Adjuvant Radiotherapy for the Multimodal Treatment of Pediatric Ewing Sarcoma

Yıl 2022, Cilt: 4 Sayı: 3, 304 - 314, 22.09.2022

Gonca Altınışık İnan , İpek Pınar Aral , Tarık Kargıoğlu , Arzu Yazal Erdem , Selma Çakmakcı , Hüseyin Furkan Öztürk , Suheyla Aytaç Arslan , Yılmaz Tezcan

https://doi.org/10.37990/medr.1093314

Öz

Aim: This study aimed to report the adjuvant radiotherapy results of pediatric patients with Ewing sarcoma who received multimodal treatment for this rare disease using modern radiotherapy (RT) techniques.
Material and Methods: Pediatric patients with Ewing Sarcoma (ES) who received adjuvant radiotherapy were evaluated retrospectively. The study’s primary endpoint was overall survival (OS) and disease-free survival (DFS). The secondary endpoint was local relapse-free survival after RT (LRFS- RT) and overall survival after RT (OS-RT).
Results: The results of 18 pediatric patients diagnosed with Ewing Sarcoma in our clinic between 09.12.2013-04.04.2021 and underwent RT for adjuvant were evaluated retrospectively. The three patients were excluded since they did not meet the inclusion criteria. The median age of the patients at the time of diagnosis was 10.5 (range 3-17). The time from diagnosis to the onset of RT was 8.6 (range 2-20) months. The median fraction dose was 180 cGy, and the median total RT dose was 50.4 (range 45-55.80) Gy. The median follow-up period of the study was 27 (range 11-86) months. The 12 (80%) patients survived, and 3 (20%) died. The median OS diagnosis of the patients was 27.3 (range 11 to 86.5) months. The overall survival of the patients after RT was median 17.3 (range 4.4-83.9) months. Recurrence (local+distant) was observed in 7 patients (46.7%); 2 (13.3%) local, 3 (20%) distant and 2 (13.3%) both. The median DFS was 24 months (range 1-86.5). Median LRFS-RT is 14.2 (range 1-83.9) months. The relationship between LRFS-RT and age (<10 vs. ≥10 years old) (p=0.050; HR:2.30; %95 CI 0.70-3.17) was significant. Significantly higher LRFS-RT was observed in the older age.
Conclusion: In patients with Ewing’s sarcoma who are at high risk of local failure after surgery, adjuvant radiotherapy could be applied to increase local control rate, with reasonable side effects.

Anahtar Kelimeler

Adjuvant Radiotherapy, Ewing Sarcoma, Pediatric Oncology

Pediatrik Ewing Sarkoma Hastalarının Multimodal Tedavisinde Adjuvan Radyoterapi

Öz

Amaç: Bu çalışmada Ewing sarkomu nedeniyle multimodal tedavi uygulanan çocuk hastaların adjuvan radyoterapi sonuçlarını bildirmeyi amaçladık.
Materyal Metot: Adjuvan radyoterapi (RT) alan Ewing Sarkomlu pediatrik hastalar geriye dönük olarak değerlendirildi. Çalışmanın birincil sonlanım noktası, Genel Sağkalım (GS) ve hastalıksız sağkalım (HS) idi. İkincil sonlanım noktaları, RT den sonra lokal nükssüz sağkalım (LRFS-RT) ve RT’den sonra genel sağkalım (GS-RT)’di.
Bulgular: Kliniğimizde 09.12.2013-04.04.2021 tarihleri arasında Ewing Sarkomu tanısıyla adjuvan RT uygulanan 18 çocuk hastanın sonuçları retrospektif olarak değerlendirildi. Üç hasta dahil edilme kriterlerini karşılamadıkları için çalışma dışı bırakıldı. Hastaların tanı anındaki ortanca yaşı 10.5 (dağılım 3-17) idi. Tanıdan RT başlangıcına kadar geçen süre 8.6 (2-20) aydı. Ortanca fraksiyon dozu 180 cGy ve ortanca toplam RT dozu 50.4 (aralık 45-55.80) Gy idi. Çalışmanın ortanca takip süresi 27 (dağılım 11-86) aydı. Oniki (%80) hasta sağ ve 3 (%20) hasta ölü idi. Hastaların ortanca GS değeri 27.3 (dağılım 11 ila 86,5) aydı. Hastaların RT sonrası GS ortanca 17.3 (aralık 4.4-83.9) aydı. Yedi hastada (%46.7) nüks (lokal+uzak) vardı; 2 (%13.3) lokal, 3 (%20) uzak ve 2 (%13.3) lokal+uzak met vardı. Ortanca HS 24 aydı (aralık 1-86.5). Ortanca LRFS-RT 14.2 (aralık 1-83.9) aydı. LRFS-RT ile yaş (<10 ve ≥yaş üstü) arasındaki ilişki (p=0.050; HR:2.30; %95 GA 0.70-3.17) anlamlıydı. İleri yaşta anlamlı olarak daha yüksek LRFS-RT gözlendi.
Sonuç: Ameliyat sonrası lokal başarısızlık riski yüksek olan Ewing sarkomlu hastalarda adjuvan radyoterapi ile lokal kontrol şansı arttırılmaya çalışılmaktadır.

Kaynakça

• 1. Smith MA, Altekruse SF, Adamson PC, Reaman GH, Seibel NL. Declining childhood and adolescent cancer mortality. Cancer. 2014 Aug 15;120(16):2497-506. doi: 10.1002/cncr.28748. Epub 2014 May 22.
• 2. Ewing J. Diffuse endothelioma of bone. Proc NY Pathol Soc. 1921;21:17
• 3. La TH, Meyers PA, Wexler LH, et al. Radiation therapy for Ewing's sarcoma: results from Memorial Sloan-Kettering in the modern era. Int J Radiat Oncol Biol Phys. 2006 Feb 1;64(2):544-50.
• 4. Schuck A, Ahrens S, Paulussen M, et al. Local therapy in localized Ewing tumors: results of 1058 patients treated in the CESS 81, CESS 86, and EICESS 92 trials. Int J Radiat Oncol Biol Phys. 2003 Jan 1;55(1):168-77.
• 5. Indelicato DJ, Keole SR, Shahlaee AH, Shi W, Morris CG, Marcus RB Jr. Definitive radiotherapy for ewing tumors of extremities and pelvis: long-term disease control, limb function, and treatment toxicity. Int J Radiat Oncol Biol Phys. 2008 Nov 1;72(3):871-7.
• 6. Nesbit ME , Gehan EA, Burgert EO, et al. Multimodal therapy for the management of primary, non- metastatic Ewing's sarcoma of bone: a long-term follow-up of the First Intergroup study. J Clin Oncol. 1990 Oct;8(10):1664-74.
• 7. Choi Y, Lim DH, Lee SH, et al. Role of Radiotherapy in the Multimodal Treatment of Ewing Sarcoma Family Tumors. Cancer Res Treat. 2015;47(4):904-912. doi:10.4143/crt.2014.158
• 8. Lopez JL, Cabrera P, Ordonez R, Ramirez GL, Fernandez JM, Ortiz MJ. Role of radiation therapy in the multidisciplinary management of Ewing's Sarcoma of bone in pediatric patients: An effective treatment for local control. Report of Practical Oncology & Radiotherapy. 2011; 16(3):103-109.
• 9. Gatta G, Capocaccia R, Stiller C, Kaatsch P, Berrino F, Terenziani M; EUROCARE Working Group.
• Childhood cancer survival trends in Europe: a EUROCARE Working Group study. J Clin Oncol. 2005 Jun 1;23(16):3742-51.
• 10. Jürgens H, Exner U, Gadner H, et al. Multidisciplinary treatment of primary Ewing's sarcoma of bone. A 6-year experience of a European Cooperative Trial. Cancer. 1988 Jan 1;61(1):23-32.
• 11. Smith MAS, Gurney JG, Ries LA. Cancer in adolescents 15 to 19 years old. In: Cancer incidence and Survival Among Children and Adolescents: United States SEER Program 1975-1995, Pub #99- 4649, Smith MAS, Gurney JG, Ries LA, et al (Eds), National Cancer Institute, Bethesda, MD 1999.
• 12. Granowetter L, Womer R, Devidas M, et al. Dose-intensified compared with standard chemotherapy for non-metastatic Ewing sarcoma family of tumors: a Children's Oncology Group Study. J Clin Oncol. 2009 May 20;27(15):2536-41.
• 13. Esmati E, Maddah Safaei A, Babaei M, Nosrati H, Momeni H. Radiotherapy for Ewing sarcoma: A 5 year experience from Iran cancer institute. Int. J. Radiat. Res., January 2016;14(1): 53-57
• 14. Wan ZH, Huang ZH, Chen LB. Survival outcome among patients with Ewing's sarcoma of bones and joints: a population-based cohort study. Sao Paulo Med J. 2017 Dec 18;136(2):116-122. doi: 10.1590/1516-3180.2017.0236230917. PMID: 29267540.
• 15. Sarı N, Cetındag MF, Ilhan I. Treatment of Extraosseous Ewing Sarcoma in Children: Single Center Experience. UHOD 2009; 19: 147-52.
• 16. Kaçmaz İE, Keçeci B, Basa CD, Sabah D. Treatment of pelvic Ewing's sarcoma: Pros and cons of chemotherapy plus definitive radiotherapy versus surgery. Acta Orthop Traumatol Turc. 2020 Jan;54(1):42-48.
• 17. Goyal S, Biswas A, Mohanti BK, Bakhshi K. Non-metastatic Ewing's sarcoma family of tumors arising from head and neck: a single institution experience. Ther Radiol Oncol 2019;3:22.
• 18. Sathyamurthy A, Singh A,Jose T, et al. Multi-modality management of extraosseous Ewing sarcoma: 10-year experience from a tertiary care centre. J Radiother Pract. 2020 Mar;19(2):1-7. doi: 10.1017/S1460396920000126
• 19. Momin FJ, Bhattacharyya M, Saikia S et al. Radiotherapy in Ewing's Sarcoma Family Tumor — experience from North-East India. Oncol Clin Pract 2021; 17, 3: 103–111
• 20. Krasin MJ, Rodriguez-Galindo C, Davidoff AM, et al. Efficacy of combined surgery and irradiation for localized Ewings sarcoma family of tumors. Pediatr Blood Cancer. 2004;43:229-236.
• 21. Krasin MJ,Davidoff AM, Rodriguez-Galindo C, et al. Definitive surgery and multiagent systemic therapy for patients with localized Ewing sarcoma family of tumors: local outcome and prognostic factors. Cancer. 2005;104:367-373.
• 22. Pan HY, Morani A,Wang WL, et al. Prognostic factors and patterns of relapse in Ewing sarcoma patients treated with chemotherapy and r0 resection. Int J Radiat Oncol Biol Phys. 2015;92:349-357.