Conformal high dose rate iridium-192 boost brachytherapy in locally advanced prostate cancer: superior prostate-specific antigen response compared with external beam treatment.

PURPOSE: Prostate-specific antigen levels are used to judge disease control of prostate cancer. No published data attest to the greater ability of conformal brachytherapy to control disease compared with conventional radiation at a single institution. This report compares the biochemical response rates in patients with stages T2b to T3c prostate cancer treated with conformal brachytherapy boost and external beam radiation with the rates in patients treated with conventional external radiation alone. MATERIALS AND METHODS: From November 1991 through November 1995, 58 patients received 45.6 Gy pelvic external irradiation and three high dose rate iridium-192 conformal boost implants of 5.5 to 6.5 Gy each. They were compared with 278 similarly staged patients treated from January 1987 through December 1991 with external beam radiation to prostate-only fields (median dose 66.6 Gy). No patient received androgen deprivation. Patient outcome was analyzed for biochemical control. Biochemical failure was defined as a prostate-specific antigen level > 1.5 ng/mL and rising on two consecutive values. If serial posttreatment prostate-specific antigen levels were showing a continuous downward trend, failure was not scored. RESULTS: Median follow-up was 43 months for the conventionally treated group and 26 months for the brachytherapy boost group. The median pretreatment prostate-specific antigen level was 14.3 ng/mL for the external-beam-radiation-alone group and 14.0 ng/mL for the brachytherapy boost group. The median Gleason scores were 6 and 7, respectively, for the two groups. The biochemical control rate was significantly higher in the brachytherapy boost treatment group. Three-year actuarial biochemical control rates were 85% versus 52% for the conformally and conventionally treated patients, respectively. In a multivariate analysis, the use of conformal brachytherapy boost and pretreatment prostate-specific antigen level were significant prognostic determinants of biochemical control. The 3-year actuarial rates of biochemical control for conformally versus conventionally treated patients, respectively, were 83% versus 72% for a pretreatment prostate-specific antigen level of 4.1 to 10.0 ng/mL, 85% versus 47% for a prostate-specific antigen level of 10.1 to 20.0 ng/mL, and 89% versus 29% for prostate-specific antigen > 20 ng/mL. When the analysis was limited to patients in both groups with a minimum 12-month follow-up, the brachytherapy boost group continued to show a higher biochemical control rate compared with the conventional radiation group (3-year actuarial rates of 86% vs 53%). DISCUSSION: These preliminary results show a significant improvement in the biochemical response rate with conformal boost brachytherapy and pelvic external radiation compared with conventional radiation alone. These results, coupled with our previously reported acceptable toxicity rates, support the use of this technique.

A prospective randomized trial evaluating colloid versus crystalloid resuscitation in the treatment of the vascular leak syndrome associated with interleukin-2 therapy.

Interleukin-2 (IL-2)-based therapy induces a vascular leak syndrome (VLS), manifested by hypotension, tachycardia, and oliguria, as is also seen with septic shock. The optimal method for treating such VLS is not known. A prospective randomized trial was undertaken to compare crystalloid and colloid fluid resuscitation for patients receiving bolus IL-2-based therapy for metastatic cancer. All patients received maintenance crystalloid fluid administration and were randomized to receive crystalloid (0.9% normal saline) or colloid (5% human serum albumin) fluid boluses to maintain acceptable vital signs and urine output. Patients refractory to fluid boluses were given dopamine for oliguria and/or phenylephrine for hypotension. Of 107 patients who completed one cycle of therapy on study, 76 completed a full treatment course (two cycles) on study. The total number of saline and albumin fluid boluses given were 9.5 +/- 0.9 versus 7.7 +/- 0.7 (p = 0.36, n = 107) for the first cycle and 19.2 +/- 1.8 versus 16.1 +/- 1.6 (p = 0.33, n = 76) for a complete course, respectively. Although patients receiving saline boluses had significantly more oliguria during a course of therapy, weight gain, number of IL-2 doses, tachycardia, hypotension, vasopressor use, hospital stay, and clinical response rates did not significantly differ between arms. Changes in hematocrit, hemoglobin, protein, albumin, blood urea nitrogen (BUN), and creatinine were analyzed, and patients receiving crystalloid showed greater decreases in albumin (p < 0.0001) and total protein (p < 0.05) as expected. A 40-fold greater cost associated with albumin suggested that crystalloid resuscitation be used to treat the VLS associated with IL-2 therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

A pilot study of the combination of interleukin-2-based immunotherapy and radiation therapy.

A clinical trial was undertaken to evaluate the feasibility of combining radiation therapy and immunotherapy. Twenty-eight patients with metastatic cancer were treated with rapid fractionation radiation up to 2,000 cGy, followed within 24 h by a course of interleukin 2 (IL-2) at 720,000 IU/kg or tumor-infiltrating lymphocytes (TILs) and IL-2 at 720,000 IU/kg. All patients tolerated treatment without any apparent increase in toxicity referable to the irradiation. Four patients had significant shrinkage of tumor at the irradiated site. Only two patients showed significant tumor shrinkage both inside and outside of the irradiated field. While rapid fractionation radiation can be safely administered in combination with immunotherapy, we observed no apparent synergy in antitumor effect in this small number of patients.

Immunotherapy with interleukin-2 and alpha-interferon in patients with metastatic renal cell cancer with in situ primary cancers: a pilot study.

A total of 12 patients with stage 4 renal cell carcinoma and primary renal tumors in situ was entered into a pilot study using treatment with interleukin-2 and alpha-interferon followed by radical nephrectomy. Of the patients 11 underwent nephrectomy after an initial course of immunotherapy. Ten patients were able to receive a second course of immunotherapy given after nephrectomy. One patient achieved a complete response of lung and mediastinal metastases without any change in the primary renal tumor but after nephrectomy the patient remained in complete remission for greater than 11 months. A total of 3 patients achieved a partial response at some extrarenal sites but they had progression elsewhere. Toxicity was similar to previous experience with this immunotherapy regimen. Therefore, we demonstrated that metastatic tumor regression is possible with primary renal tumors in situ and that aggressive interleukin-2-based immunotherapy can be tolerated in the presence of a large renal tumor.

Dissipation of some organochlorine insecticides in cropped and uncropped soil.

Dissipation of four organochlorine insecticides, viz. aldrin, HCH, chlordane and heptachlor was studied in a sandy loam soil with and without crops during a period of 10 cropping seasons. Dissipation of all chemicals followed first-order kinetics (r(2)=0.537 - 0.976) with almost similar persistence in cropped and uncropped soils for all the insecticides. The average half-lives, (t(1/2) values) for total residues of aldrin, HCH, chlordane, and heptachlor in cropped treatments were 80.7, 58.8, 93.2, and 110 days. Their respective values in fallow plots were 78.4, 83.8, 154, and 116 days. None of the parent compounds or their isomers could be detected below the 20 cm depth at the termination of the experiment. Highest residue concentrations were observed in the surface 10 cm layer in fallow plots, but in the deeper (10-20 cm) layer in cropped plots. Analysis of plants and grains showed significant residues of all the chemicals. Degradation of these compounds in cropped and uncropped plots is discussed with regard to their volatilization, microbial degradation, leaching, and plant uptake.

Dissipation of s-triazines and thiocarbamates from soil as related to soil moisture content.

Half-lives (t1/2) of two soil incorporated s-triazines (atrazine and prometon) and two thiocarbamate (EPTC and triallate) herbicides were determined in relation to soil moisture content in two California soils. Treated soils were incubated at three moisture levels in aerated glass vials at 25 +/- 1 degree C and were analyzed at 0, 7, 16, 28, 56 and 112 day intervals. Loss of herbicides in all treatments followed first-order kinetics. The t1/2-values of all herbicides decreased with increasing soil moisture and followed an empirical equation, t1/2 = aM(-b) (where t1/2 is half-life; M the moisture content; and a and b are constants). Soil moisture had a greater effect on carbamates than on s-triazines . Prometon exhibited the longest half-life in both soils, whereas EPTC was least persistent in one soil and atrazine in another. The t1/2-values for atrazine, prometon, EPTC, and triallate with medium moisture levels and 10 microg/g concentration were 34.6, 43.2, 25.4 and 38.1 days in sandy loam and 26.5, 44.4, 44.1 and 25.9 days in loamy sand, respectively. Disappearance of 50% of the applied concentrations of most of the herbicide-soil combinations (except EPTC and triallate in one soil) took longer for lower initial concentrations (1 microg/g) than for higher concentrations (10 microg/g).

Surgical treatment of localized renal cell carcinoma in von Hippel-Lindau's disease.

From 1981 to 1986, 10 patients with von Hippel-Lindau's disease underwent an operation for bilateral nonmetastatic renal cell carcinoma. Of the patients 9 underwent unilateral partial nephrectomy and contralateral radical nephrectomy, and 1 underwent bilateral nephrectomy with subsequent hemodialysis and cadaver renal transplantation. Pathologically, the tumor was stage I in 9 patients and stage III in 1. Currently, 8 patients are alive after partial nephrectomy (5 to 56 months) with good renal function (mean serum creatinine 2.0 mg. per dl.) and no evidence of malignancy; 1 of these patients underwent excision of a cerebral metastasis 2 years after partial nephrectomy. One patient is alive on dialysis after removal of the renal remnant for local tumor recurrence. The patient who underwent transplantation is free of tumor with a well functioning allograft. The distinctive features of renal cell carcinoma in von Hippel-Lindau's disease that influence the management of these patients are reviewed.

Diverticulum of the female urethral roof managed endoscopically.

We report a rare case of a diverticulum located along and draining into the roof of the urethra in a woman. This diverticulum was managed successfully endoscopically with a pediatric resectoscope. The pathophysiology of this unusual lesion is discussed, as is the rationale for endoscopic management.

Persistence of parathion and its oxidation to paraoxon on the soil surface as related to worker reentry into treated crops.

Soil and dust samples from beneath citrus trees contained relatively high concentrations of paraoxon and parathion for at least 45 days after parathion was applied at normal rates. These data indicate that parathion dripping on dry soil from sprayed crops, or sprayed directly on the soil surface, can persist for long periods and be oxidized to the highly toxic paraoxon. The residue concentrations are much higher on the loose dust particles than in the bulk soil. The data indicate that the soil or grove floor should be considered as a possible contributing source of toxicant along with foliage, or dust on foliage, to workers reentering treated fields. In any event, the data confirmed the high rates of oxidation of parathion to paraoxon on particulate matter, whether on foliage (SPEAR et al., 1974) or at the soil surface. The particulate matter appears to contribute to the accumulation of paraoxon, either by enhancing oxidation of parathion to paraoxon or by decreasing dissipation of paraoxon.