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Phase I pilot study on fast neutron teletherapy for advanced carcinomas of the head and neck region. Final report on local control rate and survival.

A final report is presented on the local control rate and length of survival for 100 patients with advanced squamous cell carcinomas of the head and neck region who received fast neutron teletherapy at the University of Washington during the period 1973 through 1977. Sixty-two patients were treated with neutrons alone and 38 were treated with a combination of neutrons and photons as part of a mixed beam fractionation scheme. The overall initial complete remission rate was 68% for the mixed beam group and 44% for the group treated with neutrons alone. Initial complete remission rates for the two groups of patients are given as a function of T-stage and N-stage and acturarial curves are presented which show the time course of local control and survival for the two treatment groups. For T3 and T4 lesions the initial complete remission rate appears to be greater using the mixed beam form of treatment than using neutrons alone. Treatment to high-dose levels using neutrons alone gave rise to significantly greater morbidity--both acute and late effects--than resulted from the mixed beam form of treatment. Local control rates and survival rates are compared with similar groups of patients treated with neutrons at other institutions.

Adult↗

Ion chamber gas-to-wall conversion factors for fast neutron dosimetry.

Modern ionising photon dosimetry is essentially entirely based upon gas-filled cavity determinations. For photons, ion chamber response is largely independent of photon energy almost perfectly transforming absorbed dose in the gas to the surrounding media. Absolute uncertainties are <1-2%. For fast neutron dosimetry, this is certainly not the case. Interpretation of the response of the cavity filling material, usually a gas, to the charged particle spectrum induced in the walls and interacting with the cavity gas is fraught with uncertainties. Despite these challenges, gas filled cavities surrounded by various mixtures, compounds and elements, have proved to be essential for integral determinations of the indirectly ionising neutrons, generating dosimetric quantities, such as kerma and absorbed dose. The transformation from gas response to wall dose is material dependent and varies with neutron energy. This study discusses recent advances in cavity response interpretation using the results from complex nuclear modelling of microscopic cross sections as well as estimates of secondary particle production enabling much improved cavity gas-to-wall media conversion factors.

Algorithms↗

Radionuclide evaluation of pulmonary function following hemithorax irradiation of normal dogs with 60Co or fast neutrons.

To assess the effects of therapeutic doses of radiation on regional pulmonary function, 28 dogs had serial chest radiographs and quantitative ventilation, perfusion, and aerosol studies at three-, six-, nine-, and twelve-month intervals after hemithorax irradiation with 60-Co-gamma photons or 15-MeV fast neutrons. Findings showed marked reductions in perfusion and aerosol deposition in the irradiated lungs of dogs in the high-dose photon and neutron groups and in the medium-dose neutron group. The effects of large photon and small neutron doses were similar (neutron RBE = 4.5). Radionuclide studies were found to be useful for detecting these alterations.

Animals↗

High energy (42-66 MeV reactions) fast neutron dose optimization studies in the head and neck, thorax, upper abdomen, pelvis and extremities.

Five hundred and fifty patients were entered into a set of dose-searching studies designed to determine normal tissue tolerance to high energy (42-66 MeV reactions) fast neutrons delivered in 12 equal fractions over 4 weeks. Participating institutions included: The Fermilab (66 MeV p+----Be), The University of Washington (50 MeVp+----Be), U.C.L.A. (45 MeVH-----Be), M.D. Anderson Hospital (42 MeVH-----Be), and The Cleveland Clinic (42 MeVp+----Be). Patients were stratified by treatment facility and then randomized to receive 16, 18 or 20 Gy for tumors located in the upper abdomen or pelvis, and 18, 20 or 22 Gy for tumors located in the head and neck, thorax or extremities. Following completion of the randomized protocols, additional patients were studied at the 20.4 Gy level in the head and neck, thorax and pelvis. Normal tissue effect scoring was accomplished using the RTOG-EORTC acute and late normal tissue effect scales. Acute Grade 3 + toxicity rates in the head and neck were 19% for 20/20.4 Gy and 20% for 22 Gy. Time adjusted late toxicity rates in the head and neck at 12 months were 15% for 20/20.4 Gy and 0% for 22 Gy. The 18 Gy treatment arm of the head and neck protocol was dropped early in the study after only two patients were accrued. For cases treated in the thorax, acute Grade 3 + toxicity rates were 6% for 18 Gy, 15% for 20/20.4 Gy and 7% for 22 Gy. Late toxicity rates at 12 months were 0% for 18 Gy, 11% for 20/20.4 Gy and 18% for 22 Gy. Acute Grade 3+ toxicity rates in the upper abdomen were 0% for 16 Gy, 8% for 18 Gy and 12% for 20 Gy. There were no Grade 3 + late toxicities in the upper abdomen. In the pelvis, acute Grade 3 + toxicity rates were 0% for 16 Gy, 3% for 18 Gy and 3% for 20/20.4 Gy. Late Grade 3 + toxicities at 24 months were 20% for 16 Gy, 5% for 18 Gy and 24% for 20/20.4 Gy. In extremities, acute Grade 3 + toxicity rates were 7% for 20 Gy and 21% for 22 Gy while at 12 months, late Grade 3 + toxicity rates were 14 and 35%, respectively. The 18 Gy treatment arm of the extremities protocol was dropped early in the study after only two patients were accrued. Factors associated with normal tissue effects in addition to treatment dose are discussed.

Abdominal Neoplasms↗

The implications of improved treatment of malignant salivary gland tumors by fast neutron radiotherapy.

The conventional treatment for cancer of the salivary glands is surgery, with or without X ray therapy. In advanced tumors (Stage III and IV), local control and 5-year survival rates are less than 35%. Radical surgery severs the facial nerve in the majority of operations on parotid gland tumors. Local control of unresectable salivary gland tumors was achieved, in 74% of cases, by fast neutron therapy. From the MRC cyclotron at Hammersmith Hospital neutrons were given to 65 patients, with locally advanced or recurrent tumors, 89% of which were Stage IV. Local control and 5-year survival rates were 72% and 50%, respectively. The facial nerve was not damaged by neutron therapy. In patients with parotid gland tumors, 77% regained or maintained function. Function was lost in 14% through recurrence and 9% remained paralyzed. The results were achieved using beams from primitive machines with serious disadvantages. The results from neutrons implicate improvements for locally advanced tumors of non-epidermal origin in other sites of the body, especially with the high energy neutrons now available from modern cyclotrons.

Adult↗

Results of fast neutron therapy of adenoid-cystic carcinomas of the head and neck at the neutron therapy facility Hamburg-Eppendorf.

Between 1977 and 1987, 30 patients with adenoid-cystic carcinomas of the head and neck region were treated, at the Hamburg-Eppendorf neutron therapy facility, with a 14 MeV-DT-generator. The present review deals with 15 patients treated before October 1986 e.g. with follow up longer than one year. These results, although preliminary, tend to confirm that fast neutrons is the best irradiation modality of adenoid-cystic carcinomas of the head and neck region, especially when surgery is not possible, or cannot be radical.

Adult↗

[The relative biological effectiveness (RBE) of fast neutrons on the Dunning rat prostate carcinoma R3327-HI].

Human prostate tumors are known to be good candidates for neutron therapy. The Dunning rat prostate tumor system R3327 was found in many studies to be an excellent model for human prostate tumors. There is still a paucity of studies on the response of the Dunning tumors to fast neutrons. Tumors of the R3327-HI subline are moderately well differentiated and mucin producing. They show one euploid cell population, a bromodeoxyuridine labelling index of 5%, a potential doubling time of 8.9 days, a volume doubling time of about ten days and a cell loss rate of 10%. Tumors were transplanted s.c. in the distal thigh of Copenhagen rats and treated with 60Co-photons (10, 20, 30, 40 Gy, 45 cGy/min) and 14-MeV-neutrons (8, 10, 12 Gy, 7 to 11 cGy/min). Tumor volumes were measured twice weekly. Growth delay was defined as time in days until the tumors reached twice their treatment volume. Linear regressions on the median growth delays of the different treatment groups were calculated. The ratio of the neutron- and photon-slopes yielded an RBE of 3.1 +/- 0.3. Additionally isoeffect-RBE values between 2.3 and 2.6 were graphically estimated.

Animals↗

RBE-LET relationships for lethal, potentially lethal and sublethal damage in mammalian cells: implications for fast neutron radiotherapy.

The dependence of relative biological effectiveness (RBE) on the linear energy transfer (LET) of radiations is described for different types of cellular damage which contribute to reproductive death. The influence of the capacity for repair of sublethal and of potentially lethal damage of mammalian cells is discussed. The analysis leads to interpretations of differences in the RBE of fast neutrons among tumours and among normal tissues and to suggestions for the application of high LET radiation in radiotherapy.

Animals↗

Complications of fast neutron therapy.

The purpose of the study was to identify the tissues and organs at risk following high-energy neutron-beam therapy for selected radioresistant tumors, estimating the separate probabilities of both normal tissue injury and of tumor recurrence, each in relation to the absorbed dose. Published statistical and anecdotal reports on the incidence of serious complications observed following fast neutron treatment directed to the cranium, head and neck, chest, upper abdomen, pelvis, and extremities are reviewed and dose-response parameters derived using bivariate probit or logistic analyses. We then calculate the conditional probability of uncomplicated control (PUC) at various doses, assuming that tumor cure and late injury are stochastically independent events. The median effective doses and coefficients of variation, derived for neutron irradiation of human brain and spinal cord, oropharynx, lung, stomach and bowel, rectum and bladder, and extremities, are tabulated and tentative "tolerance limits" estimated. Tolerance doses are shown to depend on several factors including beam quality, chemical composition, cell cycling rate, fraction-size, and follow-up time. In patients followed over 5 years, safe tolerance doses appear to range from < 14 GY for the central nervous system up to 22 GY in the oropharynx and mandible. Given well-determined dose-response data for specific normal tissues and the associated tumors, the separate probabilities of tumor control and of normal tissue injury at a given dose can be estimated. The particular treatment scheme yielding the highest PUC can usually be identified. The maximum PUC for neutron therapy, compared with other modalities, is a measure of both efficacy and safety for the procedure under study and thus provides a useful guide for comparing various modalities and treatment plans and for designing more effective treatment strategies.

Dose-Response Relationship, Radiation↗

[Relative biological effectiveness of accelerated heavy ions and fast neutrons estimated from frequency of aberration mytoses in the retinal epithelium].

Analyzed was the literature and authors' experimental data concerning lesion and recovery of epithelium cells of mice retina immediately and long after irradiation at different sources including single and partly fractionated irradiation by gamma- and X-rays, accelerated protons, helium, carbon and boron ions, and fast neutrons of the reactor range in a large spectrum of doses and LET. Reviewed are some new techniques of determining the RBE coefficient for these types of radiation; large values of the RBE coefficients for accelerated ions and neutrons (5-10 times higher than RBE coefficients calculated for the next day following irradiation) are a result of integration into calculation of the available data about the delayed disorders in retinal epithelium cell regeneration.

Animals↗