K.R. Saroja

An update on malignant salivary gland tumors treated with neutrons at fermilab

One hundred and thirteen cases of recurrent and/or unresectable malignant salivary gland tumors, treated with fast neutron therapy at Fermilab between September 1976 and December 1984, are analyzed for local control, sites of failure, and treatment-related morbidity. Sixty-three patients had major and 55 had minor salivary gland tumors. Local control was achieved in 67% of patients with major and 58% of patients with minor salivary gland tumors. In the subgroup of patients with oropharyngeal and oral cavity lesions, 19/24 (80%) had local control. However, only four of 15 patients with maxillary antrum tumors had successful control of their disease. Seventy-four percent of patients with lesions measuring 5 cm or less and 30% of patients with larger lesions had their local disease controlled. Histology did not influence the local control rate. Both observed and adjusted median survival for patients with major salivary gland tumors was 36 months. Disease-free survival was 31 months. Observed and adjusted median survivals for patients with minor salivary gland tumors are 48 and 57 months respectively. Twenty of 86 patients (23%) had major morbidity; this was directly related to the total dose delivered. In the dose range 20-24 Gy the complication rate was 16%. Most of these complications were successfully managed with minimal functional disability. We have concluded that fast neutron irradiation is an appropriate treatment for malignant salivary gland tumors.

Failure of accelerated neutron therapy to control high grade astrocytomas

Sixty-two patients with high grade malignant astrocytoma were treated with fast neutrons using three different treatment schemes to evaluate the effect of shortening the overall time. Dose and fraction number were kept constant. The total dose was 16-18 neutron Gy delivered in six fractions, weekly for 6 weeks, twice a week over 3-4 weeks, or three times a week over 2 weeks. There were no obvious differences in survival times among the three groups. We conclude that accelerated neutron therapy does not improve survival of patients with grade 3 and 4 astrocytoma.

Re-irradiation of locally recurrent tumors with fast neutrons☆

Forty-six patients with locally recurrent disease were re-irradiated with fast neutrons at Fermilab. All had received prior radical radiation therapy either with or without surgery. Six were palliative. Forty patients treated with curative intent were analyzed for local response, survival, and complications. The overall response rate was 78% (31/40); 50% (20/40) had a complete local response. Ten of 16 patients (63%) with non-epidermoid carcinomas in the head and neck regions had complete response, whereas only nine of twenty patients (45%) with epidermoid carcinomas were complete responders. In a subset of 12 patients with salivary gland type tumors, 10 had a complete response (83%). Two of these 10 patients are alive beyond 5 years. Observed median survival for the forty patients was 9.3 months, and for complete responders 14.4 months. Observed median survival for partial responders was only 7.5 months. Four of six patients treated for palliation had significant subjective improvement. Significant morbidity, Grade III or greater (EORTC/RTOG scale), was seen in only 10 patients (25%), and this was found to depend directly on the total dose delivered. We conclude that neutron beam therapy can be used as a therapeutic modality for patients with recurrent tumors with an acceptable degree of morbidity.

Neutron irradiation of human pelvic tissues yields a steep dose-response function for late sequelae

PURPOSE Analysis of the dose-response function in normal tissues following pelvic irradiation for carcinoma of the prostate. METHODS AND MATERIALS A homogeneous group of 136 patients with locally advanced carcinoma of the prostate were treated with the Fermilab high-energy neutron beam at three dose levels: 19, 20.4, and 21 Gy, using the same treatment plan and fractionation scheme for all patients. RESULTS Tumor control rates were about 83% at the three dose levels studied. However, the normal tissue complication rate (late sequelae) varied with dose: 0 out of 5 at 19 Gy, 5 out of 58 (8.6%) at 20.4 Gy, and 9 out of 73 (12.3%) at 21 Gy. CONCLUSIONS Neutron therapy to the pelvis reveals a steep dose-response function for late effects with a coefficient of variation of only 11%. This is lower than that usually observed with photons or with less uniform clinical data sets, and may be characteristic for well-planned high-LET radiotherapy.

Gadolinium neutron capture in glioblastoma multiforme cells

Purpose: A proof of principle for cell killing by Gadolinium (Gd) neutron capture in Magnevist® preloaded Glioblastoma multiforme (GBM) cells is provided. Materials and methods: U87cells were pre-loaded with 5 mg/ml Magnevist® (Gd containing compound) and irradiated using an enhanced neutron beam developed at NIU Institute for Neutron Therapy at Fermilab. These experiments were possible because of an enhanced fast neutron therapy assembly designed to use the fast neutron beam at Fermilab to deliver a neutron beam containing a greater fraction of thermal neutrons and because of the development of improved calculations for dose for the enhanced neutron beam. Clonogenic response was determined. Results: U87 cell survival after γ irradiation, fast neutron irradiation and irradiation with the enhanced neutron beam in the presence or absence of Magnevist® were determined. Conclusions: U87 cells were the least sensitive to γ radiation, and increasingly sensitive to fast neutron irradiation, irradiation with the enhanced neutron beam and finally a significant enhancement in cell killing was observed for U87 cells preloaded with Magnevist®. The sensitivity of U87 cells pre-loaded with Magnevist® and then irradiated with the enhanced neutron beam can at least in part be attributed to the Auger electrons emitted by the neutron capture event.