An isocentrically mounted stand for total body irradiation.

The purpose of this study was to construct a stand to support a patient for total body photon irradiation and to expedite the set-up and treatment by rotating the stand. As in other isocentric treatments, the midline dose is impacted less by source-to-skin distance variations. The method of immobilizing the patient is described. A 10 mm lucite plate is supported in front of the patient to increase skin dose. A matrix of holes in this plate serves to index the location of blocks used to shield the lungs. The dosimetry of the set-up is described, as is the production of tissue deficit compensators. The results of phantom studies and in vivo thermoluminescent dosimetry measurements are presented.

An estimate of the margin required when defining blocks around the prostate.

The portal films of 54 consecutive patients treated for primary prostate cancer have been compared to the simulation films. The systematic and random uncertainty in the set-up, defined by the couch movement required to move the patient to the simulated position, was determined to be 1.6 mm UP (SD 3.3 mm), 0.3 mm RT (SD 2.6 mm) and 1.3 mm IN (SD 2.4 mm). The area of fields defined on simulation films was compared with that on portal films to determine the error in block production which was -0.7 mm (SD = 0.9 mm). Five sources of uncertainty in the radiotherapy have been identified, three occur before and two during the course of treatment. A method for combining these uncertainties is proposed and used on the data obtained in this study. This provides estimates of the margin required when drawing blocks so that the minimum dose to the target is 95% of the prescription in 95% of treatments. The block margins are not uniform and range from 21 mm, when drawing the block outline to the posterior on a lateral film, to 13 m when drawing laterally on an anterior film.

Oral pilocarpine for radiation-induced xerostomia: integrated efficacy and safety results from two prospective randomized clinical trials.

PURPOSE: Pilocarpine hydrochloride administered in either a fixed-dose or in a dose-titration protocol three times a day for 12 weeks was evaluated for its ability to relieve symptoms of postradiation xerostomia and to improve saliva production. The studies were randomized, double-blind, placebo-controlled, multicenter clinical trials. A total of 369 patients who had received at least 40 Gy of radiation to the head and neck with clinically significant xerostomia were enrolled in the two studies. In the dose-titration study, 162 patients were enrolled and they received a thrice daily regimen of 2.5 mg tablets for first 4 weeks, 5.0 mg tablets for the second 4 weeks, and 10.0 mg tablets for last 4 weeks of a 12-week study. Patients in the titration study were allowed to down titrate following at least one dose escalation to alleviate bothersome side effects, if any. In the fixed dose study, 207 patients received either placebo, 5.0 mg, or 10.0 mg tablets t.i.d. for 12 weeks. METHODS AND MATERIALS: Patients were evaluated for symptomatic relief by responding to questionnaires using visual analog scales and categorical questions; and, for saliva production by sialometry. Questionnaires measured relief of intraoral dryness, improvement in overall condition (global response), oral discomfort, difficulty in speaking, chewing and swallowing, denture wearing, and usage of artificial saliva. Evaluations were conducted at baseline, and weeks 4, 8, and 12. RESULTS: There were statistically significant improvements in salivary flow in pilocarpine treatment groups vs. placebo. There was a significant improvement in the overall "global" condition of xerostomia associated with the use of pilocarpine in both studies. In the fixed-dose study, there were significant improvements in oral dryness, mouth comfort, ability to speak, and reduction in the use of oral comfort agents. The dose-titration study showed improvements in dryness that approached significance (p = 0.057) and a decreased use of oral comfort agents (p = 0.045). All pilocarpine dosages (2.5, 5.0, and 10.0 mg three times a day) were judged to be safe. Adverse experiences were those expected for a cholinergic agonist, with the most common being mild to moderate sweating. The incidence of these events increased by dose. CONCLUSION: It is concluded that in these studies pilocarpine produced clinically significant benefits with acceptable side effects and risks for the treatment of symptomatic postradiation xerostomia. The incidence of most adverse events increased with dose. Best results may require continuous treatment for more than 8 weeks with doses greater than 2.5 mg three times a day. A 5.0 mg thrice daily regimen produced the best clinical results when both efficacy and side effects were taken into consideration. There may be some patients who would experience some additional benefit by increasing the dose to 10 mg thrice daily.

The incorporation of partial shielding of the spinal cord in a tissue deficit compensator in radiotherapy of the thorax.

A method to determine the shape of a patient by placing radiopaque wires and chains on the skin and taking two isocentric X-ray films is described. The wire locations are reconstructed by X-ray stereo photogrammetry, and a beam's eye view of the wire frame structure can be obtained with reference to the original setup of the "stereo-pair" films. An algorithm for paving between the wires with triangular plates is described which allows the calculation of the tissue deficit distance and compensator thickness. The depth and distance to points on the spinal cord are calculated, and the dose rate is calculated using a standard irregular field computation program. The limit for spinal cord tolerance is specified in terms of the maximum daily dose based on an equivalent dose formula. The additional thickness of compensator, required for the posterior field compensator to satisfy the tolerance limit, is calculated. The technique readily accommodates the kyphotic and scoliotic spine and has been in routine clinical use for seven years.

A frameless method for stereotactic radiotherapy.

A frameless method for stereotactic multiple arc radiotherapy (SMART) is described. Three short gold wires are implanted in the scalp approximately 100 mm apart. These are localized in a computed tomographic or angiographic study along with the target. Subsequently the gold markers are localized on beam films and the target position calculated using a computer program ISOLOC. This program provides the couch movements required to move the target to the isocentre and a micropositioner attached to the couch is used to make the adjustment. Beam films are repeated until the movements required are less than 1 mm in any direction. It is shown that the simple procedures of implanting the markers subcutaneously do not provide a stable reference system in about 25% of patients and the markers are now screwed into the cranium. The precision of the method is evaluated by phantom studies and measurements taken during several hundred treatments.

Practical 3-D radiotherapy planning of brain tumors.

In postoperative radiotherapy of brain tumors it is usually the case that preoperative imaging studies, either CT or MRI, were performed outside of the purview of the radiation therapy department. Thus the target volume is defined in an imaging study that does not lend itself readily for entry to a 3-D treatment planning system. A method is described that adjusts the patient structure defined by scan data to an appropriate position for radiotherapy. Software tools that are simple to use have been incorporated in a 3-D treatment planning program that allows oblique treatment planes to be defined. The program provides beam's-eye-view plots of the fields that are used to overlay simulation films and will automatically describe a field blocking outline that provides a prescribed margin on the target volume or other structures that have been defined. Finally, dose calculations in arbitrary planes through the head are made and isodose plots produced.

Prostate specific antigen in the management of patients with localized adenocarcinoma of the prostate treated with primary radiation therapy.

The records of 143 patients treated at 5 institutions with external beam megavoltage irradiation for localized prostatic cancer were reviewed to evaluate post-treatment changes in prostate specific antigen (PSA) in the context of subsequent events. Complete responders were defined as patients clinically well with normal PSA, clinical failures were patients with documented local tumor recurrence or distant metastases and chemical failures were patients clinically well but with a PSA level above the upper limits of normal. Correlations with pre-treatment PSA values were also made for the 50 of 143 patients for whom pre-treatment PSA data were available. Median patient followup was 27 months (range 18 to 91 months). The data were analyzed with parametric and nonparametric univariate and multivariate statistical procedures. Pre-treatment PSA levels increased with increasing tumor stage (p = 0.004) but not with increasing summed Gleason pattern scores (p = 0.15). The probability of remaining a complete responder decreased with increasing stage (p = 0.008) but not with increasing Gleason score (p = 0.14). Increasing pre-treatment PSA correlated with clinical failure (p = 0.01) and chemical failure (p = 0.006). Of the patients with a pre-treatment PSA level of less than 4 times the upper limits of normal 83% remained as complete responders compared to 30% of those with a higher pre-treatment PSA (p = 0.0002). The return of PSA levels to the normal range within 6 months after treatment was strongly correlated with a favorable outcome when analyzed by multivariate logistic regression. The status at last followup of patients who had a normal PSA level at 6 months versus those with an elevated PSA level 6 months after treatment is 94% versus 8% for complete responders (p = 0.0001), 0% versus 60% for clinical failures (p = 0.002) and 6% versus 32% for chemical failures (p = 0.14). Similar results occurred when analyzing outcomes in relationship to PSA normalization within 12 months after treatment (p = 0.001 for clinical failures, p = 0.02 for chemical failures and p = 0.001 for complete responders). We conclude that the pre-treatment level of PSA is an independent prognostic factor for prostate cancer patients treated with primary radiation therapy, and that the failure of PSA to return to the normal range within 1 year after completion of treatment identifies a group of patients at high risk for tumor recurrence.

A method for the assessment of the output of irregularly shaped electron fields.

A simple approach to the calculation of dose in cone-collimated electron fields is presented. The method accounts for variations in lateral scatter with field size using a Clarkson Integration. The reduction in output by an irregularly shaped aperture is evaluated based on measurements of the output at various distances from the aperture in a field 2.5 cm in diameter. The first 14 months of clinical use were analysed and it is shown that in 42 out of 600 calculations, the cutout factor was less than 0.95 and that in 77% of these, the calculation method was accurate to +/- 3%.

A port film marker.

A device is described consisting of brass strips embedded in a plastic plate. When inserted in a radiation beam, it produces an image of a cross centered in the field. Cuts in the brass at defined intervals project a scale on the film used to determine a magnification factor. A marker in the lower right-hand quadrant provides rapid, unequivocal orientation of the film. This capability of orientation to a beam's-eye-view makes anatomical markers redundant.

Quality control of radiation therapy in multi-institutional randomized clinical trial for localized prostate cancer.

The National Prostatic Cancer Project (NPCP) from 1978 through 1985 compared definitive radiation therapy for Stages B2, C, D1 lesions in those who received only radiation treatment to those who received two years of additional cyclophosphamide (Cytoxan) or estramustine phosphate (Emcyt) chemotherapy. Two hundred fifty-four patients were entered and 229 evaluated for compliance of the spatial localization of the prostate through review of the simulation and port films. In 78 per cent this was satisfactory, whereas in 12 per cent it was unsatisfactory, and another 10 per cent were not evaluable. The principle cause of an unsatisfactory rating was failure to adequately cover the prostatic target volume, especially the apex which was found to be variable in location. Routine use of retrograde urethrocystography is urged as part of the localization method in patients to receive definitive external beam radiation therapy for prostate cancer. The role and impact of quality assurance programs for radiotherapy in cooperative clinical study groups is reviewed and discussed.

Treatment of invasive bladder cancer by cisplatin and radiation in patients unsuited for surgery.

Seventy patients with muscle-invading bladder carcinoma (clinical stages T2 to T4) who were not candidates for cystectomy were treated with combined cisplatin and full-dose external-beam radiation on a multi-institutional prospective protocol from 1980 through 1985. Thirty-six patients are alive, all but three without evidence of cancer. The complete response rate is 77% in the 62 patients completing planned irradiation and 70% for all patients. Among the complete responders, 73% are currently maintained, and this group has a significantly higher four-year survival than those not having a complete response and those with recurrence of disease--57% vs 11%. The observed high complete response rates in patients in all stages and the high survival rates suggest irradiation plus cisplatin therapy offers an important therapeutic gain over radiation therapy alone for invasive cancer of the bladder. These results encourage further evaluation of combining cisplatin-based, multidrug chemotherapy with irradiation in patients with locally very-advanced bladder tumors who are not suited for surgery.

A radiolucent bite-block apparatus.

A bite-block, patient immobilization apparatus has been constructed using all plastic parts. The apparatus may be used in C-T scanning without detriment to the images produced. The construction details are given and the procedure used to produce a bite block is described. A method to reduce electron backscattering onto the buccal mucosa from metal fillings is given.

Radiotherapy treatment planning using lymphoscintigraphy.

A method for the three dimensional location of lymph nodes with respect to the skin surface is described. The technique is based on the reconstruction of surface shape using isocentric radiographs taken with metal chains draped on the patient. Registration of the radiographic study to the lymphoscintigraphic study is accomplished automatically by matching the location of four radiopaque and radioisotope markers. This method allows nodes to be located in a beam's eye view with any set up of an isocentric radiotherapy machine. An accurate determination of the depth of lymph nodes is obtained, which is of value in electron beam therapy.

Adjuvant radiotherapy following radical prostatectomy: results and complications.

Between 1954 and 1978, 148 patients underwent radical perineal prostatectomy for adenocarcinoma clinically confined to the prostate gland. This report is based on 45 of these patients with microscopic extension of disease beyond the gland and a minimum 5-year followup. Of the patients 22 received adjuvant external beam radiation therapy and 23 did not. The groups were comparable with regard to significant prognostic variables. Patient selection was by surgeon preference. Local recurrences were seen in 1 of 22 patients (5 per cent) receiving adjuvant radiotherapy and 7 of 23 (30 per cent) undergoing an operation alone (p less than 0.05). Of 8 patients with local recurrence 7 died of the disease. Delayed radiotherapy of a local recurrence generally was not effective in controlling the disease. Of the 11 patients who died of prostatic cancer with a mean followup of 9.2 years 3 received adjuvant radiotherapy and 8 did not. Severe but nonfatal long-term complications were seen in 14 per cent of the irradiated patients and 6 per cent of those treated with an operation alone. Most of the complications occurred in the earlier years of the study in patients who received 60cobalt radiotherapy. When clinical stage B cancer of the prostate is found to be pathological stage C following radical perineal prostatectomy, adjuvant radiotherapy can decrease the incidence of subsequent local recurrence. The potential risk of adjuvant radiation therapy should be weighed and its use considered, particularly in patients whose tumor extends to the surgical margins or who have seminal vesicle invasion.

A basis for blocking the spinal cord in opposed field irradiation.

The concept of partial tolerance is applied to the equivalent dose formula for spinal cord tolerance to allow for the change in dose when open and blocked fields are used in a course of radiotherapy. The field arrangement considered is parallel opposed irradiation. Certain assumptions are made regarding the contribution of dose to the spinal cord from open and blocked fields, which allows for the development of an equation to calculate the number of fractions that require spinal cord shielding in the posterior field. The use of a form to facilitate these calculations is described.

Superficial bladder cancer: progression and recurrence.

The tumors in 249 patients presenting initially with stages Ta and T1 bladder cancer were analyzed for tumor progression and recurrence. Only transurethral resection and/or fulguration was used before the first recurrence. Patients who received intravesical chemotherapy after the first tumor recurrence were excluded from an analysis of progression. Progression according to stages Ta and T1, and grades I, II and III was 4, 30, 2, 11 and 45 per cent, respectively. All differences were statistically significant. Progression also correlated with nontumor dysplasia and size. High tumor grade, lamina propria invasion, atypia elsewhere in the bladder, positive urinary cytology, tumor multiplicity and large tumors were associated with shorter intervals free of disease.

Coronary artery disease following mediastinal radiation therapy.

Coronary artery disease occurred in four young men (mean age 41 years) who had received curative irradiation therapy for mediastinal malignancies 12 to 18 (mean 15) years previously. None was at high risk for developing coronary artery disease by Framingham criteria. Angiography demonstrated proximal coronary artery disease with normal distal vessels. Distribution of the lesions correlated with radiation dosimetry in that vessels exposed to higher radiation intensity were more frequently diseased. Three patients had coronary bypass grafting for intractable angina and are asymptomatic at 10 to 43 months. A total of 163 patients underwent mediastinal irradiation for lymphoma or thymoma between 1959 and 1980. Among the 29 who survived 10 or more years, five (18%) developed severe coronary artery disease, implicating thoracic radiotherapy as an important risk factor. Because of the importance of mantle irradiation in the treatment of lymphomas, the prevalence of these neoplasms, and the survival patterns following treatment, many long-term survivors may be at increased risk for the development of coronary artery disease. Recognition of the relationship between radiotherapy and coronary artery disease may lead to earlier diagnosis and more timely intervention. Standard surgical treatment may be particularly beneficial because of the relative youth of most of these patients and because the proximal distribution of typical lesions increases the likelihood of complete revascularization.