Variation in radiation sensitivity and repair kinetics in different parts of the spinal cord

Adamus-Górka, Magdalena; Brahme, Anders; Mavroidis, Panayiotis; Lind, Bengt K.

doi:10.1080/02841860701864668

Cited by 14 publications

(10 citation statements)

References 27 publications

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“…The white matter of the brain is more vulnerable to radiation than the gray matter when the changes are evaluated clinically, pathologically, or radiologically. [10][11][12][13][14][15][16][17][18][19][20] Steen et al studied the effect of therapeutic radiation on the central nervous system in pediatric brain tumor patients. 10,11 Their quantitative MRI analyses revealed that a radiation dose greater than 30 Gy was associated with a spin-lattice relaxation time decrease in the white matter in a doseand time-dependent manner 3 months after radiotherapy onwards, while such change was not detectable within the dose level under 60 Gy in the gray matter.…”

Section: Discussionmentioning

confidence: 99%

Corticospinal tract-sparing intensity-modulated radiotherapy treatment planning

Igaki

Sakumi

Mukasa

et al. 2014

Reports of Practical Oncology & Radiotherapy

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Section: Discussionmentioning

confidence: 99%

Corticospinal tract-sparing intensity-modulated radiotherapy treatment planning

Igaki

Sakumi

Mukasa

et al. 2014

Reports of Practical Oncology & Radiotherapy

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“…However, the radiation dose received by the thoracic spine is well below the recognized tolerance dose and the doses previously reported with progressive myelopathy [4, 9]. According to previous studies, the spinal cord shows a high fractionation sensitivity, typical for late-responding normal tissues and characterized by a low ratio of the linear-quadratic parameters of the cell survival curve (α/β) [9–11]. When calculating the linear-quadratic equivalent dose at 2 Gy per fraction (LQED 2 ), or the biologically equivalent dose if given in 2 Gy-fractions (for the cases when the daily fractions were higher than 2 Gy), some authors have estimated that an appropriate α/β ratio was close to 2 Gy [10], while others have favored an even lower value of 0.9 [11] or 0.87 Gy [4, 9].…”

Section: Discussionmentioning

confidence: 99%

“…According to previous studies, the spinal cord shows a high fractionation sensitivity, typical for late-responding normal tissues and characterized by a low ratio of the linear-quadratic parameters of the cell survival curve (α/β) [9–11]. When calculating the linear-quadratic equivalent dose at 2 Gy per fraction (LQED 2 ), or the biologically equivalent dose if given in 2 Gy-fractions (for the cases when the daily fractions were higher than 2 Gy), some authors have estimated that an appropriate α/β ratio was close to 2 Gy [10], while others have favored an even lower value of 0.9 [11] or 0.87 Gy [4, 9]. Using this latter value, the estimated probability of myelopathy of the cervical spinal cord was found to be 0.03% for a total dose of 45 Gy and 0.2% for 50 Gy [9], or < 1% and < 10% for 54 Gy and 61 Gy, using conventional fractionation of 1.8–2 Gy/fraction [4].…”

Section: Discussionmentioning

confidence: 99%

Radiation myelitis after pembrolizumab administration, with favorable clinical evolution and safe rechallenge: a case report and review of the literature

Carausu

Beddok

Langer

et al. 2019

j. immunotherapy cancer

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BackgroundNeurologic complications as myelitis are very rare but extremely deleterious adverse effects of both immunotherapy and radiotherapy. Many recent studies have focused on the possible synergy of these two treatment modalities due to their potential to enhance each other’s immunomodulatory actions, with promising results and a safe tolerance profile.Case presentationWe report here the case of a 68-year-old man with metastatic non-small-cell lung cancer (NSCLC) who developed myelitis after T12-L2 vertebral radiotherapy, with motor deficit and sphincter dysfunction, while on treatment with pembrolizumab (an immune checkpoint inhibitor). The spinal abnormalities detected by magnetic resonance imaging (MRI), suggestive of myelitis, faithfully matched the area previously irradiated with 30 Gy in 10 fractions, six and a half months earlier. After immunotherapy discontinuation and steroid treatment, the patient rapidly and completely recovered. On progression, pembrolizumab was rechallenged and, after 8 cycles, the patient is on response and there are no signs of myelitis relapse.ConclusionThe confinement within the radiation field and the latency of appearance are suggestive of delayed radiation myelopathy. Nevertheless, the relatively low dose of radiation received and the full recovery after pembrolizumab discontinuation and steroid therapy plead for the contribution of both radiotherapy and immunotherapy in the causality of this complication, as an enhanced inflammatory reaction on a focal post-radiation chronic inflammatory state. In the three previously described cases of myelopathy occurring after radiotherapy and immunotherapy, a complete recovery had not been obtained and the immunotherapy was not rechallenged. The occurrence of a radiation recall phenomenon, in this case, can not be excluded, and radiation recall myelitis has already been described with chemotherapy and targeted therapy. Safe rechallenges with the incriminated drug, even immunotherapy, have been reported after radiation recall, but we describe it for the first time after myelitis.

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“…Even after applying an α/β of 2 Gy an EQD 2 of 45 Gy is still considered to be safe. Using the data of Schultheiss [ 13 ], evaluating the radiation dose response for cervical spinal cord to be more sensitive than thoracic [ 14 ], we can assume that a probability of myelopathy at EQD 2 45 Gy is lower than 0.03 percent.…”

Section: Discussionmentioning

confidence: 99%

Radiation myelitis after hypofractionated radiotherapy with concomitant gefitinib

et al. 2015

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We describe the case of a 71-year-old Caucasian female with primary disseminated non-small cell cancer of the lung, presented for palliative radiotherapy of metastatic spread to the 9th and 11th thoracic vertebrae without intramedullary growth. Palliative radiotherapy with daily fractions of 3 Gy and a cumulative dose of 36 Gy to thoracic vertebrae 8-12 was performed. The patient received concomitantly 250 mg gefitinib daily. After a latent period of 16 months, the patient developed symptoms of myelitis. Magnetic resonance imaging (MRI) did not reveal any bony or intraspinal tumor progression, but spinal cord signal alteration. No response to steroids was achieved. The neurological symptoms were progressive in August 2013 with the right leg being completely plegic. The left leg was incompletely paralyzed. Deep and superficial sensitivity was also diminished bilaterally. The patient was completely urinary and anally incontinent. Contrary to the clinical findings, a follow-up MRI (July 2013) showed amelioration of the former signal alterations in the spinal cord. The diagnosis of paraneoplastic myelopathy was refuted by a negative test for autologous antibodies. At the last clinical visit in May 2014, the neurological symptoms were stable. The last tumor-specific treatment the patient is receiving is erlotinib 125 mg/d.We reviewed the literature and found no reported cases of radiation myelopathy after the treatment in such a setting. The calculated probability of such complication after radiotherapy alone is statistically measurable at the level of 0.02%. We suppose that gefitinib could also play a role in the development of this rare complication.

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Variation in radiation sensitivity and repair kinetics in different parts of the spinal cord

Cited by 14 publications

References 27 publications

Corticospinal tract-sparing intensity-modulated radiotherapy treatment planning

Corticospinal tract-sparing intensity-modulated radiotherapy treatment planning

Radiation myelitis after pembrolizumab administration, with favorable clinical evolution and safe rechallenge: a case report and review of the literature

Radiation myelitis after hypofractionated radiotherapy with concomitant gefitinib

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