Scheduling of hypoxic-tumor therapy using neutron brachytherapy.

Abstract

Fast-neutron-beam therapy and low-dose-rate fast-neutron intracavitary therapy of cervical carcinoma are effective in producing regression of advanced tumors. However, effectiveness is critically dependent on the schedule by which they are used in combination with fractionated external low-linear-energy-transfer (LET) therapy. Neutron-beam therapy is now alternated frequently with fractionated external radiotherapy (mixed beam). Intracavitary neutron therapy, scheduled before fractionated external-beam photon therapy, was maximally effective. These findings indicate that traditional concepts developed for the use of conventional low-LET therapy may need to be altered to use neutrons for therapy and to achieve improved local control of advanced cancers.

Californium-252 Neutron Curietherapy for Advanced Cervical Cancer

“…The clearance of tumor was more rapid by the early application of neutron therapy than by a delayed application, when combined with fractionated radio therapy [16,17], The results of this study indicate that effective therapy must be optimally sequenced in the treatment course and combined with modalities that increase the likelihood of tumor control. Impor tant physiological contributions of vascular factors to radiation response [11,[25][26][27] and reoxygenation was suggested by the failure of local control observed in 2 patients with severe small vessel vascular disease.…”

“…They are in accord with reports of (1) lesser radioresponsiveness of anemic patients [25]; (2) improvement in local control and survival by blood transfusions to anemic cervix tumor-bearing patients [2,25], and (3) improved control of tumors by oxygen breathing during radio therapy [13] or by high-pressure oxygen tanks used at the time of treatment [33]. In addition, this paper pro vides evidence for the importance of the time and scheduling of hypoxic tumor therapy and the great importance of reoxygenation [17]. The quantity of hypoxic tumor destroyed was probably further enhanced by the reoxygenation of hypoxic tumor because of the more effective early therapy.…”

“…The question arises as to whether conditions can be identified wherein neutron therapy can be more effective and one possibility that arises concerns sched uling of the neutron therapy. That is, it may be better to schedule the neutrons before, or early in the treat ment course, rather than after external beam therapy as a form of boost radiotherapy at the conclusion of a fractionated radiotherapy course [16,17]. Californium-252 allowed the use of low dose rate neutrons for the intracavitary brachytherapy of certain advanced cervical squamous cell cancers before, or early in the treatment course, or delayed until after the fractionated radio therapy course.…”

RBE of spleen CFU-S to low dose rate Cf-252 neutron or photon radiation

“…While such investigations will be undertaken in studies underway, it is well to note that the prognosis of the cancers treated with Cf-252 was so grave and inevitably fatal that clinical trials were needed if treatment was to be improved [16,19]. Concurrent basic biological studies also need to be carried out since observed tumor responses to neutrons were so different [14,15] that the simple adjustment of a prescribed dose by a RBE value may not only mislead but actually misguide the intent of the planned therapeutic program. The present data also revealed a low RBE without a significant change in survival curve shape.…”

CT and MR for brain tumor implant therapy using CF-252 neutrons

“…Implant radiotherapy was of several hours (4-8 h) duration and used Cf-252, a radioactive isotope of the transplutonium series which emits fast neutrons of 2.3 MeV average energy (8). NT has been carried out using specially designed hollow plastic afterloading applicators positioned in the tumor using CT scanning and orthogonal x-rays (9).…”