Incidence Of Radionecrosis Research Articles

Reirradiation Tolerance of the Human Brain

To give an overview of current available clinical data on reirradiation of glioma with respect to the tolerance dose of normal brain tissue. Clinical brain reirradiation studies from January 1996 to December 2006 were considered on radiation-induced late adverse effects-i.e., brain tissue necrosis. The studies were analyzed by using the linear quadratic model to derive information on the cumulative biologic effective tolerance dose (BED(cumulative)) and equivalent doses in 2-Gy fractions (normalized total doses, NTD(cumulative)) for the healthy human brain. The NTD(cumulative) in conventional reirradiation series (NTD(cumulative) of 81.6-101.9 Gy) were generally lower than in fractionated stereotactic radiotherapy (FSRT) (NTD(cumulative) of 90-133.9 Gy.) or LINAC-based stereotactic radiosurgery series (NTD(cumulative) of 111.6-137.2 Gy). No correlation between the time interval between the initial and reirradiation course and the incidence of radionecrosis was noted. The analysis showed the prescribed NTD(cumulative) to increase with decreasing treatment volume, which is allowed by modern conformal radiation techniques. Radiation-induced normal brain tissue necrosis is found to occur at NTD(cumulative) >100 Gy. The applied reirradiation dose and NTD(cumulative) increases with a change in irradiation technique from conventional to radiosurgery re-treatment, without increasing the probability of normal brain necrosis. Taken together, modern conformal treatment options, because of their limited volume of normal brain tissue exposure, allow brain reirradiation for palliative treatment of recurrent high grade glioma with an acceptable probability of radionecrosis.

Single dose radiosurgical treatment of recurrent previously irradiated primary brain tumors and brain metastases: final report of RTOG protocol 90-05

Purpose: To determine the maximum tolerated dose of single fraction radiosurgery in patients with recurrent previously irradiated primary brain tumors and brain metastases. Methods and Materials: Adults with cerebral or cerebellar solitary non-brainstem tumors ≤ 40 mm in maximum diameter were eligible. Initial radiosurgical doses were 18 Gy for tumors ≤ 20 mm, 15 Gy for those 21–30 mm, and 12 Gy for those 31–40 mm in maximum diameter. Dose was prescribed to the 50–90% isodose line. Doses were escalated in 3 Gy increments providing the incidence of irreversible grade 3 (severe) or any grade 4 (life threatening) or grade 5 (fatal) Radiation Therapy Oncology Group (RTOG) central nervous system (CNS) toxicity (unacceptable CNS toxicity) was < 20% within 3 months of radiosurgery. Chronic CNS toxicity was also assessed. Results: Between 1990–1994, 156 analyzable patients were entered, 36% of whom had recurrent primary brain tumors (median prior dose 60 Gy) and 64% recurrent brain metastases (median prior dose 30 Gy). The maximum tolerated doses were 24 Gy, 18 Gy, and 15 Gy for tumors ≤ 20 mm, 21–30 mm, and 31–40 mm in maximum diameter, respectively. However, for tumors < 20 mm, investigators’ reluctance to escalate to 27 Gy, rather than excessive toxicity, determined the maximum tolerated dose. In a multivariate analysis, maximum tumor diameter was one variable associated with a significantly increased risk of grade 3, 4, or 5 neurotoxicity. Tumors 21–40 mm were 7.3 to 16 times more likely to develop grade 3–5 neurotoxicity compared to tumors < 20 mm. Other variables significantly associated with grade 3–5 neurotoxicity were tumor dose and Karnofsky Performance Status. The actuarial incidence of radionecrosis was 5%, 8%, 9%, and 11% at 6, 12, 18, and 24 months following radiosurgery, respectively. Forty-eight percent of patients developed tumor progression within the radiosurgical target volume. A multivariate analysis revealed two variables that were significantly associated with an increased risk of local progression, i.e. progression in the radiosurgical target volume. Patients with primary brain tumors (versus brain metastases) had a 2.85 greater risk of local progression. Those treated on a linear accelerator (versus the Gamma Knife) had a 2.84 greater risk of local progression. Of note, 61 % of Gamma Knife treated patients had recurrent primary brain tumors compared to 30% of patients treated with a linear accelerator. Conclusions: The maximum tolerated doses of single fraction radiosurgery were defined for this population of patients as 24 Gy, 18 Gy, and 15 Gy for tumors ≤ 20 mm, 21–30 mm, and 31–40 mm in maximum diameter. Unacceptable CNS toxicity was more likely in patients with larger tumors, whereas local tumor control was most dependent on the type of recurrent tumor and the treatment unit.

The use of stereotactic radiosurgical boost in the treatment of medulloblastomas

Starting in 1992, we began using a stereotactic radiosurgical (SRS) boost for the treatment of medulloblastomas. Four patients ranging in age from 7 to 42 years old have since been treated and are the subject of this retrospective study. All patients were initially treated with a maximally debulking surgery and external beam radiotherapy, which were then followed by a stereotactic radiosurgical boost using a modified 6 MeV linear accelerator. Radiosurgical boost doses ranged from 4.50 to 10.0 Gy. Target volumes ranged from 1.1 to 8.1 cc. The procedure was well tolerated with minimal acute toxicities. All four patients are alive without evidence of recurrence (at 8 to 35 months). Acute nausea and vomiting was elicited during the radiosurgical procedure in the first patient treated. We have since begun premedicating patients with antiemetics or treating under general anesthesia. Late complications consisted of panhypopituitarism in one patient, which was thought to be attributable to the previous course of whole-brain radiotherapy. We have not observed any incidence of radionecrosis in this small cohort of patients. Our preliminary results with the use of radiosurgery for medulloblastomas are optimistic, and we would like to suggest the inclusion of a radiosurgery boost in future clinical trials for treatment of this disease.

Delayed adverse effects after irradiation of gliomas: clinicopathological analysis.

Out of 107 pts. treated with radio- and chemotherapy for low and high grade gliomas (TD: 45-65Gy), 3 cases developed pathologically documented radionecrosis (coagulative necrosis with minimal or no persistent tumor). Clinico-therapeutic modalities were analyzed for all cases and biologically equivalent doses were calculated according to NSD, ED and btu formulas. All cases of radionecrosis fell into the group of doses close to 60Gy/30fx./42d. and NSD = 1758, ED = 1340 and btu = 1161. Isodose curve reconstruction on planes corresponding to histological sections of brains with radionecrosis demonstrated that doses received by areas of necrosis were higher than the calculated mid-plane doses in two cases. Clinical and autoptic incidence of radionecrosis were 2.8% and 10% respectively. High doses of steroids during RT seemed to offer some protection against radionecrosis, while number of chemotherapy cycles did not influence the risk of radionecrosis. A higher autoptic rate of irradiated gliomas is needed in order to obtain a better understanding of a number of unresolved problems.

Late vascular effects of whole brain X-irradiation in the mouse.

The whole brains of mice were irradiated with 250 kVp X-rays at 120 rads min-1 (1.6 mm Cu HVL, TSD 50 cm), and a histological study was carried out. The dose range of X-irradiation was from 1,300 to 2,500 rads, i.e., 1,300, 1,500, 1,750, 2,000, and 2,500 rads. Eighty-six mice were used for histological examination. For microscopic examination, the mice were killed at regular postirradiation intervals between 15 and 20, 31 and 40, 41 and 50, 51 and 60, 61 and 70, 71 and 80, 81 and 90, 139 and 177 weeks. The brains were removed immediately thereafter, fixed in Bouin's solution, and embedded in paraffin. A histological examination was performed by a morphometric estimation of vascular lesions, in which the degree of the damage to the arterial system was scored in whole serial brain sections. Necrosis (encephalomalacia), atrophy, cell infiltration, and telangiectatic vascular change of the brain, caused as a result of the fibrinoid necrosis of the large arteries, were observed. Dose-dependent incidence of the fibrinoid necrosis increased between 41 and 87 weeks after irradiation. Mean score of fibrinoid necrosis increased dose dependently approximately 60 weeks after irradiation. It is suggested that scores of large vessel damage do relate to dose at 41 to 87 weeks, and can be used to quantify the vessel injury, and that fibrinoid necrosis of the large vessels may relate to the incidence of radionecrosis.

A survey of the treatment of 200 cases of basal cell carcinoma (1959-1966 inclusive).

SUMMARY The most satisfactory regime for radiotherapeutic treatment of basal cell carcinoma in this study was ten to twelve daily fractions of 400–500 rad, 5 days a week to a total dose of 4000–5000 rad. This method produced the highest cure rate with the least incidence of radionecrosis and the best cosmetic result. The use of implant methods is retained for lesions in difficult sites, i. e. the inner canthus and the nasolabial folds.

Management of squamous cell carcinoma of the floor of the mouth

Radiation therapy of squamous cell carcinoma of the floor of the mouth is an effective treatment, particularly in the early stages of the disease. From the years 1955 through 1965 seventy patients received a complete course of irradiation at the University of Michigan. An absolute five year survival rate of 41.4 per cent and a determinate survival rate of 48.3 per cent were obtained. For the period from 1955 through 1969 an actuarial relative survival of 60 per cent was found at five years. Besides the achievement of a satisfactory survival rate after irradiation, comparable if not better than that after surgical treatment, the major contribution of a complete course of radiation therapy is in controlling the primary tumor while in most instances respecting the anatomy and physiology of the mouth. We encountered serious radiation necrosis of the jaw in four patients (6 per cent). This damage is not negligible but contrasts favorably with the higher morbidity, occasional postoperative death, and deformity of the face and neck which occur after radical surgery. We hope to reduce the incidence of radio-necrosis of the jaw by the current program of preirradiation dental hygiene, thus eliminating routine dental extraction and alveolectomy.