Table 1.
Baseline characteristics of all included girls.
| All included girls(n = 104) | Treatment arms |
||||
|---|---|---|---|---|---|
| TL1 (n = 18) |
TL2/3 COPDAC-28 arm (n = 57) | TL2/3 DECOPDAC-21 arm (n = 29) | COPDAC-28 vs DECOPDAC-21 (P-value) |
||
| Age at diagnosis (years), median (IQR) | 15.6[13.7; 17.0] | 15.8 [13.9; 17.1] | 15.8 [14.4; 16.8] | 15.0 [13.2; 17.0] | 0.40 |
| (Post)pubertal at diagnosisa | 99 (95%) | 17 (94%) | 56 (98%) | 26 (90%) | 0.11 |
| Hormonal contraceptives during treatmentb | 38/87 (44%) | 7/15(47%) | 25/49 (45%) | 6/23 (26%) | 0.06 |
| GnRH-analogues during treatmentb | 17/87 (20%) | 3/15 (20%) | 9/49 (18%) | 5/22 (23%) | 1.000 |
| Ann Arbor stage of disease | |||||
| 1 | 0 (0%) | 0 (0%) | — | — | 0.10 |
| 2 | 62 (60%) | 18 (100%) | 33 (58%) | 11 (38%) | |
| 3 | 19 (18%) | 0 (0%) | 9 (16%) | 10 (35%) | |
| 4 | 23 (22%) | 0 (0%) | 15 (26%) | 8 (28%) | |
| B-symptomsc | 33 (32%) | 1 (6%) | 18 (32%) | 14 (48%) | 0.20 |
| ESR ≥ 30 mm/h | 75 (72%) | 0 (0%) | 51 (90%) | 24 (83%) | 0.50 |
| Bulky diseased | 53 (52%) | 0 (0%) | 36 (64%) | 17 (59%) | 0.78 |
| Involved tumor sites in infradiaphragmatic regione | 32 (31%) | 1 (6%) | 12 (21%) | 15 (52%) | 0.008 |
| Treatment level (TL) and ERA response | |||||
| TL1, adequate response | 16 (15%) | 16 (89%) | — | — | 0.24 |
| TL1, inadequate response | 2 (2%) | 2 (11%) | — | — | |
| TL2, adequate response | 37 (36%) | — | 24 (42%) | 13 (45%) | |
| TL2, inadequate response | 13 (13%) | — | 11 (19%) | 2 (7%) | |
| TL3, adequate response | 18 (17%) | — | 9 (16%) | 9 (31%) | |
| TL3, inadequate response | 18 (17%) | — | 13 (23%) | 5 (17%) | |
| Radiotherapy | |||||
| Received radiotherapy | 21 (20%) | 2 (11%) | 17 (30%) | 2 (7%) | 0.03 |
| Radiotherapy assigned but not given | 3 (3%) | 0 (0%) | 3 (5%) | 0 (0%) | |
| Ended study participation before end of treatment | 5 (5%) | 0 (0%) | 3 (5%) | 2 (7%) | |
| Pelvic radiotherapyf | 5 (5%) | 0 (0%) | 5 (9%) | 0 (0%) | 0.16 |
| Median follow-up, months (IQR) | 24.0 [23.0; 28.0] | 25.0 [23.0; 26.0] | 24.0 [22.0; 28.0] | 25.0 [23.0; 29.0] | 0.32 |
| End of study | |||||
| Recurrence/progression of disease | 7 (7%) | 0 (0%) | 5 (9%) | 2 (7%) | 0.58 |
| Secondary malignancy | 1 (1%) | 0 (0%) | 1 (2%) | 0 (0%) | |
| Death | 1 (1%) | 0 (0%) | 1 (2%) | 0 (0%) | |
| Lost to follow-up | 5 (5%) | 0 (0%) | 4 (7%) | 1 (3%) | |
P values were calculated by Mann–Whitney U test (continuous) or Chi-square/Fishers exact (categorical). Assigned treatment was according to the EuroNET-PHL-C2 protocol (see treatment-flow in Supplementary Fig. S1). TL1 patients receive 2× OEPA induction followed by either 1× COPDAC-28 or involved node radiotherapy. TL2/TL3 patients are randomized between the COPDAC-28 and DECOPDAC-21 treatment-arm and receive 2× OEPA induction followed by 2× (TL2) or 4× (TL3) (DE)COPDAC consolidation. Indication for radiotherapy depends on treatment response and treatment-group.
OEPA, vincristine, etoposide, prednisone, doxorubicin; COPDAC-28, cyclophosphamide, vincristine, prednisone, and dacarbazine; DECOPDAC-21, doxorubicin, etoposide, cyclophosphamide, vincristine, prednisone and dacarbazine; ESR, erythrocyte sedimentation rate; ERA, early response rate; IQR, interquartile range; TL, treatment level.
(Post)pubertal is defined as tanner stage (mammae) >1.
Reported percentages of girls using hormonal contraceptives or GNRH-analogues were calculated in post-menarchal girls.
B symptoms, i.e. unexplained fever >38.5°C, weight loss of 10% during the past 6 months and drenching night sweats.
Bulky disease is defined as contiguous tumour volume of at least 200 ml.
Including tumour sites in the porta hepatis, splenic hilum, mesenteric, upper para-aortic, lower para-aortic, iliac and inguinal area.
All patients received 19.8 Gy.