İKİ RADYOREZİSTAN TÜMÖR OLAN MALİGN MELANOM VE RENAL HÜCRELİ KARSİNOMUN BEYİN METASTAZLARININ ÖZELLİKLERİ VE SAĞKALIMLA İLİŞKİLERİ: BİR RADYOTERAPİ MERKEZİ ÇALIŞMASI

Öz

Amaç: Malign melanom (MM) ve renal hücreli karsinom (RCC), beyne sıklıkla metastaz yapan nadir ve radyorezistan tümörlerdir. Nadir olmaları nedeniyle beyin metastatik MM ve RCC ile ilgili çalışmalar sınırlıdır. MM ve RCC kaynaklı beyin metastazı (BM) gelişen hastaların karakteristik özelliklerini ve sağkalım için potansiyel prognostik faktörleri analiz etmeyi amaçladık. Gereç ve Yöntem: Bu çalışma, 1998-2020 yılları arasında bir üniversite hastanesinin radyoterapi (RT) merkezine başvuran hastaların verilerini kullanan geriye dönük-gözlemsel bir çalışmadır. Klinikopatolojik özellikler, tedavi detayları ve sonlanım verileri analiz edildi. Tek değişkenli analizler ve çok değişkenli sağkalım analizleri yapıldı. Bulgular: Çalışma döneminde merkezimizde tedavi edilen toplam 14,603 hastadan sadece 52’si (%0,004) MM veya RCC ilişkili BM vakasıydı. Çalışma popülasyonunu verileri eksiksiz olan 40 hasta oluşturmaktaydı. MM veya RCC ilişkili BM tanısında medyan yaş 57,7 olup, hastaların %25’i kadındı. MM sıklığı %52,5 ve RCC sıklığı %47,5 idi. “Primer tanı ile ilk ekstrakraniyal metastazlar arasındaki süre” ile “ekstrakraniyal metastaz tanısı ile BM arasındaki süre” arasında zayıf bir korelasyon vardı (r=0,405, p=0,021). Sağkalıma yönelik potansiyel prognostik faktörler olan “yaş, cinsiyet, yaşlı veya genç olma, primer tanı (MM veya RCC olması), ekstrakraniyal metastaz varlığı, BM sayısı, BM’nin yeri, tam yada tama yakın rezeksiyon, RT dozu, planlanan RT’nin tamamlanması, RT alanı” gibi parametrelerin hiçbiri sağkalım ile bağımsız ilişkili değildi. Sonuç: Bulgularımız, MM veya RCC hastalarında beyin metastazı geliştirdiğinde hastaya, tümöre veya tedavi tercihine ait herhangi bir olumlu prognostik faktör olmadan sağkalımın sınırlı olduğunu göstermektedir.

Anahtar Kelimeler

• beyin metastazı
• malign melanom
• radyorezistan tümör
• renal hücreli karsinom
• sağkalım

CHARACTERISTICS AND SURVIVAL OF BRAIN METASTASIS FROM TWO RADIORESISTANT TUMORS, MALIGNANT MELANOMA AND RENAL CELL CARCINOMA: A SINGLE RADIOTHERAPY CENTER STUDY

Öz

Objective: Malignant melanoma (MM) and renal cell carcinoma (RCC) are rare radioresistant tumors that often metastasize to the brain. Because of their rarity, studies on brain metastatic RCC and MM are limited. We aimed to outline the characteristics of brain metastasis (BM) patients from RCC and MM and analyze the potential prognostic factors for survival. Materials and Methods: This is a retrospective-observational study using data from patients admitted to a radiotherapy (RT) center of a university hospital between 1998-2020. Clinicopathological characteristics, treatment details, and outcome results were analyzed. Univariate and multivariate survival analyses were performed. Results: Among a total of 14,603 patients treated in our center in the study period, only 52 (0.004%) were BM cases from MM or RCC. Forty patients had complete data (median age at diagnosis of MM or RCC-related BM: 57.7; females: 25%; MM in 52.5% and RCC in 47.5%). The time between primary diagnosis and first extracranial metastases was weakly correlated with the time between diagnosis of extracranial metastasis and BM (r=0.405, p=0.021). Among the potential prognostic factors on survival [age, sex, older vs younger age group, primary diagnosis (MM vs RC), presence of extracranial metastasis, number of BM, location of BM, presence of gross total resection, dose of RT, completion of prescribed RT, field of RT], none were independently associated with survival. Conclusion: Our findings suggest that when MM or RCC patients develop brain metastasis, survival is limited without any favorable prognostic factor belonging to the patient, the tumor, or the preference of the treatment.

Anahtar Kelimeler

• brain metastasis
• malignant melanoma
• radioresistant tumor
• renal cell cancer
• survival

Kaynakça

1. 1. Badakhshi H, Engeling F, Budach V, Ghadjar P, Zschaeck S, Kaul D. Are prognostic indices for brain metastases of melanoma still valid in the stereotactic era? Radiat Oncol 2018;13:3. [CrossRef] google scholar
2. 2. Guo F, Wang J, Song L, Sun H, Yang B, Liu X, et al. Clinical features and surgical management of four peculiar cases of intracranial metastases from renal cell carcinoma. Neurol Sci 2013;34:149-56. [CrossRef] google scholar
3. 3. Ippen FM, Mahadevan A, Wong ET, Uhlmann EJ, Sengupta S, Kasper EM. Stereotactic radiosurgery for renal cancer brain metastasis: prognostic factors and the role of whole-brain radiation and surgical resection. J Oncol 2015;2015:636918. [CrossRef] google scholar
4. 4. Nieder C, Berberich W, Schnabel K. Tumor-related prognostic factors for remission of brain metastases after radiotherapy. Int J Radiat Oncol Biol Phys 1997;39(1):25-30. [CrossRef] google scholar
5. 5. Abate-Daga D, Ramello MC, Smalley I, Forsyth PA, Smalley KSM. The biology and therapeutic management of melanoma brain metastases. Biochem Pharmacol 2018;153:35-45. [CrossRef] google scholar
6. 6. Glitza Oliva I, Tawbi H, Davies MA. Melanoma Brain Metastases: Current Areas of Investigation and Future Directions. Cancer J 2017;23(1):68-74. [CrossRef] google scholar
7. 7. Clarke JW, Register S, McGregor JM, Grecula JC, Mayr NA, Wang JZ, et al. Stereotactic radiosurgery with or without whole brain radiotherapy for patients with a single radioresistant brain metastasis. Am J Clin Oncol 2010;33(1):70-4. [CrossRef] google scholar
8. 8. Ferrel EA, Roehrig AT, Kaya EA, Carlson JD, Ling BC, Wagner A, et al. Retrospective study of metastatic melanoma and renal cell carcinoma to the brain with multivariate analysis of prognostic pre-treatment clinical factors. Int J Mol Sci 2016;17(3):400. [CrossRef] google scholar

9. 9. Gutenberg A, Nischwitz MD, Gunawan B, Enders C, Jung K, Bergmann M, et al. Predictive chromosomal clusters of synchronous and metachronous brain metastases in clear cell renal cell carcinoma. Cancer Genet 2014;207(5):206-13. [CrossRef] google scholar
10. 10. Kolsi F, Mechergui H, Kammoun B, Mellouli M, Khrifech M, Zaher Boudawara M. Delayed brain metastasis from renal cell carcinoma. Urol Case Rep 2019;22:54-6. [CrossRef] google scholar
11. 11. Shuch B, La Rochelle JC, Klatte T, Riggs SB, Liu W, Kabbinavar FF, et al. Brain metastasis from renal cell carcinoma: presentation, recurrence, and survival. Cancer 2008;113(7):1641-8. [CrossRef] google scholar
12. 12. Meyners T, Heisterkamp C, Kueter JD, Veninga T, Stalpers LJ, Schild SE, et al. Prognostic factors for outcomes after whole-brain irradiation of brain metastases from relatively radioresistant tumors: a retrospective analysis. BMC Cancer 2010;10:582. [CrossRef] google scholar
13. 13. Vandenbroucke JP, von Elm E, Altman DG, G0tzsche PC, Mulrow CD, Pocock SJ, et al. Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): explanation and elaboration. Int J Surg 2014;12:1500-24. [CrossRef] google scholar
14. 14. Fowler JF. The linear-quadratic formula and progress in fractionated radiotherapy. Br J Radiol 1989;62:679-94. [CrossRef] google scholar
15. 15. Papaleontiou M, Norton EC, Reyes-Gastelum D, Banerjee M, Haymart MR. Competing causes of death in older adults with thyroid cancer. Thyroid 2021;31(9):1359-65. [CrossRef] google scholar
16. 16. Berry SD, Ngo L, Samelson EJ, Kiel DP. Competing risk of death: an important consideration in studies of older adults. J Am Geriatr Soc 2010;58(4):783-7. [CrossRef] google scholar
17. 17. Bennani O, Derrey S, Langlois O, Castel H, Laquerriere A, Freger P, et al. Brain metastasis from renal cell carcinoma. Neurochirurgie 2014;60(1-2):12-6. [CrossRef] google scholar
18. 18. Lesueur P, Lequesne J, Barraux V, Kao W, Geffrelot J, Grellard JM, et al. Radiosurgery or hypofractionated stereotactic radiotherapy for brain metastases from radioresistant primaries (melanoma and renal cancer). Radiat Oncol 2014;13:138. [CrossRef] google scholar
19. 19. Noel G, Valery CA, Boisserie G, Cornu P, Hasboun D, Marc Simon J, et al. LINAC radiosurgery for brain metastasis of renal cell carcinoma. Urol Oncol 2004;22(1):25-31. [CrossRef] google scholar