Irradiation of carcinoma of the prostate localized to the pelvis: Analysis of tumor response and prognosis

A group of 195 patients with histologically proven adenocarcinoma of the prostate limited to pelvis were treated with definitive irradiation between 1967 and December 1976. In 42 patients with Stage B adenocarcinoma, the tumor free actuarial five year survival was 80%; for 141 with Stage C it was 56%; there were no long term survivors in 12 patients with Stage D1 (extensive tumor limited to the pelvis, without distant metastasis). The pelvic failure rate was 7% in Stage B, 17% in Stage C and 25% in Stage D1. Histological differentiation of the tumor had no significant impact in survival of patients with Stage B. However, in Stage C, patients with well or moderately differentiated tumor had a five year survival of 70% in contrast to 25% in those with poorly differentiated lesions. In this group of patients 60% of the failures resulted from distant metastasis. In Stage C, 38% of the patients who were treated with doses between 5500 and 6000 rad developed pelvic failures, as opposed to 20% of those treated with a mean dose of 6500 rad and 12% in patients receiving 7000 rad or greater dose. The addition of hormonal therapy, usually castration and diethylstilbestral (DES) (5 mg daily), did not significantly affect the prognosis of patients with Stage B or C. Major complications of therapy occurred in 11% of the patients. The most common problem was urinary incontinence which was observed in 13.3% of 60 patients who had a transurethral resection (TUR) as opposed to 4.4% in 135 patients on whom this procedure was not performed. Less severe complications were noted in 18% of the patients and treated with conservative management. Leg edema developed in three of 14 patients on whom a staging laparotomy was performed (21.4%) in contrast to only three of 181 patients without such a procedure (1.6%). At the present time external irradiation is a viable alternative to radical prostatectomy in the treatment of Stage B and the modality of choice in patients with Stage C adenocarcinoma of prostate. It is important to identify prognostic factors that may optimize the effectiveness of irradiation in the management of this tumor. In order to improve the prognosis of carcinoma of the prostate, effective systemic therapy will be necessary to control micrometastasis in patients with poorly differentiated lesions.     

Tumor control in definitive irradiation of localized carcinoma of the prostate

At the Mallinckrodt Institute of Radiology, Washington University, 343 patients with carcinoma of the prostate were treated with definitive radiotherapy. All patients are available for minimal 3 year follow-up; the median period of observation is 5.2 years. The incidence of pelvic recurrence with or without distant metastases was 0% in 10 patients with Stage A2, 11% in 113 patients with Stage B, 34% in 204 patients with Stage C, and 40% in 16 patients with Stage D1. There was no significant difference in pelvic tumor control when correlated with the degree of differentiation of the tumors in each stage. In Stage B, patients who exhibited complete regression 3 months after completion of therapy had a pelvic failure rate of 5%, those with 50-75% regression-8% and less than 50% regression-18%. In Stage C, patients with more than 50% tumor regression had a pelvic failure rate of 25%, in contrast to 37% when less than 50% regression was noted at 3 months after completion of irradiation. However, there was no correlation between tumor regression and NED survival. In patients with Stage B, there was no significant correlation between doses of irradiation ranging from 6000 to 7000 cGy and pelvic tumor control. In Stage C, patients receiving doses higher than 6500 cGy had a probability of failure rate in the pelvis of 25% (40/173), in comparison with 44% with doses between 6000-6500 cGy (15/32). The 10 year NED survival for Stage A2 was 100%, Stage B-70%, and Stage C-40%. In Stage B, there was no correlation between local tumor control and 5 year overall survival. However, at 10 years 88 patients without evidence of local failure or distant metastases had a survival rate of 70% in contrast to only 25% if they recurred. In Stage C, 110 patients without local recurrence or distant metastases had a 40% 10 year survival in contrast to 20% in 55 patients who had pelvic recurrence (with or without distant metastases) and 39 patients with distant metastases only. In 105 patients with Stage B tumor controlled in the pelvis, the incidence of distant metastases was 16%, in contrast to 50% in eight patients with pelvic failure. In Stage C, only 26% of 149 patients with pelvic tumor controlled developed distant disease, versus 60% in 55 patients failing in the pelvis. Ninety-five percent of the pelvic failures and 80% of the distant metastases appeared within 5 years after therapy. The administration of hormones did not significantly influence either the probability of pelvic tumor control or the appearance of distant metastases.     

Correlation between radiation dose and tumor recurrence and complications in carcinoma of the uterine cervix: stages I and IIA.

A retrospective analysis is reported on 330 patients with carcinoma of the uterine cervix, 23 with Stage IA, 233 with Stage IB and 74 with Stage IIA disease treated with irradiation alone. The dose of irradiation delivered to the cervix, paracervical tissues or the pelvic lymph nodes was correlated with tumor control. There were no central or parametrial failures in patients with Stage IA disease. There were 4 local or marginal (central) recurrences (1.6%) and 15 (6.5%) parametrial failures in the patients with Stage IB disease. Of 74 patients with Stage IIA disease, 3 developed cervical failures (3.9%) and 4 had both central and parametrial recurrences (5.2%).A definite correlation was found between the dose of irradiation delivered to the pelvic lymph nodes and the incidence of recurrences in the patients with Stage IB disease, (about 20%) parametrial failures with doses below 4000 rad in contrast to about 5% with 4000–5000 rad and 2% with doses over 6000 rad). Among patients with Stages IB and IIA disease, the survival of those who were treated with radiation alone and who received doses less than 4000 rad was about 10% less than patients who were treated with higher doses. This difference is not statistically significant; however, it suggests strongly that higher doses of irradiation to the parametria correlate with better tumor control in the pelvis and survival. Complications were slightly higher with doses to the bladder or rectum over 8000 rad. Although it was not statistically significant, patients who had non-standard intracavitary insertions had approximately 18% complications in contrast to only 6.6% in 135 patients with adequate insertions. Factors other than total dose of irradiation, such as geometry of the pelvis, characteristics of the tumor, position of the applicator, type of applicators used, loading and dose rate are important in evaluating the effects of irradiation in tumor control and complications of carcinoma of the uterine cervix.     

Adjuvant radiation therapy for rectal cancer

Since 1976, 104 patients with rectal cancer have been treated with a new approach of combined pre- and postoperative radiation. All patients were given 500 rad preoperative irradiation on the day of or the day before surgery. Surgery in the majority of patients was an abdominal perineal resection. The disease was then staged pathologically according to Astler-Coller's modification of Duke's staging. Patients with early stage cancer (Stages A and B1) were followed with no further therapy. Patients with poor prognostic characteristics (Stages B2, C1, C2) were given postoperative pelvic irradiation (4500 rad in 5 weeks). Twenty-nine patients were found to have Stage A or B1 cancer and were followed with no further therapy. Of these 29 patients, 1 patient developed recurrence and one has died of metastatic disease. The excellent survival of patients with early tumors indicates that minimizing the role of adjuvant therapy in this group has not been detrimental to their survival. Fifteen were found to have liver metastases at laparotomy and had just a colostomy and palliative therapy. Sixty patients had Stage B2 and C disease. Thirty-one received postoperative irradiation as per protocol. Twenty-nine patients did not receive postoperative irradiation for a variety of reasons. Follow-up ranges from 1 to 7 years in these patients. Of the 29 patients with Stage B2 and C disease who should have but did not receive postoperative radiation, 10 patients (34%) have developed a recurrence in the pelvis, and 5 other patients (17%) have developed metastatic disease. Of 31 patients who received postoperative irradiation, only 2 patients (6%) developed a local recurrence and 4 patients (13%) have developed distant metastases. Survival at 3 years was 80% for patients receiving the combined treatment, as compared to 42% for those not receiving the postoperative part of the treatment protocol.     

Extended field irradiation in the treatment of patients with cervical carcinoma involving biopsy proven para-aortic nodes

Between November 1974 and November 1979, 15 patients with cervical carcinoma were treated with extended field irradiation for biopsy proven para-aortic lymph node (PALN) metastases. Treatment consisted of pelvic and para-aortic irradiation at a daily dose of 180 to 200 rad per day, delivering 4000 to 6000 rad to the pelvis and 4000 to 5000 rad to the para-aortic nodes. One or two intracavitary insertions each delivered an additional 2000 to 3500 rad to point A. The three year actual disease free survival for the 12 patients with Stage I and II disease was 50%. All six survivors remain alive without evidence of disease for 41 to 93 months, with a mean and median follow-up of 65 months. All patients dying of disease did so within 26 months, all but one dying within one year. All patients with Stage III and IV are dead of disease. Pelvic disease was controlled in 11 of 12 patients with Stage I or II disease, and in one of the three patients with Stage III and IV disease. There was no clinical indication of failure in the PALN in any patient. Nine patients failed with disseminated disease. Three of 15 patients (20%) suffered serious treatment-related complications. Two of these were attributed to the pelvic irradiation, with one patient requiring a colostomy. Thus, complications resulting from the extended field irradiation were seen in only one patient (6.7%). There was no treatment related mortality. Extended field irradiation can lead to a 50% survival in patients with Stage I and II cervical carcinoma and PALN metastases, a survival comparable to that reported in patients with involved pelvic nodes.     

Split-course versus continuous pelvis irradiation in carcinoma of the uterine cervix: a prospective randomized clinical trial of the Radiation Therapy Oncology Group

In August 1980, the Radiation Therapy Oncology Group (RTOG) completed a prospective randomized clinical trial for the comparison of a split-course versus a standard continuous course of pelvic irradiation for carcinoma of the uterine cervix Stages II-B, III-A, III-B, and IV-A. The split-course consisted of 10 fractions of 250 rad each, 5 times a week, up to 2500 rad followed by a rest period of approximately 2 weeks and then another 2500 rad was given (250 X 10). The continuous course consisted of 30 fractions of 170 rad each, 5 times per week, for a total of 5100 rad. In both groups the external pelvis irradiation was followed by intracavitary brachytherapy in the uterus and vagina, with tandem-colpostat or tandem only, for a dose of 3000 rad at point A for the former, or at 2 cm from the center of the linear source for the latter. In cases where brachytherapy was not possible, a boost of external irradiation with reduced field, with a dose of 1600 rad (200 X 8) was advised. Three hundred and one patients were registered, of which 287 are currently evaluable. No differences between the treatments were detected for the following study end-points: treatment tolerance in terms of acute normal tissue reactions and completion of therapy, tumor control in the pelvis, severe late normal tissue reactions, and survival. In the entire study population the estimated tumor control in the pelvis at two years after initiation of therapy was: 81% for Stage II-B, 67% for III-A, 53% for Stage III-B, and 32% for Stage IV-A. The estimated two-year survival was: 70% for Stage II-B, 58% for III-A, 46% for III-B, and 23% for IV-A.     

The characteristics of long-term survivors of lung cancer treated with radiation

Between 1968 and 1974, 348 patients with lung cancer were primarily treated with radiation therapy. There were 66 such patients (19%) who survived a minimum of 18 months and are the subject of this report. Of this group, 30 patients have no evidence of disease from 18-96 months, with a median follow-up of 38 months. Thirty-three patients are dead of disease. The five-year actuarial survival of the total group of 348 patients was 5.6%. There were 14 stage I and II patients who survived a minimum of 18 months, of whom 11 had no evidence of disease. Of the 42 Stage III patients, 18 presently show no evidence of disease. There were 13 patients who failed with locally recurrent disease; in this group a dose-response relationship was demonstrated. A local failure rate of 50% (4/8) was observed for patients who received fewer than 5000 rad, 22% (6/27) for patients receiving 5000-5500 rad, 18% (2/11) in patients receiving 5500-5900 rad, and 5% (1/20) for patients who received more than 5900 rad. Radiotherapeutic technique was a significant variable in local failure. Forty-six percent (6/13) of those patient failures may have been eliminated with the use of careful treatment planning with simulation. A statistically significant difference in dose was noted for patients with central recurrence, mean dose 4725 rad, 1561 RET, 81 TDF, when compared with patients with control of gross disease with radiation, mean dose 5740, 1880 RET, 108 TDF. There were four patients with marked early complications (6%) and eight patients with late complications (12%). There were no deaths attributable to radiation. Although most patients with advanced lung carcinoma die of distant disease, a significant number of patients can achieve long-term survival when radically treated with high-dose radiation therapy.     

Radiotherapeutic management of primary thyroid lymphoma

The purpose of this study was to evaluate the radiotherapeutic management of 38 patients, with malignant lymphoma of the thyroid, seen at the Mayo Clinic between 1965 and 1979. There were 8 males and 30 females with ages ranging from 34 to 90 years (mean age of 65 years). A tissue diagnosis was made in all patients and tissue was available for reclassification under the "Working Formulation" in 31 of the 38 patients. Twenty-six patients had intermediate grade histology, four low grade and one indeterminate. Twenty patients were clinical Stage IE, 14 patients Stage IIE, one patient Stage IIIE, one patient Stage IV and two patients were unstaged. All patients were treated with approximately 4000 rad megavoltage irradiation (range 2400-6000 rad) to the neck only (10 patients) or neck and mediastinum (28 patients). Twenty patients received subdiaphragmatic radiotherapy and four patients received adjuvant chemotherapy. Median follow-up was 56 months with minimum follow-up of 30 months. Overall disease-free survival at five years was 59%. Of 14 patients who experienced a recurrence, 10 (71%) failed in two or more sites. The most common site of failure was in para-aortic lymph nodes. One year survival following recurrence was 29%; however, four of six patients receiving salvage therapy survived at least two years. Patients receiving radiation treatment to the neck and mediastinum and those with no gross residual disease at the initiation of radiotherapy were less likely to develop a recurrence. Patients receiving a planned break during the course of therapy did not have reduced overall disease-free survival. However, 4 of 20 patients (20%) who received split course therapy failed within the radiation fields compared to 2 of 18 patients (11%) who had no treatment break. Only 1 of 4 patients (25%) receiving adjuvant chemotherapy survived one year. Side effects of radiotherapy were minimal. We believe the radiotherapeutic management of clinical Stage IE and IIE primary thyroid lymphoma should include treatment of the neck, axillae and mediastinum to a dose of approximately 4000 rad using a continuous course technique. Additionally, gross total removal of the disease surgically may be beneficial.     

Patterns of tumor recurrence after definitive irradiation for inoperable non-oat cell carcinoma of the lung

Preliminary analysis was carried out on a prospective randomized cooperative group study involving 375 patients with histologically proven unresectable non-oat cell carcinoma of the lung who were treated with definitive radiotherapy. The patients were randomized to one of four treatment regimens: 4000 rad split course (2000 rad in five fractions one week, two weeks rest and an additional 2000 rad, five fractions in one week) or 4000, 5000 or 6000 rad continuous courses, five fractions per week. 84 to 100 patients were accessioned to each group. The one year survival rate was about 40%; the two year survival rate was 10% to 18%. The patients who were treated with the split course had the lowest survival (10% at two years) compared with the other groups (14% to 18%). Complete and partial local tumor regression was 48 % in patients who were treated with 4000 rad, 65 % in the 5000 rad and 61 % in the 6000 rad group. The rate of initial intrathoracic recurrence was 38 % in patients who were treated with 6000 rad; 45 % in those who received 5000 rad, 51 % and 64 % with 4000 rad split or continuous course, respectively. Patients who showed complete or partial regression of the tumor following irradiation exhibited an initial local recurrence rate of 42 % and 46 % respectively in contrast to 57 % for those without tumor regression. Patients with epidermoid carcinoma had an initial local failure rate of 53%, adenocarcinoma and large cell undifferentiated carcinoma 41 %. Distant metastases concurrent with or prior to intrathoracic failure were significantly higher in the patients with adenocarcinoma or large cell adenocarcinoma (63%) than in epidermoid carcinoma (33%). The present data strongly suggest that patients who were treated with 5000 or 6000 rad had a better response, tumor control and survival than those who were treated with lower doses. Additional follow-up of patients at risk in each group will be necessary before a final conclusion is drawn. Further investigations should determine the impact that a variety of prognostic factors may have in efficacy of irradiation in patients with bronchogenic carcinoma. This information will be extremely useful in the design of future therapy for these various subpopulations of patients with different manifestations of the disease.     

Post operative radiation therapy in the management of brain astrocytomata—Retrospective study of 142 patients

A retrospective analysis of survival data of 142 patients with partially resected astrocytomapu Grades II, III, and IV is presented. All patients received post-operative radiation therapy in the period 1957–1978 inclusive. There were 27 patients with Grade II, 41 patients with Grade III, and 74 with Grade IV tumors. Two patients received a dose of 3800 and 4000 rad respectively, 86 a dose of 4000–5000 rad, and 54 a dose of 5000–6500 rad. The actuarial 5 year survival for patients with Grade II tumors was 44%, and for Grade 11126%. The one, two and three year survival rates for Grade IV were 33%, 15%, and 6.9% respectively. Median survival values were calculated according to histologic grade of malignancy for the whole group and for dead and alive patients separately. Of 27 patients with Grade II tumors, 11 patients were alive with a median survival of 63.7 months; 10 of 41 Grade III patients were alive with a median survival of 54 months; 7 of 74 Grade IV patients were alive with a median survival of 13.2 months. There was no apparent dose effect on the median survival for Grade II and III patients. Patients with Grade IV tumors bad a median survival of 12.1 months if they received doses between 4000–5000 rad and 14 months if they received doses between 5000–6500 rad. In view of the favorable 5 year survival rates of patients with Grade II and III astrocytoma, a dose of 5000 rad given as outlined in the text is both adequate and safe.     

Randomized trial of conventional versus high fractional dose radiation therapy in the treatment of advanced head and neck cancer

A prospectively randomized clinical trial was undertaken to compare conventionally fractionated radiation therapy and high fractional dose irradiation in the treatment of advanced, surgically unresectable head and neck squamous cell carcinoma. Sixty-four patients were entered into the study between 1973 and 1979 and were randomized to receive either 200 rad daily to total tumor doses of 6000-7000 rad in 6-7 weeks, or 400 rad daily to a total of approximately 4400 rad in 2-3 weeks. The distribution of patients between the two fractionation schedules was comparable regarding site of the primary tumor, extent of disease, degree of histologic differentiation and performance status. Twenty-nine of 31 (94%) patients in the 200 rad group and 29 of 33 (88%) in the 400 rad group has Stage IV disease. Twenty-six in the former group and 30 in the latter completed radiation therapy as planned. Acute skin and mucosal reactions occurred earlier in patients treated with 400 rad daily, but were of equivalent intensity and well within acceptable levels in both groups. No increase in late adverse effects was seen with high daily doses. Palliation of tumor-related symptoms and extent of tumor control were comparable in the two groups. Actuarial five year disease-free survival rates were approximately 10% in both treatment groups with a mean follow-up period of 5 1/2 years. We conclude that high fractional dose irradiation is equivalent to conventionally fractionated radiation therapy in the treatment of advanced head and neck cancer.     

A prospective trial of postoperative vaginal radium/cesium for grade 1-2 less than 50% myometrial invasion and pelvic radiation therapy for grade 3 or deep myometrial invasion in surgical stage I endometrial adenocarcinoma

A prospective trial was performed to evaluate the recurrence rate and 5-year disease-free survival rate in patients with surgical Stage I endometrial adenocarcinoma. Patients with Stage I, Grade 1 or 2 disease, less than 50% myometrial invasion, and no evidence of disease outside the corpus of the uterus were treated by hysterectomy and bilateral salpingo-oophorectomy and postoperative vaginal radium/cesium (Group 1). Patients with surgical Stage I, Grade 3 disease or deep myometrial invasion, and histologically negative paraaortic lymph nodes were treated with postoperative pelvic radiation therapy (5000-5040 cGY) (Group 2). Patients with malignant peritoneal cytologic findings also received progesterone therapy. Of the 92 Group 1 patients, there have been no recurrences and the 5-year estimated disease-free survival rate was 99%. Of the 41 Group 2 patients, there have been four (9.7%) recurrences but only one (2.4%) within the treated field (pelvis), and the 5-year estimated disease-free survival rate was 88%. Of the 133 patients, the 5-year estimated disease-free survival rate was 96%, and only one patient (0.7%) had a local pelvic recurrence. Of the 16 patients with malignant peritoneal cytologic findings who were treated with progesterone therapy, none has had a recurrence.     

Stage II carcinoma of the endometrium: results of therapy and prognostic factors

A retrospective analysis is reported of 116 patients with Stage II carcinoma of the endometrium treated definitively with combined radiation and total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH-BSO) or irradiation alone from January 1960 through December 1981. At 5 and 10 years, the overall survival for all patients was 71 and 52% and the disease-free survival was 73 and 69%, respectively. Of 90 patients in the combined therapy group, most received a preoperative intracavitary insertion (3500 mgh to the uterus and 2000 mgh to the upper vagina) and preoperative external beam pelvic irradiation (2000 cGy whole pelvis, additional 3000 cGy to parametria, with midline shield) followed in 4 to 6 weeks by a TAH-BSO. The 5 and 10 year disease-free survival for this group was 78 and 75%, respectively. The incidence of major complications was 7% for the combined therapy group. Twenty-six patients were treated with irradiation alone; most of them received two intracavitary insertions (5000 mgh to the uterus and 3000 mgh to the upper vagina) and external beam pelvic irradiation (2000 cGy whole pelvis, additional 3000 cGy to parametria). The 5 and 10 year disease-free survival was 53 and 45%, respectively. The incidence of major complications was 19%. Factors found to influence the prognosis were histologic grade of tumor, clinical and histologic degree of tumor involvement of the ectocervix, presence of residual tumor in the hysterectomy specimen and the depth of myometrial invasion.     

Sequential infusional 5-fluorouracil followed by concomitant radiation for tumors of the esophagus and gastroesophageal junction

Thirteen patients with esophageal or gastroesophageal tumors with regional disease only were treated with sequential combined therapy. Weeks 1 to 6 continuous (24 hours) infusion 5-fluorouracil (5-FU) 300 mg/m2/d; weeks 6 to 10 or 12 infusional 5-FU administered concomitantly with radiation to the primary tumor site using standard fractionation with a cumulative median dose of 5000 rad; range 4400 to 6900 rad. Surgery was performed in five patients. All patients were evaluable for assessing response to the initial 5-FU infusion and 11/13 patients demonstrated tumor regression. Of 12 evaluable patients subsequently receiving combined infusional 5-FU and concomitant radiation, all 12 achieved complete clinical (10) or pathologic (two) tumor regression. Two of five patients having surgical resection had no pathologic evidence of tumor. All patients had relief of dysphagia within 1 week of initiating chemotherapy. Acute complications of therapy included stomatitis (two patients); hand-foot syndrome (two patients), and subclavian vein thrombosis (two patients). Stricture requiring periodic dilation occurred in three patients, and one patient developed a tracheoesophageal fistula at 36 months. Local control was maintained in 12/13 evaluable patients. Four of 13 patients were alive and without disease at 12 to 46 months. Nine patients died of distant metastases at 6 to 40 months. Median survival for the whole group was 16 months. Ten of the 13 patients (77%) survived for more than 1 year and 3/13 (22%) survived more than 3 years. This pilot study demonstrates the activity of 5-FU administered on an infusion schedule in both squamous and adenocarcinoma of the esophagus and the capacity to deliver infusional 5-FU throughout standard fractionation radiation. The local control and survival data may provide a basis for expanded Phase II trials, and a comparative trial against surgery alone might also be justified.     

Results of adjuvant radiation therapy in cancer of the rectum. Thomas Jefferson University Hospital experience

From 1972 to 1981, 174 patients with cancer of the rectum surgically staged as B2 or C disease, underwent surgical resection of the tumors for cure. Eighty-eight patients received surgery only with no further adjuvant therapy, and the remaining 86 patients were treated with a combination of radiation and surgery. Twenty-nine patients received low-dose preoperative radiation (500 rad in one fraction); 26 patients received postoperative radiation (4500 rad in 5 weeks); and 31 patients received combined low-dose preoperative radiation (500 rad) and postoperative radiation (4500 rad in 5 weeks). This experience was analyzed to determine the patterns of failure and the impact of adjuvant therapy on survival. Patients undergoing surgery alone had a 26% incidence of local failure in the pelvis and a 57% incidence of distant metastasis. Patients receiving low-dose preoperative radiation had a reduction in the rate of distant metastasis (24%), but no effect on local failure (34%). On the other hand, patients receiving postoperative radiation had a reduction in the local failure rate (11%), with no effect on distant metastasis (50%). Patients who received the combined preoperative and postoperative treatment had a reduction in both the local recurrence rate (7%), and the rate of distant metastasis (13%), and these patients also had a substantial improvement in survival over surgery alone. Survival of patients undergoing surgery alone was 34% at 5 years and was not substantially different for patients undergoing low-dose preoperative irradiation (48%), or for patients receiving postoperative irradiation (29%). Survival in patients receiving combined preoperative and postoperative irradiation was substantially better (78%) than the other groups of patients.     

Cylindroma of the nasopharynx: a chronic disease

From March 1958 to October 1984, 10 patients with cylindroma (cystic adenoid epithelioma) arising in the nasopharynx were treated in our hospital. The presenting symptoms of these patients ranged in duration for 2 weeks to 8 years, with an average of 25 months. Eighty percent of the patients had destruction of the base of skull and 60% had cranial nerve involvement. Of these 10 patients, two had Stage II disease, two had Stage III, and six had Stage IV. Response was seen in this tumor at tissue doses between 5000-8000 rad. Of the seven patients at risk for 5 years, 86% survived, yet 36% of the patients died of tumor between the fifth to tenth year. Fifty percent of the patients lived beyond 10 years. Based on this experience, a dose of more than 8000 rad is advised for the primary lesion. For the neck region, radiation is indicated only when there are lymph node metastases; prophylactic radiation of the neck is not necessary. Local recurrence or single distant metastasis is amenable to radiation therapy. Among the six patients who failed in the course of follow-up, three had local recurrences, two had pulmonary metastases, and one died of cerebral vascular accident.     

Testicular seminoma: analysis of treatment results and failures

Pure testicular seminoma has historically been treated primarily with radiation therapy, and excellent results have been achieved. Recently, several aspects of the treatment of seminoma have been questioned; namely, the value of mediastinal irradiation in Stage II disease, and whether a dose response curve existed for seminoma. Because these questions have remained unanswered, we undertook a retrospective review of all patients with pure testicular seminoma treated in the Department of Radiation Oncology at Indiana University Medical Center. From 1961-1981, 54 patients with pure testicular seminoma were given megavoltage irradiation with curative intent. Thirty three patients were Stage I, with tumor confined to the testicle with no evidence of nodal spread. Fifteen patients were Stage IIA, with metastases less than 5 cm in size in the retroperitoneal nodes. Four patients were Stage IIB, with metastases greater than 5 cm in size in the retroperitoneal nodes. One patient was Stage III, with supradiaphragmatic metastases confined to the mediastinum and supraclavicular area. One patient was Stage IV, with evidence of extralymphatic metastases. The crude survival rate (corrected for intercurrent death, except for treatment toxicity) for the entire group was 87%. For Stage I, it was 91%, Stage IIA-80%, Stage IIB-75%, Stage III-100%, and Stage IV-0%. All patients had a minimum follow-up of 2 years with a range of 2 to 21 years. Evaluation of the Stage I patients reveals that 2500 rad in 3 weeks appears to be adequate in controlling microscopic disease, as there were no in-field recurrences when this dose was given. Those patients with Stage IIA and IIB disease who received greater than or equal to 3500 rad to macroscopic disease had 100% (7/7) survival and local control, while those receiving less than or equal to 3000 rad had a 66.6% (8/12) survival with three of four demonstrating persistent or recurrent abdominal disease. Thus, we feel that macroscopic disease requires 3500 rad to 4000 rad for control. All Stage II and III patients had planned mediastinal irradiation. No patients who received mediastinal irradiation recurred in the mediastinum. Whether this is because of our treatments or the natural disease process remains unanswered. Overall, we were able to salvage 12.5% (1/8) of our recurrences, while 37.5% (3/8) died from toxicity of their salvage therapy.(ABSTRACT TRUNCATED AT 400 WORDS)     

Treatment of inoperable non-small cell carcinoma of the lung with radiation therapy, with or without levamisole. A randomized trial of the Southeastern Cancer Study group

In a randomized trial, 251 patients with inoperable non-small cell lung cancer received radiation therapy (RT) with or without levamisole (2.5 mg/kg twice weekly for 1 year, or until progression). Radiation therapy was delivered to 6000-6500 rad for Stages I and II, and 4000-4500 rad by continuous or split course for Stage III disease. Responses were observed in 40% of patients receiving placebo, and in 29% of patients taking levamisole. Relapse occurred at local sites only in 53% of the placebo- and 75% of the levamisole-treated patients. The frequency of relapse in distant sites was lower (25%) in the levamisole group as compared with the placebo group (47%). No significant difference in survival was observed between the placebo and levamisole-treated groups (median survival, 48.2 and 45 weeks, respectively). Responders to radiotherapy survived significantly longer than nonresponders (median survival, 73 vs. 33.3 weeks, p = 0.001). Among responders, the median survival of patients treated with levamisole was shorter (63.9 weeks) than that of patients receiving placebo (92.7 weeks). Toxicity attributable to levamisole included severe granulocytopenia in five patients and severe nausea and vomiting in nine. It is concluded that levamisole is without significant benefit in this setting.     

Analysis of pelvic tumor control and impact on survival in carcinoma of the uterine cervix treated with radiation therapy alone

A total of 1054 patients with histologically confirmed invasive carcinoma of the uterine cervix were treated with radiation therapy alone between 1959 and 1982. All patients are available for a minimum of 3 years follow-up. Radiation therapy consisted of external irradiation to the whole pelvis (1000-2000 cGy) and parametria (for a total of 4000-6000 cGy) combined with two intracavitary radioactive source insertions (6000-7500 cGy to point A). Patients with Stage IIB, III, and IVA have been consistently treated with somewhat higher doses of external irradiation and intracavitary insertions. A small group of 54 patients with Stage IIB or IIIB had pelvic lymphadenectomy following the irradiation (1960-1964). There was a strong correlation between the tumor regression within 30 days from completion of radiotherapy and the incidence of pelvic recurrences or distant metastases for each of the anatomical stages. The 10-year survival rate for Stage IB was 76%, Stage IIA 60%, Stage IIB 45%, and Stage III 25%. Many of the deaths were due to intercurrent disease. Thus, the 10-year tumor-free survival was 80% for Stage IB, 60% for Stages IIA and IIB and 35% for Stage III. In Stage IB total doses of 6000 cGy or higher to point A resulted in 94% pelvic tumor control. In Stage IIA, the pelvic tumor control was 87% with doses of 6000 cGy to point A or higher. However, in Stage IIB the pelvic tumor control was 58% with doses below 6000 cGy, 78% with 6001-7500 cGy and 82% with higher doses. In Stage IIIB the pelvic tumor control was 42% with doses below 6000 cGy, 57% with 6001-7500 cGy and 68% with higher doses. Tumor control in the pelvis was correlated with the following 5 year survivals: Stage IB-95% (353 patients); Stage IIA-84% (116 patients); Stage IIB-84% (308 patients); Stage IIIB-74% (245 patients). The 5-year survival for patients that recurred in the pelvis was 30% for Stage IB, about 15% for Stages IIA-B and only 5% in Stage III. Patients with tumor control in the pelvis had a significantly lower incidence of distant metastases than patients who initially failed in the pelvis (9.3% vs. 58.6% in Stage IB, 21.6% vs 52.6% in Stage IIA, 19.8% vs 16.7% in Stage IIB, and 31.2% vs 50% in Stage III). In Stage IIB the figures were 19.8% and 16.7% because the initial pelvic recurrence was frequently concurrent with distant metastases.(ABSTRACT TRUNCATED AT 400 WORDS)     

Biopsy and definitive radiation therapy in stages I and II carcinoma of the female breast

One hundred-twenty patients with Stages I and 11 carcinoma of the female breast were treated by biopsy followed by definitive radiation therapy without mastectomy. The breast received 4500–5000 cGy (rad) using a 6 MV the area of the primary tumor of 2000 cGy (rad) using electrons in 99 patients (83 % ) and interstitial implantation in 21 patients (17 % ). Local recurrence was not recorded in the 43 patients with Stage I disease, while three of 77 patients (41%) with Stage II disease suffered a local recurrence. The actuarial five-year relapse-free survival was 91 % and 60 % in Stages I and II respectively. Cosmetic results were considered excellent by both physician and patient in the majority of cases. Axillary dissection was the recommended method of staging the axilla but was noted to be more morbid than axillary sampling. Electrons may be as effective as interstitial implantation as a means of supplementation following external beam therapy if specific guidelines are followed.