinical Oncology (2026-06)
Adjuvant radiotherapy versus observation following curative surgery for early-stage oral squamous cell carcinoma (AREST; CTRI/2017/07/009114).
Abstract
6000 Background: The role of adjuvant radiotherapy (RT) in early-stage, node-negative oral squamous cell carcinoma (OSCC) with one or more intermediate risk factors - such as depth of invasion (DOI) ≥5 to ≤10mm, perineural invasion (PNI), lymphovascular emboli (LVE), or poor differentiation - remains debatable and is largely based on retrospective data. This multicenter, open-label, phase III randomized controlled trial was designed to assess the impact of post-operative adjuvant RT in this setting. Methods: Patients with early-stage (pT1-T2), node-negative (pN0) OSCC undergoing adequate surgery (defined as clear margins ≥5mm and at least ipsilateral level I-III neck dissection with ≥16 nodes) with presence of one or more intermediate risk factors were screened. Eligible patients underwent stratified randomization (oral cavity subsite, PNI/LVE, and differentiation) in 1:1 ratio to either observation or adjuvant RT (60Gy in 30 fractions over 6-weeks) to the resected tumor-bed and at-risk neck nodal region after written informed consent. Primary endpoint was loco-regional recurrence-free survival (LRFS) measured from randomization to first documented event of local and/or regional recurrence from index cancer. All time-to-event outcomes were computed using Kaplan-Meier (KM) method with log-rank test for comparison and expressed as 3-year point estimates with 95% confidence intervals (CI). The planned sample size (N=392) provided 80% power at an α of 0.05 to detect a Hazard Ratio (HR) of 0.6256, assuming 3-year LRFS of 70% in the observation arm. Results: Following curative surgery, a total of 392 patients were randomized (191 to adjuvant RT; 201 to observation). Baseline characteristics were balanced between the two arms. At a median follow-up of 47.2 months (inter-quartile range=30-59.4 months), 3-year KM estimate of LRFS was 89.2% in adjuvant RT arm vs 80.9% in observation arm (HR=0.52, 95%CI=0.30-0.91; p=0.02) in the intention-to-treat (ITT) population and 91.1% vs 80.9% (HR=0.43, 95%CI=0.23-0.80; p=0.01) on per-protocol (PP) analyses. Cumulative incidence of loco-regional failure with death as competing event was 10.6% (95%CI=6.1%-15.1%) with adjuvant RT and 18.9% (95%CI=13.3%-24.6%) with observation (HR=0.52, 95%CI=0.30-0.91; p=0.021) in the ITT population and 8.7% (95%CI=4.3%-13.1%) vs 18.9% (95%CI=13.3%-24.6%) (HR=0.43, 95%CI=0.23-0.79; p=0.007) on PP analyses. Disease-free and overall survival were not significantly different between the two arms. Subgroup analysis identified oral tongue deriving higher benefit of adjuvant RT compared to buccal mucosa. Conclusions: Adjuvant RT significantly reduces risk of loco-regional recurrence for early-stage, node-negative adequately resected OSCC, particularly oral tongue. However, such reduction in loco-regional failure does not translate into significant survival benefit. Clinical trial information: CTRI/2017/07/009114.
📝 https://ascopubs.org/doi/10.1200/JCO.2026.44.16_suppl.6000

Concurrent Systemic Therapy + Radiation Timing (Speers)

TL;DRTraffic-light framework for what runs concurrent with breast/CW + RNI RT vs hold: continue endocrine + trastuzumab/pertuzumab, caution T-DXd/CDK4/6i, hold cytotoxics/PARPi.

Trials discussed

HERANCCTG N9831APHINITYKATHERINEATEMPTDESTINY-Breast05COMBARTKEYNOTE-522

Why it mattersRadiation oncology

The actionable RT read: in the DESTINY-Breast05 arm, T-DXd ILD was 10.7% sequential vs 9.6% concurrent, so timing around RT did not change ILD, and concurrency is reasonable with lung-dose limits. The 'do not ignore' signal is T-DM1 plus CNS SRS radionecrosis; hold CDK4/6i for large fields.

Concurrent Systemic Therapy + Radiation Timing (Speers)
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Concurrent Systemic Therapy + Radiation Timing (Speers)
7 details 3 trials watching

ASCO 2026 educational review / Educational Book chapter (Wong, Speers, Schaverien, Table 5). Sorts systemic agents into a continue / caution / hold framework for concurrency with breast/chest-wall + RNI RT. Evidence base is mostly retrospective, post-hoc, or small prospective series.

Context is adjuvant breast/CW + regional nodal irradiation. Plan features that raise the concurrency stakes: large lung volumes, IMN coverage, bolus, reconstruction, and CNS SRS (T-DM1 radionecrosis, T-DXd ILD).

Endocrine therapy and trastuzumab/pertuzumab are safe concurrent; T-DXd and CDK4/6i are plan-dependent; cytotoxics, veliparib, and capecitabine sequence. Default outside protocol is PK-based washout, then RT, then resume.

Agent classWith RTNotes / evidence
Endocrine therapyContinueminimal radiosensitization
Trastuzumab ± pertuzumabContinueconcurrent standard (HERA, NCCTG N9831, APHINITY)
T-DM1Continueper KATHERINE / ATEMPT; watch dermatitis, pneumonitis, CNS SRS necrosis
T-DXdCautionILD dominant; sequence/hold for high lung-dose or active pulmonary disease
PembrolizumabContinue, monitorKEYNOTE-522 concurrent tolerated; pneumonitis vigilance
CDK4/6i (palbo/ribo/abema)Hold large fieldsmostly retrospective; concurrent only in protocol
OlaparibSequencecomplete RT 2-12 wks before; RadioPARP suggests concurrent safety
Veliparib / talazoparibAvoid concurrentveliparib severe acute/late tox (TBCRC 024)
CapecitabineHold / sequenceadjuvant paradigm sequential (CREATE-X)
Cytotoxics (anthracycline/taxane/platinum)Holdsequence, do not give concurrently
MetricValue
ILD, T-DXd 5.4 mg/kg (PI)~12%; fatal ~0.9%
DESTINY-Breast05 ILD9.6% T-DXd vs 1.6% T-DM1
RT timing (T-DXd arm)10.7% seq vs 9.6% concurrent, no effect
COMBART concurrent RT/SRT40 pts; acute tox 20%

For a HER2+ patient on adjuvant trastuzumab/pertuzumab or T-DM1 needing chest-wall + nodal RT, this supports running HER2 therapy through RT with pneumonitis and CNS-SRS vigilance; it does not extend to concurrent cytotoxics, veliparib, or CDK4/6i in large fields.

📚 Sources · 🐦 1 tweet
Challenges SOC

mRCAT-III NCT06507371

ForpMMR/MSS LARC, cT3-4N0/+, tumor ≤10cm from verge, no lateral node

Pathologic complete response surrogate

61.0% vs 28.6%

P<0.0001, ITT, blinded central review

TL;DRpCR 61.0% vs 28.6% (P<0.0001) with node-sparing SCRT + tislelizumab + CAPOX vs conventional SCRT + CAPOX in pMMR LARC.

Why it mattersRadiation oncology

The RT read is a confound, not a green light for nodal omission: the experimental arm changed two things at once, tumor-bed-only targeting AND added tislelizumab, so node-sparing's own contribution to the pCR doubling (61.0% vs 28.6%) can't be isolated. Node-sparing plausibly drove the lower severe-GI toxicity, but this doesn't yet license dropping elective nodal RT.

mRCAT-III
EndpointExperimentalControlP
pCR (ITT)61.0% (47/77)28.6% (22/77)<0.0001
MPR (TRG0+1)77.9% (60/77)50.6% (39/77)<0.0001
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mRCAT-III
6 details 5 trials watching

Open-label, multicenter phase 3 RCT across 17 China hospitals; randomized 1:1, 77 pts per arm, stratified by clinical N stage (cN0 vs cN+). Primary pCR read by blinded independent central review.

pMMR/MSS rectal adenocarcinoma, cT3-4N0/+M0, tumor lower edge ≤10cm from the anal verge, ECOG 0-1, age 18-75, no positive lateral pelvic node.

Both arms CAPOX (oxaliplatin 130mg/m² d1, capecitabine 1000mg/m² d1-14). Experimental adds tislelizumab 200mg d1; control is chemo + RT only.

Both arms short-course 5Gy×5. Experimental is node-sparing (tumor bed only, spares tumor-draining nodes); control is conventional elective-nodal coverage. This target-volume contrast is the RT question.

Primary: pCR (ITT). Secondary: MPR, TRG, organ-preservation rate, EFS, OS, AEs.

Primary pCR and secondary MPR both favored the experimental arm (see figure); EFS, OS, organ-preservation not reported in source.

Experimental arm reported fewer severe GI AEs (author takeaway), plausibly from the smaller node-sparing volume; numeric AE rates not in source.

Control pCR 28.6% matches short-course RT + consolidation chemo benchmarks (RAPIDO ~28%). The novelty is a PD-1 benefit in an MSS population usually IO-refractory, with nodal-RT omission as the immunologic rationale.

pMMR/MSS cT3-4 LARC with tumor ≤10cm from the anal verge and no positive lateral node
Does not represent dMMR/MSI-H disease, upper-rectal or colon primaries, or patients needing lateral pelvic nodal treatment.

Open-label; pCR is a surrogate with EFS/OS immature; the experimental arm confounds node-sparing target volume with added tislelizumab, so the RT-attributable effect can't be isolated; N=154, single country.

Divergent MSS-rectal result from a randomized P3 with blinded-review primary; kept off practice-changing because pCR is a surrogate (EFS/OS immature) and node-sparing is confounded with added tislelizumab.

In pMMR/MSS LARC (cT3-4, tumor ≤10cm from verge), this is a trial-stage signal that neoadjuvant PD-1 may help an IO-resistant group; it does not extend to dMMR disease and does not yet displace conventional elective-nodal short-course RT off-protocol.

📚 Sources · 🐦 1 tweet
Challenges SOC

LBA8005: Concurrent Thoracic RT + Chemoimmunotherapy in ES-SCLC

ForTreatment-naïve ES-SCLC, stage IV or III ineligible for curative chemoRT

Overall survival

HR 1.14

10.0 vs 11.8 mo, 95% CI 0.84-1.56, p=0.40; OS not met

TL;DROS 10.0 vs 11.8 mo, HR 1.14 (0.84-1.56), p=0.40: concurrent thoracic RT added no benefit to durvalumab-based chemoIO in ES-SCLC.

Why it mattersRadiation oncology

The tested RT is concurrent (30 Gy/10 fx, day 21-28 with chemoIO), not CREST's consolidative post-chemo RT in responders, so the consolidative question stays open. Even the low-burden subgroup without brain or liver metastases was null (HR 1.10). Adding concurrent thoracic RT to chemoIO carries no OS benefit.

LBA8005: Concurrent Thoracic RT + Chemoimmunotherapy in ES-SCLC
ArmMedian OSHR (95% CI)p
ChemoIO + TRT10.0 mo1.14 (0.84-1.56)0.40
ChemoIO11.8 mon/an/a
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LBA8005: Concurrent Thoracic RT + Chemoimmunotherapy in ES-SCLC
SubgroupChemoIO+TRTChemoIOHR (95% CI)p
Completed 4 chemoIO courses11.9 mo12.1 mo1.02 (0.72-1.44)0.92
No brain/liver mets11.9 mo13.2 mo1.10 (0.65-1.87)0.72
LBA8005: Concurrent Thoracic RT + Chemoimmunotherapy in ES-SCLC
ArmMedian PFSHR (95% CI)p
ChemoIO + TRT5.1 mo1.10 (0.84-1.45)0.49
ChemoIO5.0 mon/an/a
7 details 5 trials watching

Randomized phase III, 1:1 (chemoIO+TRT n=115, chemoIO n=113). Stratified by liver and brain metastases. Primary: overall survival; secondary ORR, PFS, toxicity.

Treatment-naïve ES-SCLC, stage IV or stage III ineligible for curative chemoRT, ECOG 0-1, ≥1 measurable thoracic lesion. Asymptomatic or stable brain metastases allowed.

Four cycles durvalumab 1500 mg + carboplatin AUC 5 + etoposide (100 mg/m² IV days 1-3, or 200 mg/m² PO days 2-4) Q3W, then durvalumab 1500 mg Q4W maintenance.

Concurrent thoracic RT 30 Gy in 10 fractions, starting day 21-28. PCI 25-30 Gy offered to responders in both arms; WBRT 20-30 Gy for brain metastases per routine.

Primary OS not met and numerically favored chemoIO alone; PFS and both prespecified subgroups (course completers, no brain/liver metastases) were also null. Effect sizes in figures.

CREST (Slotman, Lancet 2015) used the same 30 Gy/10 fx but as consolidative RT after chemotherapy in responders, before immunotherapy, and suggested a survival benefit. Adding RT concurrently to chemoIO shows none.

treatment-naïve ES-SCLC receiving durvalumab-based chemoIO, considered for concurrent thoracic RT
Does not represent consolidative thoracic RT after chemotherapy in responders, or limited-stage SCLC.

Open-label (RT cannot be blinded). Tests only the concurrent schedule, not the consolidative timing prior data supported. No toxicity or RT-delivery data in source to explain the numerically inferior OS.

Randomised phase III, prespecified OS primary, null; contests the CREST-era expectation that thoracic RT benefits ES-SCLC, now tested concurrently with chemoIO.

In treatment-naïve ES-SCLC beginning durvalumab plus platinum/etoposide, this questions adding concurrent thoracic RT (no OS benefit); it does not extend to consolidative thoracic RT given after chemotherapy in responders.

📚 Sources · 🐦 1 tweet
Confirmatory

ctDNA and Local Regrowth/Distant Mets in Nonoperative Management of Stage II-III Rectal Cancer

ForMSS stage II-III rectal adenoca in cCR/nCR on watch-and-wait after TNT

TL;DRctDNA sensitivity 41% for local regrowth vs 74% for distant mets; positive result predicts both but can't replace endoscopy/MRI surveillance in rectal NOM.

Why it mattersRadiation oncology

The asymmetry is the actionable read: ctDNA caught only 41% of local regrowths vs 74% of distant mets, so for post-TNT organ-preservation surveillance it flags distant-met risk but can't replace endoscopy/MRI. ctDNA+ at regrowth also tracked more advanced ypT3-4 salvage pathology (75% vs 21%).

ctDNA and Local Regrowth/Distant Mets in Nonoperative Management of Stage II-III Rectal Cancer
7 details 1 trial watching

Prospective single-center cohort (MD Anderson INTERCEPT program), N=110, 2020-2024. Serial tumor-informed ctDNA (Signatera Exome), 669 samples; median follow-up 25 mo (IQR 18-37).

MSS stage II-III rectal adenocarcinoma in cCR (69) or nCR (41) after NAT, managed non-operatively. Median age 56; cT3 in 72 and cN1-2 in 60 of 110; NAT almost entirely TNT (104/110).

Regrowth-free and distant-metastasis-free survival by longitudinal and first-post-NAT ctDNA; per-sample diagnostic accuracy (±90d of each draw); salvage-surgery pathology by ctDNA status. No registered primary endpoint (observational).

Local regrowth in 23 (21%), distant mets in 12 (11%). Ever-positive ctDNA tracked worse regrowth-free and distant-met-free survival (log-rank p=0.0002 and p<0.0001). Per-sample sensitivity 41% local regrowth vs 74% distant mets.

EndpointSensitivitySpecificityAccuracy
Local regrowth41% (12/29)94% (480/509)91% (492/538)
Distant metastasis74% (31/42)97% (611/627)96% (642/669)

Consistent with the emerging ctDNA-as-prognostic signal in rectal NOM, but quantifies a sensitivity ceiling (41%) that limits its use for local-regrowth surveillance.

MSS stage II-III rectal adenocarcinoma in cCR/nCR pursuing organ preservation after TNT
Does not represent MSI-H tumors, operative-intent pts, or short-course-RT / chemoRT-only NOM pathways.

Single-center, N=110 with only 29 regrowth- and 42 distant-met-associated samples driving diagnostic estimates. Assay-specific (Signatera tumor-informed); no comparison vs imaging-alone surveillance.

Single-center prospective cohort (N=110), no interventional comparator; prognostic association consistent with emerging ctDNA-in-NOM data and reaffirms imaging/endoscopy surveillance can't be replaced.

Applies to the MSS stage II-III rectal pt in cCR/nCR pursuing watch-and-wait after TNT, in whom a negative ctDNA still can't exclude local regrowth; it does not extend to MSI-H tumors or pts not pursuing organ preservation.

  • Does ctDNA-guided surveillance improve organ-preservation outcomes vs imaging alone
    n=100 · primary completion 2025-12 · candidate match
  • Can serial ctDNA kinetics raise local regrowth sensitivity above 41%
  • Generalizability beyond single-center tumor-informed Signatera cohort
📚 Sources · 🐦 1 tweet
Caveats dominate

DeLLphi-304

ForRelapsed SCLC with brain mets, >70% prior CNS-directed therapy

TL;DRIntracranial: time-to-CNS-progression HR 0.54 ITT; in brain-mets pts CNS PFS 6.5 vs 4.2mo (HR 0.40), CNS CR 15% vs 5% for tarlatamab.

Why it mattersRadiation oncology

The RT read is intracranial control without new radiation: brain-mets CNS PFS 6.5 vs 4.2mo (HR 0.40) and CNS CR 15% vs 5%. But >70% had prior CNS-directed therapy, so this is salvage intracranial activity, not a defer-brain-RT signal in RT-naive disease. Informs sequencing systemic ahead of repeat cranial RT.

DeLLphi-304
ArmMedian CNS PFSHR (95% CI)
Tarlatamab (n=254)NE (13.7-NE)0.54 (0.39-0.75)
Chemotherapy (n=255)7.2 mo (5.6-NE)n/a
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DeLLphi-304
ArmMedian CNS PFSHR (95% CI)
Tarlatamab (n=67)6.5 mo (4.3-13.7)0.40 (0.24-0.66)
Chemotherapy (n=56)4.2 mo (2.9-5.5)n/a
DeLLphi-304
CNS endpointTarlatamab (n=67)Chemotherapy (n=56)
Complete response10 (14.9%)3 (5.4%)
Disease control rate52 (77.6%)40 (71.4%)
Median duration CNS disease control8.2 mo5.2 mo
5 details 2 trials watching

Post hoc intracranial analysis of DeLLphi-304, a phase 3 RCT of tarlatamab vs chemotherapy in relapsed SCLC. CNS endpoints were not prespecified primary. Data cutoff Jan 29 2025; median follow-up 11.4 mo (tarlatamab), 11.5 mo (chemo).

Relapsed SCLC. ITT CNS cohort n=254 tarlatamab vs 255 chemo; brain-mets subgroup n=67 vs 56. >70% of brain-mets pts had prior CNS-directed therapy.

Time to CNS progression or death (ITT, RECIST per investigator); brain-mets CNS PFS by mRANO-BM (BICR); best CNS response, CNS disease control rate, and response durations.

ITT time to CNS progression HR 0.54 (0.39-0.75), median NE vs 7.2 mo. Brain-mets CNS PFS and response detail in figures.

First DLL3xCD3 bispecific intracranial signal in SCLC; CNS control historically relied on WBRT/SRS and prophylactic cranial irradiation, not a systemic agent.

relapsed SCLC with brain mets, mostly previously treated for CNS disease
Does not represent RT-naive or symptomatic brain mets needing upfront local therapy.

Post hoc, unstratified brain-mets HRs, small subgroup N. >70% prior CNS therapy confounds de novo intracranial activity. No new safety data in source.

Post hoc CNS analysis; brain-mets HRs unstratified with small N (67 vs 56), and >70% had prior CNS-directed therapy, confounding de novo intracranial activity.

For relapsed SCLC with previously-treated brain mets, this supports systemic intracranial control as an option before committing to repeat cranial RT; it does not inform RT-naive or symptomatic brain mets, where upfront local therapy still applies.

📚 Sources · 🐦 1 tweet
Early signal

RAD-IO

ForT2-T4a N0M0 muscle-invasive urothelial bladder cancer

TL;DR12-mo DFS 40/50 (80%, 95% CI 0.67-0.89) cleared the pre-set ≥75% GO bar for durvalumab added to 5FU/MMC chemoRT in MIBC.

Why it mattersRadiation oncology

RT is standard and transferable: 55Gy/20fx to bladder, plus 46Gy/20fx elective nodal coverage in the node-positive expansion, extending durvalumab-chemoRT preservation to N+ disease. 12-mo DFS 80% (40/50, 95% CI 0.67-0.89) cleared the pre-set ≥75% GO bar vs BC2001. Moves whether to layer IO onto a hypofractionated preservation backbone.

RAD-IO
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Durvalumab (N=54): completed planned treatment 33 (61%), discontinued early 21 (39%).
Durvalumab (N=54): completed planned treatment 33 (61%), discontinued early 21 (39%).
8 details 4 trials watching

Single-arm, multi-stage feasibility and safety trial testing durvalumab added to 5FU/MMC chemoradiation for bladder preservation. Benchmarked against BC2001 historical CRT data, not a randomised comparator.

T2-T4a N0M0 urothelial muscle-invasive bladder cancer, stratified by prior neoadjuvant chemotherapy (yes vs no). A stage-1 expansion added the first 6 node-positive pts.

Durvalumab 1500 mg given neoadjuvant, synchronous, and adjuvant to 12 months post-chemoRT. Concurrent 5-FU 500 mg/m²/24h ×5 days and mitomycin C 12 mg/m².

55 Gy in 20 fractions to bladder (hypofractionated). Node-positive expansion added 46 Gy/20 fx elective nodal RT.

Primary: 12-month disease-free survival post-chemoRT, read against a GO/NO-GO framework (GO ≥75%, contextual 60-75%, NO-GO <60%).

12-mo DFS 40/50 (80%), 95% CI 0.67-0.89, clearing the ≥75% GO bar. 33/54 (61%) completed planned durvalumab; investigators reported very high bladder-preservation and DFS vs prior trial data.

AEs reported in line with component therapies (chemoRT plus durvalumab). 21/54 (39%) discontinued durvalumab early.

Benchmarked against BC2001 (James, JCO 2016), where adding 5FU/MMC to RT gave DFS HR 0.78 (0.60-1.02), p=0.07. RAD-IO's 80% 12-mo DFS is claimed higher than prior data, but the comparison is non-randomised.

T2-T4a N0M0 muscle-invasive urothelial bladder cancer suitable for bladder-preservation chemoRT
Does not represent metastatic disease, radical-cystectomy-preferred pts, or node-positive disease beyond the 6-patient expansion.

Single-arm with a historical benchmark and no concurrent IO comparator; 12-mo DFS is an early surrogate; small N (~50 evaluable); node-positive experience limited to 6 pts.

Single-arm feasibility stage, no randomised IO comparator; benchmarked against historical BC2001. 12-mo DFS an early surrogate at small N; met pre-set GO bar for further evaluation only.

In T2-T4a N0M0 MIBC opting for bladder preservation, this supports durvalumab layered onto 5FU/MMC chemoRT as worth further evaluation; it does not yet establish that IO improves on chemoRT alone, and node-positive experience rests on only 6 expansion pts.

📚 Sources · 🐦 3 tweets

Management of MIBC After Pathologic Complete Response

TL;DRReview of perioperative MIBC management after pCR: sandwich IO regimens continue adjuvant regardless of response, cisplatin-chemo alone moves to surveillance.

Trials discussed

SWOG 8710ABACUSCHECKMATE-274KEYNOTE-905VOLGANIAGARAVESPERKEYNOTE-B15

Overall survival: HR 0.50.
Overall survival: HR 0.50.
8 details 3 trials watching
  • 🔍 pCR used as primary endpoint in signal-seeking phase 2 trials
  • 🔍 pCR co-primary (not standalone) endpoint in phase 3 registrational trials
  • 🔍 High-risk residual disease (≥ypT2 or N+) post-neoadjuvant chemo → adjuvant therapy (CHECKMATE-274)
  • 💊 Post-pCR management by regimen
    • Sandwich IO (NIAGARA, EVP): continue planned adjuvant regardless of pathologic response
    • NIAGARA: resume durvalumab 8 mo post-cystectomy
    • Cisplatin-based chemo alone: surveillance after pCR is standard
  • 📊 pCR (pT0N0) post-neoadjuvant chemo = strong prognostic marker: SWOG 8710 85% 5-yr OS if pT0
  • 📐 Meta-analysis: pooled RR 0.19 for RFS with pCR
  • 📊 Perioperative regimens across trials
    TrialSettingComparisonResult
    NIAGARACis-eligibleGem/Cis + periop durvalumab24-mo OS 82.2% vs 75.2%
    VESPERCis-eligibleddMVAC vs Gem/Cis5-yr OS 66% vs 57%
    KEYNOTE-905Cis-ineligiblePeriop EVP vs cystectomy aloneOS HR 0.50
    KEYNOTE-B15Cis-eligiblePeriop EVP vs Gem/CisOS improved (under FDA review)
  • ⚠️ Not all pts in perioperative trials completed adjuvant therapy, often due to toxicity
📚 Sources · 🐦 1 tweet
Confirmatory

Genomic Classifier + NCCN Risk Stratification (Abstract 5000)

ForNCCN high-risk/very-high-risk localized prostate cancer

TL;DR22-gene GC independently prognostic (MFS/DM/OS, p<0.001); combined NCCN+GC score reclassifies ~¼ of high-risk pts to gate AAP intensification on an RT+ADT backbone.

Why it mattersRadiation oncology

~¼ of NCCN ≥HR pts are clinical/GC-discordant, so the 22-gene GC reclassifies who reaches CT-VHR (≥3 pts) and has AAP added onto the fixed RT+ADT backbone. The intensification it triggers carries STAMPEDE M0 magnitude (MFS HR 0.53, OS HR 0.60). It sharpens the intensification decision, not RT dose or target.

Genomic Classifier + NCCN Risk Stratification (Abstract 5000)
+2 more figures
Genomic Classifier + NCCN Risk Stratification (Abstract 5000)
EndpointHR (add AAP)95% CIp
MFS0.530.44-0.64<0.0001
OS0.600.48-0.73<0.0001
Genomic Classifier + NCCN Risk Stratification (Abstract 5000)
7 details

Retrospective validation of the 22-gene GC (Decipher) layered on NCCN clinical risk in NCCN ≥ high-risk localized prostate (NRG cohort), externally benchmarked to STAMPEDE M0 curves (Attard, Lancet 2022). Not a prospective RCT.

NCCN high-risk and very-high-risk localized prostate cancer, all planned for definitive RT+ADT.

CT-HR (≤2 pts) → RT+ADT; CT-VHR (≥3 pts) → RT+ADT+AAP (abiraterone acetate + prednisone) intensification.

GC is independently prognostic for MFS, DM, and OS over clinical variables (multivariable, p<0.001). Roughly one-quarter of NCCN ≥HR pts are clinical/GC-discordant, reclassifying risk band and the intensification call.

ComponentCategoryPoints
NCCN clinicalHigh-risk+1
NCCN clinicalVery-high-risk+2
GC (Decipher)< 0.60
GC (Decipher)0.6-0.85+1
GC (Decipher)> 0.85+2

AAP intensification magnitude is borrowed from STAMPEDE M0 (Attard, Lancet 2022), not generated here; GC prognostic value aligns with prior Decipher/NRG validation.

NCCN high-risk and very-high-risk localized prostate cancer on definitive RT+ADT
Does not represent intermediate- or low-risk disease, node-positive or metastatic disease, or the radical-prostatectomy pathway.

Prognostic, not predictive: no randomized biomarker×treatment interaction showing CT-VHR pts gain more from AAP. Intensification benefit imported from an external trial's average effect.

Retrospective GC prognostic validation, not a randomized predictive-biomarker trial; consistent with prior Decipher/NRG data. Intensification benefit borrowed from STAMPEDE, not shown to be GC-predictive.

In NCCN high-risk/very-high-risk localized prostate planned for definitive RT+ADT, this supports GC-informed CT-VHR (≥3 pts) selection for AAP intensification; it does not extend to intermediate-/low-risk disease or change RT dose or target.

  • Does GC-guided AAP intensification improve outcomes prospectively?
  • Is GC predictive of differential AAP benefit, not just prognostic?
  • Optimal AAP intensification threshold in clinical/GC-discordant pts
📚 Sources · 🐦 2 tweets
Early signal

A-DREAM

FormHSPC deep responder (PSA<0.2) after 18-24mo ADT + ≥12mo ARPI

TL;DR41% remained treatment-free with eugonadal testosterone recovery at 18mo after interrupting ADT+ARPI in deep-responding mHSPC (1° EP met, one-sided p=0.0249).

Monday clinic

In metastatic HSPC deep responders (PSA<0.2 after ≥18mo ADT and ≥12mo ARPI, predominantly low-volume), this supports discussing a monitored ADT+ARPI holiday with scheduled PSA/imaging; it does not extend to incomplete responders or high-volume disease.

Median time to eugonadal T 9.0mo. T recovery by 18mo 52 (66.7%); treatment-free 18mo 45 (57.7%); primary endpoint (treatment-free + T recovery) 32 (41.0%), 80% CI 33.1-48.9%, one-sided p 0.0249
Median time to eugonadal T 9.0mo. T recovery by 18mo 52 (66.7%); treatment-free 18mo 45 (57.7%); primary endpoint (treatment-free + T recovery) 32 (41.0%), 80% CI 33.1-48.9%, one-sided p 0.0249
+2 more figures
A-DREAM
A-DREAM
8 details 4 trials watching

Phase 2 single-arm Alliance trial. N=78 eligible metastatic HSPC deep responders interrupt ADT+ARPI. Enrolled 07/2022-03/2024; median follow-up 26.9mo.

Entry required PSA<0.2 (stable/falling) after 18-24mo ADT and 12mo ARPI. Median age 70 (49-90); 64.9% low-volume, 35.1% high-volume (CHAARTED); 51.3% had prior local radiation, 29.5% metastasis-directed radiation.

Primary: treatment-free with eugonadal testosterone (≥150 ng/dL) at 18 months. Exploratory: rPFS, TTNT, OS, cost.

Primary met: 32/78 (41.0%) treatment-free and eugonadal at 18mo (80% CI 33.1-48.9%, one-sided p=0.0249). 57.7% were treatment-free at 18mo and 66.7% recovered testosterone; median time to eugonadal T 9.0mo.

Disease control held through interruption: rPFS 15/78 events, OS 4/78 events, both medians not reached. The 41% primary is capped by slow testosterone recovery, not progression, so the endpoint understates short-term oncologic safety in this older cohort.

metastatic HSPC deep responders (PSA<0.2 after ≥18mo ADT + ≥12mo ARPI), low-volume-predominant
Does not represent incomplete responders, high-volume disease, or patients unwilling to accept delayed testosterone recovery.

Single-arm with no randomised comparator against continued therapy, so the survival cost of interruption is unquantified. Median follow-up 26.9mo is short for mHSPC; durability of treatment-free intervals is unproven.

Single-arm phase 2, N=78, no randomised comparator vs continued therapy; primary endpoint met but interruption safety needs longer follow-up and randomisation.

📚 Sources · 🐦 1 tweet
Confirmatory

ARACOG (AFT-47)

ForAdvanced prostate cancer (mHSPC/mCRPC/nmCRPC) starting an ARSI

TL;DRMCCD -36.1 (enza) vs -15.8 (daro), P=0.009 at 24 wk: enzalutamide worse for cognition; randomized open-label phase 2, N=111 advanced prostate.

Monday clinic

In advanced prostate cancer pts where cognitive tolerability drives ARSI selection, this randomized head-to-head supports darolutamide over enzalutamide for cognitive sparing; it does not address efficacy or compare against apalutamide or abiraterone.

ARACOG (AFT-47)
Arm (N)Max-changed domainMedian % changeP
Darolutamide (48)PALFAM (visual mem/exec)-15.80.009
Enzalutamide (47)SWM (working mem/exec)-36.1n/a
+1 more figure
ARACOG (AFT-47)
7 details 2 trials watching

Randomized open-label phase 2, N=111, darolutamide vs enzalutamide, stratified by age (<65, 65-80, >80). US academic centers only; enrolled 8/2021 to 3/2025, crossover permitted.

Advanced prostate cancer across mHSPC, mCRPC, and nmCRPC. Required acceptable enzalutamide co-pay; predominantly White, with most non-White pts randomized to enzalutamide.

Darolutamide provided by the study vs enzalutamide through standard of care, an asymmetry that could bias crossover and adherence.

Primary: between-arm % change from baseline to 24 wk in Maximally Changed Cognitive Domain (MCCD), from 5 remotely delivered CANTAB tests. Crossovers scored at crossover in their randomized arm.

MCCD median change -36.1 (enza, N=47) vs -15.8 (daro, N=48), P=0.009: greater cognitive decline on enzalutamide.

First randomized head-to-head of cognition for these two ARSIs; direction fits darolutamide's minimal blood-brain-barrier penetration vs enzalutamide's CNS exposure.

advanced prostate cancer pts (mHSPC, mCRPC, nmCRPC) choosing between darolutamide and enzalutamide
Does not represent apalutamide, abiraterone, or head-to-head efficacy comparisons.

Open-label with a functional endpoint; enzalutamide via standard of care may have altered crossover. CANTAB is a research tool, not a clinical diagnostic; small N and race-by-arm imbalance limit inference.

Randomized head-to-head met its prespecified cognitive endpoint; aligns with darolutamide's known low CNS penetration. Phase 2, open-label, small N keep it below practice-changing.

📚 Sources · 🐦 2 tweets

Precision Oncology: Applying New Biomarkers in GU Cancers

TL;DRBiomarker round-up: tissue HRR/tumor-suppressor testing is SOC, but genomic classifiers show 24% clinical-risk discordance and lack ARPI-era validation.

Trials discussed

ENZAMETCHAARTED

Why it mattersRadiation oncology

For RT readers using genomic classifiers to gate ADT intensification with salvage or definitive RT, the session's caution transfers: Decipher was discordant with clinical risk in 24% of high-risk pts (tissue available in only 427 of 3816), and its validation cohorts predate ARPIs. Treat the score as hypothesis-generating, not a settled gate.

Biomarker vs clinical-risk concordance in high-risk prostate: 24% discordant (tissue n=427 of 3816).
Biomarker vs clinical-risk concordance in high-risk prostate: 24% discordant (tissue n=427 of 3816).
+1 more figure
Precision Oncology: Applying New Biomarkers in GU Cancers
9 details 4 trials watching
  • 🔍 ENZAMET biomarker cohort: 1,071 consented, GEP N=764, final Decipher cohort N=634 (56% of enrolled)
  • 📊 Tissue-panel testing for HRR + tumor-suppressor loss is called SOC in prostate
  • 📊 Landscape-slide annotations, approx. eligible fraction: Lu-177 PSMA ~90%, PARP inhibitors ~10-20%, pembrolizumab ~3%
  • 📊 Decipher genomic classifier discordant with clinical risk in 24% of high-risk events
  • 📊 Decipher DPMC ≤0.85 subgroup: ADT+enza+docetaxel had worse OS than ADT+enza (triplet cohort N=320)
  • ⚠️ Discordance from tissue-available subset (n=427) of n=3816; representativeness of full trial population uncertain
  • ⚠️ Source classifier trials predate ARPIs; applicability to current ARPI-based SOC questioned
  • ⚠️ Confounded: docetaxel not randomized, with more high-volume disease + older pts → selection bias, not a validated predictor
  • 🔬 ASCO26 education session (J. Lang): a biomarker is useful only if it changes management; GU therapy selection stays biomarker-limited
📚 Sources · 🐦 1 tweet
Caveats dominate

ENZAMET + Decipher (Part 2)

FormHSPC on ADT + enzalutamide, Decipher genomic classifier available

TL;DRDecipher >0.85 predicts docetaxel OS benefit on an ADT+enza backbone (HR 0.75 vs 1.94, interaction p=0.04); ≤0.85 can skip docetaxel.

Monday clinic

In mHSPC starting ADT + enzalutamide, a Decipher score >0.85 is where the docetaxel OS benefit concentrates while ≤0.85 sees little added benefit; the read informs docetaxel selection, not any radiotherapy decision.

ENZAMET + Decipher (Part 2)
Treatment armDecipher >0.85 vs ≤0.85 OS HRp
ADT + ENZA3.02 (1.50-5.76)
ADT + ENZA + Doce1.08 (0.60-1.71)0.73
+1 more figure
ENZAMET + Decipher (Part 2)
Decipher stratumUnweighted HR (doce vs none)IPTW-weighted HR
≤0.852.78 (1.49-5.21)1.94 (0.95-3.96)
>0.851.13 (0.71-1.79)0.75 (0.43-1.33)
7 details

Preplanned biomarker analysis of the phase 3 ENZAMET RCT. Decipher genomic classifier (DPMC, cutpoint >0.85) applied to the ADT + enzalutamide backbone cohort, N=320.

Metastatic hormone-sensitive prostate cancer on an ADT + enzalutamide backbone with an available Decipher score. A low-volume subset was analysed separately.

ADT + enzalutamide ± early docetaxel. Docetaxel was given at investigator discretion (a stratification factor), so the docetaxel comparison is not randomised.

Two-part signal: Decipher >0.85 is prognostic for worse OS on ADT+enza, and by IPTW interaction (p=0.04) predicts OS benefit from added docetaxel; ≤0.85 derives little benefit. Effect sizes in the figures.

Consistent with docetaxel OS benefit in CHARTED and STAMPEDE for high-volume/high-risk mHSPC; positions Decipher as a molecular refinement of that selection. Presented as Level 1B evidence.

mHSPC pts on an ADT + enzalutamide backbone with a Decipher score
Does not represent pts managed without a Decipher score, or on systemic backbones other than ADT + enzalutamide.

Docetaxel not randomised (IPTW-weighted, residual imbalance after scoring); the high-Decipher benefit's CI crosses 1 and rests on a subgroup interaction. Hypothesis-generating, not yet practice-defining.

Post-hoc biomarker-by-docetaxel interaction; docetaxel not randomised (IPTW-weighted, residual imbalance acknowledged). High-Decipher benefit CI crosses 1, rests on interaction p=0.04, strengthened only after weighting.

  • Prospective validation of Decipher-guided docetaxel selection in mHSPC
  • Whether DPMC ≤0.85 pts can safely omit docetaxel
  • Decipher predictive value across other intensification agents (ARSI, PARP)
📚 Sources · 🐦 1 tweet
Confirmatory

TALAPRO-3

ForHRR-deficient metastatic prostate cancer

Imaging-based progression-free survival surrogate

HR 0.48

95% CI 0.36-0.65, P<0.001; 3yr rPFS 77% vs 56% (ITT)

TL;DR3yr rPFS 77% vs 56%, HR 0.48 (0.36-0.65), adding talazoparib to enzalutamide/ADT in HRR-deficient metastatic prostate cancer.

Monday clinic

In HRR-deficient metastatic prostate cancer, this supports intensifying enzalutamide/ADT with talazoparib, benefit steepest in the BRCA subgroup; it does not extend to HRR-intact disease.

TALAPRO-3
PopulationHR (95% CI)Median rPFS, mo
ITT0.48 (0.36-0.65)NC vs 45.8
BRCA0.37 (0.22-0.61)NC vs 35.1
Non-BRCA0.57 (0.39-0.82)NC vs NC
6 details 2 trials watching

Randomized, placebo-controlled trial: talazoparib+enzalutamide vs placebo+enzalutamide, 300 vs 299 pts. Published NEJM May 30, 2026.

HRR-deficient metastatic prostate cancer, enzalutamide/ADT backbone both arms. Prespecified BRCA (104/103) and non-BRCA HRR (196/196) strata.

Talazoparib (PARP inhibitor) added to enzalutamide plus ADT; control substituted placebo for talazoparib on the same ARSI backbone.

Primary: imaging-based (radiographic) PFS. OS and other secondaries not reported in source.

ITT 3yr rPFS 77% vs 56%, P<0.001; per-population HRs and medians in the figure. Benefit concentrated in the BRCA subgroup.

Extends PARP+ARSI combinations (TALAPRO-2, PROpel, MAGNITUDE) that established the class in HRR-altered mCRPC toward the enzalutamide/ADT-backbone metastatic setting.

HRR-deficient metastatic prostate cancer on an enzalutamide/ADT backbone, BRCA-enriched
Does not represent HRR-intact disease or PARP-inhibitor use outside HRR alterations.

Primary endpoint is rPFS, a surrogate; OS not reported in source. Non-BRCA benefit is modest, so the HRR-wide result leans on BRCA. Talazoparib medians not reached, so follow-up is immature.

Randomized phase 3, rPFS primary hit (HR 0.48); but rPFS is a surrogate and OS not reported. Aligns with PARP+ARSI direction (TALAPRO-2, PROpel, MAGNITUDE).

📚 Sources · 🐦 1 tweet
Confirmatory

PREPEC

ForSkin/nipple-sparing mastectomy, implant reconstruction, prevention/therapeutic

Physical well-being (chest), BREAST-Q, 24mo surrogate

Δ4.8 pts (79.2 vs 74.3)

95% CI 1.0-8.7, p=0.01; 24mo, pre- vs sub-pectoral

TL;DRPre-pectoral implant improved 2yr chest well-being +4.8 pts (BREAST-Q, p=0.01) vs sub-pectoral, but more unplanned implant loss (21% vs 15%).

Monday clinic

In pts undergoing skin- or nipple-sparing mastectomy (therapeutic or risk-reducing) who choose implant reconstruction, this supports pre-pectoral placement for better 2yr patient-reported chest well-being, weighed against numerically higher unplanned implant loss (21% vs 15%).

PREPEC
Endpoint (24mo)Pre-pectoral (N=191)Sub-pectoral (N=189)Difference
Physical well-being, chest (BREAST-Q)79.2 (75.5-82.8)74.3 (70.7-78.0)4.8 (1.0-8.7), p=0.01
+1 more figure
PREPEC
Unplanned implant loss/replacement (24mo)Pre-pectoralSub-pectoralAdj. difference (95% CI)
Crude % (n/N)21.1% (41/194)14.5% (27/186)5.7% (-2.4 to 13.8)
8 details 3 trials watching

International randomized phase 3 trial (OPBC-02): pre- vs sub-pectoral implant reconstruction after skin- or nipple-sparing mastectomy. Open-label; patient-reported primary endpoint analyzed by multiple imputation and linear mixed models.

Women undergoing skin- or nipple-sparing mastectomy for cancer treatment or risk reduction, opting for implant reconstruction. Primary QoL analysis N=191 pre- vs 189 sub-pectoral.

Primary: long-term patient-reported physical well-being (chest), BREAST-Q, at 24 months. Main secondary safety: unplanned loss or replacement of expander/implant.

BREAST-Q chest well-being 79.2 vs 74.3 at 24mo, difference 4.8 (95% CI 1.0-8.7, p=0.01), favoring pre-pectoral. Longitudinal completion 83-95%.

Point estimate showed more implant loss with pre-pectoral (21.1% vs 14.5%), failing the trial's non-inferiority safety hypothesis; the adjusted-difference 95% CI (-2.4 to 13.8) crosses zero.

women choosing implant-based reconstruction after skin- or nipple-sparing mastectomy, therapeutic or risk-reducing
Does not represent autologous (flap) reconstruction or non-implant approaches.

Open-label with a patient-reported primary endpoint, so awareness of implant type could bias PROs. The 4.8-point gain is significant but modest, and the safety signal trended against pre-pectoral.

A major RCT in an area of genuine equipoise. It supports pre-pectoral for patient-reported chest well-being while flagging a higher implant-loss signal, so the choice reads as a real trade-off, not a clean win.

Randomized phase 3, primary endpoint met, but a modest patient-reported surrogate and an unmet non-inferiority safety endpoint keep it short of practice-changing.

📚 Sources · 🐦 1 tweet
Challenges SOC

ROADS

ForResected brain metastasis > 2 cm, post-op cavity RT candidates

Time to surgical bed recurrence local control

NR vs 17 mo

Surg bed recurrence 1% GammaTile vs 12% SRS

TL;DRSurgical bed recurrence 1% vs 12% and 2yr OS 62% vs 36% favoring intraoperative GammaTile brachytherapy over post-op SRS for resected brain mets >2cm.

Why it mattersRadiation oncology

The safety tradeoff the headline buries: leptomeningeal disease ran 10% with GammaTile vs 3% with SRS, even as surgical-bed recurrence fell to 1% vs 12%. Radiation necrosis was comparable (8% vs 7%). This moves the intraoperative-brachytherapy-vs-staged-cavity-SRS decision for resected mets >2 cm, where SRS local control is weakest.

ROADS
EndpointGammaTileSRS
Time to surg bed recurrenceNR17 mo
Surg bed recurrence-free survivalNR11 mo
2-yr OS62%36%
8 details 2 trials watching

Randomized trial, N=230, resected brain metastasis > 2 cm. GammaTile (Cs-131 collagen-tile brachytherapy) placed in the cavity at resection vs post-op stereotactic radiosurgery. ASCO 2026 final results. Primary: time to surgical bed recurrence and surgical-bed recurrence-free survival.

Resected brain metastasis > 2 cm, the larger-cavity setting where single-fraction post-op SRS local control is weakest. Histology / primary tumor not specified in source.

Experimental: intraoperative permanent Cs-131 seed brachytherapy (GammaTile) at resection. Control: post-op cavity SRS. Dose, fractionation, and cavity margin not reported in source.

Both primary endpoints and 2yr OS favored GammaTile. Safety: radiation necrosis comparable (8% vs 7%), leptomeningeal disease higher with brachytherapy (10% vs 3%).

Post-op cavity SRS is the current standard for resected brain mets (N107C, Mahajan). ROADS challenges it, favoring intraoperative brachytherapy on local control.

pts with a resected brain metastasis > 2 cm who are candidates for post-op cavity radiotherapy
Does not represent intact (unresected) brain mets or resection cavities ≤ 2 cm.

Abstract-only, not yet peer-reviewed; open-label. The 2yr OS advantage is large for a local therapy and OS was not a stated primary endpoint, raising the question of baseline arm imbalance.

Randomized, primary endpoint (surg bed control) hit favoring intraop brachy over the post-op SRS standard; but abstract-only, open-label, and the large OS gain warrants scrutiny.

In pts with a resected brain metastasis >2 cm needing cavity radiotherapy, this supports intraoperative brachytherapy as an alternative to post-op SRS for local control; it does not extend to intact (unresected) mets or cavities ≤2 cm.

📚 Sources · 🐦 1 tweet
Early signal

CHRYSALIS-2

ForTreatment-naïve atypical EGFR-mutant advanced NSCLC

TL;DRmOS 41.0 mo (95% CI 27.7-NE) with 1L amivantamab + lazertinib in treatment-naïve atypical EGFR-mutant NSCLC; single-arm, n=49.

Monday clinic

In treatment-naïve atypical EGFR-mutant advanced NSCLC, a population with few standard targeted options, this single-arm 41-mo median OS supports amivantamab+lazertinib as a candidate 1L regimen; it does not extend to common EGFR (exon19del/L858R) disease, where randomised data already guide practice.

Median OS 41.0 mo (95% CI 27.7-NE). Median follow-up 31.3 mo.
Median OS 41.0 mo (95% CI 27.7-NE). Median follow-up 31.3 mo.
+1 more figure
Time on treatment: median 13.3 mo (range <0.1-53.2); 39% on treatment >2 years.
Time on treatment: median 13.3 mo (range <0.1-53.2); 39% on treatment >2 years.
8 details

Single-arm cohort, n=49, no randomised comparator. Median follow-up 31.3 mo.

Treatment-naïve (1L) atypical EGFR-mutated advanced NSCLC. Responses durable regardless of demographics, baseline mutations, and disease characteristics.

IV amivantamab + lazertinib. Median treatment duration 13.3 mo (range <0.1-53.2); 39% on treatment >2 years.

Median OS 41.0 mo (95% CI 27.7-NE), ~3.5 years. No clear association between EGFR variant subtype and OS.

With longer follow-up, safety consistent with prior reports; no new safety signals.

Extends the durable 1L amivantamab+lazertinib OS signal from common EGFR (exon19del/L858R) to atypical variants.

treatment-naïve atypical EGFR-mutant advanced NSCLC
Does not represent common EGFR (exon19del/L858R) or pretreated disease.

Single-arm, n=49, no randomised comparator. Atypical EGFR is a heterogeneous class; per-variant efficacy not detailed in source.

Single-arm cohort (n=49), no randomised comparator in atypical EGFR NSCLC; durable but single-arm design caps the read at early-signal despite 31-mo follow-up.

  • Efficacy by specific atypical EGFR variant
  • Randomised comparison vs other 1L options in atypical EGFR
📚 Sources · 🐦 1 tweet
Early signal

ESAONA

ForTreatment-naive EGFR-mutant NSCLC with brain metastases

TL;DRiORR 95.5% vs 79.6% (p=0.0004) and icPFS HR 0.46 favoring asandeutertinib over osimertinib in 1L EGFR-mut NSCLC brain mets.

Why it mattersRadiation oncology

The RT-relevant read is upfront local therapy: iORR 95.5% vs 79.6% and intracranial PFS not reached (HR 0.46) strengthen deferring upfront SRS/WBRT in favor of TKI in EGFR-mut brain mets. No head-to-head vs radiosurgery, so it moves sequencing, not RT omission at progression.

7 details 5 trials watching

Randomised phase 2, N=224 (111 asandeutertinib vs 113 osimertinib), 1L EGFR-mutant NSCLC with brain metastases. All efficacy endpoints BICR-assessed. Blinding not specified in source.

Treatment-naive (1L) EGFR-mutant NSCLC with brain metastases. Mutation subtype, symptomatic status, and prior brain RT not reported in source.

Asandeutertinib (next-generation EGFR TKI) vs osimertinib. Dose and schedule not reported in source.

Intracranial endpoints (response, icPFS) drove the result and cleared significance more decisively than the borderline overall PFS benefit. Full arm comparison in the table above.

EndpointAsandeutertinibOsimertinibHR (p)
iORR95.5% (89.8-98.5)79.6% (71.0-86.6)p=0.0004
Intracranial PFSNR17.5 mo (15.18-NA)HR 0.46, p=0.0020
Overall PFSNR17.2 mo (15.18-19.55)HR 0.64, p=0.0473

Any TRAEs 99.1% vs 95.6%; serious TRAEs numerically higher with asandeutertinib (10.8% vs 7.1%). Fatal and discontinuation rates not reported in source.

Osimertinib is the established CNS-active 1L EGFR TKI (FLAURA). Asandeutertinib raises the intracranial bar in phase 2, but no OS or phase 3 head-to-head yet.

treatment-naive EGFR-mutant NSCLC with brain metastases
Does not represent EGFR-wildtype disease or brain metastases progressing on a prior EGFR TKI.

Phase 2 with immature time-to-event data (medians not reached); overall PFS benefit borderline (p=0.0473); no OS; blinding not specified.

Strong intracranial activity revives whether a CNS-active TKI can defer upfront brain-directed RT/SRS in EGFR-mutant NSCLC. Phase 3 confirmation vs osimertinib, plus OS and durability, is needed before displacing the standard.

Randomised phase 2; strong intracranial ORR but time-to-event immature (medians NR), overall PFS borderline (p=0.0473), no OS. Needs phase 3 before displacing osimertinib.

In treatment-naive EGFR-mutant NSCLC with brain metastases, this supports a TKI-first, SRS-deferred read; it does not extend to EGFR-wildtype disease or brain mets progressing on a prior EGFR TKI.

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Early signal

OptiTROP-Lung05 NCT06448312

For1L IIIB/IIIC-IV PD-L1≥1% NSCLC, EGFR/ALK wild-type

Progression-free survival (BICR) surrogate

HR 0.35

95% CI 0.26-0.47, p<0.0001; median NR vs 5.7 mo

TL;DRmPFS NR vs 5.7 mo, HR 0.35, adding Sac-TMT (TROP2 ADC) to pembrolizumab in 1L PD-L1+ NSCLC.

OptiTROP-Lung05
ArmPFS events n (%)Median PFSHR (95% CI)
Sac-TMT+Pembro66 (31.7%)NR (13.6-NE)0.35 (0.26-0.47)
Pembro128 (62.4%)5.7 mo (4.3-7.0)
+2 more figures
OptiTROP-Lung05
PD-L1 TPSmPFS combomPFS pembroHR (95% CI)
≥50%NR9.5 mo0.47 (0.29-0.77)
1-49%NR4.3 mo0.28 (0.19-0.41)
OptiTROP-Lung05
ArmOS events n (%)Median OSHR (95% CI)
Sac-TMT+Pembro33 (15.9%)NR0.55 (0.36-0.85)
Pembro54 (26.3%)NR
8 details 2 trials watching

Phase 3, open-label, multicenter RCT (NCT06448312); 1:1, N=413. Primary PFS by BICR crossed its interim efficacy boundary at 194 events; median follow-up 10.5 mo.

1L stage IIIB/IIIC or IV NSCLC, PD-L1 TPS ≥1% (22C3), EGFR/ALK wild-type, ECOG 0-1. Stratified by histology, PD-L1 (1-49 vs ≥50), ECOG.

Sac-TMT (TROP2 ADC) 4 mg/kg Q2W + pembrolizumab 400 mg Q6W vs pembrolizumab alone; pembro capped at 18 cycles.

ORR 70.2% vs 42.0%. PFS gain held across PD-L1 strata, strongest in TPS 1-49% where pembro monotherapy is weakest. OS immature, formal testing pending.

Current 1L PD-L1+ NSCLC standard is pembrolizumab ± chemotherapy. This tests a chemo-free ADC+IO doublet; no head-to-head vs chemo-IO.

1L advanced/metastatic PD-L1≥1%, EGFR/ALK wild-type NSCLC
Does not represent EGFR/ALK-altered, PD-L1-negative, or previously-treated patients.

Open-label; OS immature at 10.5-mo follow-up and formally untested; PFS reported at an interim efficacy boundary. No safety data in source.

PFS crossed an interim efficacy boundary; key-secondary OS descriptive/immature at 10.5-mo f/u; open-label. Strong but not yet mature enough to move 1L SOC.

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Living Longer, Living Better: Can We Have It All?

TL;DRASCO26 GU discussant on curative-intent trade-offs: bladder-sparing chemoRT + IO feasibility, and ctDNA over pathology for adjuvant RCC selection.

Trials discussed

EV209EV309RAMPART

Why it mattersRadiation oncology

The RT read is delivery feasibility: layering durvalumab onto 55 Gy/20 fx chemoRT left radiotherapy fully intact (100% completed full dose), so the 39% early durvalumab stops reflect IO tolerability, not RT. Supports adding IO to bladder-preservation chemoRT, but bladder-intact and QoL endpoints remain immature.

vs leading data
  • RAMPART (adjuvant RCC): non-clear-cell subgroups have few pts/events and wide CIs; no proven adjuvant IO benefit in non-clear-cell RCC
  • Session throughline: organ sparing (bladder) and biomarker-refined de-escalation (ctDNA over pathology) without sacrificing cure
Living Longer, Living Better: Can We Have It All?
Componentn (%)
Full 55 Gy/20 fx RT delivered54 (100%)
RT with no extension/delay47 (87%)
Chemo discontinued early12 (22%)
Durvalumab completed33 (61%)
Durvalumab discontinued early21 (39%)
+1 more figure
Living Longer, Living Better: Can We Have It All?
6 details 3 trials watching
  • 🔍 Bladder preservation thread: durvalumab added to mitomycin C / 5-FU chemoRT (55 Gy/20 fx) in MIBC
  • 💊 Durvalumab drove the early discontinuations (toxicity / PD); chemoRT delivery itself was not compromised
  • 🔍 EVP (enfortumab vedotin + pembrolizumab) bladder-sparing trials in MIBC
    FeatureEV209EV309
    PopulationCystectomy-eligibleIneligible / refusing
    StagecT2-4a N0 MIBCcT2-4a N0 MIBC
    N240390
    Regimen9 cycles EV + 1 yr pembro9 cycles EV + 1 yr pembro
    EndpointscCR, 2 yr BIEFSBIEFS, OS
  • 📊 Adjuvant pembro (Choueiri, ASCO26): ctDNA stratifies DFS better than pathologic features; ctDNA-positive pts fare far worse in both arms
  • ⚠️ Feasibility signal only; bladder preservation, function, symptom burden, safety and QoL all await longer f/u
  • 🗞️ Rini ASCO26 GU discussant: can curative-intent GU therapy raise cure rates while preserving organ function and QoL?
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Challenges SOC

Neo-CRAG

ForHigh-risk locally advanced gastric/EGJ (cT3N2-3 to cT4), fit for D2 resection

Disease-free survival surrogate

mDFS 52.7 vs 24.4 mo

HR 0.750 (95% CI 0.607-0.928), P=0.008

TL;DRAdding neoadjuvant chemoRT (45Gy/25fx) to periop XELOX improved mDFS 52.7 vs 24.4mo (HR 0.75) and mOS 67.5 vs 37.6mo in high-risk LAGC.

Why it mattersRadiation oncology

The RT read is clean attribution: both arms share the XELOX backbone and the CRT arm got dose-reduced chemo during RT, yet locoregional recurrence halved (9.4% vs 18.3%) with more ypN0 and downstaging. On 45Gy/25fx, this revives neoadjuvant chemoRT for high-risk D2-resected gastric/EGJ, on a non-FLOT backbone.

Neo-CRAG
EndpointCRTCTHR (95% CI), P
Median DFS52.7 mo24.4 mo0.750 (0.607-0.928), P=0.008
3-yr DFS55.6%42.4%
Median OS67.5 mo37.6 mo0.781 (0.628-0.970), P=0.025
5-yr OS50.1%44.2%
7 details 2 trials watching

Phase 3 open-label RCT, 1:1, N=620 (310/arm), 13 Chinese referral centers, enrolled 2013-2022. Primary: disease-free survival; secondary OS, pCR, R0, safety.

High-risk locally advanced gastric/EGJ adenocarcinoma: cT3N2-3M0, cT4aN+M0, or cT4bNanyM0; 36.3% EGJ (Siewert II/III). All planned standardized D2 gastrectomy.

Both arms: 3 cycles preoperative + 3 cycles adjuvant XELOX (oxaliplatin 130, capecitabine 1000 BID D1-14, Q3W) around D2 gastrectomy.

CRT arm only: concurrent 45 Gy/25 fx begun after chemo cycle 1, with dose-reduced XELOX (oxaliplatin 100, capecitabine 825) during RT. RT is the sole added variable between arms.

Primary DFS met and secondary OS positive, both favoring CRT; pathologic downstaging, ypN0, and locoregional control also improved (see figure and table).

Contrasts with CRITICS and TOPGEAR, where adding radiotherapy to a chemo backbone did not improve survival. A positive DFS/OS here reopens neoadjuvant chemoRT in high-risk, D2-resected LAGC.

high-risk locally advanced gastric/EGJ (Siewert II/III) adenocarcinoma, cT3N2-3 to cT4b, fit for D2 gastrectomy on a XELOX backbone
Does not represent FLOT-backbone, metastatic, or Western populations with lower D2-resection rates.

Open-label; non-FLOT XELOX backbone limits transfer to current perioperative standard. Single-country (China) with high D2-resection quality; DFS (not OS) was the primary endpoint.

Randomised phase 3, primary DFS and OS both hit, but positive chemoRT diverges from negative CRITICS/TOPGEAR; non-FLOT XELOX backbone limits transfer to current SOC.

In high-risk cT3N2-3/cT4 gastric or EGJ adenocarcinoma planned for D2 gastrectomy on a XELOX backbone, these data support a DFS/OS and locoregional-control benefit from adding neoadjuvant chemoRT; the signal does not extend to FLOT-backbone or metastatic patients.

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Caveats dominate

SPIN Score (Celiac Plexus SRS) NCT03323489

ForPancreatic cancer, intractable retroperitoneal pain, celiac SRS candidates

TL;DR89% pain response at SPIN 2 vs 32% at SPIN 0 for celiac SRS; post-hoc selection score, n=90.

Why it mattersRadiation oncology

Response is threshold-gated on baseline pain (>6 → 65.8%, rising to 85.7% at >8), and the strongest predictor was neurotoxic-chemo exposure (multivariate OR 5.1). The RT decision this moves is timing: refer for celiac SRS before neurotoxic agents. SRS dose/fractionation not reported in source (parent Lancet Oncol trial).

9 details

Post-hoc predictor analysis of the pivotal single-arm phase 2 celiac plexus SRS trial (NCT03323489, Lancet Oncol 2024). 90 evaluable pts; univariate/multivariate logistic regression with 500-iteration bootstrap internal validation.

Pancreatic-cancer pts with intractable retroperitoneal (celiac) cancer pain treated on the phase 2 SRS trial. Age and BMI were the prior-reported predictors; median baseline values not in source.

Celiac plexus radiosurgery, target D12-L2. Dose and fractionation not reported in source (specified in the parent Lancet Oncol trial), so transferability of the technique can't be judged here.

Pain response = ≥2-point reduction in average BPI-SF pain from baseline to 3 weeks. Score performance judged by optimism-corrected AUC.

Two independent predictors (severe baseline pain, no prior neurotoxic chemo) build a 0-2 score with a monotonic response gradient (see tables). Discrimination modest, AUC 0.714 corrected.

SPIN scorePain responsen
032%31
153%40
289%19
PredictorUnivariate ORMultivariate OR
Neurotoxic chemo exposure5.33 (2.13-13.4), p<0.0015.1, p=0.009
Baseline pain intensity1.73, p=0.0031.8, p=0.003
Age1.06, p=0.014dropped (collinearity)
Therapy line0.65, p=0.04dropped (collinearity)

Celiac plexus SRS is a novel non-invasive palliative option recently added to NCCN guidelines. This analysis converts the parent trial's flat response into an actionable selection score and argues for earlier use, before neurotoxic chemotherapy.

pancreatic-cancer pts with intractable retroperitoneal pain evaluated for celiac plexus SRS
Does not represent pts already exposed to neurotoxic chemotherapy (lower predicted response) or non-pancreatic retroperitoneal pain.

Post-hoc, single-arm data; predictors are associative. Internal bootstrap validation only (optimism-corrected AUC 0.714), external validation required. Subjective 3-week pain endpoint; score not prospectively tested.

Post-hoc predictor modeling of a single-arm phase 2; internal bootstrap validation only, external validation pending. Associations, not a prospectively validated selection tool.

In pancreatic-cancer pts with severe retroperitoneal pain and no prior neurotoxic chemo (SPIN 2), this supports earlier celiac plexus SRS, where 89% (n=19) achieved pain response; it does not extend to SPIN-0 pts, whose response was 32% (n=31).

  • External validation of the SPIN score in an independent cohort
  • Whether earlier SRS before neurotoxic chemo improves outcomes prospectively
  • Durability of pain response beyond 3 weeks
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Confirmatory

Wait or Treat? NCT05236946

ForAsymptomatic brain mets, EGFR/ALK-mutant metastatic NSCLC, on TKI + chemo

Intracranial PFS local control

Sub-HR 0.35

95% CI 0.21-0.59, p<0.001; favors upfront RT

TL;DRUpfront cranial RT cut 2y intracranial progression (21.7% vs 50%, sub-HR 0.35) but no OS gain; survival numerically favored delayed (HR 1.45).

Why it mattersRadiation oncology

The primary endpoint actually favored upfront RT (2y intracranial progression 21.7% vs 50%, sub-HR 0.35), yet OS trended toward delayed (2y 48% vs 60%) with 6% radiation necrosis vs none. Better CNS control bought no survival and added toxicity, so upfront cranial RT can be safely deferred to intracranial progression.

Wait or Treat?
EndpointUpfront RTDelayed RT
Events2047
1-yr intracranial PD8.7% (2.9-14.5)25.7% (16.8-34.7)
2-yr intracranial PD21.7% (12.6-30.8)50% (39.2-60.9)
Sub-HR (95% CI)0.35 (0.21-0.59), p<0.001ref
8 details 4 trials watching

Phase 3 open-label RCT, 1:1, N=208 (105 upfront cranial RT vs 103 delayed) at a single center (Tata Memorial). Median follow-up 30.6 mo; stratified by GPA and synchronous vs metachronous BM.

Metastatic EGFR- or ALK-mutant NSCLC with radiologically measurable, completely asymptomatic brain metastases, ECOG 0-2. Both arms received TKI + chemotherapy.

Delayed arm held cranial RT until intracranial progression or patient request, with MRI brain q3mo for year 1 then q6mo. RT dose, fractionation, and technique (SRS vs WBRT) not reported in source.

Primary: intracranial PFS. Secondary: OS, PFS, toxicity, ORR, neurocognition, PROM.

Primary endpoint met for intracranial control but did not translate to survival; the OS trend and radiation-necrosis signal both favored deferral. See the intracranial-progression figure and survival table for effect sizes.

First randomized evidence on RT timing in this population. Consistent with the CNS-active TKI era (osimertinib, alectinib, lorlatinib), where strong systemic intracranial control supports deferring RT.

asymptomatic brain metastases in EGFR/ALK-mutant metastatic NSCLC on TKI plus chemotherapy
Does not represent symptomatic brain mets, oncogene-negative NSCLC, or pts needing immediate neurologic intervention.

Open-label and single-institution. Powered for intracranial PFS, not OS, so the survival and necrosis signals favoring deferral are secondary. RT technique not reported.

Randomized phase 3, primary intracranial-PFS endpoint met, but no OS benefit and less necrosis with deferral; backs the emerging TKI-first, defer-RT approach in oncogene-driven NSCLC.

In asymptomatic brain metastases from EGFR/ALK-mutant metastatic NSCLC on TKI plus chemo, this supports deferring cranial RT until intracranial progression; it does not extend to symptomatic brain mets or oncogene-negative NSCLC.

📚 Sources · 🐦 3 tweets