1. Faculty of Medical Science, Stip and Clinic of Oncology and Radiotherapy, Skopje R.Macedonia Ewing sarcoma: a case report D-r Marija Karakolevska - Ilova

2. MATERIAL AND METHODS 17 year old patient Pain and swelling of the right femoral region for 4 weeks with intermittent temperature ( 02.05.2007year) Laboratory – normal CT on right femoral bone : changed sceletal structure in distal part of right femoral bone with soft tissue substrate in deep musculature without involvement of peripheral musculature. Sceleton scan : pathological accumulation of the lower and middle third of the right femur, great trochanter of the right femur and right parietal bone. FNAB – classification group 5 - cytomorphologycal Biopsio femoris lat. dex. - histophatologycal - immunohistohemical Ewing sarcoma - PNET

3. Initial treatment with: -Radyotherapy : 3D conformal delivery treatment with TCT (1,25Mev), depth = 6sm, field: 10x30 sm, TTD=50Gy (25fr/2Gy) (11.06.2007 – 13.07.2007 ) followed by - Chemotherapy : IV courses with : Cyclophosphamide 1000mg 1-3 d, Doxorubicin 30mg 1-3d, Etoposid 200 mg 1-3d, MESNA 4000mg 1-3 d. followed by II courses of Cyclophosphamide 500mg 1-3 d, Etoposid 200mg 1-3 and Vinkristine 2mg -Blood support is achieved with GSF and antifungal drug after each course. - At the end of chemotherapy the surgeon was consulted for reevaluation for surgery, and no surgery was performed.

4. Follow up: 2008: Stable disease. ECOG PS =0, X-rays of the lung : normal, ultrasound of abdomen: normal, laboratory: normal ( every 3 months ) 2009: Stable disease. ECOG PS =0, X-rays of the lung: normal, ultrasound of abdomen: normal, laboratory: normal ( every 3 months ) 2010: ECOG PS=0, X-rays of the lung: normal, ultrasound of abdomen: normal, laboratory: normal ( every 3 months ) until 1.10.2010 when the pacient came with: - Cephalea - Vomiting and fatigue - Left side facial pain - Egzophtalmus on the left eye Examinations : CT of brain: Exspansive mass in middle fossa witch is compromasing the temporal lobe and left frontal lobe. It penetrates into the left orbit with dislocation of the eye bulge anteriorly. Scan sceleton(Tc99m): Recidiv localis

5. Treatment:  Brain metastases: 3D conformal radiotherapy delivery with TTD=48Gy ( 24fr/2Gy ) local on the tumor site bad  Antiedematous therapy followed by  Chemotherapy: I-III courses with Cyclophosphamide 500mg 1-3d, Etoposid 200mg 1-3, Vincristine 2mg, IV-V course continued with Doxorubicin 30mg 1-3d, VI-VII course with Ifosfamid 4000mg, Vepesid 150mg, Mesna 6000mg.  During the treatment and 6 months after CT on brain was performed : no sings of local relapse were found ( 15.11.2011)  ( 1.12.2011) – Tumefaction on the right parietal bone – 3-4sm. FNAB – classification group 5  Sceleton scan : pathological accumulation in right femur, right temporal bone and right sixth rib

6. Bisphosphonate therapy was added 3D conformal RT locally on tumefaction of the right parietal bone with TTD=39Gy  After 2 months : cephalea - recidiv retrobulbaris ( 28.02.2012 )  The patient was treated with palliative chemotherapy with Docetaxel 120 mg ( VI courses )  4 months after : -Egzophtalmus on the left eye - LDH : 889; 913  Treatment : Whole brain irradiation TTD=30Gy with Temozolomide.  At the moment the patient is with deteriorated general condition, with paresis of the left lower limb

7. DISCUSSION -Ewing's sarcoma has a propensity to metastasize to the lung, bone and bone marrow. This tumor can also involve the CNS with a relatively low incidence – 1-8%. -The literature suggests the incidence may be increasing with the increase in use of chemotherapy and with patients living longer. -Between 20-25% of patients are diagnosed with metastatic disease. -Studies investigating CNS involvement of Ewing's sarcoma have reported that spread through direct extension from the skull is more frequent than hematogenous spread. -Prognostic factors that confer poorer outcome are: serum LDH level, axial localization or older age ( > 15 years), size and volume, incomplete or no surgery for local therapy and time of relaps ( < 24 months ).

8.  LDH elevated at time of CNS relapse – LDH has to be evaluated during the whole treatment.  Patients with metastases and recurrent disease still fare poorly, with 5- year survival rates of 20% witch highlights the need for novel chemotherapeutic agents, bisphosphonates and targeted therapy