Miguel Awschalom

Physical characterization of neutron beams produced by protons and deuterons of various energies bombarding beryllium and lithium targets of several thicknesses

Protons of 35 and 65 MeV and deuterons of 35 MeV were used to bombard beryllium and lithium targets of various thicknesses. Four types of experiments were conducted in order to characterize the neutron fields. They were (1) central axis depth-dose measurements in a water phantom, (2) dose buildup at small depths in tissue-equivalent plastic, (3) microdosimetric measurements and LET distributions, and (4) neutron yields and energy spectra at an angle of 0 deg. The results generally show that (a) the central axis depth doses for the 35 and 65 MeV particles roughly approximate those of 60Co and 4-MeV bremsstrahlung photons, respectively, (B) the neutron dose buildups are more rapid than those of the above-mentioned photon sources, (C) the microdosimetric spectra show differences which are consistent with the measured neutron energy spectra, and (D) P-Li compared to p-Be neutron spectra have larger high-energy particle flux for similar target and beam configurations.

Response of pancreatic cancer to local irradiation with high‐energy neutrons

Seventy‐seven patients with locally advanced, nonresectable, biopsy‐proven adenocarcinoma of the pancreas were treated by palliative bypass surgery followed by intensive neutron beam irradiation of the primary tumor site. Three dose levels, under 20, 21 to 23, and 24 to 25 Gy, were studied with the use of a treatment plan that included all known disease within a limited target volume, generally under 21. Symptomatic palliation was achieved in the majority of patients. The median survival time was 6 months. One patient remained alive and well without evidence of tumor 5 years after irradiation. Two were free of tumor at autopsy (one had died of intercurrent disease and one of radiation‐related complications). A common cause of death was metastatic dissemination. Complication rates were dosedependent; life‐threatening complications did not exceed 12% with doses of less than 23 Gy. Autopsies from 19 patients were reviewed. In all, the pancreatic tumor site showed extensive reactive fibrosis. Local control was achieved in two patients, but most had both residual tumor in the pancreas and metastases. Six patients had centrolobular veno‐occlusive liver disease. These patients had all received the higher (22–24 Gy) neutron doses. Six patients had hemorrhagic radiation gastroenteritis. Mild skin atrophy and bone marrow hypoplasia were seen in the irradiated volumes. The kidneys and spinal cord showed no radiation effects. The authors conclude that neutron irradiation can provide a good local response with marked regression and fibrosis of the tumor. This response, coupled with many deaths due to metastases, suggests that combined treatment with neutrons and chemotherapy would be worth exploring.

Response of sarcomas of bone and of soft tissue to neutron beam therapy

A total of 51 patients were treated at Fermilab for sarcoma of bone (25 patients) and soft tissue (26 patients). Neutrons were delivered in twice weekly fractions over 6-7 weeks to total doses between 18 and 26 Gy. Long-term local control (greater than 2 years) was achieved in 24 patients (47%). Overall local control rates were 44% in the bone sarcomas and 50% in the soft tissue tumors. Chondrosarcoma appeared relatively more responsive with 9 out of 16 (56%) controlled, compared to osteogenic sarcoma with 2 out of 9 (22%) controlled. Among the soft tissue tumors, liposarcoma (5/7 controlled) and neurogenic sarcoma (3/3 controlled) appear to be more responsive than other tumors. The overall survival rate was 40% in the entire series. These results are comparable with international experience in neutron therapy of sarcomas of bone and soft tissues. Out of 263 soft tissue sarcomas treated with neutrons only to full dosage throughout the world, 152 (58%) were locally controlled. Similarly out of 74 sarcomas of bone so treated, 44 (60%) were controlled.

CLINICAL EVALUATION OF NEUTRON BEAM THERAPY: CURRENT RESULTS AND PROSPECTS (1983)

Some 9000 patients throughout the world have been treated by some form of neutron beam therapy. These include patients with advanced nonresectable tumors in many different sites treated with a variety of neutron beam generators varying widely in beam energy. Protocols were largely nonrandomized and included both mixed beam studies (neutrons + photons) and neutrons alone in varying doses. In spite of wide variation in equipment, treatment technique, and philosophy, some consistent trends have been identified: (1) in general, the neutron results have been at least as good as those of the photon controls measured in terms of local control, although the incidence of significant side effects have been higher; (2) in none of the randomized studies conducted so far, largely comprising epidermoid carcinomas of the head and neck, has a clear survival advantage for neutrons over photon controls been demonstrated at a statistically significant level; (3) results with mixed beam studies have been uniformly equivocal, with marginally significant differences in favor of the experimental groups compared with the photon controls; (4) adenocarcinomas of the gastrointestinal tract (GI) tract, including tumors of the salivary gland, pancreas, stomach, and bowel, appear to be responsive to high linear energy transfer (LET) radiation; (5) nonepidermoid, radioresistant tumors (sarcoma of bone and soft tissue and melanoma) yield a consistantly high local control rate, with neutron irradiation strikingly superior to those reported with photon therapy; and (6) in the central nervous system, both normal tissues and tumors appear to be exceptionally sensitive to neutron irradiation, therapeutic ratios are small, and the prospect of cure remains remote. It is concluded that neutrons are efficacious for certain specific tumor types, but that essentially new study designs, based on nonrandomized matched case comparisons, will be required to prove the merit of the new modality.

Kermas for various substances averaged over the energy spectra of fast neutron therapy beams: a study in uncertainties.

Kermas for various substances averaged over the energy spectra of fast neutron therapy beams, as well as ratios of average kermas relative to muscle, were calculated in an attempt to estimate the uncertainties introduced in these quantities by the poor knowledge of the elemental kerma functions, actual neutron energy spectra, and composition of tissues and other materials. Average kermas have uncertainties of the order of 7%-25%, while for ratios of average kermas the uncertainties are of the order of 2%-5% for materials of clinical interest. It is concluded that the ratio of average kerma of muscle to A-150 tissue-equivalent plastic should be 0.93 +/- 0.03 for the new p + Be clinical neutron beams.

Fast neutrons in the treatment of salivary gland tumors

Fast neutrons were used in the management of 30 patients with advanced salivary gland tumors. Twenty-two patients are the subject of this analysis. Neutrons were used as the primary mode of management in only seven patients. The remaining patients either had recurrent disease after surgery and/or radiation, or received post-operative treatment with neutrons. After a minimum follow-up of one year, 66% of the patients are alive with no evidence of disease. Control in the treatment volume is as high as 72%, which suggests a significant improvement in the local control of advanced salivary gland tumors. However, longer periods of observation are necessary for more definitive conclusions.

Pancreatic carcinoma: Results with fast neutron therapy

Abstract Results of therapy in 31 of 50 patients who were treated for advanced pancreatic carcinoma at Fermi National Accelerator Laboratory are presented here. To date, six patients are alive and four are free of disease. Since the main reason for failure was lack of control of primary tumor, the tumor dose has been increased by 15 %. Based on our results, a nationwide study has been launched to assess the effectiveness of neutrons vs. photons in the treatment of locally advanced pancreatic carcinoma.

CHARACTERIZATION OF A p(66)Be(49) NEUTRON THERAPY BEAM: I. CENTRAL AXIS DEPTH DOSE AND OFF-AXIS RATIOS

Results of measurements of central axis depth doses, off-axis ratios, and wedge filter effects are presented for a p(66)Be(49) neutron beam. All measurements were made and are reported in tissue equivalent solution. Algorithms that reproduce the various measured characteristics of the beam are also discussed.

Tolerance of the human spinal cord to high energy p(66)Be(49) neutrons

The risk of post irradiation myelopathy was evaluated in 76 patients followed for 1-5 years after neutron irradiation of the cervical and thoracic regions. No overt myelopathy was observed. Forty-six patients received doses (central cord dose) in excess of 10 Gy, 9 received doses in excess of 12 Gy, and 5 received doses between 13 and 17 Gy, all without any evidence of spinal cord injury. On careful questioning, a subjective transient neuropathy (a tingling sensation in one extremity) was reported by 6 patients, but this was apparently unrelated to dose. A review of available literature revealed a total of 14 patients with myelopathy, 13 of whom received doses in excess of 13 Gy delivered with relatively low energy neutrons generated by the deuteron + beryllium reaction. It is concluded from these studies that the tolerance limit for the human spinal cord irradiated with high energy [p(66)Be(49)] neutrons is close to 15 Gy, above which the risk of cord injury becomes significant. Central cord doses of 13 Gy or less appear to be well tolerated with little, if any, risk of myelopathy. These conclusions are valid for a treatment time of 4 weeks or more with two or more fractions per week (9 or more fractions). The RBE for the human spinal cord irradiated under the above conditions compared with conventionally fractionated photon therapy does not exceed 4.0.

Response of epidermoid and non-epidermoid cancers of the head and neck to fast neutron irradiation: The Fermilab experience

One hundred and six patients with locally advanced cancers of the head and neck were treated with neutrons at the Fermilab Neutron Therapy Facility. Of these, 44 patients were previously untreated, 33 were recurrent following attempted surgery and 29 patients had previously received a full course of radiation therapy with conventional radiation. Results were analyzed to study the influence of stage, previous management, site of origin and tumor histology on local control of the disease. The most significant factor determining the outcome in this series of patients is the histological type. For epidermoid carcinoma, long term local control was achieved in 17/35 patients (49%) in the previously unirradiated group. With non-epidermoid tumors (adenocarcinoma, cylindroma, muco-epidermoid carcinoma), the local control rate was 28/39 (72%). Disease-free survival analysis also shows a survival advantage in non-epidermoid lesions treated with neutrons. It is concluded that neutron beam therapy may probably be the treatment of choice for non-resectable or recurrent non-epidermoid cancers of the head and neck and requires a clinical trial to establish this observation.