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Following mastectomy, patients aged 35 to 76 years with operable breast cancer underwent postoperative irradiation of the chest wall and regional lymph nodes. They were then assigned at random to receive no further therapy (NT), ovarian irradiation (R) 2000 rads in 5 days, or ovarian irradiation in the same dosage plus prednisone (R + P) 7.5 mg daily for up to five years. A total of 703 eligible patients received the randomly assigned treatment. The median follow up was 21 years with a range of 14 to 25 years. Overall, there was a delay in recurrence (p = 0.03) and survival was prolonged (p = 0.19) for patients who received R, but in neither case was the difference significant after adjusting for the multiplicity in our data. Overall, patients who received R + P experienced a significant delay in recurrence (p = 0.0003) and a significantly prolonged survival (p = 0.005), even after adjusting for multiple comparisons. In premenopausal patients who received R, the recurrence of breast cancer was delayed and survival prolonged, but not significantly. In premenopausal women aged 45 years or more, R + P therapy significantly prolonged survival (p = 0.0004), while the delay in recurrence although significant (p = 0.02) was only marginally so after allowance for multiple comparisons. No value was demonstrated for ovarian irradiation with or without prednisone therapy in postmenopausal patients. A new finding in this review was that contralateral breast cancer as the first failure was reduced by R + P compared to NT in the overall group.

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Carcinoma of the bladder is commonly treated for cure with external beam radiation. Whilst short-term results are associated with a good chance of disease control there is little information about the long-term results of such therapy. We present a retrospective review of the Princess Margaret Hospital experience in treating transitional cell carcinoma of the bladder and emphasis on the long-term follow-up of patients treated with radiotherapy (XRT). Between 1972 and 1980, 355 patients were treated with a radical course of external beam radiation. The overall survival was 20% at 10 years and the cause-specific survival was 32%. Radiation treatment resulted in a long-term bladder preservation in at least 25% of patients. The majority of long-term survivors without evidence of relapse were patients with T1 (solitary tumours), T2 and T3a tumours. This subgroup represents patients with disease favourable for treatment with radiation. Factors affecting response to the XRT and survival included T stage and tumour bulk. Radiation complications were frequent and were usually associated with local disease recurrence.

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In a Phase I-II study, half-body radiotherapy was used to treat 14 dogs with multicentric lymphoma. Using this technique, a radiation dose of 7 Gray (Gy) was delivered to one half of the body in a single exposure. The other half of the body was treated approximately 28 days later. Of 14 treated dogs, 11 (79%) had a measurable decrease in tumor size. Five dogs achieved a complete or partial remission with a mean duration of 102 and 54 days, respectively. In predicting response to therapy, poor prognostic factors included large tumor burdens, advanced disease stage, and chemotherapy-resistant tumors. Side effects of treatment were divided chronologically into acute (radiation sickness, tumor lysis), subacute (bone marrow suppression), and chronic (radiation pneumonitis, lymphoma-cell leukemia) syndromes. Complications were more severe in tumor-bearing dogs when compared with healthy control animals. Dogs with small tumor burdens and minimal internal disease had fewer complications compared with those with more advanced disease.

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Eight healthy mongrel dogs were treated with half-body irradiation (HBI) in a pilot study to evaluate the technique and radiotolerance of different organs. Cranial and caudal half-body fields were established using the 13th thoracic vertebra as the dividing point. Under general anesthesia, either 7 or 8 Gray (Gy) were delivered to one half of the body using opposing radiation portals. The other half of the body was similarly treated 28 days later. The dogs were monitored for 12 months. Significant radiation effects included transient bone marrow suppression and radiation sickness. There were no serious or life-threatening problems, but the 8 Gy group consistently showed more severe clinical signs and histologic changes than the 7 Gy group. Total body irradiation in two fractions of 7 or 8 Gy given 1 month apart appears to be a safe treatment that can be developed for therapy in veterinary oncology.

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From 1971 to 1981, twenty patients with poor-prognosis metastatic gestational trophoblastic neoplasia (GTN) were treated with moderate-dose methotrexate (1 g) and folinic-acid rescue (MD-MTX-FAR) as initial therapy. Seven (35%) were cured with MD-MTX-FAR, and salvage chemotherapy was successful in an additional seven, for a total cure rate of 70%. The ultimate outcome is similar to that reported for MAC triple therapy during this era. Hematologic and mucosal toxicity were negligible and no serious complications were encountered. We now use combination chemotherapy in patients with poor-prognosis GTN as first-line treatment. However, these results suggest that there may be advantages to the incorporation of MD-MTX-FAR in combination regimens in place of low-dose methotrexate, because of reduced toxicity and potential benefits for the prophylaxis and treatment of cerebral metastases.

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The results of a pilot study using adjuvant chemotherapy and sequential half-body irradiation (HBI) for nonmetastatic Ewing's sarcoma are presented. Seventeen patients received Cyclophosphamide, Vincristine, and Adriamycin (8 cycles), followed by sequential radiation treatment of the upper (500 cGy) and lower (600 cGy) half body. Survival at 3 years was 49%. These results are contrasted with those for 18 concurrently treated patients who received standard adjuvant therapy. Overall 5-year survival and relapse-free survival for these 35 consecutive patients was 61 and 53%. The pilot protocol was given on an out-patient basis with limited and acceptable acute toxicology. Further study is necessary to determine the value of the pilot protocol.

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A retrospective analysis of 82 patients with cancer of the colon above the peritoneal reflection who received postoperative local abdominal irradiation was undertaken to assess the survival, patterns of failure, and toxicity of treatment. Forty-eight patients (adjuvant group) had a complete resection, but were felt to be at high risk for local relapse and received postoperative local abdominal irradiation. Thirty-four patients had gross residual disease following surgery. The 5-year actuarial survival and local relapse free survival were 67 and 67%, respectively, in the adjuvant group. In this group, local relapse was observed in 9 of 28 patients with Stage C disease in contrast to 3 of 20 patients with Stage B2 disease; 1 of 14 patients with lesions in the right colon failed locally compared to 11 of 35 patients with lesions in the left. Only 2 of the 34 patients with gross residual disease remained relapse free from 93% of patients having a component of local failure. The majority of the treatment morbidity was seen in patients with gross residual disease. Prospective randomized studies should be done to determine the efficacy of postoperative irradiation in patients with colon carcinoma who are at high risk for local recurrence following surgical resection.

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Thirty-five patients with clinically staged non-metastatic squamous carcinoma of the oesophagus were treated with radiation combined with mitomycin C, and 5-fluorouracil (5-FUra) infusion. Twenty patients were planned for a split course regimen 2250-2500 cGy in 10 fractions and chemotherapy. This dose of radiation to be repeated with another course of chemotherapy after 4 weeks rest. Fifteen patients were planned for a single course 4500-5000 cGy in 20 fractions and a single course of chemotherapy. Thirty-one patients are available for a minimum follow-up of one year, 26 patients for a minimum follow-up of 2 years. All 35 patients are included in the survival and local relapse-free analysis. Survival at one year is 47% and at 2 years 28%. The local relapse-free rate at both one and 2 years is 48%. There was an improvement in survival and local relapse-free rate for the single course regimen compared to the split course; 2 years survival 48% versus 12% (p = 0.24) local relapse-free rate 79% versus 27% (p = 0.07). All patients receiving radiation and chemotherapy were compared with historical controls treated by radiation alone. This matching procedure was done independent of knowledge of outcome (two controls were matched/case). Patients were matched for age, sex. TNM stage, and total radiation dose. There was a significant difference in survival p = 0.004 and local relapse-free rate p = 0.05 for patients receiving radiation and chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

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Between 1970 and 1979, 372 patients with squamous cell carcinoma of the tonsil were treated with primary irradiation therapy, with salvage surgery for failures. The median age was 60 years and the male to female ratio was 2:1. The staging system used was the 1974 UICC TNM system. There were 47 T1 lesions (13%), 161 T2 lesions (43%), and 164 T3 lesions (44%). Regional nodes were not palpable in 173 (46%); 122 had N1 nodes (33%), 6 had N2 nodes (2%) and 71 had N3 nodes (19%). All patients received external beam radiation which was supplemented in 68 patients with a radioactive implant for disease into adjacent tongue. The overall survival for all patients was 38% at 5 years and 54% when corrected for intercurrent disease. Local control was 87% for T1 lesions, 68% for T2 lesions and 50% for T3 lesions. Regional control was 96% for N0, 67% for N1 and 37% for N2-3. A detailed dose-time-volume analysis revealed that increasing volume improved local control in T1 and T2 lesions (77% had local control if the volume was greater than 80 cm2 versus 53% if the volume was less than 80 cm2, p = 0.014), except for T3 lesions. Increasing the dose in the range of 5000 to 6500 rad had no significant effect on primary control in any stage of disease. The addition of a radioactive implant did not increase local control if disease extended into the tongue (57% local control if implant, 52% if no implant). This study demonstrates the significance of adequate treatment volume in local control for carcinoma of the tonsil. No significant dose response was found and subsequent surgery was not compromised when a moderate dose of radiation was used.

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Treatment of cancer of the antrum and nasopharynx often includes the radiation of tissues close to an uninvolved eye. One treatment method consists of using an anterior high energy X ray beam directed to the tumor through the eye. To maintain a high dose adjacent to and behind the eye while reducing the entrance dose to the eye, build-up material is placed on the skin and a tunnel cut through to the eye. When the build-up material is tissue-like, the tunnel can be several centimeters in height and scattered radiation from the tunnel walls will largely offset the build-up properties of the beam. Using higher density build-up material, the dose to the superficial layers of the eye can be reduced almost to the limit set by the open beam characteristics. This technique has been used successfully for 8 years.

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Twenty-two normal volunteers and 32 patients with either benign prostatic hypertrophy or prostatic carcinoma were examined by magnetic resonance imaging (MRI). The images were of high quality and clearly demonstrated the prostate gland and the surrounding anatomy but were of limited value in differentiating between benign and malignant prostatic disease. Using a specific pulse sequence, the authors were able to visualize what they believed to be the periprostatic venous plexus and suggest that the demonstration of this venous plexus may be of value in showing extraglandular spread of carcinoma of the prostate.

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Four patients with refractory rheumatoid arthritis were treated with total body irradiation administered in two sittings, 300 to 400 rads to each half of the body. All four patients had taken antimetabolites prior to receiving total body irradiation, and two continued to use them after total body irradiation. Two patients had taken alkylating agents before, and one had used them after total body irradiation. All patients showed clinical improvement. However, in two patients myeloproliferative disorders developed: a myelodysplastic preleukemia at 40 months after total body irradiation in one and acute myelogenous leukemia at 25 months in the other. Total body irradiation differs from total nodal irradiation in the total dose of irradiation (300 to 400 rads versus 2,000 to 3,000), and in the duration of the therapy (two sittings versus treatment over several weeks to months). Furthermore, the patients in the total body irradiation study frequently used cytotoxic drugs before and/or after irradiation, whereas in one total nodal irradiation study, azathioprine (2 mg/kg per day or less) was permitted, but no other cytotoxic agents were allowed. Rheumatologists may therefore face a binding decision when deciding to treat a patient with rheumatoid arthritis with either a cytotoxic drug or irradiation.

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A retrospective analysis of 55 patients treated with whole abdominal irradiation following surgical excision for cancer of the colon is presented. Three groups of patients were given whole abdominal irradiation, eight with gross residual tumor following surgery, 17 with peritoneal seeding, and 30 who had complete surgical excision of the tumor but were felt to be at high risk for relapse. Only one of the eight patients with gross residual tumor, and one of the 17 with peritoneal metastases, are currently alive and well, with the majority dying from local or peritoneal metastases. The 5 year actuarial survival for the 30 patients irradiated following complete surgical excision is 55%. The treatment was well tolerated and few complications were observed. It is concluded that whole abdominal irradiation is ineffective for the treatment of colon cancer if peritoneal metastases are present, or if gross residual tumor is left behind following surgery. A randomized controlled clinical trial is being organized to test whether total abdominal irradiation is of benefit in terms of survival in high risk colon cancer patients following complete surgical removal.

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Between 1970 and 1978, 202 patients with carcinoma of the prostate were treated with radical external beam radiation with curative intent. Intracapsular disease was present in 38% and the remaining 62% had disease extending through the prostatic capsule. The overall survival is 72% at five years, and despite the large number of patients with advanced disease the five-year disease-free survival is 46%. Significant prognostic factors include: i) tumor, grade, ii) extent of primary disease, iii) procedure done to determine diagnosis (TURP vs. needle biopsy) and iv) tumor dose. There was a significant improvement in survival at a minimum dose of 5000 Gy. Prostate carcinoma is radiosensitive and a dose-response relationship in treatment has been demonstrated by this review.

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Forty-five patients with glomus tumors in the temporal bone region were treated by radiation therapy. Only three patients had recurrence or progression of tumor during the follow-up period of 3 to 23 years (median, 10 years). No patient died from uncontrolled glomus tumor. The majority of patients noted symptomatic relief after radiation, but objective neurologic deficits usually remained unchanged or showed only partial improvement. The most commonly used radiation dose was 3500 cGy tumor dose delivered in 15 fractions in 3 weeks by a homolateral wedge technique from megavoltage radiation apparatus. This dose is less than that usually recommended for glomus tumors. From these results and from review of the literature, it is suggested that a moderate radiation dose of 3500 cGy in 3 weeks is effective treatment for glomus tumors, even if complete tumor involution does not occur.

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Our work with total body irradiation (TBI) for acute leukemia in relapse dates from 1959. Following reports of the Seattle experience, we treated a small number of patients in remission--lowering the dose to 500 rad given at 50 rad/min, based in part on our experience with radiation pneumonitis complicating upper HBI. We have treated 51 patients since July 1979, with an actuarial survival of 65% overall, and 85% for patients 35 years-old or less. A specially designed cobalt-60 unit is used, which allows very large fields and high exposure rates. Dose is calculated at midplane and a homogeneity of +/- 5% obtained.

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Three hundred seventy-two patients with squamous cell carcinoma of the tonsil were treated with primary irradiation of curative intent. Surgery was saved for subsequent treatment failure. The overall survival was 38 percent at 5 years. Local control was 63 percent for all patients. T1 and T2 lesions were controlled in 87 percent and 68 percent of patients, respectively, and T3 lesions were controlled in 50 percent of patients. Patients with healthy (N0) nodes and those with mobile nodes had a high degree of regional control, but fixed nodes were controlled in only 37 percent of patients with radiation alone. The most common site of treatment failure was in the primary tumor, which accounted for 45 percent of relapses, and isolated nodal relapses were present in only 24 percent of patients. Subsequent surgery was possible in 47 percent of patients in whom initial treatment failed. A higher degree of subsequent control was obtained with more aggressive surgery compared with simple local resection. There was a high rate of second respiratory tract malignancy, in fact, after 2 years, patients were dying more commonly of their second respiratory tract malignancies than of cancer of the tonsil.

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The results of radical radiotherapy with surgery in reserve for 136 patients with stage T1 and T2 NO supraglottic laryngeal carcinoma seen during a 20-year period are analyzed herein. Approximately one half of all patients were alive and well five years after treatment, while one fifth of patients died of supraglottic cancer. The cancer in two thirds of these patients was locally controlled by irradiation; of particular note was an 11% to 18% recurrence rate in patients whose necks were initially noted to be free of cancer. Analysis of the results of irradiation treatment disclosed a major reduction in nodal recurrence from the use of irradiation fields larger than 7 X 7 cm (3%, as compared with 19% with a smaller irradiation field). During the 20-year period of the study, there was a major reduction observed in tumor-related deaths; this is attributed to the use of larger irradiation fields and more aggressive use of surgery for irradiation failures. The results obtained are compared herein with the results of primary surgery, and conclusions are drawn as to the optimal management of early-stage supraglottic cancer.

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