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About · curated by Nick Boehling, MD · @nb2276

2026-05-21

digest generated 2026-08-11

EORTC 22922 at 20 yrs: IM-MS nodal RT cut breast cancer mortality (HR 0.82, p=.006) but added non-cancer deaths (HR 1.26, p=.002), OS flat at 61.0% vs 61.8%.
Nodal RT's ledger is the day's thread: EORTC 22922 shows the breast-cancer-mortality gain fully offset by late cardiac/pulmonary deaths after 15 yrs, while RxPONDER's S1007 analysis finds LRR already <1% with or without RNI in RS≤25 N1 disease. Bladder is the counterweight: adjuvant pelvic IMRT after RC halved locoregional failure (HR 0.43) with no survival signal.

Breast

Two reads on regional nodal RT arriving together: a 20-yr randomised toxicity ledger and a genomic-era observational LRR floor.

Challenges SOC

SWOG S1007

ForHR+/ERBB2- breast, 1-3 positive nodes, Oncotype RS ≤25

TL;DR5yr LRR 0.85% with RNI vs 0.55% without after BCS+RT in RS≤25 N1 disease; IDFS unchanged by RNI.

Why it mattersRadiation oncology

The number that moves the RNI decision is 0.55% 5yr LRR after BCS+RT without RNI, and equally low LRR in the endocrine-alone arm. Chemotherapy omission on a low RS does not by itself justify adding supraclavicular coverage. Target-volume detail beyond supraclavicular is not reported in source.

Monday clinic

In HR+/ERBB2- N1 disease with RS ≤25 treated with BCS and whole-breast RT, this argues low RS alone does not compel nodal irradiation; it does not speak to RS >25, higher nodal burden, or ERBB2+ disease.

The longer read
9 details

Secondary analysis of the randomized SWOG S1007 trial (endocrine therapy alone vs chemotherapy then endocrine therapy). Radiotherapy data were prospectively collected across diverse practice settings, but RNI receipt itself was not randomized. Data analyzed June 2022 to April 2023.

Hormone receptor-positive, ERBB2-negative breast cancer with 1 to 3 involved nodes and Oncotype DX 21-gene Recurrence Score ≤25. 4871 female patients had radiotherapy forms; median age 57 (range 18-87).

RNI defined as targeting at least the supraclavicular region. 3947 (81.0%) reported radiotherapy receipt; of 3852 with complete target information, 2274 (59.0%) received RNI. Dose, fractionation, and internal mammary coverage are not reported in source.

Cumulative incidence of locoregional recurrence by locoregional treatment received, plus association between invasive disease-free survival and locoregional therapy, adjusted for menopausal status, treatment group, recurrence score, tumor size, nodes involved, and axillary surgery.

Median follow-up 6.1 years. See the LRR and IDFS tables above; IDFS did not differ by RNI receipt in either menopausal stratum.

Locoregional treatment5yr LRR
BCS + RT with RNI0.85%
BCS + RT without RNI0.55%
Mastectomy + PMRT0.11%
Mastectomy, no RT1.7%
GroupHR (95% CI)P
Premenopausal1.03 (0.74-1.43).87
Postmenopausal0.85 (0.68-1.07).16

MA.20 and EORTC 22922 established the regional irradiation question in node-positive disease, both without an overall survival gain, in cohorts assembled before genomic risk stratification. This analysis reads that question in the population those trials could not define, biologically favorable N1, and finds an LRR floor low enough that a relative benefit has little absolute room to operate.

HR+/ERBB2- breast cancer with 1 to 3 positive nodes and Oncotype RS ≤25 treated with modern surgery and systemic therapy
Does not represent RS >25, ERBB2-positive or triple-negative disease, or ≥4 involved nodes.

Radiotherapy information was recorded only in the first year after randomization, forcing a 1-year landmark that excludes the earliest events. Target detail stops at supraclavicular coverage, so internal mammary treatment cannot be separated, and the low absolute event count leaves the IDFS confidence intervals wide enough to accommodate a small effect in either direction.

The finding that matters is the floor, not the comparison: with 5yr LRR at or below 1.7% in every locoregional strategy examined, the population has too few events for regional irradiation to demonstrate meaningful absolute benefit. The explicit conclusion is that omission of chemotherapy is not an independent indication for RNI, which addresses a specific compensatory reflex rather than the general RNI question.

Prospectively collected RT data in a large trial cohort, but RNI receipt was not randomized; observational comparison, so an unmeasured-confounding read is unavoidable.

  • Does any favorable N1 subgroup (3 nodes, RS near 25) still warrant RNI?
  • Internal mammary coverage contribution, unseparable in this dataset
  • Longer follow-up for late locoregional events in HR+ disease

Sourced from Jagsi et al.

📚 Sources · 📄 1 paper
📄 PAPER Jagsi; Barlow; Woodward et al. · JAMA oncology (2023-08)
Radiotherapy Use and Incidence of Locoregional Recurrence in Patients With Favorable-Risk, Node-Positive Breast Cancer Enrolled in the SWOG S1007 Trial.
Abstract
IMPORTANCE: Little is known about regional nodal irradiation (RNI) practice patterns or rates of locoregional recurrence (LRR) with and without RNI in patients with limited nodal disease and favorable biology treated with modern surgical and systemic therapy, including approaches that de-escalate those latter treatments.<br/><br/>OBJECTIVE: To investigate how often patients with low-recurrence score breast cancer with 1 to 3 nodes involved receive RNI, incidence and predictors of LRR, and associations between locoregional therapy and disease-free survival.<br/><br/>DESIGN, SETTING, AND PARTICIPANTS: In this secondary analysis of the SWOG S1007 trial, patients with hormone receptor-positive, ERBB2-negative breast cancer, and a Oncotype DX 21-gene Breast Recurrence Score assay result of no more than 25, were randomized to endocrine therapy alone vs chemotherapy then endocrine therapy. Prospectively collected radiotherapy information was collected from 4871 patients treated in diverse settings. Data were analyzed June 2022 to April 2023.<br/><br/>EXPOSURE: Receipt of RNI (targeting at least the supraclavicular region).<br/><br/>MAIN OUTCOME(S) AND MEASURE(S): Cumulative incidence of LRR was calculated by locoregional treatment received. Analyses were assessed for associations between invasive disease-free survival (IDFS) and locoregional therapy, adjusted for menopausal status, treatment group, recurrence score, tumor size, nodes involved, and axillary surgery. Radiotherapy information was recorded in the first year after randomization, so survival analyses were landmarked as starting at 1 year among those still at risk.<br/><br/>RESULTS: Of 4871 female patients (median [range] age, 57 [18-87] years) with radiotherapy forms, 3947 (81.0%) reported radiotherapy receipt. Of 3852 patients who received radiotherapy and had complete information on targets, 2274 (59.0%) received RNI. With a median follow-up of 6.1 years, the cumulative incidence of LRR by 5 years was 0.85% among patients who received breast-conserving surgery and radiotherapy with RNI; 0.55% after breast-conserving surgery with radiotherapy without RNI; 0.11% after mastectomy with postmastectomy radiotherapy; and 1.7% after mastectomy without radiotherapy. Similarly low LRR was observed within the group assigned to endocrine therapy without chemotherapy. The rate of IDFS did not differ by RNI receipt (premenopausal: hazard ratio [HR], 1.03; 95% CI, 0.74-1.43; P&#x2009;=&#x2009;.87; postmenopausal: HR, 0.85; 95% CI, 0.68-1.07; P&#x2009;=&#x2009;.16).<br/><br/>CONCLUSIONS AND RELEVANCE: In this secondary analysis of a clinical trial, RNI use was divided in the setting of biologically favorable N1 disease, and rates of LRR were low even in patients who did not receive RNI. Disease-free survival was not associated with RNI receipt; omission of chemotherapy among patients similar to those enrolled in the S1007 trial is not an independent indication for use of RNI.
Challenges SOC

EORTC 22922/10925

ForStage I-III breast, central/medial tumor or involved axilla, post-ALND

Overall survival

61.0% vs 61.8% at 20yr

HR 1.00, p=.967; primary endpoint not met

TL;DR20yr OS 61.0% vs 61.8% (HR 1.00, p=.967): IM-MS nodal RT cut breast cancer mortality but added non-cancer deaths.

Why it mattersRadiation oncology

The breast cancer mortality gain (22.4% vs 18.6%, HR 0.82) is real and was fully offset by non-breast-cancer deaths (15.8% vs 20.4%, HR 1.26) that only emerged after 15 years. Cardiac disease ran 15.2% vs 11.7%. In a 1996-2004 planning era, that trade gates IM-MS coverage on achievable heart dose, not on nodal risk alone.

Monday clinic

In a woman with a medial or central stage I-III tumor being considered for IM chain coverage, this supports treating the cardiac dose constraint as co-equal with nodal risk; it does not speak to modern DIBH or proton delivery, where the competing-mortality arm may not hold.

The longer read
9 details

Prospective multicenter randomized phase 3 trial, accrual 1996-2004, 4004 pts, with an RT quality-assurance program built in. The last analysis was planned at 20 years on the assumption that any survival effect of IM-MS-RT would be delayed. Median follow-up 22.2 years.

Women ≤75 yrs, unilateral histologically confirmed breast adenocarcinoma, stage I-III. Gate was tumor location or nodal status: centrally or medially located primary irrespective of axillary involvement, or any quadrant with axillary involvement. Median age 54.

Randomization was to internal mammary and medial supraclavicular (levels 3-4) nodal irradiation or not, layered on standard breast or chest wall treatment. Dose and fractionation are not given in the source excerpt. Planning ran in the two-dimensional and early-conformal era, when IM coverage at least doubled heart dose.

Primary: overall survival. Secondary: disease-free survival, distant metastases-free survival, breast cancer mortality, any breast recurrence.

Lung fibrosis 6.3% vs 3.2%, cardiac fibrosis 2.7% vs 1.7%, cardiac disease 15.2% vs 11.7% with IM-MS-RT. Severe (grade 3-4) events were uncommon and near-equal: cardiac 1.9% vs 1.7%, lung 0.3% vs 0.0%, so the excess sits in lower-grade, chronic morbidity rather than catastrophic events.

MA.20 and DBCG-IMN both read regional nodal RT positively at roughly ten-year horizons, and DBCG-IMN reported an OS gain. This trial covers the same anatomic question at twice that follow-up and shows the disease-specific gain surviving while the survival gain does not, which is the read those trials were too short to produce.

stage I-III breast cancer with medial or central primaries or involved axilla, treated with 1996-2004 era planning and postoperative systemic therapy of that period
Does not represent contemporary heart-sparing delivery, hypofractionated regional nodal schedules, or patients staged and treated with modern systemic regimens.

Systemic therapy was left to physician and institutional preference across an eight-year accrual, so the systemic backbone is heterogeneous and predates current regimens. The competing-mortality signal is a cause-of-death attribution over two decades in a population whose baseline cardiovascular risk rises independently, and the source does not report a cardiac-specific mortality breakdown separating RT-attributable from age-attributable death.

The two effects are both real and point opposite ways: HR 0.82 on breast cancer mortality, HR 1.26 on other deaths, netting HR 1.00 on OS. That arithmetic is the finding, and it argues the relevant question is not whether IM-MS coverage works but whether its cost can be engineered down.

EndpointControlIM-MS-RTEffect size
Overall survival61.8%61.0%HR 1.00, p=.967
Disease-free survival49.0%48.2%HR 0.97 (0.89-1.06), p=.5148
Distant metastasis-free survival59.8%58.9%HR 0.97 (0.88-1.08), p=.578
Breast cancer mortality22.4%18.6%HR 0.82 (0.72-0.95), p=.006
Death not from breast cancer/unknown15.8%20.4%HR 1.26, p=.002

Randomised, prespecified 20yr primary analysis, adequate power, endpoint reported honestly. Divergence from the 10yr-era read of nodal RT is internally valid, not a design artifact.

  • Does modern heart-sparing delivery erase the excess non-cancer mortality?
  • Which subgroups have enough breast cancer risk to justify the trade?
  • Cardiac surveillance interval for irradiated long-term survivors

Sourced from Kaidar‐Person, Orit et al.

📚 Sources · 📄 1 paper
📄 PAPER Kaidar‐Person, Orit; Weltens, Caroline G.; Fortpied, Catherine et al. · CA: A Cancer Journal for Clinicians (2026-05)
Twenty‐year results of the randomized European Organization for Research and Treatment of Cancer trial 22922/10925 evaluating internal mammary chain and medial supraclavicular lymph node irradiation in stage I–III breast cancer
Abstract
Abstract European Organization for Research and Treatment of Cancer trial EORTC 22922/10925 evaluated internal mammary and medial supraclavicular (IM‐MS) lymph node irradiation (IM‐MS‐RT) in patients with stage I–III breast cancer. Eligible patients had involved axillary nodes and/or centrally/medially located tumors regardless of nodal involvement. The primary end point was overall survival, secondary end points were disease‐free survival, distant metastases‐free survival, breast cancer mortality, and any breast recurrence. Between 1996 and 2004, 4004 patients were randomized. The median patient age was 54 years. At a median follow‐up of 22.2 years, 1550 (38.7%) patients died, of whom 796 (51.4%) died from breast cancer. At 20 years, the overall survival rate was 61.8% in the control group versus 61.0% in the IM‐MS‐RT group (hazard ratio [HR], 1.00; p = .967); the disease‐free survival rate was 49.0% versus 48.2%, respectively (HR, 0.97; p = .515); and the distant metastases‐free survival rate was 59.8% versus 58.9%, respectively (HR, 0.97; p = .578). The breast cancer mortality rate was 22.4% in the control group and 18.6% in the IM‐MS‐RT group (HR, 0.82; p = .006), whereas the rate of deaths not from breast cancer or from unknown causes was 15.8% versus 20.4%, respectively (HR, 1.26; p = .002). Lung fibrosis, cardiac fibrosis, and cardiac diseases were more frequent after IM‐MS‐RT versus no IM‐MS‐RT (6.3% vs. 3.2%, 2.7% vs. 1.7%. and 15.2% vs. 11.7%, respectively); and the rates of severe cardiac and lung morbidities (scores of 3 or 4) were 1.9% versus 1.7% and 0.3% versus 0.0%, respectively. Breast cancer mortality at 20 years was statistically significantly lower after IM‐MS‐RT, but deaths not from breast cancer increased after 15 years, resulting in no long‐term benefit of IM‐MS‐RT on overall survival. Therefore, the authors strongly call for very long‐term follow‐up of treatments for prognostically favorable cancers such as breast cancer.

Bladder

First randomised support for adjuvant pelvic RT after cystectomy, in a control arm that predates adjuvant IO.

Challenges SOC

Bladder Adjuvant Radiotherapy

ForPost-cystectomy MIBC, pT3-4 / pN+ / margin+ / ≤10 nodes dissected

2-year locoregional recurrence-free survival local control

87.1% v 76.0%

HR 0.43 (95% CI, 0.20 to 0.96), P = .04

TL;DR2yr LRFS 87.1% vs 76.0% with adjuvant pelvic IMRT after RC, HR 0.43 (0.20-0.96), P=.04; DFS/BCSS/OS not significant.

Why it mattersRadiation oncology

The RT read is the target volume and the technique: stoma-sparing IG-IMRT, 50.4Gy/28fx to cystectomy bed plus pelvic nodes, with no additional severe toxicity reported. That combination is deliverable in a standard department today, so this moves the offer-vs-observe decision for a pT3-4 or pN+ postcystectomy patient rather than leaving adjuvant pelvic RT as a historical toxicity concern.

Monday clinic

In a postcystectomy MIBC patient with pT3-4, pN+, positive margin, or ≤10 nodes dissected who has completed perioperative chemotherapy, this supports discussing adjuvant pelvic RT for locoregional control; it does not address patients who received adjuvant immunotherapy.

The longer read
10 details

Multicenter phase III RCT, 1:1 adjuvant RT versus observation after radical cystectomy. 153 patients randomly assigned June 2016 to May 2024 (Obs 76, RT 77), stratified by nodal involvement and chemotherapy timing. Median follow-up 47 months.

Nonmetastatic urothelial MIBC, high risk after RC by any one of T3-4, N1-3, positive margin, or ≤10 nodes dissected. Baseline load was heavy: 62% pT3-T4 and 41% pN+.

Over 90% received systemic chemotherapy (71% neoadjuvant, 20% adjuvant). None received immunotherapy in either arm.

Stoma-sparing IG-IMRT, 50.4Gy in 28 fractions, prescribed to the cystectomy bed and pelvic nodes. Elective nodal coverage was part of the treated volume, not an optional add-on.

Primary: 2-year locoregional recurrence-free survival. Secondary: disease-free survival, bladder cancer-specific survival, overall survival.

The primary endpoint was met; secondary endpoints all favored RT numerically without reaching significance. See the endpoint table for arm-level rates and hazard ratios.

EndpointRTObsHR (95% CI)
LRFS (1°)87.1%76.0%0.43 (0.20-0.96), P=.04
DFS71.6%58.7%0.62 (0.36-1.05)
BCSS79.6%65.0%0.59 (0.33-1.10)
OS70.4%57.4%0.78 (0.49-1.26)

The authors report no additional severe toxicity with adjuvant pelvic IMRT. Grade-level AE breakdown is not reported in the source abstract.

postcystectomy nonmetastatic urothelial MIBC with pT3-4, pN+, positive margin, or ≤10 nodes dissected, over 90% chemotherapy-treated
Does not represent patients who received adjuvant immunotherapy, organ-preserved trimodality patients, or nonurothelial histology.

The primary endpoint is a 2-year locoregional readout under a 47-month median follow-up, so the headline reports early control rather than durability. Accrual spanned eight years, during which adjuvant immunotherapy entered practice in this exact population, and the control arm reflects none of it.

Adjuvant pelvic RT after cystectomy has been an open question since the older Egyptian NCI randomized experience, which used larger fields and conventional technique. This is the modern IMRT-era answer, and it lands positive on local control only, not survival.

A HR of 0.43 on locoregional control with an upper CI bound of 0.96 is a real but fragile signal in 153 patients. The consistent numeric direction across DFS (HR 0.62), BCSS (HR 0.59), and OS (HR 0.78) is reassuring but underpowered, and none of it settles whether locoregional control converts to survival.

CONSORT flow
Randomized 153
Adjuvant RT
allocated 77
2yr LRFS 87.1%
Observation
allocated 76
2yr LRFS 76.0%

Randomised, prespecified 2yr LRFS primary endpoint met in a setting where adjuvant RT is not standard. Small N and borderline CI limit confidence, not internal validity.

  • Does locoregional benefit persist alongside adjuvant immunotherapy
  • Does 2yr LRFS gain translate to survival with longer follow-up
  • Which high-risk feature drives the benefit: pN+, margin, or nodal yield

Sourced from Murthy et al.

📚 Sources · 📄 1 paper
📄 PAPER Murthy; Maitre; Pal et al. · Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2026-05)
Bladder Adjuvant Radiotherapy: Phase III Multicenter Randomized Controlled Trial of Adjuvant Radiotherapy or Observation for Postcystectomy Muscle-Invasive Bladder Cancer.
Abstract
PURPOSE: To report the primary analysis of a multicenter, phase III randomized trial of adjuvant radiotherapy (RT) after chemotherapy and radical cystectomy (RC) in patients with high-risk muscle-invasive bladder cancer (MIBC).<br/><br/>METHODS: Patients with nonmetastatic urothelial MIBC at high risk after RC (any one of: T3-4, N1-3, margin positive, &#x2264;10 nodes dissected) were randomly assigned 1:1 to adjuvant RT or observation (Obs), stratified by nodal involvement (yes/no) and chemotherapy (neoadjuvant/adjuvant/none). Stoma-sparing IG-IMRT 50.4Gy in 28 fractions was prescribed to the cystectomy bed and pelvic nodes. The primary end point was 2-year locoregional recurrence-free survival (LRFS), and the secondary end points were disease-free survival (DFS), bladder cancer-specific survival (BCSS), and overall survival (OS).<br/><br/>RESULTS: From June 2016 to May 2024, 153 patients were randomly assigned (Obs = 76, RT = 77), with 62% and 41% of patients having pT3-T4 and pN+ stages, respectively. Over 90% of the patients received systemic chemotherapy (71% neoadjuvant and 20% adjuvant), and none received immunotherapy. After a median follow-up of 47 months, the 2-year LRFS was significantly higher with adjuvant RT versus observation (87.1% v 76.0%, hazard ratio [HR], 0.43 [95% CI, 0.20 to 0.96], P = .04). The DFS was 71.6% versus 58.7% (HR, 0.62 [95% CI, 0.36 to 1.05]), BCSS was 79.6% versus 65.0% (HR, 0.59 [95% CI, 0.33 to 1.10]), and OS was 70.4% versus 57.4% (HR, 0.78 [95% CI, 0.49 to 1.26]) for RT and Obs, respectively.<br/><br/>CONCLUSION: Adjuvant pelvic IMRT after radical cystectomy and perioperative chemotherapy suggests an improvement in locoregional control in patients with high risk urothelial MIBC with no additional severe toxicity.