Brain necrosis after fractionated radiation therapy: Is the halftime for repair longer than we thought?

Bender, Edward T.

doi:10.1118/1.4762562

Cited by 13 publications

(5 citation statements)

References 52 publications

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“…Another potential reason may be that we did not wait long enough in between delivering fractions. A prior report [22] gives a repair halftime for radiation necrosis to be 38.1 (6.9–76) hours based on human data. Thus, irradiating every other day instead of every day may result in additional sparing of damage.…”

Section: Discussionmentioning

confidence: 99%

Minimal difference between fractionated and single-fraction exposure in a murine model of radiation necrosis

Boria

Pérez-Torres

2019

Radiat Oncol

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Purpose Despite the success of fractionation in clinical practice to spare healthy tissue, it remains common for mouse models used to study the efficacy of radiation therapy to use minimal or no fractionation. The goal of our study was to create a fractionated mouse model of radiation necrosis that we could compare to our single fraction model. Methods Precision X-Ray’s X-Rad 320 cabinet irradiator was used to irradiate the cerebrum of mice with four different fractionation schemes, while a 7 T Bruker magnetic resonance imaging (MRI) scanner using T2 and post-contrast T1 imaging was used to track the development of radiation necrosis over the span of six weeks. Results All four fractionation schemes with single fraction equivalent doses (SFED) less than 50 Gy for the commonly accepted alpha/beta ratio (α/β) value of 2–3 Gy produced radiation necrosis comparable to what would be achieved with single fraction doses of 80 and 90 Gy. This is surprising when previous work using single fractions of 50 Gy produced no visible radiation necrosis, with the results of this study showing fractionation not sparing brain tissue as much as expected. Conclusion Further interpretation of these results must take into consideration other studies which have shown a lack of sparing when fractionation has been incorporated, as well as consider factors such as the use of large doses per fraction, the time between fractions, and the limitations of using a murine model to analyze the human condition.

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Section: Discussionmentioning

confidence: 99%

Minimal difference between fractionated and single-fraction exposure in a murine model of radiation necrosis

Boria

Pérez-Torres

2019

Radiat Oncol

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“…In this work the clinical toxicities endpoints were divided into two categories, intermediate and severe, depending on their impact on patients Quality of Life (QoL), as detailed in Table 2 , in brackets. Late neurological toxicity with devastating clinical consequences or potentially life-threatening, such as blindness [ 12 ], brain, brainstem and spinal cord necrosis [ 15 ], temporal lobe injury [ 35 ], were defined as severe. Otherwise, other relevant rare adverse effects, which still have a significant but less tremendous impact on patients QoL, were referred as intermediate.…”

Section: Materials and Methodsmentioning

confidence: 99%

“…Patients are so qualified to receive PT if the difference in the predicted risks between the photon and the proton plan is larger than a defined threshold, e.g., 10% for a Grade 2 toxicity, which represents the minimal potential benefit to qualify the patient for PT [ 10 ]. Modelled side effects of radiotherapy (RT) in orbital, sinonasal, and skull-based districts have been developed including ocular toxicity [ 11 ], visual impairment [ 12 , 13 , 14 ], radiation necrosis [ 12 , 15 , 16 ] and cognitive deterioration [ 17 , 18 ]. However, for most of the above-mentioned side effects, only photon-derived NTCP models are available, often without external validation.…”

Section: Introductionmentioning

confidence: 99%

A Patient Selection Approach Based on NTCP Models and DVH Parameters for Definitive Proton Therapy in Locally Advanced Sinonasal Cancer Patients

Mirandola

Russo

Bonora

et al. 2022

Cancers

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(1) Background: In this work, we aim to provide selection criteria based on normal tissue complication probability (NTCP) models and additional explanatory dose-volume histogram parameters suitable for identifying locally advanced sinonasal cancer patients with orbital invasion benefitting from proton therapy. (2) Methods: Twenty-two patients were enrolled, and two advanced radiation techniques were compared: intensity modulated proton therapy (IMPT) and photon volumetric modulated arc therapy (VMAT). Plans were optimized with a simultaneous integrated boost modality: 70 and 56 Gy(RBE) in 35 fractions were prescribed to the high risk/low risk CTV. Several endpoints were investigated, classified for their severity and used as discriminating paradigms. In particular, when NTCP models were already available, a first selection criterion based on the delta-NTCP was adopted. Additionally, an overall analysis in terms of DVH parameters was performed. Furthermore, a second selection criterion based on a weighted sum of the ΔNTCP and ΔDVH was adopted. (3) Results: Four patients out of 22 (18.2%) were suitable for IMPT due to ΔNTCP > 3% for at least one severe toxicity, 4 (18.2%) due to ΔNTCP > 20% for at least three concurrent intermediate toxicities and 16 (72.7%) due to the mixed sum of ΔNTCP and ΔDVH criterion. Since, for some cases, both criteria were contemporary fulfilled, globally 17/22 patients (77.3%) would benefit from IMPT. (4) Conclusions: For this rare clinical scenario, the use of a strategy including DVH parameters and NTCPs when comparing VMAT and IMPT is feasible. We showed that patients affected by sinonasal cancer could profit from IMPT compared to VMAT in terms of optical and central nervous system organs at risk sparing.

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“…To account for potential complications following radiotherapy, normal tissue complication probabilities (NTCP) for various OAR were computed using different published models in the literature. These included effects on neurocognition (change in estimated intellectual quotient (IQ) [27,28] or delayed recall on the Wechsler Memory Scale-III Word List [29]), neuroendocrine dysfunctions (e.g., adrenocorticotropic or growth hormone deficiency, central hypothyroidism [30,31]), CNS necrosis [28,31,32], hearing loss or tinnitus [31], vision impairment [33,34], alopecia or erythema [35] or xerostomia [36]. Detailed information on the respective NTCP model for each OAR can be found in Table A1.…”

Section: Photon Treatment Planning and Comparative Evaluation Of Trea...mentioning

confidence: 99%

Proton Therapy for Advanced Juvenile Nasopharyngeal Angiofibroma

Hoeltgen,

Tessonnier,

Meixner

et al. 2023

Cancers

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Purpose: To provide the first report on proton radiotherapy (PRT) in the management of advanced nasopharyngeal angiofibroma (JNA) and evaluate potential benefits compared to conformal photon therapy (XRT). Methods: We retrospectively reviewed 10 consecutive patients undergoing PRT for advanced JNA in a definitive or postoperative setting with a relative biological effectiveness weighted dose of 45 Gy in 25 fractions between 2012 and 2022 at the Heidelberg Ion Beam Therapy Center. Furthermore, dosimetric comparisons and risk estimations for short- and long-term radiation-induced complications between PRT plans and helical XRT plans were conducted. Results: PRT was well tolerated, with only low-grade acute toxicities (CTCAE I–II) being reported. The local control rate was 100% after a median follow-up of 27.0 (interquartile range 13.3–58.0) months. PRT resulted in considerable tumor shrinkage, leading to complete remission in five patients and bearing the potential to provide partial or complete symptom relief. Favorable dosimetric outcomes in critical brain substructures by the use of PRT translated into reduced estimated risks for neurocognitive impairment and radiation-induced CNS malignancies compared to XRT. Conclusions: PRT is an effective treatment option for advanced JNA with minimal acute morbidity and the potential for reduced radiation-induced long-term complications.

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Brain necrosis after fractionated radiation therapy: Is the halftime for repair longer than we thought?

Cited by 13 publications

References 52 publications

Minimal difference between fractionated and single-fraction exposure in a murine model of radiation necrosis

Minimal difference between fractionated and single-fraction exposure in a murine model of radiation necrosis

A Patient Selection Approach Based on NTCP Models and DVH Parameters for Definitive Proton Therapy in Locally Advanced Sinonasal Cancer Patients

Proton Therapy for Advanced Juvenile Nasopharyngeal Angiofibroma

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