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.

Long-term follow-up of radical retropubic prostatectomy for prostate cancer.

OBJECTIVES: The ultimate outcome of patients after radical prostatectomy is often predicted from statistical projections of short-term follow-up. Only actual long-term follow-up can demonstrate true outcome. METHODS: One hundred thirty-one patients underwent retropubic prostatectomy for clinically organ confined prostate cancer and have been followed for a minimum of 22.5 years. Preoperatively, all but 12 had clinically palpable cancer. RESULTS: Overall survival in these patients was similar to an age-matched population, with 65% alive at 15 years, and 23% alive at 25 years. Thirty-seven percent of the patients recurred and 24% of all the patients died of prostate cancer. For patients with pathologically organ confined disease, 27% recurred, while those with extension outside the gland or positive nodes had an 83% recurrence rate. Although, the median time to recurrence was 7 years, recurrences occurred at a steady-state throughout the length of follow-up. Patients with higher grade tumors, even if organ confined, were significantly more likely to recur. CONCLUSIONS: In a cohort of patients treated with radical prostatectomy for predominantly palpable disease, long-term follow-up (79% deceased) reveals that 37% will recur and 24% will die of prostate cancer. Almost half the recurrences occurred after 10 years, indicating that reports with shorter follow-up will underestimate the recurrence rate.

A prospective, randomized, double-blind, placebo-controlled study of orbital radiotherapy for Graves' ophthalmopathy.

CONTEXT: Although widely used for more than 85 years, the efficacy of radiotherapy for Graves' ophthalmopathy (GO) has not been established convincingly. OBJECTIVE: To evaluate the efficacy of radiotherapy for GO. DESIGN: Prospective, randomized, internally controlled, double-blind clinical trial in a tertiary care academic medical center. PARTICIPANTS: The patients were ethnically diverse males and females over age 30 seen in a referral practice. The patients had moderate, symptomatic Graves' ophthalmopathy (mean clinical activity score, 6.2) but no optic neuropathy, diabetes, recent steroid treatment, previous decompression, or muscle surgery. Forty-two of 53 consecutive patients were enrolled after giving informed consent and fulfilling study entry criteria. Eleven eligible patients declined to participate because of inconvenience, desire for alternative therapy, or concern about radiation. INTERVENTION: One randomly selected orbit was treated with 20 Gy of external beam therapy; sham therapy was given to the other side. Six months later, the therapies were reversed. MAIN OUTCOME MEASURES: Every 3 months for 1 year, we measured the volume of extraocular muscle and fat, proptosis, range of extraocular muscle motion, area of diplopia fields, and lid fissure width. Effective treatment for GO will modify one or more of these parameters. RESULTS: No clinically or statistically significant difference between the treated and untreated orbit was observed in any of the main outcome measures at 6 months. At 12 months, muscle volume and proptosis improved slightly more in the orbit that was treated first. CONCLUSIONS: In this group of patients, representative of those for whom radiotherapy is frequently recommended, we were unable to demonstrate any beneficial therapeutic effect. The slight improvement noted in both orbits at 12 months may be the result of natural remission or of radiotherapy, but the changes are of marginal clinical significance.

The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma, II: characteristics of patients enrolled and not enrolled. COMS Report No. 17.

OBJECTIVES: To describe characteristics of patients evaluated for the Collaborative Ocular Melanoma Study (COMS) randomized clinical trial of iodine 125 brachytherapy for choroidal melanoma by enrollment status, and to compare characteristics of patients enrolled with those of patients with tumors of eligible size who did not enroll in order to assess the extent to which findings from the clinical trial can be generalized to future patients. METHODS: For all patients diagnosed with choroidal melanoma and evaluated for the clinical trial at COMS centers from November 1986 through July 31, 1998, selected data were transmitted to the COMS Coordinating Center, Baltimore, Md, where they were integrated and analyzed. Data included ophthalmic and medical history, examination findings, and visual acuity measurements recorded prior to enrollment; standardized A- and B-scan echographic examination findings; and wide-angle fundus photographs and fluorescein angiograms. RESULTS: Of 8712 patients with choroidal melanoma, 5046 had tumors of eligible size; of these, 2882 (57%) were eligible for enrollment, and 1317 (46% of eligible patients, 26% of patients with tumors of eligible size) enrolled. Most differences between eligible and ineligible patients corresponded to eligibility and exclusion criteria. However, ineligible patients were older and had thicker tumors than eligible patients. Eligible patients who enrolled were slightly older and had larger tumors than those who did not enroll. Nearly half (48%) of enrolled patients had choroidal melanoma with the apex located temporal to the fovea, compared with 40% of eligible patients not enrolled and 29% of ineligible patients. CONCLUSIONS: This trial was designed to yield internally valid treatment comparisons through random assignment to treatment at time of enrollment. Information from this and other studies document that enrolled patients were similar to other patients with choroidal melanoma who were treated with 125I brachytherapy. These findings support the external validity of the trial and applicability of treatment findings to all patients who meet the criteria used to judge eligibility for the trial.

The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma, III: initial mortality findings. COMS Report No. 18.

OBJECTIVES: To report initial mortality findings from the Collaborative Ocular Melanoma Study (COMS) randomized clinical trial of iodine 125 brachytherapy vs enucleation for treatment of choroidal melanoma. METHODS: Patients were evaluated for eligibility at 43 participating clinical centers in the United States and Canada. Eligible consenting patients were assigned randomly at the time of enrollment to enucleation or 125I brachytherapy. Patients were examined at specified intervals after enrollment for data collection purposes. Findings presented herein are based on data received by September 30, 2000. Data for each patient were analyzed with the treatment group to which the patient was assigned randomly at the time of enrollment. RESULTS: During the 11(1/2)-year accrual period, 1317 patients enrolled; 660 were assigned randomly to enucleation and 657 to 125I brachytherapy. Only 2 patients in the enucleation arm were found to have been misdiagnosed when histopathology was reviewed centrally. All but 17 patients (1.3%) received the assigned treatment. Adherence to the brachytherapy protocol was excellent, with 91% of patients treated per protocol. Based on time since enrollment, 1072 patients (81%) had been followed for mortality for 5 years and 416 (32%) for 10 years. A total of 364 patients had died: 188 (28%) of 660 patients in the enucleation arm and 176 (27%) of 657 patients in the brachytherapy arm. The unadjusted estimated 5-year survival rates were 81% and 82%, respectively; there was no clinically or statistically significant difference in survival rates overall (P =.48, log-rank test). The adjusted estimated risk ratio for 125I brachytherapy vs enucleation was 0.99 (95% confidence interval [CI], 0.80-1.22). Five-year rates of death with histopathologically confirmed melanoma metastasis were 11% and 9% following enucleation and brachytherapy, respectively; after adjustment, the estimated risk ratio was 0.91 (95% CI, 0.66-1.24). CONCLUSIONS: Mortality rates following 125I brachytherapy did not differ from mortality rates following enucleation for up to 12 years after treatment of patients with choroidal melanoma who enrolled in this COMS trial. The power of the study was sufficient to indicate that neither treatment is likely to increase or decrease mortality rates by as much as 25% relative to the other.

Collaborative ocular melanoma study (COMS) randomized trial of I-125 brachytherapy for medium choroidal melanoma. I. Visual acuity after 3 years COMS report no. 16.

OBJECTIVE: To report visual acuity during the first three years after iodine 125 (I(125)) brachytherapy for medium-sized choroidal melanoma and to identify important baseline and treatment factors associated with posttreatment visual acuity in a group of patients who were treated and observed prospectively as part of a large, randomized clinical trial. DESIGN: Observational case series within a randomized, multicenter study. PARTICIPANTS: Patients enrolled in the Collaborative Ocular Melanoma Study randomized trial of I(125) brachytherapy versus enucleation had choroidal melanoma of at least 2.5 mm but no more than 10.0 mm in apical height, and no more than 16.0 mm in largest basal dimension. One thousand three hundred seventeen patients enrolled from February 1987 through July 1998; 657 patients were assigned to I(125) brachytherapy. Visual acuity data for 623 patients who received I(125) brachytherapy as randomly assigned and who have been observed for at least 1 year were analyzed for this report. METHODS: Under study protocol, an ophthalmic evaluation, including best-corrected visual acuity measurement of each eye, was performed at baseline, every 6 months thereafter for 5 years, and once yearly thereafter. Two poor vision outcomes, visual acuity of 20/200 or worse that was confirmed at the next follow-up examination and loss of six lines or more of visual acuity from baseline that was confirmed at the next follow-up examination, were analyzed to identify baseline and treatment characteristics that were associated with posttreatment visual acuity. RESULTS: At baseline, median visual acuity in the eye with choroidal melanoma was 20/32, with 70% of eyes having 20/40 or better and 10% of eyes having 20/200 or worse visual acuity. Three years after I(125) brachytherapy, median visual acuity was 20/125, with 34% having 20/40 or better and 45% having 20/200 or worse visual acuity, including eyes that were enucleated within 3 years of treatment. Life-table estimates of percentages of patients who lost six or more lines of visual acuity from baseline, a quadrupling of the minimum angle of resolution, with this finding confirmed at the next 6-month follow-up examination, were 18% by 1 year, 34% by 2 years, and 49% by 3 years after treatment. Life-table estimates of percentages of patients with baseline visual acuity better than 20/200 whose visual acuity decreased to 20/200 or worse, confirmed at the next follow-up examination, were 17% by 1 year, 33% by 2 years, and 43% by 3 years after treatment. As soon as a poor vision outcome was observed, improvement of visual acuity to a level that no longer met the definition for a poor vision outcome was rare. Greater baseline tumor apical height and shorter distance between the tumor and the foveal avascular zone (FAZ) were the factors most strongly associated with loss of six or more lines of visual acuity after treatment. These two factors and baseline visual acuity also were strongly associated with visual acuity 20/200 or worse after treatment. Patient history of diabetes, presence of tumor-associated retinal detachment, and tumors that were not dome shaped also were associated with greater risk for both of the poor vision outcomes. CONCLUSIONS: Forty-three percent to 49% of treated eyes had substantial impairment in visual acuity by 3 years after I(125) brachytherapy, defined as a loss of six or more lines of visual acuity from the pretreatment level (49% of eyes) or visual acuity of 20/200 or worse (43% of eyes) that was confirmed at the next 6-month examination. Patients with a history of diabetes and patients whose eyes had thicker tumors, tumors close to or beneath the FAZ, tumor-associated retinal detachment, or tumors that were not dome shaped were those most likely to have a poor visual acuity outcome within 3 years after I(125) brachytherapy.

Preliminary results of three-dimensional conformal radiotherapy as salvage treatment for a rising prostate-specific antigen level postprostatectomy.

The purpose of this study is to determine the effectiveness of three-dimensional conformal radiotherapy delivered to the fossa of the prostate and seminal vesicles as salvage treatment for a prostate-specific antigen (PSA) level that becomes undetectable and subsequently begins to rise postprostatectomy. Between August 1994 and December 1997, 14 patients with prostate cancer whose PSA became undetectable after a radical prostatectomy subsequently developed a rising PSA, had no evidence of metastatic disease, and were treated with three-dimensional conformal radiotherapy at the University of California, Davis Cancer Center. Gleason scores ranged from 4 to 9 (29% of the patients had a Gleason score > or =8). The seminal vesicles were involved in three (21%) cases and the surgical margins were involved in seven (50%) cases. PSA values ranged from 0.3 to 6.7 (median: 0.7) ng/ml at the start of radiotherapy. Daily 1.8-2.0-Gy fractions were administered to total doses at isocenter ranging from 60.6 to 74.2 (median: 64.9) Gy. None of the patients received hormonal therapy. Follow-up ranged from 13 to 36 (median: 22) months. For patients with a preradiotherapy Hybritech PSA < or = 1.0 ng/ml, the Kaplan-Meier estimate of the 2-year biochemical disease-free survival rate is 67%, whereas for patients with a preradiotherapy PSA more than 1.0 ng/ml, the 2-year biochemical disease-free survival rate is 20% (p = 0.17). Because of the small number of patients, the difference is not statistically significant. A positive microscopic margin had no impact on the results obtained with salvage radiotherapy. Only one of four patients with a poorly differentiated adenocarcinoma remains free of disease. Acute toxicity was mild and did not require medication (Radiation Therapy Oncology Group grade I): four (29%) patients experienced genitourinary morbidity and three (21%) patients experienced gastrointestinal morbidity. With regard to late toxicity, one (7%) patient developed a urethral stricture requiring dilatation (Radiation Therapy Oncology Group grade III). All five patients who were potent at the start of radiotherapy remain potent. Medicare's median reimbursement for salvage three-dimensional conformal radiotherapy in this study ($7,512 in 1999 U.S. dollars) is equivalent to its reimbursement for a 17-month course of goserelin hormonal therapy. Patients with prostate cancer who develop an undetectable followed by a rising PSA postprostatectomy should be referred for salvage treatment with radiotherapy when their PSA is still less than or equal to 1.0 ng/ml. Salvage three-dimensional conformal radiotherapy is well tolerated and is less expensive than more than 17 months of goserelin.

Acute toxicity of three-dimensional conformal radiotherapy in prostate cancer patients eligible for implant monotherapy.

PURPOSE: To assess the acute toxicity of three-dimensional conformal radiotherapy (3D-CRT) in prostate cancer patients eligible for implant monotherapy. METHODS AND MATERIALS: Between December 1991 and June 1998, 198 prostate cancer patients were treated with 3D-CRT at the University of California Davis Medical Center. Fifty-two of these patients had a prostate-specific antigen (PSA) level /= Grade 3, e.g., hourly nocturia, gross hematuria, diarrhea requiring parenteral support, narcotics for pain control, or catheterization for acute urinary retention, was observed. CONCLUSION: Although relatively high doses of radiation are delivered to prostate cancers with 3D-CRT compared with conventional radiotherapy, 3D-CRT is surprisingly well-tolerated. No patients in the cohort eligible for implant monotherapy experienced acute toxicity >/= Grade 3.

Primary central nervous system non-Hodgkin's lymphoma (PCNSL): survival advantages with combined initial therapy? A final report of the North Central Cancer Treatment Group (NCCTG) Study 86-72-52.

PURPOSE: We herein report updated survival and toxicity data on the entire cohort of 53 eligible patients treated on North Central Cancer Treatment Group (NCCTG) protocol 86-72-52, which is now closed. METHODS AND MATERIALS: An initial report was published in this journal in 1995. No substantive changes in the conclusions of that report were identified in this analysis. Median survival was 9.6 months for the entire cohort; median survival for the 20 patients who completed the prescribed protocol treatment was 20.7 months. The hematologic and non-hematologic toxicity distributions are virtually the same as those reported in the original paper. RESULTS: Results are given for the entire group and for subsets defined by age < or = 60 versus > 60 years, and < 70 versus > or = 70 years of age. CONCLUSIONS: No significant differences were observed in any of the outcome variables by age group. There was, however, a nonsignificant suggestion of poorer outcome in those who were > 60 years of age.

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.

Ten-year outcomes for pathologic node-positive patients treated in RTOG 75-06.

PURPOSE: This study was conducted to see what fraction of prostate cancer patients with biopsy-proven nodes are free of cancer 10 years after radiation treatment. METHODS AND MATERIALS: RTOG protocol #75-06 included 90 patients with biopsy-proven pelvic nodal involvement treated with radiation. They have been continuously follow-up since treatment. When feasible, current prostate-specific antigen (PSA) levels have been solicited from patients clinically cancer-free (no evidence of disease, NED) at 10 years, to confirm cure. RESULTS: The 10-year survival was 29%, the 10-year clinical NED survival 7%. PSA levels were obtained in 2 of 5 10-year clinical NED patients, they were both less than 0.8 ng/ml. The 2 proven cures were both clinical stage T-3, Gleason Score 6 and 8, and had 2 and 1 positive nodes, respectively. Multivariate analysis showed Gleason sum was significantly associated with clinical survival without disease. CONCLUSION: A small fraction of node-positive patients are cured at 10-year follow-up by radiation therapy (2 of 90 with PSA +3 of 90 by clinical endpoints). Innovative treatment programs should be directed at node-positive patients in an effort to improve the fraction cured.

The role of stereotactic radiosurgery in the treatment of malignant skull base tumors.

PURPOSE: To determine the efficacy and toxicity of stereotactic radiosurgery in the treatment of malignant skull base tumors. METHODS AND MATERIALS: Thirty-two patients with 35 newly diagnosed or recurrent malignant skull base tumors < or = 33.5 cm3 were treated using the Leksell Gamma unit. Tumor histologies included: adenoid cystic carcinoma [12], basal cell carcinoma [1], chondrosarcoma [1], chordoma [8], nasopharyngeal carcinoma [3], osteogenic sarcoma [2], and squamous cell carcinoma [8]. RESULTS: After a median follow-up of 2.3 years, 83% +/- 15% (+/-95% confidence interval) of patients experienced a symptomatic response to treatment. Local control at the skull base was 95 +/- 9% at 2 years and 78 +/- 23% at 3 years. Local-regional control above the clavicles was 75 +/- 15% at 1 year and 51 +/- 20% at 2 years. Overall and cause specific survival were identical, 82 +/- 13% at 1 year, 76 +/- 14% at 2 years, and 72 +/- 16% at 3 years. One patient developed a radiation-induced optic neuropathy 12 months after radiosurgery. CONCLUSION: Stereotactic radiosurgery using the Leksell Gamma Unit can provide durable tumor control and symptomatic relief with acceptable toxicity in the majority of patients with malignant tumors 4 cm or less in size involving the skull base. Further evaluation of more patients with longer follow-up is warranted.

Histopathologic study of eyes after iodine I 125 episcleral plaque irradiation for uveal melanoma.

OBJECTIVES: To describe the histopathologic findings attributable to irradiation in eyes with uveal malignant melanoma treated with iodine I 125 brachytherapy and to compare these findings with those reviewed in a previous study that compared histopathologic findings in eyes enucleated after proton beam teletherapy with those seen in eyes in a nonirradiated control group. METHODS: The slides from 22 eyes with uveal melanoma that had undergone enucleation after the administration of 125I brachytherapy were studied. The histopathologic features of the tumor and the retina were graded. Results were compared with findings from a previously reported group of 47 proton beam-treated eyes and its control group. RESULTS: Patient age, time between irradiation and enucleation, and ciliary body involvement were similar for the 125I brachytherapy-treated group and the proton beam-treated group and its control group. This allows comparison of the histopathologic findings. Comparing the 125I brachytherapy- and proton beam-treated groups, most histopathologic features were similar with nominally statistically significant differences only for cell type, number of mitotic figures, and fibrous metaplasia of the retinal pigment epithelium adjacent to the tumor. CONCLUSIONS: Irradiation of uveal melanoma induces changes in the tumor and in the surrounding retina. Brachytherapy and charged particle therapy are the 2 principal methods of irradiation. This study demonstrates that similar changes are produced by 125I plaque irradiation and proton beam irradiation.

Localization of the prostatic apex for radiotherapy treatment planning using urethroscopy.

PURPOSE: To assess the ability of computed tomography (CT) scans and retrograde urethrograms to accurately define the prostatic apex in the craniocaudad dimension, using urethroscopy as a reference. METHODS AND MATERIALS: Plain film radiographs of the pelvis were obtained in 15 patients with early-stage adenocarcinoma of the prostate, with the tip of a urethroscope held in place at the external sphincter, which most closely approximates the prostatic apex. The scope was then withdrawn, and a retrograde urethrogram was performed. Immediately afterwards, a CT scan of the pelvis was obtained. Because differential filling of the bladder and rectum affects the position of the prostatic apex, patients voided prior to rather than in between the three consecutive studies. RESULTS: The urethroscopy-defined prostatic apex was located 4 +/- 8 mm (mean +/- SD) superior to the CT-defined apex, 13 +/- 3 mm (mean +/- SD) superior to the urethrogram tip and 30 +/- 7 mm (mean +/- SD) superior to the ischial tuberosities. There was significant interobserver variability in the location of the prostatic apex as determined by CT scans. Placement of the inferior border of the radiation portals at the ischial tuberosities would have resulted in irradiation of > or = 20 mm bulbar urethra, as defined by the dye column of the retrograde urethrogram, in 6 out of 15 (40%) of the patients and irradiation of < 10 mm bulbar urethra in 2 out of 15 (13%) of the patients. CONCLUSION: Because the prostate blends inferiorly with the urogenital diaphragm, CT scans do not allow one to precisely localize the prostatic apex. Due to anatomic variability, the ischial tuberosities do not allow one to accurately localize the prostatic apex. Retrograde urethrograms provide helpful supplemental information regarding the position of the prostatic apex for radiotherapy treatment planning.

Influence of an oligodendroglial component on the survival of patients with anaplastic astrocytomas: a report of Radiation Therapy Oncology Group 83-02.

PURPOSE: Seven percent of patients with high grade gliomas enrolled in RTOG 83-02 had mixed astrocytoma/oligodenroglial elements on central pathology review. It has often been assumed that the most aggressive histologic component of a tumor determines biologic behavior; however in this trial, the survival of patients who had mixed glioblastomas/oligodenrogliomas was significantly longer than that of patients with pure glioblastomas (GBM). We therefore evaluated the effect of an oligodendroglial component on the survival of patients who had anaplastic astrocytomas (AAF) treated in the same trial. METHODS AND MATERIALS: One hundred nine patients who had AAF and 24 patients with mixed AAF/oligodendrogliomas (AAF/OL) were enrolled in a Phase I/II trial of randomized dose-escalation hyperfractioned radiotherapy plus BCNU. AAF/OL patients were older and more likely to have had more aggressive surgery than AAF patients. Other pretreatment characteristics were balanced between groups, as was assigned treatment. RESULTS: The median survival time for AAF was 3.0 years versus 7.3 years for AAF/OL (p = 0.019). In a multivariate analysis, adjusting for extent of surgical resection and age, an oligodendroglial component was an independent prognostic factor for survival. CONCLUSION: The results support the concept that AAFs with an oligodendroglial component have a better prognosis than pure AAF tumors, similar to the effect seen among patients with glioblastoma multiforme tumors. This better survival outcome should be taken into consideration in the design and stratification of future trials. Additionally, in contrast to patients with GBMs, patients who have AAF/OL have the potential for prolonged survival; therefore, late sequelae of treatment (both radiation and chemotherapy) must be weighed more heavily in the benefits to risks analysis.

Randomized trial of radiation therapy (RT) plus dibromodulcitol (DBD) versus RT plus BCNU in high grade astrocytoma.

PURPOSE: We performed a randomized trial to compare survival distributions and toxicity of radiation therapy (RT) and DBD with RT and BCNU in patients with high-grade astrocytoma. METHODS: A total of 238 patients with supratentorial grade 3 and grade 4 astrocytoma were studied. Patients were stratified by age, extent of surgery, tumor grade, and performance score and randomly assigned to receive RT 55-60 Gy and either DBD, 200 mg/m2 orally on Days 1-10 every five weeks or BCNU, 200 mg/m2 intravenously every seven weeks. Median age was 60 years; 62% were 55 years or older. Eighty-three percent had subtotal resection, 58% had grade 4 tumors, and 83% had performance scores of 0-2. RESULTS: Survival distributions for all patients in the two arms were similar, with median survival of 41 weeks in each arm. Time to progression distributions were virtually identical, with medians of 22 weeks. BCNU produced significantly greater hematologic toxicity; median leukocyte and platelet nadirs on the first cycle were 3.6 vs. 4.7 (P = 0.0001) and 117 vs. 162 (P < 0.0001), and overall platelet nadirs were 80.5 vs. 114 (P = 0.0019). Non-hematologic toxicities were also significantly greater with BCNU, including nausea (57% vs. 31%; P < 0.0001) and vomiting (45% vs. 17%; P < 0.0001). CONCLUSION: This trial found no evidence of differences in treatment efficacy when either DBD or BCNU is combined with radiation therapy for patients with high-grade astrocytoma.

Stereotactic radiosurgery for glomus jugulare tumors: a preliminary report.

PURPOSE: This study was conducted to evaluate the toxicity and efficacy of stereotactic radiosurgery treatment of glomus jugulare tumors. METHODS AND MATERIALS: Between March 1990 and January 1995, nine patients underwent stereotactic radiosurgery with the Leksell Gamma Knife Unit for glomus jugulare tumors. Previous treatment had failed in four patients. The seven female and two male patients had a median age of 67 years. RESULTS: The median time from stereotactic radiosurgery to the most recent clinical follow-up was 20 months (range 7-65 months). Subjectively, 7 of 9 patients noted a decrease in the intensity of their symptoms. Objectively, 8 of 9 tumors remained stable in size by serial magnetic resonance imaging scans and one was smaller. There was no acute or chronic toxicity. CONCLUSION: This early experience suggests that stereotactic radiosurgery is a promising treatment for glomus jugulare tumors.

Primary testicular seminoma: prognostic significance of nuclear DNA ploidy pattern.

OBJECTIVE: To evaluate the impact of nuclear DNA content on outcome of patients with testicular seminoma. METHODS: Formalin-fixed paraffin-embedded blocks taken from 111 patients with primary testicular seminoma were studied by flow cytometry for nuclear DNA content. The results of ploidy status were correlated with histopathologic features, tumor progression and patients' survival. RESULTS: 48% of the tumors were DNA diploid and 52% were DNA aneuploid. None of the patients with DNA diploid seminoma had an advanced stage seminoma at the time of diagnosis. Progression after therapy or cancer-related death occurred only in patients who had DNA aneuploid testicular tumors. CONCLUSIONS: Nuclear DNA ploidy pattern provides important prognostic information for patients with testicular seminoma.