Adaptive Radiotherapy — Board Review Summary

PART I — DEFINITION, RATIONALE, AND HOW ONLINE ART WAS BUILT

Quick Definition: What Is Online ART?

Online adaptive radiotherapy is the process of adjusting the daily treatment plan in response to observed changes in target and/or organ-at-risk geometry while the patient remains on the treatment table. In practical terms, it condenses what would traditionally be 1-2 weeks of planning work into a single session lasting roughly 15-90 minutes.

Why ART Emerged from the Limitations of Standard IGRT

  • Static RT plans cannot account for substantial day-to-day anatomic variation.
  • Upper abdominal and pelvic sites are especially vulnerable because OAR position may change enough to invalidate an otherwise acceptable plan.
  • ART therefore aims to preserve target coverage while avoiding unplanned OAR overdosing.

Three Core Pieces Required to Make ART Possible

RequirementWhy it mattersBoard-style takeaway
1. On-board imaging of adequate qualityMust visualize target and OAR changes reliably enough to justify re-planningNo meaningful adaptation without anatomy you can trust
2. Paired TPS for rapid re-contouring and re-optimizationAdaptation has to happen in real time while the patient remains on the tableSpeed and contouring logic are part of the technology, not an afterthought
3. Online pre-treatment QAEvery adapted plan still needs to be safe to deliverNew workflows still require old-fashioned rigor

How Platforms Were Vetted: Stepwise Development Path

StepMR-guided exampleKey result
Imaging studyOriginal low-field 0.35T MRgRT platformNo imaging dose, 4 or 8 f/s, automatic gating, TruFISP-based imaging; MRI visualized soft tissue better than standard C-arm CBCT
In silico workflow / TPS testingSimulated delivery of 50 Gy / 5 fx SMARTLarge daily anatomic shifts observed; predicted 63% daily ART need to protect OARs; adaptation predicted to reverse 100% of those OAR violations
Pilot / Phase I trialAdaptive upper-GI SMART pilotDemonstrated feasibility and safety before broader efficacy testing
Board pearl: the slide deck explicitly argues that ART platforms should be developed in a repetitive, stepwise fashion: imaging validation, dosimetric/in silico testing, then feasibility and safety trials. That sequence is itself testable.

Current Clinical Platform Landscape

Platform typeClinical use timelinePractical note
MR-guided ARTIn clinical use since 2014Best soft-tissue visualization and integrated motion management
CT-guided ARTIn clinical use since 2018Typically higher throughput and easier integration into conventional IGRT-heavy workflows
C-arm linac adaptiveFDA 510(k) cleared in January 2026Important because C-arm linacs are the most globally common treatment platform

PART II — CLINICAL PILLAR #1: SAFE DOSE ESCALATION

Phase I Adaptive SMART: Upper GI / LAPC Feasibility

Phase I adaptive upper-GI SMART pilot (example LAPC, N = 10) established that online adaptive SBRT was safe and feasible. The key result was that the initial plan violated OAR constraints in 70 of 95 fractions, and online ART resolved all of those violations, with 0 grade 3+ acute GI toxicities.

SMART Pancreas Phase II Trial

FeatureDetails
PopulationBorderline resectable / locally advanced pancreas
Platform / conceptMRI-guided online ART
Dose50 Gy / 5 fx (BED10 = 100 Gy), subject to strict OAR constraints
Primary endpointCTCAE grade 3+ definitely related GI toxicity within 90 days
Primary resultZero definitely treatment-related grade 3+ toxicities; primary endpoint met
2-year local controlNearly 80% overall; about 70% in LAPC; >90% in BR disease that proceeded to resection
2-year OS contextBR SMART about 60.1%; LAPC SMART about 34.3%
Why SMART matters: it is the clearest example in the deck that ART is not just about convenience; it is about making an otherwise aggressive, ablative prescription deliverable without unacceptable GI toxicity.

Current and Ongoing GI / Hepatobiliary Adaptive Trials

TrialDisease / questionAdaptive takeaway
ARTIACT-guided ART for BR/LAPCSingle-arm phase II evaluating whether CTgART reduces acute and late toxicity compared with historical controls
NRG GI-011 "LAP-100"Phase III dose-escalated RT in LAPCAllows both CT- and MR-guided online ART
NRG GI-012 "HELIO-RT"HCC with macrovascular invasion, IO +/- SBRTAlso allows both CTgART and MRgART

HCC Example: Why Daily Adaptation Matters

In the HCC HELIO-RT example, a day-1 plan met stomach and bowel constraints, but by day 2 the large bowel constraint of < 33 Gy to 0.5 cc was violated, with parts of bowel exceeding 40 Gy. Post-adaptation, bowel was protected while target coverage was maintained. This is the board-style illustration of why ART matters for mobile upper-abdominal anatomy.

PART III — CLINICAL PILLAR #2: MARGIN REDUCTION

DARTBOARD Phase II Randomized Trial

FeatureDetails
Core strategy1 mm PTV margin with daily ART instead of 5 mm standard IGRT margin
Dosimetric effectReduced parotid and submandibular gland dose, smaller targets
Primary endpointXerostomia Questionnaire (XQ) at 1 year
Workflow timingCBCT to end of RT: 33 min; door-in to door-out: 39.4 min; MD contour time: 12.6 min; MD at console: 22 min

DARTBOARD Toxicity and Oncologic Outcomes

OutcomeIGRTDARTComment
Dermatitis grade 2+31%8%Statistically lower with adaptive treatment
Mucositis grade 2+92%75%Trend favoring ART
Dysphagia grade 2+81%75%No clear difference
Dysphagia grade 3+19%8%Numerically lower with ART
Safety signal: median follow-up was about 18 months, there were no marginal recurrences, and the single local recurrence was in-field and salvaged. That is exactly the kind of disease-control reassurance required for margin-reduction strategies.

PART IV — CLINICAL PILLAR #3: EXTREME HYPOFRACTIONATION, SAFELY

SMART ONE Phase II Trial

FeatureDetails
Patients / lesions30 patients, 32 sites treated
Platform0.35T MR-Linac
Design goalSingle-fraction SBRT with grade 3+ toxicity <15%
Adaptive useOnline ART used in 17/32 sites (53%)
Primary safety resultAcute grade 3+ toxicity 10%; late grade 3+ toxicity 0%; zero definitely or probably related to SBRT
VolumesMedian GTV 3.7 cc; median PTV 15.8 cc

SMART ONE Prescription Table

Target locationPrescriptionBED10
Lung30-34 Gy x 1120-149.6 Gy
Liver35-40 Gy x 1157.5-200 Gy
Adrenal25 Gy x 187.5 Gy
Abdominal / pelvic LN25 Gy x 187.5 Gy
Kidney25 Gy x 187.5 Gy
Pancreas25 Gy x 187.5 Gy

MOMENTUM Registry and the Prostate Model

The prospective MOMENTUM registry across 1.5T MRgART sites now contains over 8,000 patients, about 98,000 MRI scans, and 33,800 dose plans. One registry-generated hypothesis is that MRgART may lower toxicity in 5-fraction prostate regimens relative to historical standards, whereas that advantage is less obvious with conventional fractionation.

HERMES Randomized Phase II Trial

FeatureArm 1Arm 2
PopulationIntermediate-risk / lower high-risk prostate cancer
Adaptive strategyDaily ART for all patients, 3 mm PTV for all
Dose36.25 Gy / 5 fx24 Gy / 2 fx
BoostCTV to 40 GyGTV SIB to 27 Gy / 2 fx
Primary endpointAcute grade 2+ GU toxicity, benchmarked against a 62% historical rate (PACE-B based)
Board pearl: HERMES is not just a prostate trial; it is a proof-of-concept that ART may help push SBRT toward fewer fractions while maintaining acceptable toxicity. The slide explicitly frames the next step as the larger SABR-DUAL phase II/III effort.

ARCHER (NRG GU-015) — Phase III Bladder Trial

FeatureDetails
QuestionCan 5-fraction adaptive SBRT be non-inferior to 20-fraction hypofractionated RT for bladder-intact event-free survival?
ART requirementMandatory ART, CT- or MR-guided
Systemic therapyConcurrent chemo allowed: weekly cisplatin, gemcitabine, or 5-FU + mitomycin-C
Primary endpoint3-year BI-EFS with a 10% non-inferiority margin (HR < 1.32)
Sample sizeN = 486
PTV margins shown on slideAdaptive arm approximately 7 mm vs conventional arm 1 to 1.5 cm

PART V — IMPLEMENTATION: HOW TO BUILD AN ART PROGRAM

ART Has Reached the Mainstream

The deck emphasizes that online ART is no longer a niche physics project. There are now published safety white paper guidelines addressing quality, personnel, and workflow, and ART has already entered phase III cooperative-group trials.

The Roadmap to Launch

PhaseCore tasks
Pre-workChoose platform and supporting technologies; identify champions; align with department strategy
Team preparationTrain the whole team; build workflows and procedures by disease site / indication
Go-live and beyondPeer support, quality assurance, continuing education, and program growth

Platform Selection: MR-Linac vs CT-Guided ART

PlatformStrengthsTradeoffs
MR-LinacReal-time MR guidance; cine MRI gating; continuous motion management; excellent soft-tissue visualizationSlower throughput and setup limitations for standard IGRT-style workflow
CT-guided ARTBuilt on high-throughput CBCT platforms; broader day-to-day clinical versatility; lower capital costMotion management is less intrinsically robust and may require paired technologies (ABC, surface guidance, etc.)

Where to Start: Choose High-Yield Champion Sites

The speaker's own center started with pancreas SBRT and prostate SBRT with nodal SIB, explicitly because they had the volume and the physician/physics champions to support them. The board-style implementation lesson is simple: volume does not appear from thin air; ART programs start where there is real clinical pull and committed local expertise.

Operational Pieces That Need to Exist Before Go-Live

  • Coverage model: choose it deliberately and expect it to evolve.
  • Team-wide training: ASTRO task-force guidance recommends broad multidisciplinary training, not just physician and physics education.
  • Adaptive school curriculum: system overview, clinical rationale, planning templates, imaging, case-based ART, documentation, billing, and even retention quizzes.
  • Handoff design: communicate goals of ART, what to re-contour, what constraints matter most, key anatomy issues, setup needs, and whether the patient may need analgesics or anxiolytics.
  • Documentation: the ASTRO white paper includes practical templates.
  • Ongoing quality culture: regular peer review and continuing education remain essential after launch.

PART VI — FUTURE DIRECTIONS: SIM-FREE WORKFLOWS AND NEW PLATFORMS

FAST METS: Direct-to-Unit / Sim-Free Palliative ART

FAST METS treated 47 patients using a simulation-free ETHOS-based adaptive workflow for palliative treatments. Diagnostic CT was used to pre-plan, symptom review was performed before arrival, and final plan recalculation / optimization occurred on the treatment unit. Average total treatment time, including consult, was 85 minutes, with average on-couch adaptive time of 30 minutes.

ONE-STOP Phase II Trial

FeatureDetails
ConceptSimulation-free, one-fraction CT-guided stereotactic adaptive treatment for early-stage NSCLC or oligometastatic lung lesions
Primary endpointFeasibility of the sim-free workflow in at least 70% of selected patients
Prescription targetLow-risk peripheral lung lesions suitable for 34 Gy x 1
Inclusion highlightsTarget <5 cm, >2 cm from proximal bronchial tree / mediastinum, estimated SI motion ≤1 cm
Status shown on slide10 / 10 patients successfully accrued and treated
Board pearl: for the purpose of ONE-STOP, a backup conventional sim CT was still obtained for dosimetric comparison and as a rescue plan if direct-to-unit treatment could not be completed. "Sim-free" does not mean "no safety net" in early clinical development.

Adaptive on Additional Systems

  • C-arm linac adaptive RT: first commercial platform announced in 2024, CE mark granted 9/16/24, FDA 510(k) cleared 1/19/2026.
  • Proton online ART: the deck highlights one of the first online ART proton cases at WashU in June 2024, within the PARTy clinical trial framework.
  • Functional MR / biologic guidance: the lecture flags MRgART and BgART as the next layer of adaptation beyond purely geometric replanning.

Where ART Is Likely to Land Long-Term

The speaker's long-term view is that ART becomes a versatile, common solution rather than a niche technique: not used in every case, but applicable in most modalities and treatment styles, much like IMRT, VMAT, and SBRT eventually became.

CROSS-CUTTING HIGH-YIELD POINTS

  • Definition: online ART = same-day re-contouring / re-optimization on the treatment table.
  • Three prerequisites: adequate on-board imaging, fast paired TPS, and online pretreatment QA.
  • Development logic matters: imaging study → in silico workflow testing → pilot / phase I → larger prospective trials.
  • MRgRT low-field platform: 0.35T, no imaging dose, 4 or 8 f/s, automatic gating, better soft-tissue visualization than standard C-arm CBCT.
  • In silico pancreas SMART: daily ART predicted to be needed in 63% of fractions to protect OARs.
  • Phase I adaptive upper-GI SMART: OAR violations in 70/95 fractions, all resolved by ART, with 0 grade 3+ acute GI toxicity.
  • SMART pancreas phase II: 50 Gy / 5 fx, BED10 100 Gy, with zero definitely related grade 3+ GI toxicity.
  • HELIO-RT liver example: large bowel constraint on the slide was < 33 Gy to 0.5 cc; adaptation corrected a day-to-day violation.
  • DARTBOARD: margin reduction from 5 mm to 1 mm lowered dermatitis and produced no marginal recurrences.
  • SMART ONE: 1-fraction SBRT on 0.35T MR-Linac; ART used in 53% of sites; 10% acute grade 3+, 0% late grade 3+, and zero definitely/probably related events.
  • SMART ONE key doses: lung 30-34 Gy x 1, liver 35-40 Gy x 1, adrenal / kidney / pancreas / abdominal-pelvic LN 25 Gy x 1.
  • HERMES: prostate daily ART with 36.25 Gy / 5 or 24 Gy / 2 regimens, all with 3 mm PTV.
  • ARCHER: phase III bladder trial; mandatory ART; 5-fx SBRT vs 20-fx hypofractionated RT; N = 486.
  • ART is now mainstream: safety white paper exists, and cooperative-group phase III trials are open.
  • Platform tradeoff: MR offers superior visualization and motion management; CT-guided adaptive offers higher throughput and versatility.
  • Implementation lesson: start with high-volume disease sites and true local champions.
  • Sim-free future: FAST METS and ONE-STOP show that ART can compress consult + planning + treatment into a single visit for selected indications.
  • C-arm adaptive and proton adaptive mark the expansion of ART beyond ring-gantry MR/CT adaptive systems.

CONSOLIDATED DOSE AND WORKFLOW TABLE

Use case / trialDose / margin / workflowWhy it matters
Upper-GI / pancreas SMART development50 Gy / 5 fxCanonical ablative adaptive GI example
SMART pancreas phase II50 Gy / 5 fxAblation with strict OAR governance and favorable early safety
HCC adaptive exampleLarge bowel constraint < 33 Gy to 0.5 ccIllustrates day-to-day OAR violation rescue
DARTBOARD1 mm PTV vs 5 mmMargin reduction as a therapeutic-index tool
SMART ONE lung30-34 Gy x 1Extreme adaptive hypofractionation
SMART ONE liver35-40 Gy x 1Single-fraction adaptive liver SBRT
SMART ONE adrenal / pancreas / kidney / A/P LN25 Gy x 1Single-fraction adaptive multi-site use
HERMES arm 136.25 Gy / 5 fxAdaptive prostate SBRT reference arm
HERMES arm 224 Gy / 2 fxMore extreme adaptive prostate hypofractionation
ONE-STOP34 Gy x 1Simulation-free direct-to-unit lung workflow
FAST METSAverage on-couch adapt time 30 minDemonstrates palliative sim-free feasibility

KEY LANDMARK TRIALS (memorize)

Trial / studyTopicOne-line takeaway
Noel et al. 2015MRgRT imaging qualityLow-field MR provided superior soft-tissue visualization vs standard C-arm CBCT
Henke et al. 2016In silico SMARTPredicted daily ART need in 63% of fractions and reversal of all modeled OAR violations
Henke et al. 2018Phase I adaptive upper-GI SBRTFeasible and safe; 70/95 fractions needed adaptation to fix OAR problems
Parikh et al. 2023SMART pancreas phase II design50 Gy / 5 fx ablative adaptive pancreas platform trial
Chuong et al. 2024SMART pancreas outcomesAbout 80% 2y LC overall with favorable BR/LAPC survival context
DARTBOARD (Scher et al. 2025)Margin reduction1 mm PTV adaptive strategy reduced dermatitis and produced no marginal failures
SMART ONE (Chuong et al. 2025)Extreme adaptive hypofractionationSingle-fraction MR-guided SBRT was feasible with acceptable toxicity
MOMENTUM registry1.5T MRgARTLarge prospective registry now generating site-specific hypotheses and trial ideas
HERMES (Cooper et al. 2025)Adaptive prostate SBRTRandomized phase II platform for 5-fx vs 2-fx daily adaptive prostate treatment
NRG GU-015 ARCHERAdaptive bladder preservationPhase III non-inferiority test of 5-fx adaptive SBRT vs 20-fx hypoRT
FAST METS (Nellison et al. 2023)Sim-free palliative ARTShowed direct-to-unit adaptive workflows can be practical in selected palliative cases
ONE-STOPSim-free lung SBRTProspective test of direct-to-unit 34 Gy x 1 CT-guided adaptive lung treatment
ARTIACT-guided pancreas ARTExtends adaptive evaluation beyond MR-guidance for BR/LAPC
NRG GI-011 / GI-012Phase III GI / liver adaptive integrationMarks ART's transition into cooperative-group phase III trial design