Hyperfractionated External Beam Radiation Therapy in the Treatment of Murine Transgenic Retinoblastoma

Hayden, Brandy C.; Murray, Timothy G.; Cicciarelli, Nicole; Αλεξανδρίδου, Αναστασία; Hernandez, E.; Wu, Xiaodong; Markoe, Arnold M.; Feuer, William J.; Fulton, Lilia; O’Brien, Joan M.

doi:10.1001/archopht.120.3.353

Cited by 10 publications

(3 citation statements)

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“…In this murine retinoblastoma model, the TCD 50 has recently been found to be 3370 rad (33.7 Gy) for those animals administered radiation therapy in 120-rad (1.2-Gy) fractions twice per day. 66 In our study, the TCD 50 for those animals administered salvage EBRT after failed carboplatin therapy decreased to 1410 rad (14.1 Gy). The radiation enhancement ratio, which describes the potential enhancement of combined therapy of carboplatin and radiation in this tumor model, is calculated to be 2.39.…”

Section: Commentmentioning

confidence: 48%

External Beam Radiation "Salvage" Therapy in Transgenic Murine Retinoblastoma

et al. 2004

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Objective: To determine the efficacy of low-dose "salvage" external beam radiation therapy (EBRT) following failed subconjunctival carboplatin chemotherapy in a murine model of heritable retinoblastoma. Methods: Eighty-four eyes from 8-week-old, simian virus 40, T-antigen-positive mice were treated with 6 serial subconjunctival carboplatin injections (100 µg/25 µL). At 12 weeks of age, 64 eyes received EBRT for a total dose of 480 (4.8 Gy), 1200 (12.0 Gy), 1560 (15.6 Gy), or 3000 (30.0 Gy) rad. Twenty eyes received no additional therapy following subconjunctival carboplatin injections. Ten eyes received a total dose EBRT of only 3000 rad. Eight eyes received subconjuctival injections of only an isotonic sodium chloride solution. Ten eyes served as untreated controls. Main Outcome Measures: Eyes were enucleated at 20 weeks to assess the presence of tumor on histopathological examination. Results: Salvage therapy using low-dose EBRT was able to reestablish tumor control in a dose-dependent manner. Increasing the EBRT dose to 3000 rad resulted in 100% tumor control. The dose-dependent curves were significantly different between the treatment groups-EBRT alone vs salvage EBRT after receiving subconjunctival carboplatin injections (PϽ.001). Conclusion: Low-dose hyperfractionated salvage EBRT following failed primary subconjunctival carboplatin chemotherapy is efficacious in the treatment of retinoblastoma in this animal model. Clinical Relevance: Salvage EBRT using a reduced total radiation dose could be associated with a radiationrelated treatment enhancement in pediatric retinoblastoma.

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Section: Commentmentioning

confidence: 48%

External Beam Radiation "Salvage" Therapy in Transgenic Murine Retinoblastoma

et al. 2004

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“…Hayden et al 12 used a murine model to realize the value of hyperfractionated EBRT. They treated 220 eyes with a total dose ranging from 10 to 76 Gy in 1.2 Gy, 2 Gy and 5 Gy fractions.…”

Section: History Of Ebrt In Management Of Rbmentioning

confidence: 99%

Role and Alternative Modalities of External Beam Radiotherapy in the Management of Retinoblastoma

Pehlivan¹

2012

UHOD

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Retinoblastoma (RB) is the most common orbital tumor of childhood. Treatment strategy depends on number, loalization and extent of disease (unilateral vs bilateral) involvement. Currently, significant improvements in treatment and long survival rates have been achieved in management of this tumor group that mandates for search of more sophisticated novel treatment modalities to reduce the risks of treatment related side effects and secondary malignancies. In recent years, both the role and techniques of radiation therapy (RT) have significantly changed in parallel to the improvements in technology. Present review aims to discuss the current treatment modalities in RB, and the role and alternative techniques of RT in the light of recent literature.Keywords: Retinoblastoma, External beam radiotherapy, Toxicity, Chemotherapy, Secondary malignancy ÖZET Retinoblastoma Tedavisinde Eksternal Radyoterapinin Rolü ve Radyoterapi SeçenekleriRetinoblastoma (RB) çocukluk ça¤›n›n en s›k orbital tümörü olup hastal›¤›n tedavisi tümörün say›s›, büyüklü¤ü, lokalizasyonu ve tutulu göz say›s›na göre farkl›l›klar göstermektedir. Uzayan yaflam süresi ile belirginleflen radyoterapi (RT) ve/veya kemoterapiye ba¤-l› yan etkilerle ikincil tümör riskini en aza indirebilecek tedavi alternatiflerinin aranmas›n› zorunlu k›lm›flt›r. Di¤er tedavi seçeneklerinde elde edilen baflar›lar sonucu eksternal RT'nin tedavideki rolündeki de¤iflimin yan› s›ra, RT tekniklerinde de teknolojiye paralel ilerlemeler kaydedilmifltir. Dolay›s›yla güncel derlemede, RB tedavisinde kullan›lan de¤iflik tedavi seçenekleri ve özellikle RT'nin de¤iflen rolü ile tekniklerinin ayr›nt›l› olarak tart›fl›lmas› amaçlanm›flt›r.

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“…The experiments were commonly carried out using an orthovoltage (200-300 kV) x-ray tube and a lead shield with an opening positioned over the tumor, [5][6][7] or using a linear accelerator and thick lead blocks. 10 Subsequently, these simple nonconformal single-field approaches were used for studies of glioblastoma multiforme, 11 retinoblastoma, 12,13 and repair kinetics of kidney 14 in mice, and for lung cancer fractionation studies in rats. 15 Dose in clinical radiotherapy is, however, typically delivered with multiple beams in multiple fractions.…”

Section: Introductionmentioning

confidence: 99%

Modality comparison for small animal radiotherapy: A simulation study

et al. 2013

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Purpose: Small animal radiation therapy has advanced significantly in recent years. Whereas in the past dose was delivered using a single beam and a lead shield for sparing of healthy tissue, conformal doses can be now delivered using more complex dedicated small animal radiotherapy systems with image guidance. The goal of this paper is to investigate dose distributions for three small animal radiation treatment modalities. Methods: This paper presents a comparison of dose distributions generated by the three approachesa single-field irradiator with a 200 kV beam and no image guidance, a small animal image-guided conformal system based on a modified microCT scanner with a 120 kV beam developed at Stanford University, and a dedicated conformal system, SARRP, using a 220 kV beam developed at Johns Hopkins University. The authors present a comparison of treatment plans for the three modalities using two cases: a mouse with a subcutaneous tumor and a mouse with a spontaneous lung tumor. A 5 Gy target dose was calculated using the EGSnrc Monte Carlo codes. Results: All treatment modalities generated similar dose distributions for the subcutaneous tumor case, with the highest mean dose to the ipsilateral lung and bones in the single-field plan (0.4 and 0.4 Gy) compared to the microCT (0.1 and 0.2 Gy) and SARRP (0.1 and 0.3 Gy) plans. The lung case demonstrated that due to the nine-beam arrangements in the conformal plans, the mean doses to the ipsilateral lung, spinal cord, and bones were significantly lower in the microCT plan (2.0, 0.4, and 1.9 Gy) and the SARRP plan (1.5, 0.5, and 1.8 Gy) than in single-field irradiator plan (4.5, 3.8, and 3.3 Gy). Similarly, the mean doses to the contralateral lung and the heart were lowest in the microCT plan (1.5 and 2.0 Gy), followed by the SARRP plan (1.7 and 2.2 Gy), and they were highest in the single-field plan (2.5 and 2.4 Gy). For both cases, dose uniformity was greatest in the single-field irradiator plan followed by the SARRP plan due to the sensitivity of the lower energy microCT beam to target heterogeneities and image noise. Conclusions:The two treatment planning examples demonstrate that modern small animal radiotherapy techniques employing image guidance, variable collimation, and multiple beam angles deliver superior dose distributions to small animal tumors as compared to conventional treatments using a single-field irradiator. For deep-seated mouse tumors, however, higher-energy conformal radiotherapy could result in higher doses to critical organs compared to lower-energy conformal radiotherapy. Treatment planning optimization for small animal radiotherapy should therefore be developed to take full advantage of the novel conformal systems.

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Hyperfractionated External Beam Radiation Therapy in the Treatment of Murine Transgenic Retinoblastoma

Cited by 10 publications

References 55 publications

External Beam Radiation "Salvage" Therapy in Transgenic Murine Retinoblastoma

External Beam Radiation "Salvage" Therapy in Transgenic Murine Retinoblastoma

Role and Alternative Modalities of External Beam Radiotherapy in the Management of Retinoblastoma

Modality comparison for small animal radiotherapy: A simulation study

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