Radiotherapy as initial treatment for bulky stage II testicular seminomas.

Sixteen consecutive patients with bulky stage II seminoma were treated with primary radiotherapy from 1971 to 1982. Bulky stage II seminoma was defined as either Union Internationale Contre le Cancer (UICC) stage IIC (retroperitoneal metastases greater than 5 cm) or IID (palpable retroperitoneal metastases) with no evidence of visceral or supradiaphragmatic disease. The median age was 38 years (range, 26 to 52) and the median size of retroperitoneal disease was 11.5 cm (range, 5 to 25 cm). Patients were treated with generous radiation ports (such as wide hockey-stick or whole abdomen) often followed by boosts to the sites of bulky disease. Median tumor dose was 3,235 cGy (range, 2,700 to 5,668 cGy). Mediastinal (with or without supraclavicular) prophylactic radiation was administered to 15 of the 16 patients with a median dose of 2,590 cGy (range, 1,200 to 3,700 cGy). Treatment toxicity was mild. All 16 patients achieved a complete remission (CR) with radiotherapy. Median follow-up from the time of diagnosis was 60 months, and all patients are currently disease-free. Two patients recurred after therapy but were rendered disease-free with further radiation. These two relapsing patients have remained disease-free, following initial recurrence, for 8 years. The excellent results obtained with modern imaging and radiotherapeutic techniques justify radiotherapy as the initial treatment of choice for bulky stage II seminomas.

Patterns of failure in primary testicular non-Hodgkin's lymphoma.

Patterns of failure were analyzed in 30 patients with testicular non-Hodgkin's lymphoma: 16 had stage IE disease, ten had stage IIE, and four had stage IV. After orchiectomy, two of the 16 patients with stage IE disease received no additional therapy, one received multiagent chemotherapy, and 13 received pelvic and para-aortic radiation. Twelve patients with stage IE disease had progression, and the median time to progression was 12 months. Of the 14 patients with extratesticular involvement (stage IIE or IV), one (stage IV) received no treatment after orchiectomy, three (stage IIE) received para-aortic and pelvic radiation, and ten (seven stage IIE and three stage IV) received multiagent chemotherapy with or without radiation. Eight of the patients with stage IIE or IV disease had progression, and the median time to progression was 11 months. Widespread extranodal progression was observed in 17 of the 20 patients who had progression. The tendency of testicular lymphoma for early systemic progression suggests a need for multiagent chemotherapy in initial management.

Prostate-specific antigen as a pretherapy prognostic factor in patients treated with radiation therapy for clinically localized prostate cancer.

PURPOSE: This study was conducted to determine the value of prostate-specific antigen (PSA) as a pretherapy prognostic factor for localized prostate cancer treated with primary irradiation (RT). PATIENTS AND METHODS: Between March 1987 and December 1990, 254 patients with pretherapy PSA determinations were treated for clinical stage A2 to C prostate adenocarcinoma. In conjunction with other prognostic factors, pretherapy PSA was evaluated to determine whether it had independent predictive value for disease outcome. RESULTS: Pretherapy PSA was highly and directly correlated with clinical stage, tumor grade, and acid phosphatase level. With a median follow-up duration of 24 months, 241 patients (95%) were fully assessable for disease outcome. In these patients, PSA and tumor grade were the sole independent predictive factors for tumor relapse (ie, clinically determined and/or increasing PSA level). The combination of pretherapy PSA and tumor grade information defined groups of patients with distinctly different outcome. For patients in low- (favorable PSA and tumor grade), intermediate- (favorable PSA or tumor grade), and high- (adverse PSA and tumor grade) risk categories, the actuarial rates of survival free of tumor relapse or increasing PSA level were 94%, 77%, and 42% at 3 years, respectively (P < .0001). CONCLUSION: Pretherapy PSA is a strongly independent prognostic factor for disease outcome following primary RT. The combination of adverse pretherapy PSA and unfavorable tumor grade identified a cohort of patients with a high risk of early treatment failure in whom combined modality therapy may be appropriately investigated.

Phase III comparative evaluation of PCNU and carmustine combined with radiation therapy for high-grade glioma.

PURPOSE: We performed a randomized trial to compare survival distributions and toxicity of radiation therapy (RT) and PCNU with those of RT and carmustine (BCNU) in patients with malignant glioma. PATIENTS AND METHODS: A total of 346 patients with histologically verified supratentorial grade 3 and grade 4 astrocytoma were studied. After surgery, patients were randomly assigned to receive RT 60 Gy in 30 fractions and either PCNU 100 mg/m2 or BCNU 200 mg/m2 every 7 weeks for 1 year and every 10 weeks for the second year. RT and chemotherapy were started within 72 hours of randomization and usually on the same day. Of 334 assessable patients, 72% had partial or radical resection and 71% had grade 4 tumors. Median age was 59 years, and 85% had performance scores of 0 to 2 (Eastern Cooperative Oncology Group [ECOG]). The follow-up duration of 51 living patients ranged from 10.3 to 63.2 months, with a median of 36.2 months. RESULTS: The median survival duration in each group was 47 weeks, and median time to progression was 28 weeks. PCNU produced significantly more leukopenia and thrombocytopenia, whereas BCNU produced significantly more nausea, vomiting, and irritation. CONCLUSION: PCNU has no therapeutic advantage at this dose and schedule and does not warrant further study as a single agent for patients with high-grade glioma.

Prospectively randomized clinical trial of three intensive chemotherapy regimens for the treatment of advanced unfavorable histology non-Hodgkin's lymphoma.

Three hundred thirty-two eligible patients with advanced (Ann Arbor stage III or IV) non-Hodgkin's lymphoma of aggressive histologic subtype (Rappaport classification diffuse histiocytic [DH], diffuse poorly differentiated lymphocytic [DPDL], diffuse mixed [DM], or diffuse undifferentiated [DU]) were randomly assigned to receive induction chemotherapy with one of three intensive regimens in a clinical trial conducted by the Eastern Cooperative Oncology Group (ECOG) between 1978 and 1983. Chemotherapy regimens consisted of cyclophosphamide, vincristine, prednisone, and doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH) (COPA) administered in 3-week cycles; cyclophosphamide plus doxorubicin plus prednisone beginning day 1, with vincristine plus bleomycin day 15 of each 3-week cycle (COPA + Bleo); or cyclophosphamide plus doxorubicin plus procarbazine beginning day 1, and bleomycin plus vincristine plus prednisone beginning day 15 of each 4-week cycle (CAP-BOP). The median patient follow-up from study entry for patients still alive is 5 years. The three regimens were not significantly different with respect to complete response (CR) rates (43% to 46%), time to progression of malignant disease (median, 1.0 to 1.7 years), or survival (5-year survival, 34% to 45%), although duration of complete remission appeared to be shorter in patients receiving COPA (P = .03). COPA + Bleo and CAP-BOP were significantly more toxic than the COPA regimen. This study did not demonstrate any substantial therapeutic advantage associated with the addition of a fifth or sixth chemotherapy drug, or with treatment administered on a more frequent administration schedule, compared with the COPA regimen in this population of patients with advanced diffuse non-Hodgkin's lymphoma. The relatively small proportion of long-term disease-free survivors treated with COPA underscores the need for prospective clinical trials of new and more effective treatments for patients with these potentially curable tumors.

Sequencing and schedule effects of cisplatin plus etoposide in small-cell lung cancer: results of a North Central Cancer Treatment Group randomized clinical trial.

PURPOSE: The combination of etoposide (E) and cisplatin (P) is an accepted standard therapy for small-cell lung cancer (SCLC); however, the optimal sequencing and administration schedule has not been defined. This study was designed to evaluate different sequencing and administration schedules of E and P in the treatment of SCLC. PATIENTS AND METHODS: Five hundred fifty-two eligible patients with limited-(LD) and extensive-stage (ED) SCLC were randomized to receive one of the following regimens: arm A, P 30 mg/m2 by intravenous (IV) bolus followed by E 130 mg/m2 bolus; arm B, E 130 mg/m2 bolus followed by P 30 mg/m2 bolus; arm C, E 130 mg/m2 by 24-hour infusion and P 30 mg/m2 bolus at the end of each 24-hour infusion of E; arm D, E 130 mg/m2 by 24-hour infusion and P 45 mg/m2 by 24-hour infusion on day 2 and 3 only. Two 3-day induction cycles of IV EP were administered 4 weeks apart. Subsequent therapy was the same for all arms, consisting of four cycles of cyclophosphamide, doxorubicin, and vincristine (CAV) at 4-week intervals. Consolidative thoracic radiation therapy (TRT) and prophylactic cranial irradiation (PCI) were administered to responders. RESULTS: The overall response rate (84%) was similar in all treatment arms. Treatment arm A was associated with the best complete response (CR) rate (52%), the most favorable median survival time (MST) of 15 months, and a 26% 2-year survival rate. Patients with LD on arm A had a MST of 20 months and a 42% 2-year survival rate. Multivariate analysis indicated that extent of disease, performance status, arm of therapy, and sex were significant independent factors influencing survival. Toxicity of the four regimens was similar, except for greater thrombocytopenia on arm D. CONCLUSION: The bolus administration of EP with E following P for the first two cycles of chemotherapy was the most effective regimen, with especially encouraging survival for LD patients.

Therapeutic radiation and hyperparathyroidism. A case-control study in Rochester, Minn.

A case-control study was conducted among residents of Rochester, Minn, to assess the influence of prior therapeutic radiation on the risk of primary hyperparathyroidism. Fifty-one cases of surgically proven primary hyperparathyroidism diagnosed from 1975 through 1983 were each matched by age and gender to two control subjects, with radiation exposure documented through preexisting medical records. The overall odds ratio for any prior therapeutic radiation therapy was 1.9 (95% confidence interval, 0.9 to 4.4) and it was 2.3 (95% confidence interval, 0.9 to 5.7) when limited to those with prior head and neck radiation. Among women, the figures were 2.9 (95% confidence interval, 1.1 to 7.5) for any prior therapeutic radiation and 3.4 (95% confidence interval, 1.2 to 10.2) for head and neck exposure. This study confirms the association between primary hyperparathyroidism and prior therapeutic radiation exposure, at least for women in this population.

The consequences of treatment and disease in patients with primary CNS non-Hodgkin's lymphoma: cognitive function and performance status. North Central Cancer Treatment Group.

Per protocol, patients with primary CNS non-Hodgkin's lymphoma in an intergroup phase II trial conducted by the North Central Cancer Treatment Group and the Eastern Cooperative Oncology Group had their cognitive functions measured using the Folstein and Folstein Mini-Mental Status Examination (MMSE) and their physical functions measured using the Eastern Cooperative Oncology Group Performance Score (PS) at study entry, at each treatment evaluation, and at quarterly intervals thereafter until disease progression or death. Of the 53 eligible participants who began therapy, 46 (87%) had baseline MMSE scores recorded, 36 (68%) had at least one follow-up MMSE, and 32 (60%) had both, while 52 (98%) had baseline PS, 49 (92%) had at least one follow-up PS, and 48 (91%) had both. Patterns of MMSE and PS values over time were studied in each individual, in the group as a whole, in the 20 patients who completed the study regimen, in the 23 who survived more than a year, and in patients who were classified as nonprogressors at each key evaluation. For each patient, all recorded values were plotted versus time, with dates of disease progression and death included, to look for signs of decline in cognitive or physical function preceding adverse events. Long-term declines in scores of both cognitive and physical function were observed in many treated patients with primary CNS non-Hodgkin's lymphoma. Nearly all patients who were alive more than 52 weeks after study entry had a demonstrable decline in cognitive and physical functionality. Such declines may occur before disease progression is documented; they may also occur in some patients who have long-term follow-up without evidence of disease progression. Declining MMSE and PS was a poor predictor of disease progression. There was no association of PS and toxicity. The data from this study demonstrated the considerable difficulties we encountered conducting an ancillary study such as this within a multicenter clinical trial. Firstly, the test instruments written into the protocol were unable to tell if the declines seen were due to disease, treatment, co-morbidity, or other factors. Secondly, the missing data created difficulties in interpreting outcome.

Differential diagnosis between radiation and tumor plexopathy of the pelvis.

We studied 20 patients with lumbosacral radiculoplexopathy from radiation treatment and 30 patients with plexus damage from pelvic malignancy. Indolent leg weakness occurred early in radiation disease, whereas pain marked the onset of tumor plexopathy. Eventually, all radiation cases had weakness, which was bilateral in most of them and painless in one-half of them. Tumor patients typically had unilateral weakness, which was painful in all of them. Radiation disease often resulted in serious neurologic disability. Of the tumor patients, 86% were dead within 3 1/2 years after onset of neurologic symptoms.

Alzheimer's disease and prior therapeutic radiation exposure: a case-control study.

Few risk factors have been identified for dementing illness to date. To evaluate prior therapeutic radiation exposure as a potential risk factor for Alzheimer's disease, we carried out a retrospective case-control study using the Rochester Epidemiology Resource. Cases were all incident cases of AD from 1960 through 1974 (N = 392) identified in an ongoing study of the condition in this community. One age- and sex-matched control for each case was selected from all registrations for care during the year of onset in the case. There were 86 cases and 89 controls with prior radiation exposure, and the variable used to describe exposure was absorbed dose. Most of the exposure was small doses: 11 individuals received greater than 1,000 centigray (3 cases, 8 controls). Using the logistic regression methods of Breslow and Day, the estimated odds ratio for any prior therapeutic radiation exposure was 0.95 (95% CI, 0.66 to 1.37). When the exposure variable was limited to head exposure only, the odds ratio was 0.65 (95% CI, 0.32 to 1.31). It is unlikely that the risk associated with therapeutic radiation in the development of Alzheimer's disease is greater than 1.4.

Computer-assisted stereotaxic biopsy for the diagnosis of primary central nervous system lymphoma.

Primary CNS lymphoma was diagnosed in 13 patients after stereotaxic biopsy of indeterminate intracerebral mass lesions. Two patients also had laser extirpation of CT-visible tumor. The group consisted of 10 men and 3 women, aged 17 to 81 (mean, 55 years; median, 60 years). The lesions on CT were characteristically hyperdense, homogeneously contrast-enhancing, and associated with mild to moderate mass effect. Five patients had more than one lesion visible on CT. Complete staging procedures for occult systemic lymphoma were negative in all 13 patients. The majority (eight) of the tumors were of the diffuse, large-cell type. Five biopsy specimens underwent special immunostaining as a supplemental diagnostic effort. Two patients with small lymphocytic tumors demonstrated features consistent with T cell phenotype. Two patients with diffuse, large-cell tumors were confirmed as B cell phenotype by monotypic immunoglobulin light chain content. Primary CNS lymphomas represent a treatable group of primary brain tumors. Because of their tendency to develop in deep cerebral regions, they are often inaccessible to conventional neurosurgical techniques. We propose that stereotaxic neurosurgery can provide safe and accurate diagnosis, which is a prelude to planning comprehensive management.

Long-term follow-up of radiotherapy for prostate cancer.

PURPOSE: To determine the long-term outcome of radiotherapy for prostate cancer. METHODS AND MATERIALS: A total of 136 consecutive patients with prostate cancer underwent primary radiotherapy. All but 4 patients received 6000 cGy to the prostate. The minimal follow-up was 22.9 years. RESULTS: Of the 136 patients, 93 had Stage B (T2), 9 Stage A (T1), and 34 Stage C (T3). Sixty-nine percent of the patients developed recurrence, and 51% of all patients died of prostate cancer. The recurrences developed at a steady state throughout the length of follow-up. One half the recurrences occurred after 10 years, and recurrence was still observed >20 years after treatment. The survival rate at 5, 10, 15, 20, and 25 years was 81%, 59%, 37%, 16%, and 10%, respectively. The recurrence-free survival rate at 25 years was 17%. The median survival for Grade 3-4 patients was 6.3 years and for Grade 1-2 patients was 13.0 years. The median survival for those with T1 tumors was 12.9 years; T2 tumors, 12.4 years; and T3 tumors, 9.5 years. CONCLUSION: Despite favorable early results, with long-term follow-up, patients continued to experience prostate cancer recurrence. Unless they died an intercurrent death, they were highly likely to develop recurrence and die of prostate cancer. The conclusions from treatment studies with <15 years of follow-up should be viewed as preliminary.

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.

Radiotherapeutic management of adult intraspinal ependymomas.

Twenty-two adults with ependymomas of the spinal cord were treated with surgery and postoperative radiation between January 1963 and December 1983. The median age was 47 years. Nineteen patients had grade 1 lesions, two had grade 2 and one grade 3. Ten patients had the myxopapillary histologic subtype (all grade 1) and 12 had the cellular variant. There were 15 distal cord lesions originating from the conus medullaris, filum terminale and/or cauda equina. The remaining seven lesions arose more proximally. Fourteen patients had localized lesions involving one to three vertebral segments, while the remaining eight had extensive ependymomas spanning six to thirteen vertebral segments. The median time from onset of symptoms to diagnosis was 3 years. Surgical treatment consisted of biopsy only in three patients, subtotal removal in eleven patients and total removal in eight patients. Radiation was given to the spine only in all cases. Five patients received whole spine radiation; seventeen received partial spine treatment, appropriate for the length of the primary lesion. The median dose was 5000 cGy (range 3600-5700 cGy). The disease free survival at 5 and 10 years was 81 and 71%, respectively. Overall survival at 5 and 10 years was 95%. Seven of twenty-two (32%) patients failed. Factors analyzed for prognostic significance included age, sex, histology, extent of primary, location of primary within the cord, extent of surgical resection and dose. Too few grade 2 and 3 patients precluded meaningful statistical analysis of grade as a prognostic factor. Neither age, sex, histology, extent of primary, location of primary, nor extent of surgical removal significantly affected disease free or overall survival (p greater than 0.05). Four of nineteen (21%) patients with grade 1 lesions failed, while all three patients with grade 2 and 3 lesions did so. Half of the eight patients with extensive ependymomas failed compared to three of fourteen (21%) with limited ones. Six of seventeen (35%) patients failed at doses less than or equal to 5000 cGy while only one of five (20%) failed at doses greater than 5000 cGy. Patterns of failure were analyzed for the seven patients who failed. Six of the seven failures (86% of the failure group, 27% of the overall group) were local, that is, within the initial radiation field at the site of the original tumor. A single patient (grade 2) failed in the posterior fossa while remaining NED in the spinal cord (a head CT scan at initial work-up was negative).(ABSTRACT TRUNCATED AT 400 WORDS)

Postoperative radiotherapy of intracranial ependymoma in pediatric and adult patients.

In 33 patients undergoing operation and postoperative irradiation for intracranial ependymomas between January 1963 and December 1983, the tumor was grade 1 or 2 in 26 (79%) patients and grade 3 or 4 in 7 (21%). Operation consisted of only biopsy in 1 (3%), subtotal removal of tumor in 28 (85%), and gross total resection in 4 (12%). All patients received brain irradiation with a median dose of 4800 cGy. Seventeen (52%) patients also received spinal axis irradiation (median dose, 3000 cGy) which included 5 with high-grade tumors and 12 with low-grade infratentorial tumors. The relapse-free and overall survival rates at 5 years were 61% and 62%, respectively. Prognostic factors analyzed for statistically significant survival differences included age, sex, hydrocephalus, site, grade, extent of operation, extent of brain field, spinal axis irradiation, and brain dose. Grade was the only significant factor found: the 5-year survival of patients with low-grade ependymomas, 71%, was significantly better (p less than 0.04) than that of patients with high-grade ependymomas, 29%. Among the 31 patients evaluable for patterns of failure, treatment failed in 12 (39%) (10 only in the brain, 1 in the brain and spinal cord, and 1 only in the spine). All but one of the brain failures were at the site of the original primary lesion. Treatment failed in 4 of the 6 (67%) patients with high-grade tumor but in only 8 of the 25 (32%) with low grade tumor. Among the 7 low-grade infratentorial ependymomas treated with brain irradiation only, there was 1 treatment failure (in the spine; salvaged with further irradiation). Among the 12 patients with low-grade infratentorial tumors who received spinal axis irradiation, treatment failed in 1 (8%) (in the spine and also in the brain; patient subsequently died of disease). Nineteen (58%) patients remain alive; all but 2 of the patients who had recurrence died of their disease. This retrospective study suggests that: (a) patients with high-grade tumors have significantly poorer survival compared with those with low-grade tumors; (b) the main cause of death in ependymoma patients is intracranial failure at the primary site; and (c) craniospinal axis irradiation may not be necessary for patients with low-grade infratentorial ependymoma (localized irradiation alone may be adequate).

Radiotherapeutic considerations in the treatment of hemangioblastomas of the central nervous system.

Twenty-seven hemangioblastomas of the central nervous system were treated at the Mayo Clinic with radiation therapy from January 1963 to August 1983. Six patients had von-Hippel Lindau syndrome, and four presented with polycythemia. The median age among the 15 males and 12 females was 48 years (range 20-68). Two clinical groups were apparent: those that received postoperative radiation therapy for clinically suspect, or microscopically positive margins (6 patients) and those who underwent therapy for gross residual disease (20 patients). One patient did not fall into either group because his initially unresectable tumor was treated with planned pre-operative radiotherapy to 40 Gy and was subsequently successfully cured by surgery. Because the combined modality approach did not allow assessment of local control with radiation alone, he was excluded from the gross residual cohort in terms of time-dose relationship analysis. The cohort with gross residual disease was particularly unfavorable as 12 of these patients had developed 17 local recurrences prior to radiation. Three had multiple lesions, and four had the von-Hippel Lindau syndrome. In-field disease control appeared to be improved when patients were treated more aggressively. Patients treated to a dose of 50 Gy manifested local control in 4/7 (57%) vs 4/12 (33%) in patients treated to less than 50 Gy. In-field local control was also better if patients received a TDF greater than 75 (local control in 66%) vs a TDF of 65-75 (local control in 22%). Actuarial analysis of in-field disease control showed more aggressive treatment improved control whether analyzed by dose level (greater than or equal to 50 Gy vs less than 50 Gy, or TDF greater than 75 vs less than 75). Four of the six patients who received radiation therapy for microscopically positive or clinically suspect margins achieved local control. Both patients manifesting in-field relapse were successfully surgically salvaged. Overall survival for the entire group of 27 patients was 85%, 58%, 58%, and 46% at 5, 10, 15, and 20 years, respectively. Recurrence-free survival was 76%, 52%, and 42% at 5, 10, and 15 years, respectively. Half of all in-field recurrences had occurred by 2 years, but the remaining half recurred from 5.6 to 14.4 years. Patients who developed in-field failure usually died from disease with a median survival of only 1.5 years, but surgical salvage was accomplished in 4/12. Hydro-myelia developed in two patients and required operation. Surveillance for systemic tumors also was important and revealed seven benign and four malignant tumors.(ABSTRACT TRUNCATED AT 400 WORDS)

Management of subdiaphragmatic early-stage Hodgkin's disease.

Twenty-six patients with Stage IA-IIB Hodgkin's disease confined below the diaphragm were treated at the Mayo Clinic over a 9-year period (1974-1982). Ten of the twenty-six patients presented with intra-abdominal disease alone, and the remaining 16 patients presented with palpable inguinal-femoral adenopathy. One hundred thirty patients with pathologically staged supradiaphragmatic disease were treated over the same period and serve as a comparison group. The median age of 52 years among patients with subdiaphragmatic disease was significantly higher than the median age of 27 years in supradiaphragmatic group. There was no difference in sex distribution between the two groups. One-fifth of the subdiaphragmatic patients presented with B symptoms compared to one-tenth in the supradiaphragmatic group. No significant histological differences were seen. The majority of patients were treated with radiation therapy alone. The overall failure rate was 42% in the subdiaphragmatic group versus 22% in patients with supradiaphragmatic disease. All of the failures occurred in patients treated with radiotherapy alone. Stage and the presence of B symptoms were the most important prognostic factors. The type of subdiaphragmatic presentation (intra-abdominal versus inguinal-femoral) did not influence the outcome. Despite decreased 5-year recurrence-free survival (57% subdiaphragmatic vs. 79% supradiaphragmatic, p = 0.03), the overall 5-year survival rate of 85% is comparable to that of patients with supradiaphragmatic disease. It appears that inverted Y irradiation alone is sufficient for patients with Stage IA disease, but that patients with B symptoms or Stage II disease require more aggressive initial therapy if recurrence-free survival is to be improved.

External beam irradiation for retinoblastoma: patterns of failure and dose-response analysis.

Eighteen children with retinoblastoma (25 eyes) were treated with external beam radiation at the Mayo Clinic between January 1977 and January 1987; 15 eyes were in groups I to III and 10 were in groups IV and V (Reese-Ellsworth classification). The median number of tumors per eye was 3. Radiation therapy consisted of 4- or 6-MV photons. Doses varied from 39 to 51 Gy in 1.8- to 3.0-Gy fractions. Fourteen eyes were treated through lateral fields by anterior segment-sparing techniques, and 11 eyes were treated by an anterior approach with no attempt at anterior segment sparing. All patients survived (median follow-up, 31.5 months). Cataracts developed in five eyes at a median of 23 months, four in eyes treated with anterior segment-sparing techniques. Of the 15 group I to III eyes, 6 required additional treatment; 4 were salvaged with cryotherapy or photocoagulation and 2 were enucleated. Of the 10 group IV and V eyes, 8 required additional treatment; 4 were salvaged with cryotherapy or photocoagulation, 1 with persistent disease is being followed closely, and 3 were enucleated. Ten (71%) of the 14 eyes treated with anterior segment-sparing techniques required additional treatment (9 of the 10 for tumors anterior to the equator). Four (36%) of the 11 eyes treated with an anterior approach required additional treatment (3 of the 4 for tumors in the posterior pole of group IV or V eyes). Ninety percent of the tumors 10 disc diameters or smaller (1 disc diameter = 1.6 mm) were controlled independently of dose and fractionation used when they were not in the low-dose area of the anterior retina of an eye treated with an anterior segment-sparing technique. We find that use of lateral, anterior segment-sparing techniques has a high risk of anterior retinal tumor development and cataract formation and should be abandoned in favor of techniques that treat the entire retina. A dose of 45 Gy in 1.8-Gy fractions appears to be adequate for local control of tumors smaller than 10 disc diameters. Larger tumors may require additional treatment.

Local control and complications after radiation therapy for primary orbital lymphoma: a case for low-dose treatment.

Orbital involvement at the time of initial presentation is unusual in non-Hodgkin's lymphoma. In an effort to identify potential ways of improving the radiotherapeutic management of this disease, the records of 22 patients were reviewed retrospectively. All had biopsy-proven orbital non-Hodgkin's lymphoma, and the minimal, median, and maximal durations of follow-up in surviving patients were 4.8 years, 7.0 years, and 17.4 years, respectively. Permanent local control was achieved in 21 of the 22 patients (96%). Complications were scored according to a grading scheme in which grade 1 was the least significant complication and grade 4 was blindness as a result of radiation therapy. Of the 12 patients who received a radiation dose less than 35 Gy, 6 developed a grade 1 or grade 2 complication. Of the 10 patients treated with greater than or equal to 35 Gy, 6 experienced a complication, 1 of whom had a grade 4 complication resulting in blindness and another who developed a severe keratitis, which was scored as a grade 3 complication resulting in decreased visual acuity. At last follow-up, 10 patients were alive at 4.8 to 17.4 years after completion of radiation therapy, 4 had died of intercurrent disease at 3 months to 10.6 years, and 8 had died of disease at 3 months to 15.8 years. Actuarial survival for the entire group was 75% at 5 years and 48% at 10 years. Survival in patients with Stage I AE disease (lymphoma confined to orbit) at presentation was 87% at 5 years and 50% at 10 years, and survival in patients with Stage II A through Stage IV disease was 36% at 5 years and at 10 years. Primary orbital lymphoma is an indolent disease characterized by prolonged survival after radiation therapy. Excellent local control can be achieved with radiation doses of 20 Gy to 35 Gy. Higher doses may result in an increased risk of complications.

Correlation of pretherapy prostate cancer characteristics with histologic findings from pelvic lymphadenectomy specimens.

PURPOSE: The purpose of this study was to identify pretherapy factors associated with pelvic lymph node involvement (LNI) in patients with localized prostatic carcinoma (CaP), and to develop a model that would allow for estimation of this risk at the time of initial diagnosis. METHODS AND MATERIALS: Between January 1988 and December 1992, 2439 patients with clinical Stage T1a-3cN0-XM0 CaP underwent radical retropubic prostatectomy and bilateral pelvic lymph node dissection as sole initial therapy at a single medical institution. Preoperative factors were evaluated for their association with pelvic LNI in univariate and multivariate logistic regression analysis. A model was developed that incorporated independent predictive variables, and probability plots were generated to estimate the likelihood of pelvic LNI in the patient with a new diagnosis of localized CaP. RESULTS: Within clinical tumor stage, three groups (Tla-2a, T2b-c, and T3) were identified in which the observed rate of pelvic LNI was distinctly different. Gleason primary grades were also combined (1-2, 3, and 4-5) because of a similar observation. Univariate analysis identified clinical tumor stage (p < 0.0001), Gleason primary grade (p < 0.0001), and serum prostate-specific antigen (p < 0.0001) as factors associated with pelvic LNI. Each of these variables retained independent significance (p < or = 0.0002) in the multivariate model. Patient age (p = 0.12) and history of prior transurethral resection of the prostate (p = 0.36) were not found to correlate with this endpoint. Probability plots provided an estimate of the likelihood for pelvic LNI according to the combination of pretherapy clinical tumor stage, Gleason primary grade, and serum prostate-specific antigen level. CONCLUSION: Clinical tumor stage as determined by digital rectal examination, Gleason primary grade of the diagnostic biopsy specimen, and pretherapy serum prostate-specific antigen value can be combined to estimate the probability of pelvic LNI for the patient with a new diagnosis of localized CaP. This information may be of value in directing the pretherapy diagnostic evaluation, as an aid in radiation therapy treatment planning, and in the conduct of clinical research efforts.