CHN HYPOPMRT (10-year) NCT00793962
ForHigh-risk breast cancer, post-mastectomy and axillary dissection
HR 1.13
90% CI 0.77-1.66; 9.6% hypofractionated vs 8.6% conventional
TL;DR10yr LRR 12.0% (43.5 Gy/15fx) vs 10.3% (50 Gy/25fx), HR 1.19 (95% CI 0.79-1.82); G1-2 pulmonary fibrosis 19.7% vs 11.7%.
Late lung is the additive read: G1-2 pulmonary fibrosis 19.7% with hypofractionation vs 11.7% (p=0.008), against no G4-5 late toxicity and no brachial plexopathy at median 11.5 yr. Fields were chest wall plus supraclavicular only, so the plexus safety transfers to that volume, not to IMN-inclusive RNI.
In high-risk breast cancer after mastectomy and axillary dissection, this supports 43.5 Gy in 15 fractions to chest wall and supraclavicular region as an alternative to 50 Gy in 25; it does not extend to reconstruction or IMN-inclusive fields, which the source does not describe.
Late lung is the additive read: G1-2 pulmonary fibrosis 19.7% with hypofractionation vs 11.7% (p=0.008), against no G4-5 late toxicity and no brachial plexopathy at median 11.5 yr. Fields were chest wall plus supraclavicular only, so the plexus safety transfers to that volume, not to IMN-inclusive RNI.
11 details 3 trials watching
Open-label, phase 3, randomized, non-inferiority trial at a single national cancer center in China, 1:1. 820 enrolled (June 2008 to June 2016), 810 in mITT (409 conventional, 401 hypofractionated). Median follow-up 11.5 yr (IQR 9.6 to 13.8).
Women with high-risk breast cancer after mastectomy and axillary dissection. Stage, nodal burden, receptor status, systemic therapy and reconstruction status are not given in the source.
43.5 Gy in 15 fractions over 3 weeks vs 50 Gy in 25 fractions over 5 weeks, to the chest wall and supraclavicular region. Technique, IMN or axillary coverage, bolus and boost are not described in the source.
Primary: 5-year cumulative incidence of locoregional recurrence. Secondary: DFS, OS, late radiation-related toxicity. Outcomes through 10 years were analyzed descriptively.
LRR and fibrosis by arm are in the table. 10-yr DFS (65.2% vs 69.9%) and OS (72.9% vs 77.5%) showed no significant difference; the source does not make the arm order explicit for these two.
| Endpoint | 43.5 Gy/15 fx | 50 Gy/25 fx | Effect |
|---|---|---|---|
| 5-yr LRR (1° EP) | 9.6% | 8.6% | HR 1.13 (90% CI 0.77-1.66; 95% CI 0.72-1.79) |
| 10-yr LRR | 12.0% | 10.3% | HR 1.19 (95% CI 0.79-1.82) |
| Late G1-2 pulmonary fibrosis | 19.7% | 11.7% | p=0.008 |
No G4-5 late toxicity and no brachial plexopathy in either arm. G1-2 pulmonary fibrosis was more frequent with hypofractionation: 19.7% vs 11.7%, p=0.008. Other late endpoints (lymphedema, skin, cardiac) are not reported in the source.
The START trials established moderate hypofractionation mainly for whole-breast RT after breast conservation, with few mastectomy pts and limited nodal irradiation. This trial fills that PMRT plus supraclavicular gap with long follow-up. DBCG Skagen and HypoG-01 address hypofractionated nodal RT, and RT CHARM and FABREC address the reconstructed chest wall.
The source does not restate the non-inferiority margin, and the 10-yr 95% CI reaches 1.82. Fibrosis ascertainment method is not stated, and grading was unblinded. Accrual ran 2008 to 2016 with RT technique undescribed, so transfer to modern planning is uncertain.
The 10-yr data show no late divergence in locoregional control and no plexus injury after a hypofractionated supraclavicular field. What it leaves open is whether the low-grade fibrosis excess is specific to this schedule and era, and whether the result holds with IMN coverage or reconstruction.
Randomized phase 3 with non-inferiority already shown at 5 yr per source; 10-yr read is descriptive, single-center, open-label. Aligns with the field's adoption of hypofractionated PMRT.
- Does hypofractionated PMRT hold with IMN-inclusive regional nodal fields? recruiting Conventionally Fractionated vs. Hypofractionated Comprehensive Nodal Irradiation for Breast Cancer Using Pencil Beam Scanning Proton Therapy Phase 3n=276 · primary completion 2038-02 · phase 3 hypo vs conv proton RNI, IMN in target volume
- Safety of hypofractionated PMRT with breast reconstruction n=506 · primary completion 2029-03 · phase 3 43.5 Gy/15fx vs 50 Gy/25fx after implant reconrecruiting Hypofractionated vs. Conventionally Fractionated Postmastectomy Radiotherapy After Implant-Based Reconstruction Phase NAn=534 · primary completion 2033-10 · randomized NI, 1° EP unplanned reoperation, implant recon
- Is the G1-2 pulmonary fibrosis excess clinically relevant with modern planning?
📚 Sources · 📄 1 paper
Abstract
The longer read
The question this update answers is not whether moderate hypofractionation works after mastectomy, which the 5-year primary analysis already addressed, but whether that answer survives the interval in which late recurrences and late normal-tissue injury declare themselves. Brachial plexus injury in particular has a long latency, so a median follow-up of 11.5 years is the feature that should carry weight with a radiation oncologist. On tumor control the arms did not drift apart: the hazard ratio for locoregional recurrence was 1.13 at 5 years and 1.19 at 10 years.
That 10-year estimate needs an honest read. The long-term analysis is descriptive, the source does not restate the non-inferiority margin, and a 95% interval of 0.79 to 1.82 cannot exclude a modest relative excess of locoregional failure with the shorter course. The point estimates of 10.3% and 12.0% sit close together, but this is a trial with 810 analyzed pts and a low event rate, so the data are best taken as absence of a late divergence signal and not as a second formal non-inferiority test. DFS and OS did not differ, which is reassuring, though neither was the endpoint the trial was built around.
The toxicity findings pull in two directions. The plexus result is the more transferable one: a supraclavicular field treated to 43.5 Gy in 15 fractions produced no brachial plexopathy and no grade 4 to 5 late toxicity with more than a decade of observation. The lung finding points the other way, with grade 1 to 2 pulmonary fibrosis at 19.7% vs 11.7% (p=0.008). The source does not say whether this was radiographic or symptomatic, how it was ascertained, or what planning technique was used. Accrual ran from 2008 to 2016 at one center, and grading was unblinded, so a reader cannot tell whether contemporary planning with explicit lung constraints would narrow the gap or whether the difference is a real fractionation effect on lung.
Against the trials that define practice, the contribution is the setting. The START trials established moderate hypofractionation largely in whole-breast RT after breast conservation, with few mastectomy pts and limited nodal treatment, which left postmastectomy nodal irradiation as the least supported use. This trial addresses exactly that gap with randomized data. The schedule delivers a higher total dose over the same number of fractions than the UK regimen most Western centers adopted, so the control result transfers in direction more than in exact prescription, and the fibrosis excess may be specific to this schedule.
What the result does not reach is as important. The fields were chest wall and supraclavicular region only; the source describes no internal mammary coverage, no reconstruction, and a population staged by axillary dissection. Those are the settings where DBCG Skagen, HypoG-01, RT CHARM and FABREC are the relevant evidence, not this trial. The conclusion would be weakened if late events were under-ascertained in long-term follow-up at a single center, or if the fibrosis signal proved to have symptomatic consequences the abstract does not report.