Radiation oncology: contributions of the United States in the last years of the 20th century.

The advancements in radiation oncology in the past 50 years in the United States were probably more dramatic than those in the first half of the 20th century. Not only were there major technical achievements, but there was also an associated increase in the overall cure rates of cancer, from 20% at 5 years 50 years ago to now nearly 60% at 5 years. The cure rates in selected tumor sites at 5 years in 1950 and in 2000, respectively, were as follows: breast, 50% and 80%; colon and rectum, 40% and 85%; lung, 5% and 15%-20%; prostate, 40% and 80%; Hodgkin disease, 50% and more than 90%; cervix, 40% and 70%-80%; uterus (endometrium), 80% and more than 90%; bladder, 30% and 50%; head and neck, 30% and 60%; and esophagus, 2% and 15%. Much of this has been due to a broader array of techniques in radiation therapy available for treatment but also because of new emphasis on combined integrated modalitities (surgery, radiation therapy, and chemotherapy). New imaging techniques have contributed substantially, allowing better selection of patients for treatment and better selections of treatment modalities.

Bone metastasis: review and critical analysis of random allocation trials of local field treatment.

PURPOSE: Compare and contrast reports of random allocation clinical trials of local field radiation therapy of metastases to bone to determine the techniques producing the best results (frequency, magnitude, and duration of benefit), and relate these to the goals of complete relief of pain and prevention of disability for the remaining life of the patient. METHODS AND MATERIALS: Review all published reports of random allocation clinical trials, and perform a systematic analysis of the processes and outcomes of the several trial reports. RESULTS: All trials were performed on selected populations of patients with symptomatic metastases and most studies included widely diverse groups with regard to: (a) site of primary tumor, (b) location, extent, size, and nature of metastases, (c) duration of survival after treatment All trial reports lack sufficient detail for full and complete analysis. Much collected information is not now available for reanalysis and many important data sets were apparently never collected. Several of the variations in patient and tumor characteristics were found to be much more important than treatment dose in the outcome results. Treatment planning and delivery techniques were unsophisticated and probably resulted in a systematic delivery of less than the assigned dose to some metastases. In general the use and benefit of retreatment was greater in those patients who initially received lower doses but the basis and dose of retreatment was not documented. Follow-up of patients was varied with a large proportion of surviving patients lost to follow-up in several studies. The greatest difference in the reports is the method of calculation of results. The applicability of Kaplan-Meier actuarial analysis, censoring the lost and dead patients, as used in studies with loss to follow-up of a large number of patients is questionable. The censoring involved is "informative" (the processes of loss relate to the outcome) and not acceptable since it results in artificial elevation of the frequency of response. Overall, higher dose fractionated treatment regimens produced a better frequency, magnitude, and duration of response than lower dose single-fraction regimens. Relapse after initial response was frequent. The "median duration of relief" was much shorter than the "median duration of survival" post-treatment. Thus the "net pain relief" is far less than the goal of pain relief for the total duration of life after treatment. CONCLUSIONS: The pain relief obtained in all studies is poor and our care practices need to be improved. Many patients never achieved complete relief and for most who did, the duration of relief was much less than their period of survival after treatment. Higher dose, fractionated treatments produced a greater frequency, magnitude, and duration of response with an improved "net pain relief." Additional trials with selection of comparable cases, good definition of extent of disease, exemplary treatment, and complete follow-up are required.

A multirod collimator for neutron therapy.

PURPOSE: To design, construct, and commission a multirod collimator for producing irregularly shaped fields in neutron radiation therapy. To demonstrate the reliability and applicability of this device to routine use with a superconducting cyclotron for neutron therapy. METHODS AND MATERIALS: A multirod collimator has been designed, constructed, and thoroughly tested to investigate its radiological properties; neutron transmission characteristics, beam profiles, and penumbral widths as a function of field size and depth in a phantom, and the spatial resolution of the rod array, have been measured. A wide variety of irregularly shaped fields, used routinely in neutron radiation therapy, have been produced, including fields that incorporate partial transmission blocks. The performance of the collimator has been closely monitored over a period of 20 months to accurately assess reliability. RESULTS: The multirod collimator has been in routine use for 32 months, and during this time a total of 7025 neutron fields has been treated. For the latter 20 months of this period, detailed performance records show that collimator failure has caused 28.4 h of downtime during the patient treatment day. Only 5.25 h of this downtime was experienced in the last 12 months (0.22% of the available treatment time). The results of collimator attenuation and beam profile measurements show that the radiological properties of the collimator are comparable to those of other collimator systems used for neutron radiation therapy. Isodose measurements in a water phantom show that the spatial resolution of the rods is superior to that of the leaves used in neutron multileaf collimators. The ability of the multirod collimator to produce many irregularly shaped fields commonly encountered in neutron radiation therapy has been demonstrated. Shaped fields for prostate, head and neck, soft tissue sarcomas, lung, thyroid, rectum, bladder, colon, breast, pancreas, and gynecological tumors have been produced. For some prostate cases, the device has been used to produce partial transmission blocks. CONCLUSIONS: A novel multirod collimator has been designed, constructed, and successfully applied in the routine treatment of neutron radiation therapy patients.

RBE variation between fast neutron beams as a function of energy. Intercomparison involving 7 neutrontherapy facilities.

In fast neutron therapy, the relative biological effectiveness (RBE) of a given beam varies to a large extent with the neutron energy spectrum. This spectrum depends primarily on the energy of the incident particles and on the nuclear reaction used for neutron production. However, it also depends on other factors which are specific to the local facility, eg, target, collimation system, etc. Therefore direct radiobiological intercomparisons are justified. The present paper reports the results of an intercomparison performed at seven neutrontherapy centres: Orléans, France (p(34)+Be), Riyadh, Saudi Arabia (p(26)+Be), Ghent, Belgium (d(14.5)+Be), Faure, South Africa (p(66)+Be), Detroit, USA (d(48)+Be), Nice, France (p(65)+Be) and Louvain-la-Neuve, Belgium (p(65)+Be). The selected radiobiological system was intestinal crypt regeneration in mice after single fraction irradiation. The observed RBE values (ref cobalt-60 gamma-rays) were 1.79 +/- 0.10, 1.84 +/- 0.07, 2.24 +/- 0.11, 1.55 +/- 0.04, 1.51 +/- 0.03, 1.50 +/- 0.04 and 1.52 +/- 0.04, respectively. When machine availability permitted, additional factors were studied: two vs one fraction (Ghent, Louvain-la-Neuve), dose rate (Detroit), influence of depth in phantom (Faure, Detroit, Nice, Louvain-la-Neuve). In addition, at Orléans and Ghent, RBEs were also determined for LD50 at 6 days after selective abdominal irradiation and were found to be equal to the RBEs for crypt regeneration. The radiobiological intercomparisons were always combined with direct dosimetric intercomparisons and, when possible in some centres, with microdosimetric investigations.

Radiological properties of a prototype multi-rod collimator for producing irregular fields in photon radiation therapy.

A prototype multi-rod collimator for producing irregular fields in photon radiation therapy has been designed and built. The mechanical details of the design and operation of the multi-rod collimator are discussed. Beam profiles for an approximately 10 x 10 cm2 field have been measured at various depths in phantom, and compared with profiles obtained using the secondary collimator jaws alone and with cast metal blocks. The ability of the collimator to produce irregular fields is demonstrated with reference to some commonly encountered therapy fields and the ability to produce central blocks and island blocks is discussed. Isodose curves for selected irregular fields are presented.

A superconducting cyclotron for neutron radiation therapy.

The physical and clinical specifications of a neutron therapy facility utilizing a superconducting cyclotron are presented. The cyclotron and its support system are described. Details of the operation of the cyclotron in a hospital environment are given; the requirements of the helium liquifier and cryogenic system are described together with a summary of its mode of operation. The simplicity of the cyclotron control system is discussed. The physical characteristics of the neutron beam are described. The central axis percent depth dose curve is equivalent to that of a 4 MV x-ray beam. The depth of maximum dose occurs at approximately 9 mm depth and the surface dose is between 40% and 45%. The multirod collimator allows for the production of irregularly shaped fields of size up to 26.5 x 30 cm, without excessive exposure to operating personnel.

Bone metastasis from cervical cancer.

BACKGROUND: This retrospective analysis examines the frequency, distribution, and the pattern of disease progression of bone metastasis in patients treated for cervical cancer and the use and results of palliative intent radiation therapy. METHODS: Charts, films, and other available records were reviewed for the 41 patients with bone metastasis of the 496 patients with invasive cervical cancer treated at the Gershenson Radiation Oncology Center, Detroit, Michigan, from 1980 through 1989. RESULTS: Several patterns of bone metastasis were observed: (1) direct extension into bone from the parametrial extensions of the primary or recurrent pelvic tumor, (2) direct extension into bone from parenchymal metastasis to distant lymph nodes or lung, (3) regional hematogenous metastasis compatible with Batson's venous plexus distribution, and (4) systemic hematogenous metastasis to distant bones. Eighty percent of the patients were irradiated, and of those, 70% experienced pain relief. CONCLUSIONS: Bone metastasis in patients with cervical cancer is an infrequent but significant occurrence with associated severe dysfunction, other signs of local and distant failure, and short life expectancy. Radiation therapy provides moderate palliation for treatable patients.

Eye metastasis from carcinoma of the breast: diagnosis, radiation treatment and results.

The experience at the Gershenson Radiation Oncology Center of 32 cases of metastases to the eye or orbit from breast cancer are presented with a review of the literature. The 32 patients were referred for radiation therapy in the period of 1980-1991. Eighteen patients had metastasis to the choroid, 2 patients had involvement of other parts of the eye (anterior chamber +/- choroid), and 11 patients had orbital metastasis. In one patient, the diffuse nature of the disease prevents subsite assignment. Ten of the patients with eye metastases also had brain or meningeal metastases (8 patients concurrent with eye metastases). Four of the 32 patients had bilateral choroidal metastases. A complete course of radiation therapy was delivered to 28 patients, one patient was not treated and 3 patients received only partial treatment because of general deterioration due to other widespread metastases from breast cancer. Of 21 evaluable patients, 15 had definite improvement. There was no progression of the eye metastases in the other 6 patients. The rest (7 patients) were lost to detailed follow-up of the response of the eye metastases. Four patients are still alive without any severe long-term side-effects. The diagnosis, treatment and outcome is presented with a review of the literature. The importance of emergency treatment for rapidly progressing lesions is stressed as well as the need for detailed treatment planning, careful delivery of daily treatments with a high degree of reproducibility and precision to prevent possible damage to sensitive normal structures.

Transmission measurements in multi-rod arrays: a design study for a multi-rod collimator.

The results of transmission measurements for neutrons, cobalt-60 gamma-rays, and 10 and 15 MV photons made with close-packed arrays of tungsten rods are presented. These results indicate that tungsten rod arrays of reasonable thickness can provide for primary or secondary collimation of all these radiation beams. Development work on a collimation system utilizing the multi-rod concept which is capable of producing irregularly shaped fields and suitable for use in photon or neutron radiation therapy is described.

Primary radiation therapy as an alternative to mastectomy for early-stage breast cancer.

Breast conservation surgery followed by radiation therapy for definitive treatment of patients with early stage (limited extent) breast cancer (Stage I and Stage II) has been reported by several retrospective and prospective randomized trials to provide comparable local control, disease-free survival, and overall survival to patients treated with mastectomy. Excisional biopsy of the breast lump and associated axillary dissection are required prior to initiation of radiation therapy in order to remove all known tumor and to reduce the dose of radiation required for cure. The axillary dissection is therapeutic for extension into the axillary volume as well as a prognosticator that aids in the selection of patients for adjuvant systemic therapy. Although certain patients may be adequately served without radiation therapy by excisional removal of the tumor and a margin of surrounding normal breast tissue, this population still needs to be defined. Adequate patient selection and the use of good surgical and radiation therapy techniques results in good to excellent cosmesis in 80 to 90 per cent of treated patients. The treatment alternatives, if presented to patients deemed as appropriate candidates, will aid the patients in making an informed consent decision. Wider application and availability of this alternative to mastectomy may have a significant positive impact on our female population by encouraging women to seek detection of breast cancer through breast self-examination and mammography because the desirable alternative reduces the fear of loss of the breast and self image.

Radiation therapy alone in the treatment of carcinoma of the uterine cervix: a 20-year experience.

A retrospective analysis is reported on the results of irradiation alone in the treatment of 970 patients with histologically proven invasive carcinoma of the uterine cervix. The development of the radiation therapy techniques, survival, pelvic tumor control, and major sequelae of therapy are described in detail. The tumor-free 5-year survival rate was 100% in 29 patients with stage IA, 85% in 312 cases with stage IB, 70% in 98 patients with stage IIA, 68% in 276 patients with stage IIB, 45% in 237 stage III cases, and one survivor in 18 stage IV patients. No pelvic recurrences or distant metastases were observed in stage IA patients. In stage IB the overall incidence of pelvic recurrences was 7.3%, in stages IIA and IIB 14%, and in stage III 37%. Distant metastases were noted in 13% of the patients with stage IB, 22% of those with stages IIA and IIB, and 32% of patients with stage III tumors. Higher doses of irradiation delivered with intracavitary insertions and extenal beam were correlated with a lower incidence of pelvic recurrences in stages IIA, IIB, and III. However, doses to point A over 7000 cGy did not improve pelvic tumor control in stage IB. Grade 2 treatment sequelae were observed in about 10% of all patients and grade 3 complications in approximately 4% of the patients with stage I and 8% in those with more advanced tumors (IIA and beyond). The need is emphasized to carefully evaluate the dosimetric aspects of new techniques, including phantom studies before they are applied to patients. A close integration of external and intracavitary irradiation will result in better tumor control and fewer complications.