Evidence Of Radiation Necrosis Research Articles

Craniospinal Reirradiation Using Proton Beam Radiotherapy in the Treatment of Pediatric Recurrent Medulloblastoma

<h3>Purpose/Objective(s)</h3> Craniospinal irradiation (CSI) is an essential part of medulloblastoma treatment even without any evidence of leptomeningeal metastasis. In case of recurrence, it is important to assess several factors to consider reirradiation course. These factors include prior radiation doses, time interval between radiotherapy courses and cumulative dose. In cases of leptomeningeal dissemination reirradiation of the entire craniospinal axis is needed, but may be accompanied by severe toxicity. Proton therapy may reduce toxicity without reducing treatment doses. <h3>Materials/Methods</h3> Proton beam craniospinal reirradiation (CSRI) course was conducted to 18 patients with recurrent medulloblastoma. Median dose to craniospinal axis during primary treatment was 30.6 Gy (24-36). Sixteen patients had additional local boost to recurrent and metastatic sites. In all cases we've made a dose gradient in the border zone to avoid irradiation of vertebral bodies. Eight patients had High Dose Chemotherapy (HDCT) before CSRI. The minimal interval between HDCT and CSRI was 2 months. Median dose at primary CSI was 23.7 Gy (23.4-36). Seven patients had reirradiation previously, two of them had CSRI with total dose of 18 Gy. <h3>Results</h3> Median time between two CSI courses was 33 months (19-126). Median follow-up period was 9 months (2-18). Six patients had disease progression, five of them died because of progression during the next 1.5 years after CSRI. Average time to progression was 13.3 ± 1.6 months (95% CI 10.1-16.4). During treatment we observed strong evidence of progressing thrombocytopenia (avg = 95 * 10⁹) with minimal values occurring during third week (p < 0.001). There was a non-significant decrease of hemoglobin and neutrophiles level (p_hemoglobin=0.4, p_neutrophiles=0.07). One patient had severe bone marrow hypoplasia during the treatment which required blood and platelet transfusion and neutrophil stimulation. The rest of the patients' hematological toxicity resolved without medical intervention. Only one patient had interruption during treatment because of COVID-19 infection. All the patients except one received chemotherapy after CSRI. None of them had any evidence of radiation necrosis or other radiological changes during the whole follow-up period. <h3>Conclusion</h3> CSRI is mostly used for medulloblastoma patients with refractory disease and leptomeningeal progression. Proton therapy may help to deliver curative doses with limited hematological toxicity and to minimize or completely avoid gastrointestinal toxicity. Probably it may lead to long-term disease control for such group of patients.

RTHP-01. PENTOXIFYLLINE AND VITAMIN E FOR THE TREATMENT OF RADIATION NECROSIS AFTER STEREOTACTIC RADIOSURGERY

Abstract BACKGROUND The combination of oral pentoxifylline (Ptx) and vitamin E (VitE) has been used to treat radiation-induced fibrosis and soft tissue injury. A 2008 study showed an average decrease in edema with the use of Ptx + VitE in 11 patients with suspected radiation necrosis after stereotactic radiosurgery (SRS). Here we review outcomes in patients prescribed Ptx + VitE at our institution for the treatment of radiation necrosis. METHODS 48 patients were included in this analysis. All patients were treated with SRS, had evidence of radiation necrosis, and had MR imaging before and after starting Ptx + VitE. The radiation oncologist’s impression of the imaging in the electronic medical record was used to score response to treatment. Official radiology reports were also reviewed. RESULTS 43.8% of patients showed evidence of improvement, 18.8% showed no change, and 25% showed worsening radiation necrosis on imaging after starting Ptx + VitE. One patient had a mixed response; 5 patients (10.4%) had disease progression. The median time to response assessment after starting Ptx + Vit E was 3.17 months. 9 patients progressed significantly on Ptx + VitE and required Bevacizumab, hyperbaric oxygen therapy or surgery. Patients who had multiple lesions treated with SRS were less likely to show improvement on imaging after Ptx + VitE (p=0.037). 34 patients were also prescribed dexamethasone, either before (7), with (16), or after starting (11) Ptx + VitE. Use of dexamethasone was not associated with improved response to Ptx + VitE (p=0.471). 3 patients stopped Ptx + VitE due to reported side effects. CONCLUSION Ptx + VitE appears safe for the treatment of radiation necrosis, but randomized data are needed to assess efficacy.

Maximally safe resection followed by hypofractionated re‐irradiation for locally recurrent ependymoma in children

Treatment failure in children with ependymoma is relatively common, with the majority of events consisting of local failure. Salvage therapy for these children historically had poor results, with repeated local recurrences. To improve these outcomes, we began to offer hypofractionated re-irradiation after resection at first local recurrence. To minimize the duration of therapy, we chose a hypofractionated regimen that has been shown to be well tolerated in adult patients. We performed a review of the experience at the Children's Hospital in Denver and at the Department of Radiation Oncology at the University of Colorado Denver from 1995 to 2008 with hypofractionated re-irradiation after maximally safe resection in children with locally recurrent ependymoma. Six children with locally recurrent ependymoma were seen in that time period. After maximally safe resection, all six received hypofractionated radiation therapy of 24-30 Gy delivered in three fractions. With a median follow-up of 28 months from the time of re-irradiation, all six children are alive with no evidence of disease. Three children had evidence of radiation necrosis, either clinically or based on imaging, but none required significant intervention. Hypofractionated re-irradiation after resection for locally recurrent ependymoma is well tolerated. This approach also appears to provide good local control. Additional follow-up is required to determine the efficacy and potential late effects of hypofractionated re-irradiation in this patient population.

Phase II study of accelerated fractionation radiation therapy with carboplatin followed by PCV chemotherapy for the treatment of anaplastic gliomas

Purpose: To conduct a Phase II one-arm study to evaluate the long-term efficacy and safety of accelerated fractionated radiotherapy combined with i.v. carboplatin for patients with previously untreated anaplastic gliomas. Methods and Materials: Between 1988 and 1992, 90 patients received 1.9–2.0-Gy radiation 3 times a day with 2-h infusions of 33 g/m 2 carboplatin for two 5-day cycles separated by 2 weeks. After radiotherapy, patients received procarbazine, lomustine (CCNU), and vincristine (PCV) for 1 year or until the tumor progressed. Results: Ninety patients were evaluable for analysis. Histologically, 69 had anaplastic astrocytoma; 14, anaplastic oligoastrocytoma; and 7, anaplastic oligodendroglioma. Gross total resection was performed in 20 (22%), subtotal resection in 45 (50%), and biopsy in 25 (28%); reoperation (total or subtotal resection) was performed in 50 (56%) patients. A multivariate analysis showed that a younger age ( p = 0.026), Karnofsky performance score (KPS; p = 0.009), and brain necrosis ( p = 0.0002) were predictive of a better survival. Results from analysis of extent of surgery (biopsy, subtotal resection, gross total resection) approached significance ( p = 0.058). Radiation dose, irradiated tumor volume, and techniques used (boost and fields) were not significant variables. The median survival (MS) of all anaplastic glioma patients was 28.1 months; for anaplastic astrocytoma patients, MS was 28.7 months and 40.8 months for the combined anaplastic oligodendroglioma/oligoastrocytoma patients. Long-term survival occurred in 25% of anaplastic glioma patients who were alive 8.6 years after treatment was initiated. Treatment-induced necrosis was documented by surgery or autopsy in 19 (21%) patients; 21 (23%) had a mixed pattern of necrosis and tumor; and an additional 13 (14%) patients who did not have surgical or autopsy demonstration of predominant radiation necrosis had magnetic resonance imaging (MRI) evidence of radiation necrosis. Serious clinical neurologic deterioration and/or dementia requiring full-time caregiver attention were observed in 9 (10%) patients. Conclusion: When comparable selection criteria are applied, the rate of MS in this study is inferior to results attainable with current radiation and chemotherapy approaches, although the rates of long-term survival are comparable. Theoretically, patients failing therapy and dying earlier than anticipated may be because of excessive central nervous system (CNS) toxicity resulting from the combination of accelerated fractionated irradiation, intensive carboplatin chemotherapy before each radiation fraction, and postirradiation PCV chemotherapy. On the other hand, patients with treatment-induced necrosis survived significantly longer than patients who did not demonstrate MRI or histologic evidence of necrosis (MS, 106 months vs. 18–33 months).

Dose-escalation with proton/photon irradiation for Daumas-Duport lower-grade glioma: results of an institutional phase I/II trial

Purpose : The role of dose escalation with proton/photon radiotherapy in lower-grade gliomas was assessed in a prospective Phase I/II trial. We report the results in terms of local control, toxicity, and survival. Materials and Methods : Twenty patients with Grade 2/4 ( n = 7) and Grade 3/4 ( n = 13) gliomas according to the Daumas-Duport classification were treated on a prospective institutional protocol at Massachusetts General Hospital/Harvard Cyclotron Laboratory between 1993 and 1996. Doses prescribed to the target volumes were 68.2 cobalt Gray equivalent (CGE, 1 proton Gray = 1.1 CGE) to gross tumor in Grade 2 lesions and 79.7 CGE in Grade 3 lesions. Fractionation was conventional, with 1.8 to 1.92 CGE once per day. Eligibility criteria included age between 18 and 70 years, biopsy-proven Daumas-Duport Grade 2/4 or 3/4 malignant glioma, Karnofsky performance score of 70 or greater, and supratentorial tumor. Median age of the patient population at diagnosis was 35.9 years (range 19–49). Ten tumors were mixed gliomas, one an oligodendroglioma. Results : Five patients underwent biopsy, 12 a subtotal resection, and 3 a gross total resection. Median interval from surgery to first radiation treatment was 2.9 months. Actuarial 5-year survival rate for Grade 2 lesions was 71% as calculated from diagnosis (median survival not yet reached); actuarial 5-year survival for Grade 3 lesions was 23% (median 29 months). Median follow-up is 61 months and 55 months for 4 patients alive with Grade 2 and 3 patients alive with Grade 3 lesions, respectively. Three patients with Grade 2 lesions died from tumor recurrence, whereas 2 of the 4 survivors have evidence of radiation necrosis. Eight of 10 patients who have died with Grade 3 lesions died from tumor recurrence, 1 from pulmonary embolus, and 1 most likely from radiation necrosis. One of 3 survivors in this group has evidence of radiation necrosis. Conclusion : Tumor recurrence was neither prevented nor noticeably delayed in our patients relative to published series on photon irradiation. Dose escalation using this fractionation scheme and total dose delivered failed to improve outcome for patients with Grade 2 and 3 gliomas.