Kraniyal Radyotoksisite
Özet
Radyoterapi (RT), primer ve metastatik santral sinir sistemi tümörlerinin yönetiminde küratif, adjuvan ve palyatif amaçlarla yaygın olarak tercih edilen hayati bir tedavi yöntemidir. Ancak tedavi sürecinde, önceden sınırları belirlenmiş olan normal beyin dokularının radyasyon tolerans limitlerinin aşılması, hastalarda geri dönüşü olmayan kraniyal radyotoksisite riskini beraberinde getirmektedir. Akut dönem yan etkileri arasında bulantı, kusma, baş ağrısı ve nöbet gibi geçici reaksiyonlar gözlenirken, geç dönemde ortaya çıkan bilişsel işlev bozuklukları ve radyasyon nekrozu doğrudan doğruya uygulanan toplam doz ve tedavi edilen beyin volümü ile ilişkilidir. Bu komplikasyonları en aza indirmek adına stereotaktik radyocerrahi ve fraksiyone konformal RT tekniklerinde kritik organ kısıtlamalarına gidilmektedir. Özellikle çocuk hastalarda 18 Gy üzerindeki dozlar zekâ seviyesinde ve akademik başarıda ciddi düşüşlere neden olmakta, supratentorial alanların ışınlanması kognitif gerilemeyi tetiklemektedir. Erişkinlerde ise büyük fraksiyon dozları ilerleyici unutkanlık, ataksi, demans ve lökoensefalopati gibi ağır nörotoksik tablolar oluşturabilmektedir. Toksisitenin tam olarak tespit edilebilmesi için hastaların tedavi sonrası en az 5 yıl izlenmesi ve süreçte hipokampüs ile beyin sapı gibi hassas yapıların maksimum hassasiyetle korunması gerekmektedir.
Radiation therapy (RT) serves as an essential curative, adjuvant, and palliative treatment modality widely utilized in the management of primary and metastatic brain tumors. However, a major clinical challenge involves avoiding the radiation tolerance thresholds of normal brain structures to prevent severe cranial radiotoxicity, which can manifest as radiation necrosis and permanent neurocognitive deficits. While acute side effects including nausea, vomiting, headaches, and seizures are typically transient and medically manageable, late-onset complications like cognitive deterioration are tightly linked to the cumulative dose, volume of tissue irradiated, and fractionation parameters. To reduce these debilitating long-term morbidities, conformal radiation techniques and stereotactic radiosurgery strictly limit exposure to critical organs, such as keeping the total brainstem dose under 54 Gy. Pediatric populations exhibit heightened sensitivity; whole-brain radiation doses exceeding 18 Gy are proven to cause significant intelligence point drops and psychological distress. In adults, high fractionated doses or combined chemotherapeutic regimens can induce progressive memory loss, ataxia, leukoencephalopathy, and dementia. Consequently, an accurate and comprehensive evaluation of these long-term neurocognitive impairments necessitates rigorous patient follow-up for a minimum of 5 years post-RT, prioritizing advanced protective strategies such as hippocampal sparing.
Referanslar
Halperin EC, Wazer DE, Perez CA, Brady LW. Perez & Brad- y’s Principles and Practice of Radiation Oncology Seventh Edition. Copyright © 2019 Wolters Kluwer, Printed in China, PA 2540-2647.
Leonard L. Gunderson, Joel E. Tepper. CLINICAL RADIATION ONCOLOGY. FOURTH EDITION. 1600 John F. Kennedy Blvd. Ste 1800 Philadelphia, PA 620-637.
LawrenceYR, Lı XA, Naqa IE, Hahn CA, Marks LB, Merchant TE et al. Radiation Dose–Volume Effects In The Brain. I. Int J Radiat Oncol Biol Phys. 2010;76(3):20-27.
Shaw E, Scott C, Souhami L, et al. Single dose radiosurgical treatment of recurrent previously irradiated primary brain tumors and brain metastases: Final report of RTOG protocol 90-05. Int J Radiat Oncol Biol Phys 2000;47:291–298.
Fowler JF. The linear-quadratic formula and progress in frac- tionated radiotherapy. Br J Radiol 1989;62:679–694..
Hill JM, Kornblith AB, Jones D, et al. A comparative study of the long term psychosocial functioning of childhood acute lymphoblastic leukemia survivors treated by intrathecal methotrexate with or without cranial radiation. Cancer. 1998;82:208–218.
Waber DP, Turek J, Catania L, et al. Neuropsychological outcomes from a randomized trial of triple intrathecal chemotherapy compared with 18 Gy cranial radiation as CNS treatment in acute lymphoblastic leukemia: Findings from Dana-Farber Cancer Institute ALL Consortium Protocol 95-01. J Clin Oncol. 2007;25:4914–4921
Smibert E, Anderson V, Godber T, et al. Risk factors for intellectual and educational sequelae of cranial irradiation in childhood acute lymphoblastic leukaemia. Br J Cancer. 1996;73:825–830.
Merchant TE, Kiehna EN, Li C, et al. Modeling radiation dosimetry to predict cognitive outcomes in pediatric patients with CNS embryonal tumors including medulloblastoma. Int J Radiat Oncol Biol Phys. 2006;65:210–221.
DeAngelis LM, Delattre JY, Posner JB. Radiation-induced dementia in patients cured of brain metastases. Neurology. 1989; 39:789–796.
Armstrong CL, Hunter JV, Ledakis GE, et al. Late cognitive and radiographic changes related to radiotherapy: Initial prospective findings. Neurology. 2002;59:40–48.
Gregor A, Cull A, Stephens RJ, et al., for theUnited Kingdom Coordinating Committee for Cancer Research (UKCCCR) and the European Organization for Research and Treatment of Cancer (EORTC). Prophylactic cranial irradiation is indicated following complete response to induction therapy in small cell lung cancer: Results of a multicentre randomised trial. Eur J Cancer. 1997;33:1752–1758.
Vigliani MC, Sichez N, Poisson M, et al. A prospective study of cognitive functions following conventional radiotherapy for supratentorial gliomas in young adults: 4-Year results. Int J Radiat Oncol Biol Phys. 1996;35:527–533.
Miotto EC, Junio AS, Silva CC, Cabrera HN, Machado MAR, Benute GRG et al. Cognitive impairments in patients with low grade gliomas and high grade gliomas. Arq Neuropsiquiatr. 2011;69(4):596-601.
Omuro AMP, Ben-Porat LS, Panageas KS, et al. Delayed neurotoxicity in primary central nervous system lymphoma. Arch Neurol. 2005;62:1595–1600.
Lai R, Abrey LE, Rosenblum MK, DeAngelis LM. Treat- ment-induced leukoencephalopathy in primary CNS lymphoma: a clinical and autopsy study. Neurology. 2004;62:451-456.
Abrey LE, DeAngelis LM, Yahalom J: Longterm survival in primary CNS lymphoma. J Clin Oncol. 1998;16:859-863.
Shah GD, Yahalom J, Correa DD, et al. Combined immunochemotherapy with reduced whole-brain radiotherapy for newly diagnosed primary CNS lymphoma. J Clin Oncol. 2007;25: 4730–4735.
Uy NW, Woo SY, Teh BS, et al: Intensity-modulated radiation therapy (IMRT) for meningioma. Int J Radiat Oncol Biol Phys. 2002;53:1265–1270.
Merchant TE, Chitti RM, Li C, et al: Factors associated with neurological recovery of brainstem function following pos- toperative conformal radiation therapy for infratentorial ependymoma. Int J Radiat Oncol Biol Phys. 2010;76:496–503.
