Publication de Nicole Delepine : Ewing's sarcoma : long term favourable outcome in children with combinated modality therapy and conservative surgery

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Publié sur : 41th Annual Meeting ASCO - 2005
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Ewing's sarcoma : long term favourable outcome in children with combinated modality therapy and conservative surgery
G. Delepine, F. Delepine, A. Tabbi, H. Cornille, Nicole Delepine

Ewing's sarcoma : long term favourable outcome in children with combinated modality therapy and conservative surgery



Standard treatment : chemotherapy and surgery avoiding radiotherapy



Patients


From november 1985 to january 2000, 21 children aged de 4.5 to 18 were treated by EWDD protocol for localized Ewing's sarcoma.
Ewing's sarcoma


Tumor location


Ewing's sarcoma

Femur : 4
Iliac : 5
Rib : 4
tibia :3
Fibula : 1
spine : 1
sacral : 1
radial : 1
mandibular : 1

Prognostic factors


18/21 PATIENTS HAD AT LEAST ONE CLASSICAL BAD PROGNOSTIC FACTOR (tumoral volume >100ml or central location).
Ewing's sarcoma


EW DD2 INDUCTION CHEMOTHERAPY


Ewing's sarcoma


Response to preoperative chemotherapy


18 y old girl with a huge pleural infusion leading to discovery of a rib tumor with little pain. Very impressive radiologic response in 6 weeks.
Ewing's sarcoma


Response to preoperative chemotherapy


Decrease of tumoral diameter : 38 %
Decrease of tumoral volume : 76%
Ewing's sarcoma


Decrease of tumoral diameter : 28 %
Decrease of tumoral volume : 63%
Ewing's sarcoma


Decrease of tumoral diameter : 50 %
Decrease of tumoral volume : 88%
Ewing's sarcoma


Decrease of tumoral size : 66%
Decrease of tumoral volume : 95%
Ewing's sarcoma


Standard treatment excluded radiotherapy


In this protocol early extra tumoral en bloc resection without radiotherapy was the standard local treatment.
It was performed in all cases without risk of neurological sequellaes.
3 patients with contaminated margins received postoperative radiotherapy.

Why all our patients were operated ?


In the litterature, risk of local reccurence following radiotherapy reaches 20% to 50%.
Ewing's sarcoma


All patients were operated EARLY


In our surgical experience (1) early resection is a significant prognostic factor.
Ewing's sarcoma


All limb tumors were resected


Some cases of reconstructive procedures used after resection of femoral Ewing.
Ewing's sarcoma


All pelvic tumors were resected


16 Y old girl with a huge IIB tumor of iliac wing.
En bloc resection after 6 weeks chemotherapy.
Skeletal reconstruction using cement. Excellent oncologic and fonctionnal results with 15 years follow up.
Ewing's sarcoma


Even huge pelvic tumors were resected


Resection of huge tumors are challenges but most important for prognosis.
Early resection of huge tumoral mass can prevent chemoresistance.
Ewing's sarcoma


Even sacroiliac tumors


17 years remission after en bloc resection and reconstruction with cement.
Ewing's sarcoma


POSTOPERATIVE CHEMOTHERAPY


Postoperative chemotherapy alternated :
- 6 IPA (Ifosfamide 6 gr/sqm, Cisplatinum 125 mg/ m², Pirarubicine 35 mg/ m²)
- 3 Cyclophosphamide(150 mg/m² 7d) +Pirarubicine (35 mg/m² d 8)
- 12 weeks of Vincristine (2 mg/ m² x 12), Actinomycine D (2 mg/ m² x 6)

EW.DD2 PROTOCOL. POST OPERATIVE CHEMOTHERAPY


Ewing's sarcoma


TREATMENT TOLERANCE


Tolerance of preoperative chemotherapy is excellent and permits best conditions for the surgery.
Toxicity of postoperative chemotherapy is heavier
1- 20% Vincristine induced multinevritis.
2- 1 Vesical grade 4 toxicity induced by Ifosfamide.
3- 1 Renal toxicity following a course of IPA.
4- Anthracyclines (pirarubicine) low toxicity : only two ECG transitory anomalies.

Late complications related to treatment


We observed two colic cancers in patients treated by this protocol.
Patients were even free survivors when colic cancer occured, respectively 13 years and 15 years following treatment.
Both patients received post operative radiotherapy after contaminated resection of sacroiliac tumors.
Both patients are in CR for the second cancer.

Oncologic results


Ewing's sarcoma

EW DD. 21 children with localized Ewing .Median follow up : 10 years (min 5 , max 19,5). 20/21 patients are DFS.( 15 / 04 / 2005)

CONCLUSION 1


This serie shows the excellent long term prognosis of children with localized Ewing's sarcoma treated by this protocol derived from Hayes, with shorter (6 weeks) bidrug induction.
And systematic conservative surgery.
Followed by six drugs postoperative chemotherapy.

CONCLUSION 2


This serie confirms the results of Hayes on patients treated by surgery : 10/11 operated patients were DFS.
Therapy for localized ewing's sarcoma. Hayes J.Clin.oncol. 1989, 7, 2, 208-213.

This serie also confirms the good prognosis of young patients observed in the multicentric italian SE 91 study published by Rosito.
Rosito P. et al Cancer,1999;86:421-428.
Ewing's sarcoma


CONCLUSION 3


It emphases the low toxicity of this chemotherapy.
And underlines the risks of radiotherapy even at mild doses (2 second cancers out of 3 patients irradiated) and the need to avoid it as often as possible.




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