Gynecologic
Adjuvant endometrial: PORTEC-3 defines what chemo adds to pelvic RT, plus two dosimetry papers on vaginal cuff brachy.
Postoperative endometrial cancer with electronic brachytherapy (Axxent)
ForPostop endometrial cancer, FIGO IA to IVA, adjuvant VBT ± pelvic EBRT
TL;DRAxxent eBT vs replanned Ir-192 HDR: bladder D2cc 63.8% vs 70.1%, rectum 61.2% vs 68.4% of prescription; one G2 acute toxicity in 94 pts.
The prescription copied Ir-192 doses onto a 26 keV source with no RBE adjustment, so the OAR %PD reductions are physical-dose figures and the higher V150/V200 sits at the mucosa. Low acute mucositis at 25 Gy/5 fx and 15 Gy/3 fx is reassuring, but vaginal stenosis and late effects are untested here.
In postop endometrial pts needing vaginal cuff brachytherapy at a centre with no HDR afterloader, this supports eBT as feasible on acute toxicity; it does not inform late vaginal toxicity or cuff control vs Ir-192 HDR. The longer read
Ir-192 prescriptions were applied to a 26 keV source without RBE correction (cited RBE 1.29 to 1.85 at 5 mm), so the bladder and rectal %PD reductions are physical dose and the mucosa carries higher V150/V200. Acute toxicity at 25 Gy/5 fx and 15 Gy/3 fx was low; late vaginal effects remain untested.
11 details
Single-centre series of 94 pts treated with Axxent eBT, Sept 2015 to Oct 2017. Each eBT plan was replanned a posteriori for Ir-192 and Co-60 (282 plans); toxicity scored by RTOG. Mean follow-up 14 mo (4 to 25).
Postoperative endometrial cancer, mean age 65.9 (33 to 84), FIGO IA through IVA. 33 pts (35%) received chemo before RT.
eBT alone 25 Gy/5 fx (n=37, stage IA plus seven IB1) or pelvic EBRT 23 × 2 Gy then eBT 15 Gy/3 fx (n=57), twice weekly. Dose prescribed at 5 mm from a 2.5 to 3.5 cm cylinder; 50 kVp source, TG-43 planning, no RBE correction.
Only one G2 acute event. At 1 month, vaginal G1 5.3%, rectal G1 1.1%, urinary G1 2.1%, no G2.
PORTEC-2 established vaginal brachytherapy as adjuvant RT for high-intermediate risk disease using conventional HDR; this series does not test eBT against that clinical benchmark. A cited multicentre eBT series reported bladder V50% 11.5 ± 9.7% and rectum 17.4 ± 10.9%, in the same range as here.
Higher V150/V200 places hotter dose at the vaginal mucosa, where late stenosis would show and 14 mo cannot capture it. TG-43 without heterogeneity correction may misstate low-energy dose in tissue.
The OAR advantage comes from rapid dose fall-off at low energy, the same property that concentrates dose near the applicator surface. Whether uncorrected RBE translates into more late mucosal toxicity, or whether RBE-based de-escalation would cost control, remains open.
| OAR parameter | Axxent eBT | Ir-192 HDR |
|---|---|---|
| Bladder D2cc (%PD) | 63.8% | 70.1% |
| Bladder V50% | 7.2% | 12.7% |
| Bladder V35% | 15.2% | 28.2% |
| Rectum D2cc (%PD) | 61.2% | 68.4% |
| Rectum V50% | 7.9% | 14.3% |
| Rectum V35% | 16.7% | 32% |
Single-centre uncontrolled series, 14 mo mean f/u; HDR comparison is replanning, not a treated arm; no late toxicity or local control data at meaningful follow-up.
- Late vaginal mucosal toxicity with uncorrected RBE
- Vaginal cuff control vs Ir-192 HDR at longer follow-up
- Should eBT prescriptions be RBE-adjusted?
📚 Sources · 📄 1 paper
Abstract
PORTEC-3 NCT00411138
ForHigh-risk endometrial cancer, FIGO 2009 stage I-III, post-hysterectomy
HR 0.76
95% CI 0.54–1.06, p=0.11, OS not met; co-primary FFS HR 0.71, p=0.022
TL;DR5y FFS 75.5% vs 68.6% (HR 0.71, p=0.022) with CRT over pelvic RT alone; co-primary 5y OS 81.8% vs 76.7% not met (HR 0.76, p=0.11).
Pelvic control was 91% with RT alone, so chemotherapy is not buying locoregional control here; 48.6 Gy pelvic EBRT (plus brachy boost in 47%, balanced by arm) stays the backbone in both arms. The RT question left open is whether pelvic RT can be dropped once chemo is given, which GOG-258 tests and its abstract suggests costs vaginal and nodal control.
In stage III high-risk endometrial cancer, this supports discussing concurrent cisplatin plus adjuvant carboplatin/paclitaxel with pelvic RT for failure-free survival; in stage I-II disease the FFS estimate (HR 0.85, p=0.47) does not clearly justify the added toxicity. The longer read
Pelvic control was 91% with RT alone, so chemo adds nothing locoregionally and 48.6 Gy pelvic EBRT plus indicated brachy boost stays the backbone. The RT decision this trial leaves open is omission of pelvic RT once chemo is given, where GOG-249 and the GOG-258 abstract both show more pelvic and nodal failure without it.
The regimen is demanding: all 4 carboplatin and paclitaxel cycles were completed by 79% and 71%, G3+ AEs ran 60% vs 12%, and G2+ neuropathy persisted at 3y in 8%. The FFS gain concentrates in stage III, and the authors flag a larger benefit in women over 70 and at least as much benefit in serous or clear cell histology.
10 details 4 trials watching
Open-label, international, randomised phase 3 at 103 centres across six GCIG groups; 1:1 by biased-coin minimisation, stratified by centre, lymphadenectomy, stage and histology. 686 enrolled, 660 in the ITT analysis; median follow-up 60.2 mo.
High-risk endometrial cancer, FIGO 2009: stage IA EEC grade 3 with LVSI, IB EEC grade 3, EEC stage II or III, or serous / clear cell stage IA (with invasion) to III. WHO PS 0-2, no upper age limit; median age 62, stage III in 46% vs 43%.
Experimental arm added cisplatin 50 mg/m² x2 concurrent, then 4 cycles carboplatin AUC5 + paclitaxel 175 mg/m². Both cisplatin cycles completed by 92%; all 4 carboplatin and paclitaxel cycles by 79% and 71%.
Pelvic EBRT 48.6 Gy in 1.8 Gy fractions in both arms; 45.0-50.4 Gy delivered in 100% vs 98%. Vaginal brachy boost for cervical invasion, given in 46% vs 48%.
Co-primary: overall survival and failure-free survival, ITT, Cox-adjusted for stratification factors.
G3+ AEs during treatment 60% vs 12% (p<0.0001). G2+ neuropathy persisted at 3y in 8% vs 1%.
Direction matches the pooled NSGO-EC-9501/EORTC-55991 + ManGO Iliade analysis (PFS 78% vs 69%, OS trend 82% vs 75%), here in a larger trial with concurrent plus adjuvant chemo. GOG-249 found chemo + VBT no better than pelvic EBRT in stage I-II with more pelvic and para-aortic recurrence; the GOG-258 abstract reported no OS/RFS gain for CRT over chemo alone but more vaginal and nodal failures without RT.
Final analysis was time-based, with OS events at 69% of the number required, so a 5% OS difference was below what the trial could detect. RT plan QA outside ANZGOG was still pending, and the stage and age subgroup reads are exploratory.
CRT buys FFS, not OS, at 5y, at the price of a fivefold G3+ toxicity rate and persistent neuropathy. The authors read the stage I-II FFS gain as not outweighing toxicity, so the combined regimen fits individual counselling, mainly in stage III.
| Endpoint | CRT | RT alone | Effect |
|---|---|---|---|
| 5y OS | 81.8% (77.5–86.2) | 76.7% (72.1–81.6) | HR 0.76 (0.54–1.06), p=0.11 |
| 5y FFS | 75.5% (70.3–79.9) | 68.6% (63.1–73.4) | HR 0.71 (0.53–0.95), p=0.022 |
| Stage III 5y OS | 78.7% | 69.8% | HR 0.71 (0.45–1.11), adjusted p=0.074 |
| Stage III 5y FFS | 69.3% | 58.0% | HR 0.66 (0.45–0.97), adjusted p=0.014 |
| Stage I–II 5y FFS | 80.8% | 76.6% | HR 0.85 (0.54–1.33), p=0.47 |
| G3+ AEs during treatment | 198 (60%) | 41 (12%) | p<0.0001 |
| G2+ neuropathy at 3y | 20 (8%) | 1 (1%) | p<0.0001 |
CONSORT flow
Randomised phase 3 met co-primary FFS but missed OS with only 69% of required OS events; direction matches pooled NSGO-EC-9501/ManGO data. Toxicity cost tempers adoption.
- Does the OS difference emerge with longer follow-up?
- Is pelvic RT still needed in stage III when chemotherapy is given? not yet Chemotherapy vs Chemoradiotherapy for Post-operative Endometrial Cancer Patients With P53-mutation Phase 2/3n=294 · primary completion 2028-08 · randomizes chemo alone vs CRT, p53abn stage I-IVA
- Can stage I-II pts be spared chemotherapy toxicity safely? n=590 · primary completion 2026-12 · molecular profile assigns CRT vs RT, stage I-IIn=316 · primary completion 2030-01 · RT + durvalumab vs RT ± chemo in MMRd ECn=600 · primary completion 2030-12 · RT + progestin vs RT + chemo, high-risk NSMP
📚 Sources · 📄 1 paper
HDR vaginal brachytherapy cylinder dosimetry
ForPost-hysterectomy endometrial cancer, adjuvant HDR vaginal cuff brachytherapy
TL;DRSurface SD 6% vs 18% with surface vs 0.5-cm depth prescription (2-cm cylinder). Omitting dome optimization points gave hot spots >150% and cold spots <60%.
The actionable physics: the dome needs optimization points. Without them the apex runs cold (50-65%) or hot (140-170%) depending on tip space, and the 0.5-cm depth prescription hides surface SD up to 18%. If you switch to a surface prescription, M = 1.00 + 0.64/L + 1.23/S gives the surface dose that keeps the 0.5-cm dose unchanged.
For post-hysterectomy endometrial pts on single-channel cylinder VBT, this supports checking that apex and dome points are in the optimization and reporting both surface and 0.5-cm doses. It gives no outcome evidence for changing an established 0.5-cm depth prescription. The longer read
The actionable physics: the dome needs optimization points. Without them the apex runs cold (50-65%) or hot (140-170%) depending on tip space, and the 0.5-cm depth prescription hides surface SD up to 18%. M = 1.00 + 0.64/L + 1.23/S converts a depth dose to its surface equivalent if you switch conventions.
12 details
A treatment-planning study with no patients. Plato BPS 14.2.4 plans were built on Nucletron radiographic cylinders (tip space ~0.5 cm) and CT/MR-compatible cylinders (tip space 0.6-0.8 cm). Dose uniformity at each depth was measured as the mean dose (MD) and SD across dose points spaced evenly around the dome and along the cylinder.
Cylinders were 2.0, 2.5, 3.0, 3.5 and 4.0 cm in diameter, with active lengths of 3 to 8 cm (upper third to the whole vagina). Prescription was to the surface (P0) or to 0.5-cm depth (P5), with or without optimization points on the curved end (NEP). The worked illustration used 7 Gy × 3 fractions.
Primary measures: MD and SD at the surface and at 0.5-cm depth. Dose fall-off was the ratio of MD at 0.75 cm to MD at 0.5 cm.
Surface prescription gave surface SD 6% vs 18% with P5 (2-cm cylinder, 0.8-cm tip), with almost the same fall-off beyond 0.5 cm. NEP plans produced hot spots >150% and cold spots <60%. A shorter tip space raised dosimetric uncertainty >30%.
The paper frames its result against the ABS 2000 guidance (dome optimization points, report doses at both surface and 0.5 cm) and an ABS survey in which >90% prescribe to 0.5 cm. It also cites Sorbe's randomized 2.5 vs 5.0 Gy × 6 trial, in which higher dose increased atrophy, bleeding and shortening.
The M regression was fit on only two lengths × two diameters, using one vendor's applicators and TPS. The claim that a lower surface dose reduces atrophy and shortening is extrapolated from other trials, not measured.
A 0.5-cm depth prescription delivers its intended depth dose only when dome points are included, and the surface dose it gives varies with cylinder size and tip space. Prescribing to the surface with a geometry-scaled dose fixes the surface number. Whether that changes toxicity remains open.
Planning-system dosimetry with no patients or outcomes. 'Surface prescription is optimal' rests on mucosal dose uniformity, a surrogate never tied to toxicity or vaginal control here.
- Does surface prescription reduce vaginal atrophy or shortening clinically?
- Does the M factor hold on modern 3D image-guided planning?