onc brain

Multicenter, open-label, non-inferiority phase 3, randomized 1:1. 432 pts enrolled April 14, 2010 to July 1, 2019; median follow-up 7.2 years. Non-inferiority margin not reported in source.

Newly diagnosed stage I-II DLBCL achieving CR/CRu after anthracycline-based chemo with/without rituximab. Age criterion printed as '=15 years' in the portal text. Bulk, IPI and PET status at response not reported in source.

30 Gy vs 40 Gy consolidative involved-site/field RT. Fraction size, technique and the split between involved-site and involved-field volumes are not reported in source.

Primary: 5-year PFS, tested for non-inferiority of 30 Gy. Also reported: OS, locoregional recurrence, acute and late toxicity including second malignancies.

Primary endpoint met (table). OS and locoregional recurrence showed no difference between arms; the source gives no rates or HRs for either.

Acute and late toxicities, including second malignancies, were comparable between arms. No rates or grades reported in source, so no measured toxicity advantage for 30 Gy.

The source states no prior randomized trial compared these two doses in DLBCL specifically. The UK NHL dose-reduction RCT (Lowry et al.) asked a similar de-escalation question in aggressive NHL more broadly, and ILROG guidance already favors the lower consolidative dose after CR, so this result is concordant with that direction.

Enrollment spans 2010 to 2019 with rituximab optional and response graded as CR/CRu, so systemic therapy and response assessment may not match current PET-adapted practice. Mixed involved-site/field volumes are not broken out. Abstract only: no event counts, no margin.

With PFS near 90% in both arms and locoregional recurrence no different, the higher dose bought no measurable disease control in pts already in CR. What the trial does not settle is whether the lower dose reduces late effects (not shown at 7.2 years) and whether any RT is needed after a PET-negative response.

Randomised phase 3, prespecified non-inferiority primary met at 7.2-year median f/u; source calls 30 Gy the new standard. Caveats: margin and fractionation unreported, rituximab optional.

International randomised, unmasked, factorial phase 3, 136 centres across six trial groups in 11 countries. N=1608 accrued 2007-2014; median f/u 6.6 yr.

Women ≥18y with unilateral, histologically proven non-low-risk DCIS after breast-conserving surgery with ≥1 mm clear radial margins.

WBI either 50 Gy/25 fx (n=831) or 42.5 Gy/16 fx (n=777), randomised in a 4-arm factorial or chosen per centre. Boost 16 Gy/8 fx to tumour bed after WBI.

Primary: time to local recurrence. Toxicity reported as G2+ breast pain and induration.

Boost raised G2+ breast pain (14% vs 10%, p=0.003) and G2+ induration (14% vs 6%, p<0.001).

Older DCIS trials (NSABP B-17, EORTC 10853) established WBI after lumpectomy but did not test boost; the EORTC boost trial tested it only in invasive disease. This is the first randomised boost evidence in DCIS.

The fractionation-sensitivity result is not reported in the source abstract, so hypofractionation non-inferiority in DCIS cannot be read from it. Toxicity is assessor-unmasked, and no survival endpoint is reported.

A boost roughly halves local recurrence hazard in non-low-risk DCIS at a real cost in G2+ breast morbidity. It does not settle which non-low-risk subsets carry enough baseline risk to justify that trade.

Adequately powered phase 3 RCT, primary endpoint hit with 6.6-yr median f/u; first randomised boost data in DCIS. Qualified by unmasked design and added G2+ toxicity.

Phase III noninferiority RCT, 17 centers, accrual 2015-2021. ITT cohort n=2,908 (1,444 at 50Gy, 1,464 at 40Gy). Accrual continued until 3-year lymphedema estimates were reported in 1,012 patients.

High-risk breast cancer with an indication for locoregional radiotherapy, the population where nodal coverage has kept 25 fractions standard in Denmark. Median age 57 (range 23-86).

Standard arm 50Gy/25fx, experimental arm 40Gy/15fx, both delivered to the locoregional volume rather than breast or chest wall alone. That target volume is the whole point: it is where the morbidity concern lives.

Primary: arm lymphedema at 3 years, with an assumed 10% incidence under 50Gy/25fx and noninferiority predefined as maximum 5 percentage points excess. Cancer endpoints (locoregional recurrence, distant recurrence, breast cancer mortality, all-cause mortality) were assessed within 8 years.

Lymphedema 8.0% vs 9.4%, OR 0.84 (0.62-1.14), P=.27, comfortably inside the margin. Cancer-outcome HRs are tabulated above and show no difference by random assignment.

The UK hypofractionation programme (START A/B, then FAST-Forward) established 40Gy/15fx and shorter for breast and chest wall, but node-positive patients receiving comprehensive regional coverage were a small fraction, which left the nodal question open. Skagen 1 tests exactly that gap prospectively with morbidity as the primary endpoint.

Median lymphedema follow-up of 4.1 years captures the 3-year endpoint but not the later plateau, and the abstract reports no brachial plexopathy, shoulder, cardiac, or pulmonary late toxicity. The BC mortality HR 1.25 (0.93-1.66) runs the wrong way with a CI that does not exclude harm; the trial was sized for lymphedema, not survival.

The trial removes the specific objection that blocked hypofractionated nodal RT rather than merely adding another positive fractionation result. It does not settle very-long-term arm and shoulder function, nor whether the same holds with a simultaneous integrated boost or in reconstructed chest walls.

Phase III, prespecified noninferiority margin met on the morbidity endpoint that blocked nodal hypofractionation, with 8yr recurrence and mortality HRs showing no difference.

Prespecified IPD meta-analysis of two open-label, randomised (1:1) phase 3 trials in the STAMPEDE platform, run at 113 UK and Swiss sites. N=1974, randomised 2011-2016, with no overlapping controls. Median follow-up was 72 mo.

High-risk non-metastatic prostate cancer on conventional imaging: N+, or N0 with at least two of T3/T4, Gleason 8-10, or PSA ≥40 ng/mL. Pts relapsing with high-risk features were also eligible. Median age was 68, and 774 (39%) were node-positive. Clinically significant cardiovascular disease was excluded.

All pts received 3 yr ADT. The combination arm added abiraterone 1000 mg + prednisolone 5 mg daily for 2 yr, and the second trial also added enzalutamide 160 mg. If RT was omitted, treatment could continue until progression.

Per local guidelines: 74 Gy/37 fx to prostate + SVs or a hypofractionated equivalent. RT was mandated for N0 and encouraged for N+. RT was planned in 85% overall: 99% of N0, 71% of N+ and 7% of previously treated pts.

Primary: MFS, which was changed from OS before any efficacy inspection and approved by the steering committee on Dec 2, 2019. Secondary endpoints were OS, prostate cancer-specific survival, biochemical failure-free survival, PFS and toxicity.

Both trials showed the benefit on their own: MFS HR 0.54 in the abiraterone trial and 0.53 in the abiraterone + enzalutamide trial, with no between-trial heterogeneity (I² p=0.90).

Grade 3+ AEs in the first 24 mo were 37% vs 29% in the abiraterone trial and 58% vs 32% in the abiraterone + enzalutamide trial. The main drivers were hypertension and ALT elevation. There were 7 grade 5 events, all in the combination arms.

The backbone is long-course ADT with prostate RT, which the authors frame as standard for this population. Adding enzalutamide to abiraterone also gave no extra benefit here, consistent with the modest rPFS gains and absent OS benefit the authors cite from that combination in mCRPC.

Staging used conventional imaging only. Toxicity was reported only for the first 2 yr, and data on subsequent therapy are unreliable. Heterogeneity by PS 1-2 (HR 0.86, 0.58-1.28) makes the benefit less certain in less fit men.

Abiraterone intensification improved MFS and OS on top of ADT whether or not RT was planned. Enzalutamide added toxicity without extra efficacy. Open questions are the right duration, the benefit after prostatectomy, and the benefit in PSMA-staged disease, none of which were tested.

Pooled IPD from two randomised phase 3 trials, 72-mo f/u, with both MFS and OS improved. The OS→MFS switch was prespecified before efficacy was seen. Authors call it a new standard.

International phase 3 randomized trial (BIG 2-04 MRC/EORTC SUPREMO), 125 UK sites plus 27 European and 21 international sites. N=1607 ITT (808 CWI, 799 no CWI), randomized August 2006 to April 2013, database lock June 2024. Median follow-up 9.6 years.

"Intermediate-risk" post-mastectomy disease: pT1N1, pT2N1, pT3N0, or pT2N0 with grade 3 and/or LVI. All had mastectomy, an axillary procedure, and systemic therapy. Baseline systemic exposure: 85% chemotherapy, 79% endocrine, 19% trastuzumab.

Chest wall 40 to 50 Gy in the irradiation arm. Nodal volumes were not part of the randomized question: supraclavicular fossa treated in only 97/808 irradiated patients, internal mammary chain in 12/808. Twelve patients in the no-irradiation arm received SCF treatment.

Primary: overall survival at 10 years. Secondary: chest-wall recurrence, regional recurrence, disease-free survival, distant metastasis-free survival, cause of death, radiation-related adverse events.

The historic case for postmastectomy RT in node-positive disease rests on the EBCTCG overview, where the locoregional-control gain translated into a mortality benefit. SUPREMO tests that inheritance in the 1-3 node and high-risk node-negative band under contemporary systemic therapy and finds the recurrence signal preserved (HR 0.45) but the survival signal absent (HR 1.04).

The chest-wall recurrence benefit rests on 29 events total with a CI upper bound of 0.99, so the point estimate is unstable. Accrual ran 2006-2013, predating routine dual HER2 blockade, extended adjuvant CDK4/6 inhibition, and current genomic risk stratification, all of which lower the baseline recurrence rate this trial was powered against.

A flat OS with a halved chest-wall recurrence is the signature of a locoregional intervention operating below the threshold where local control converts into survival. At 1.1% vs 2.5%, the absolute chest-wall event rate in both arms is low enough that no plausible salvage-to-mortality pathway could move a 10-year OS curve. The result reframes PMRT in this band as a local-control decision to be weighed against RT morbidity, not as a survival decision.

Adequately powered phase 3, prespecified OS primary, 9.6yr median follow-up, modern systemic backbone. Supports omitting PMRT in a population where guidelines still often recommend it.

Prospective randomized phase 3 noninferiority trial, 1:1, 67 hospitals in Sweden, Denmark, Germany, Greece and Italy. 2766 enrolled Jan 2015 to Dec 2021; per-protocol population 2540 (1335 sentinel-node biopsy only, 1205 completion dissection). Median follow-up 46.8 months (range 1.5 to 94.5).

cN0, T1 to T3 breast cancer with one or two sentinel-node macrometastases (>2mm). Preoperative axillary ultrasound was mandatory; suspicious nonpalpable nodes were still eligible even with FNA-confirmed metastasis. Additional micrometastases and extracapsular extension were allowed, and both breast-conserving surgery (63.3% / 64.3%) and mastectomy (36.7% / 35.7%) were eligible. Mean age 61.

RT including nodal target volumes was given to 89.9% (1192/1326) of the sentinel-node-only group and 88.4% (1058/1197) of the dissection group. Whole-breast RT was mandatory after breast-conserving surgery, but the protocol stipulated no specific target volumes or doses, deferring to national guidelines. QA on 1154 plans showed eCRF-to-plan concordance of 99.3% for breast or chest wall and 96.6% for nodal volumes.

Primary: overall survival (switched from breast cancer-specific survival in 2020 on DSMB advice). Prespecified secondary endpoints were recurrence-free survival, breast cancer-specific survival and patient-reported outcomes. Noninferiority required the upper CI bound for recurrence or death below 1.44.

No clinical lymphedema measurements were performed; arm morbidity relies on the LYMPH-ICF, QLQ-C30, QLQ-BR23 and EQ-5D questionnaires at 1, 3, 5 and 10 years. Only 1-year data from a Swedish-Danish subpopulation are published; 3-year data for the whole trial are not yet available.

Consistent with ACOSOG Z0011 and AMAROS, but the authors place SENOMAC alongside AMAROS and OTOASOR rather than Z0011, SINODAR-ONE or POSNOC, because nodal irradiation was routine here. Where the earlier trials enrolled nearly 40% micrometastasis-only pts, one T3 patient between them, and only 248 mastectomies (17.4%) in AMAROS, SENOMAC filled each of those gaps.

Detailed nodal level doses and volumes are not yet reported, so the RT dose actually treating the residual axilla is unquantified. Withdrawal was higher in the dissection arm, reflecting pts' wish to avoid the operation. The ER+/HER2+ subgroup HR of 0.26 (0.07-0.96) rests on 3 versus 10 events among 13 subgroups and should not be read as a real interaction.

The completion dissection arm shows what is being left behind: 34.5% (403/1167) had additional non-sentinel-node metastases, rising to 51.3% with two macrometastases, and 9.9% were upstaged to pN2 with 3.0% pN3. Noninferior recurrence-free survival despite that residual burden is a statement about what systemic therapy plus nodal RT can control, not about the axilla being clean.

Prespecified noninferiority met with wide margin to boundary; enrolls the mastectomy, T3 and ECE subgroups Z0011 and AMAROS excluded, resolving the residual uncertainty.

Randomized, unblinded phase 3 noninferiority trial run by NRG Oncology, 278 sites across North America and 6 other countries, accrual May 2011 to June 2014. 2,354 randomly assigned, 2,255 eligible (sequential 1,118, concurrent 1,137). Median follow-up 7.3 years.

Post-lumpectomy and axillary surgery, selected for higher risk of ipsilateral breast recurrence. Median age 55 (IQR 47-64), 35.6% under 50; 96.8% invasive, 52.7% grade 3, 29.6% ER-negative, 16.7% LVI, 16.7% close (<2 mm) or focally positive margins, 16.3% node-positive, 61.8% received chemotherapy.

Sequential arm: WBI 50 Gy/25F or 42.7 Gy/16F, then boost 12 Gy/6F (84.9%) or 14 Gy/7F. Concurrent arm: WBI 40 Gy/15F with an 8 Gy/15F integrated boost at 0.53 Gy per day. 3DCRT in 1,290 (59%), photons in 1,614 (73.8%). QART scored contours and plans per protocol or acceptable variation in 92.8% and 91.9%.

Primary: IBR as first recurrence, noninferiority margin an HR upper 90% CI limit of 2.12, powered at 80% off an assumed 1.59% 5-year sequential-arm IBR. Secondary: DFS, OS, adverse events, and cosmesis (patient BCTOS, physician global cosmetic score, blinded central digital photo review).

56 IBR events, 24 sequential and 32 concurrent. Cause-specific hazards and Fine-Gray gave the same HR 1.31, and noninferiority held against each sequential WBI fractionation separately. The protocol-specified superiority test was not significant, and post-hoc analyses by stratification variable showed no treatment interactions.

Grade >2 treatment-related toxicity was uncommon with no difference in grade 3-4 events (p=0.81); radiation dermatitis, fatigue, and breast pain were the most prevalent events. Physician-rated excellent/good cosmesis at 3 years was 85.9% sequential vs 82.4% concurrent (p=0.34), photo review 64.2% vs 72.0% (p=0.11).

The boost itself was established by EORTC 22881-10882, where 16 Gy sequential cut IBR but added treatment time and worsened fibrosis. IMPORT HIGH tested integrated boosts on a 40 Gy/15F backbone and found 48 Gy acceptable while its 53 Gy arm carried more induration. NRG 1005 answers the delivery question at scale rather than the dose question.

Cosmetic assessment thinned badly over time: blinded photo review response fell from 79.7% at baseline to 47.1% at 3 years, and physician rating from 90.3% to 50.5%, so the cosmesis conclusions rest on roughly half the cohort with unblinded delivery. The QoL substudy also had imbalances, more stage II sequentially (39.7% vs 32.5%) and more IMRT concurrently (27.1% vs 18.5%).

The point estimate favors sequential (HR 1.31) even as the confidence bound clears the margin, so this is a noninferiority conclusion in the honest sense, not equivalence. With 7-year IBR at 2.2% and 2.6%, the absolute difference is under a percentage point in a deliberately high-risk cohort, which is the frame in which trading 6 to 7 fractions is reasonable.

Adequately powered phase III, prespecified noninferiority margin met at 7.3yr median f/u, with cosmesis and toxicity co-endpoints also noninferior. Removes 6-7 fractions.