onc brain

Phase 3 RCT, N=1465 randomised at 39 UK centres. Primary endpoint is biochemical/clinical failure; the side-effect endpoints presented here are secondary. Early toxicity assessed to 18 weeks, late toxicity at 2 years.

Localised prostate cancer, with the slides naming the high-risk localised group as most likely to benefit from the interventions under test. Full eligibility criteria not stated in the source.

20-fraction moderately hypofractionated IMRT in all arms. Randomisation is to prostate alone (388), prostate + focal boost (464), or prostate + pelvic nodes + focal boost (462), so the trial separates the boost question from the nodal question. Prescription dose and boost dose level not stated in the source slides.

Primary: biochemical/clinical failure, not reported at this presentation. Secondary (reported here): early bowel and bladder side effects to 18 weeks and late G2+ events at 2 years.

Nodal RT increased early bowel side effects, resolving by 18 weeks. Late cumulative rates were reported for the 973 (74%) patients with at least 2 years' follow-up.

The nodal question in prostate RT is currently split: POP-RT favoured whole-pelvis RT on biochemical failure-free survival while PEACE-2 was null on its nodal comparison, and both used conventional or near-conventional fractionation. PIVOTALboost is the first randomised test of pelvic nodal coverage in a 20-fraction schedule, so its eventual efficacy readout is the one that transfers to how most UK and increasingly non-UK practice actually delivers prostate RT.

The late analysis rests on the 74% with 2 years of follow-up, so a differential drop-out by arm would bias the comparison, and cumulative-incidence estimates at 2 years cannot address the fibrotic and stricture toxicity that appears at 5 to 10 years. The source does not state the grading instrument, and a clinician-graded versus patient-reported difference materially changes the size of a G2+ bowel signal.

A safety readout without its efficacy partner cannot move the nodal decision on its own, but it does close off one of the two arguments against nodal coverage in the hypofractionated era. The remaining argument is whether pelvic nodal RT does anything for disease control, which this trial is powered to answer and has not yet reported.

Randomised phase 3, but this is the secondary toxicity readout only; the biochemical/clinical failure primary endpoint is unreported, so it settles safety, not benefit.

Phase III equivalence trial, 1:1 randomisation, n=520, accrued 2005-2013, median follow-up 15 years. Powered at 80% against a 5-year estimated IBTR of 3% with a 5% equivalence margin. Survival outcomes analysed ITT; toxicity and cosmesis per protocol after 14 withdrawals.

Post-breast-conserving-surgery early breast cancer: pT <25 mm, final surgical margins ≥5 mm, age >40 years. A selected, low-risk population by design.

PBI arm: 30Gy in 5 fractions delivered by IMRT (n=260). WBI arm: 50Gy in 25 fractions plus a 10Gy in 5-fraction tumour-bed boost (n=260).

No endpoint separated the arms at 15 years. The IBTR point estimate favours WBI (HR 1.57, 95% CI 0.82-3.04, p=0.17) but the confidence interval spans unity.

Florence remains the only randomised test of a 5-fraction IMRT PBI schedule with follow-up this long; other external-beam PBI randomisations used different dose and fractionation, so their recurrence rates are not directly interchangeable with this one. The direction here, a numerically higher IBTR concentrated in new primaries, is the pattern PBI trials have consistently reported when they separate the two.

The trial was sized for 5-year equivalence, so the 15-year IBTR comparison is a long-term description rather than a powered test, and the upper CI bound of 3.04 leaves room for a real excess. The relapse-versus-new-primary split is an adjudicated distinction, not a molecularly confirmed one, and it carries the entire reassurance.

The result supports continuing PBI in Florence-eligible pts rather than expanding the indication. It does not settle whether the new-primary excess is a genuine consequence of leaving untreated breast tissue unirradiated, which is biologically the expected cost of the approach and would not be captured by any local-control endpoint.

Randomised phase III with mature 15-yr follow-up; no significant difference on any oncological endpoint. Supports an already guideline-listed de-escalation rather than establishing a new one.

Three-arm randomised multicentre trial, 1:1:1, N=2617 across 76 UK hospitals, recruited 2009-2015. Annual clinical follow-up to 10 years; PRO and photographic assessment collected only to 5 years.

Women ≥18 after breast conserving surgery for invasive early breast cancer, pT1-3, pN0-pN3a, M0, all requiring a tumour bed boost. Described as a higher-than-average risk group.

40Gy/15F + 16Gy/8F sequential boost (N=871), 48Gy/15F SIB at 3.2Gy/F (N=874), 53Gy/15F SIB at 3.5Gy/F (N=872). The SIB arms escalate to the regions at highest risk with a modest dose reduction to whole breast distant from tumour, all delivered in 3 weeks.

Endpoint reported here: ipsilateral breast tumour relapse at 10 years. The original sample size calculation assumed a 5% control rate at 5 years. Absolute OS difference and clinician-assessed normal tissue effects also reported.

The 5-year ordering holds at 10 years: the two lower-dose groups sit close together and 53Gy/15F stays highest. Both absolute OS differences vs 40Gy/15F have intervals containing zero.

Moderate/marked effects at 10 years were given as bounds across all randomised groups: <18% breast distortion or shrinkage, <10% induration, <2% telangiectasia, <2% breast oedema. No per-arm split reported in source.

EORTC 22881-10882 established the tumour bed boost itself; IMPORT HIGH asks how to deliver it and whether more dose helps. At 10 years, integration works and escalation does not, the same ranking the 5-year publication (Coles et al. Lancet 2023;401:2124-37) reported.

PRO and photographic assessment stopped at 5 years, so the 10-year toxicity comparison rests on clinician scoring reported as all-group bounds, not per-arm rates. Observed IBTR also ran below the 5% control rate the sample size calculation assumed.

The practical read is fraction count, not dose: a boost folded into 15 fractions removes the separate 16Gy/8F phase with no 10-year IBTR cost, while 53Gy/15F returns nothing. What the trial does not settle is whether the same integration transfers to 5-fraction whole-breast schedules.

Mature 10yr follow-up of a 2617-pt randomised trial; extends the 5-year Lancet 2023 read rather than changing it. No formal 10yr non-inferiority margin stated in source.

Phase III randomised non-inferiority trial, 1:1, run across Denmark, Norway and Germany from 2009-2014. These are the prespecified 10-year analyses of toxicity, recurrence and survival, at a median follow-up of 12.8 years.

1,882 women with node-negative breast cancer or DCIS. After exclusions (13 and 16), 933 and 936 women were analysed in the two arms, with 917 carried into the morbidity analysis of one arm.

Whole-breast irradiation only: 50 Gy in 25 fractions versus 40 Gy in 15 fractions. No regional nodal irradiation question is posed, and boost details are not reported in the source slides.

Primary: grade ≥2 breast induration at 3 years, requiring two consecutive visits or the final follow-up. Morbidity was scored at years 0, 1, 2, 3, 4, 5 and 10; recurrence and survival are the co-reported 10-year outcomes.

The toxicity endpoint is the positive result here: 10-year grade 2-3 induration 24.7% with 50 Gy vs 19.5% with 40 Gy, HR 0.76 (0.62-0.92), p=0.005. The fibrosis advantage of hypofractionation is durable, not an early-follow-up artefact.

START-B and the UK 10-year hypofractionation data established 40 Gy/15 fr as at least equivalent for control with less normal-tissue effect; DBCG HYPO reproduces that direction in a contemporary node-negative and DCIS population treated 2009-2014, in an era of CT planning and modern systemic therapy rather than the 1990s cohorts.

Breast induration is a clinician-scored endpoint and the source does not state whether assessment was blinded, which matters when the two arms are trivially distinguishable by treatment duration. Locoregional recurrence, distant failure and breast cancer mortality are reported only as 'no significant difference' with no event counts or confidence intervals in the source, so the precision of the non-inferiority claim cannot be judged from these slides.

A 5.2-percentage-point absolute reduction in decade-level grade 2-3 induration is a real cosmetic and symptomatic difference in a population most of whom will never recur. The OS HR of 0.81 (0.63-1.04) is directionally in favour of the shorter schedule but is not significant and should not be read as a survival benefit of hypofractionation.

Randomised phase III, prespecified 10-yr analysis, 12.8-yr median follow-up, primary toxicity endpoint favours 40 Gy/15 fr. Reinforces already-standard moderate hypofractionation rather than changing it.

Pre-planned secondary analysis of the HypoG-01 phase III trial, analysed ITT. N=1,260, median follow-up 4.8 years. Reported as a patterns-of-failure and dosimetric mapping study, not a re-test of the parent efficacy endpoint.

Randomisation was 40 Gy/15 fractions over 3 weeks vs 50 Gy/25 fractions over 5 weeks, each with a tumour-bed boost. Contouring followed ESTRO guidelines, which is what makes the in-volume/marginal classification interpretable rather than institution-specific.

Primary event was the first oncological event: locoregional recurrence, distant recurrence, or second malignancy. LRR was classified against the CTV as in-volume (within CTV), marginal (outside CTV but ≥50% prescribed dose), or out-of-volume (<50%). Planned dose at each recurrence site was re-estimated on the original planning CT.

118 first events. Distant recurrence and second malignancy dominated (61 and 37); LRR was the least common first event at 20/118. Among 30 iLRR sites, 20 (67%) were in-volume and 19/30 were nodal, mainly levels 1 and 2.

The dosimetric read is retrospective by construction: dose at the recurrence site is estimated on the initial plan CT, so anatomic change and registration error over a median 4.8 years both push sites toward an in-volume label. The event count also caps what can be concluded, since 30 sites split across two arms leaves the "not obviously different" claim underpowered rather than negative.

START-B and FAST-Forward established that moderate and ultra-hypofractionation do not cost local control, but neither mapped recurrence sites against the CTV. The contribution here is geographic rather than actuarial: it tests whether the *volume*, not the *dose per fraction*, is where hypofractionated regional treatment could fail.

A 67% in-volume rate reframes residual LRR as a biology problem, not a coverage problem: pts recurred where dose was delivered. The nodal concentration in levels 1 and 2 is the one signal worth watching, since those are the levels most variably treated when surgical axillary management is de-escalated.

Pre-planned secondary analysis, descriptive only. No per-arm effect size or statistical comparison in source; 30 iLRR sites cannot exclude an arm difference.

Population-based Dutch cohort from the Netherlands Cancer Registry linked to pathology, on behalf of the DBRT group. Treatment years 2012-2016, follow-up to 10 years. Observational, no randomisation and no adjusted comparison reported in source.

Breast-conserving treatment with or without an RT boost, N=31,348 across the three risk strata. Stratification is by a count of five risk factors: age ≤40, grade 3, triple-negative, guideline-indicated systemic therapy not adequately given, and no pCR after neoadjuvant chemo in TNBC or HER2+.

Whole-breast RT with or without a tumour bed boost. Boost dose, fractionation, technique (photon vs electron vs SIB) and the WBRT schedule are not reported in the source slides, which limits transfer to a specific departmental protocol.

Primary: ipsilateral breast tumour recurrence (IBTR), histologically confirmed, identified by an algorithm over pathology report codes and free text. Reported as cumulative incidence at 5 and 10 years by risk-factor count. Benchmarked against the Assisi thresholds: omission acceptable at <3% 10yr IBTR with boost, <6% without.

IBTR was low in every stratum. The only cell crossing an Assisi threshold was ≥3 risk factors treated with a boost at 10 years, and even there the no-boost value in the same stratum was lower.

EORTC 22881-10882 established that a boost roughly halves IBTR, and that trial's control-arm event rates were an order of magnitude above these. IMPORT HIGH and the 2024 Assisi think tank both moved the field toward de-escalating or restricting the boost; this cohort supplies the contemporary absolute rates those recommendations assumed but could not show.

Boost was allocated by guideline-based risk, so the boost groups are adversely selected and the raw contrast understates any boost effect; the higher rate in the ≥3 boost group is the visible signature of that confounding. The ≥3 no-boost cell holds only 149 pts, and the 'uncertain' stratum (592 / 944) shows a boost-no-boost gap wide enough to suggest unmeasured risk is driving allocation there too.

The finding is about absolute rather than relative benefit: a preserved 50% relative reduction applied to a 1.2% 10-year event rate is not worth five extra fractions and a fibrosis penalty. What the cohort cannot say is whether the boost is the reason those low-risk rates are low, since roughly half the low-risk group received one.

Registry cohort, no randomisation and no adjusted effect estimate; boost allocation confounded by risk. Supports the direction already set by IMPORT HIGH and Assisi thresholds.

Prospective EORTC OligoCare registry cohort, interim analysis. 57 institutions, enrolment July 2019 to July 2025. No randomisation and no comparator arm; technique and dose were chosen by the treating institution.

2447 eligible pts with 3533 lesions. Median age 69 (range 28-94), 69% male. Primaries reported for the local-control breakdown were prostate (1021), NSCLC (530), colorectal (518) and breast (378).

SABR to oligometastatic lesions across bone (869 non-vertebral, 515 spine), lung (807), non-regional nodes (558), liver (306), brain (231) and other (247) sites. Minimum PTV dose was the technical factor most associated with outcome; specific dose and fractionation schedules are not reported in source.

Local in-field progression, reported as cumulative incidence with 99% CI, at 1 and 3 years. Median follow-up 31 months, minimum 6 months.

Overall local in-field progression 5.0% at 1yr and 11.4% at 3yr, ie 88.6% local control at 3yr. By primary, colorectal was the outlier and prostate the best.

Randomised oligometastatic SABR trials (SABR-COMET, STOMP, ORIOLE) were built on much smaller, more selected cohorts and reported survival or progression endpoints rather than lesion-level in-field control at this scale. This registry does not test the SABR question those trials asked; it reports what in-field control looks like once SABR is delivered in routine multi-institutional practice.

Dose and fractionation were institution-chosen, so the minimum-PTV-dose association is confounded by target site, prior irradiation and case selection. No PTV dose threshold, no per-primary dose data and no toxicity are reported in source, so the technical conclusion cannot be translated into a planning constraint.

The CRC finding is the one that changes a plan: worst local control despite the highest median dose per fraction points at intrinsic radioresistance rather than underdosing, and the authors call for escalation or combination strategies. The de novo versus repeat OMD gap is reported as a dose effect, which is plausible but is exactly the kind of comparison a registry cannot separate from the reasons a lesion is being re-treated.

Prospective multi-site registry, no randomised comparator, institution-chosen technique. Large real-world cohort supports existing SABR practice in OMD rather than testing it.