Evaluation of bladder dose in intensity-modulated radiation therapy of the prostate.

Day-to-day variation in bladder and rectal filling affects prostate location and positioning accuracy. Systems using ultrasonic localization or gold seed placement are most often used to help correct for these changes. At some institutions, patients are instructed to empty their rectum and fill their bladders prior to treatment in an attempt to standardize the prostate location, displace small bowel out of the radiation field, and move some of the bladder wall away from the high-dose area. Although instructed to come to treatment with a full bladder, it is presumed that there is variability in bladder filling each day of treatment, depending on the amount of fluids consumed and time to treatment. We have reviewed daily bladder volumes on a subset of 5 prostate patients, all of them prescribed to receive 7560 cGy in 42 fractions, and have evaluated the dosimetric consequences of bladder volume changes from full to two-third or one-third filling. All of these patients' positions were verified daily with ultrasonic localization. Those measurements have been used to help analyze the actual treated bladder volumes for comparison with the treatment plan. We find that, in general, maximum filling only occurred on the initial simulation/image acquisition day and was typically smaller on all the following treatment days. Based on our dose-volume model, we estimate that average bladder daily doses were 8-50% higher than predicted by the initial intensity-modulation radiation therapy (IMRT) plan.

Radiation therapy with concomitant and adjuvant cisplatin and paclitaxel in high-risk cervical cancer: long-term follow-up.

INTRODUCTION: Chemo-potentiation of radiation improves survival in women with cervical cancer. Our group has previously demonstrated the tolerability of weekly paclitaxel combined with cisplatin during radiation therapy. We sought to determine the efficacy of this regimen in patients with "high risk" cervical cancer, and to determine the short- and long-term toxicity of this approach. METHODS: We prospectively enrolled surgically staged patients with positive peritoneal cytology, resectable nodal metastases, or primary tumor > 6 cm. Patients were treated using external beam radiation with concomitant cisplatin (50 mg/m2) during weeks 1, 4, and 7, and weekly paclitaxel (50 mg/m2), followed by four courses of adjuvant cisplatin (50 mg/m2) and paclitaxel (135 mg/m2). Toxicity, overall, and disease-free survival were evaluated. RESULTS: Twenty-three patients were enrolled, and 21 were evaluable. Patient allotment by FIGO stage was: IB1 - seven, IB2 - five, IIA - two, IIB - four, IIIB - two, IV - three. Twenty patients (95%) completed radiation treatment (median dose to point A was 8278 cGy). Seventeen patients (81%) completed all chemotherapy. At a median follow-up of 58 months the overall survival was 68%. Overall survival for patients with clinical Stage I and II disease was 82% at a median of 64 months. Hematologic toxicity was common but rarely resulted in treatment delays. Late complications requiring intervention (obstruction, fistula, significant lymphocyst) occurred in 11 patients (52%). CONCLUSION: The combination of paclitaxel and cisplatin appears efficacious in "high-risk" cervical cancer patients. Hematologic toxicity was common but tolerable. Long-term survival was common in these patients, however late toxicity was significant. This regimen should be investigated in collaborative phase III trials.

Autologous stem cell transplantation for high-risk Ewing's sarcoma and other pediatric solid tumors.

The prognosis for many pediatric and young adult patients with solid tumors that have metastasized at the time of diagnosis or have relapsed after therapy remains very poor. The steep dose-response curve of many of these tumors to alkylating agents makes myeloablative chemotherapy followed by autologous stem cell transplantation (ASCT) an attractive potential therapy. The role of ASCT for these high-risk patients is yet to be conclusively determined. We have transplanted 36 patients on two consecutive protocols with a variety of histological diagnoses. Overall survival (OS) was 63% (95% CI: 47-79%) at 1 year and 33% (95% CI: 16-50%) at 3 years. Patients with a diagnosis of Ewing's sarcoma (ES) or desmoplastic small round cell tumor (DSRCT) had significantly better survival than those with other diagnoses with estimated 3-year OS of 54% (95% CI: 29-79%) for this group of patients (P = 0.03). There were two transplant-related deaths both attributable to hepatic veno-occlusive disease. Median follow-up among survivors is 3.5 years (range: 0.6-7.9 years). These data justify continued investigation of ASCT as a consolidation therapy in patients with metastatic or relapsed ES and DSRCT.

Preclinical studies targeting normal and leukemic hematopoietic cells with Yttrium-90-labeled anti-CD45 antibody in vitro and in vivo in nude mice.

A study was undertaken to investigate the suitability of using a high affinity (Kd = 1.1 nM) anti-CD45 monoclonal antibody for delivering the high energy beta-particle emitting isotope (90)Y to lymphohematopoietic target cells in vivo. The antibody, AHN-12, recognized the tyrosine phosphatase CD45 expressed on the surface of normal and malignant hematopoietic cells and studies showed that it reacted with both CD45-expressing normal peripheral blood cells and leukemia cells from patients. The antibody was readily labeled with (90)Y using the highly stable chelate 1B4M-DTPA and the radioimmunoconjugate was designated (90)Y-anti-CD45. The agent selectively bound to CD45(+) B cell line Daudi, but not CD45(-) control cells and significantly (p = 0.007) more bound to Daudi tumors growing in athymic nude mice than did a control non-reactive antibody. Moreover, biodistribution data correlated well to an anti-Daudi effect observed against established tumors in nude mice. The effect was dose dependent and irreversible with the best results in mice receiving a single dose of 137 microCi (90)Y-anti-CD45. These mice displayed a significantly (p < 0.0095) better anti-tumor effect than a control (90)Y-labeled antibody and survived over 135 days with no evidence of tumor. Histology studies showed no significant injury to kidney, liver, or small intestine even at 254 microCi, the highest dose tested. Because radiolabeled anti-CD45 antibody can be used to deliver radiation selectively to lymphohematopoietic tissue, these data indicate that this agent may be used to improve treatment of hematopoietic malignancies, particularly leukemia and lymphoma, when combined with hematopoietic stem cell transplantation in a future clinical trial.

In vivo diode dosimetry for routine quality assurance in IMRT.

Due to the complexity of IMRT dosimetry, dose delivery evaluation is generally done using a treatment plan in which the optimized fluence distribution has been transferred to a test phantom for accessibility and simplicity of measurement. The actual patient doses may be reconstructed in vivo through the use of electronic portal imaging devices or films, but the assessment of absolute dose from these measurements is time-consuming and complicated. In our clinic we have instituted the use of routine diode dosimetry for IMRT patients following the same procedure used for standard radiation therapy patients in which each new treatment field is checked at the start of treatment. For standard cases the dose at dmax is calculated as part of the monitor unit calculation. For the IMRT cases, the dose contribution to the dmax depth for each field is taken from the treatment plan. We found that about 90% of the diode measurements agreed to within +/- 10% of the planned doses (45/51 fields) and 63% (32/51 fields) achieved +/- 5% agreement. By using this direct in vivo method to verify the clinical doses delivered, we have been able to make a uniform startup procedure for all patients while simplifying our IMRT QA process.

Outcome of second hematopoietic cell transplantation in Hurler syndrome.

Hurler syndrome (HS) is an autosomal recessive, inherited metabolic storage disorder due to deficiency of lysosomal alpha-L-iduronidase (IDU) enzyme activity. Untreated patients develop progressive mental retardation and multisystem morbidity with a median life expectancy of 5 years. Allogeneic hematopoietic cell transplantation (HCT) can achieve stabilization and even improvement of intellect, with long-term survival. However, children with HS have an increased incidence of graft failure, usually with concomitant autologous marrow reconstitution. Between 1983 and 2000, 71 Hurler children underwent HCT at the University of Minnesota. Of these 71, 19 (27%) experienced graft failure. We report HCT outcomes in all 11 Hurler patients receiving a second HCT at the University of Minnesota. Median age at second HCT was 25 months (range, 16 to 45 months); median time from first HCT was 8 months (range, 4 to 18.5 months). The conditioning regimen consisted of cyclophosphamide/TBI/ATG (n = 8) or busulfan/cyclophosphamide/ATG (n = 3). The source of bone marrow was an unrelated donor in six, matched sibling in four, and mismatched related in one. Five of the 11 grafts were T cell depleted prior to infusion. Overall, 10 of 11 patients showed donor-derived engraftment, of whom three developed grade 3 to 4 acute GVHD. Five of 11 patients are surviving a median of 25 months (range, 2 months to 12 years) with an overall actuarial survival of 50% (95% CI, 27% to 93%) at 4 years. All five show sustained donor engraftment with normalization of IDU activity levels. Three of five evaluable patients demonstrated stabilization of neuropsychological function after second HCT. Currently, allogeneic donor-derived hematopoiesis provides the only chance for long-term survival and improved quality of life in Hurler patients. While graft failure in Hurler patients requires further investigation, a timely second HCT can be well-tolerated and beneficial.

Using a belly board device to reduce the small bowel volume within pelvic radiation fields in women with postoperatively treated cervical carcinoma.

OBJECTIVE: The purpose of this study was to attempt to reduce the small bowel volume in cervical cancer patients undergoing radiation therapy using the belly board device and a four-field technique. METHODS: From 1994 through 1997, twenty-one patients with cervical cancer were referred to the University of Minnesota Medical Center and underwent surgical staging with or without radical hysterectomy followed by postoperative external beam radiotherapy for various indications including positive nodal disease (n = 11), lymph-vascular space invasion (n = 2), poor histology (n = 3), parametrial disease (n = 4), and positive vaginal margin (n = 1). RESULTS: The median age of the 21 patients was 42 years (25-54 years) and a median external beam pelvic radiation dose of 4775 cGy (range, 4200-5075 cGy) was administered. All patients were evaluated for amount of small bowel in the field in both the supine and prone positions, with and without the belly board device (BBD), using a four-field technique. With a full bladder, abdominal radiographs with contrast were obtained to evaluate the volume of small bowel within the radiation fields. In most patients, the BBD was effective at minimizing the amount of small bowel in the lateral fields, whereas a prone position on the treatment table (without the BBD) spared the most small bowel with the AP/PA fields. Therefore over a 2-day cycle, the most small bowel sparing was obtained with the patients treated prone on the BBD for the lateral fields on Day 1 and prone on the table for the AP/PA fields on Day 2. Patients had FIGO stage IB (n = 18), IA2 (n = 1), and IIA (n = 2). The median follow-up was 37 months (24-65 months). No significant acute gastrointestinal or genitourinary toxicity was experienced and no patients have experienced a bowel obstruction to date. CONCLUSIONS: The BBD may offer a means for positioning the mobile small intestine out of the radiation field and improving the tolerance of radiotherapy. The BBD provides a noninvasive technique for reduction of acute and chronic gastrointestinal morbidity.

A phase I study of RSR13, a radiation-enhancing hemoglobin modifier: tolerance of repeated intravenous doses and correlation of pharmacokinetics with pharmacodynamics.

PURPOSE: Preclinical studies indicate that RSR13 oxygenates and radiosensitizes hypoxic solid tumors by decreasing the oxygen (O(2))-binding affinity of hemoglobin (Hb). A Phase I open-label, multicenter dose and frequency escalation study was conducted to assess the safety, tolerance, pharmacokinetics, and pharmacodynamic effect of daily RSR13 administration to cancer patients receiving concurrent palliative radiotherapy (RT). METHODS AND MATERIALS: Eligibility criteria included the following: ECOG performance status < or =2; resting and exercise arterial oxygen saturation (SaO(2)) > or =90%; an indication for palliative RT, 20-40 Gy in 10-15 fractions. RSR13 was administered i.v. via central vein over 60 min immediately before RT. Patients received supplemental O(2) via nasal cannula at 4 L/min during RSR13 infusion and RT. Plasma, red blood cell (RBC), and urine RSR13 concentrations were assayed. The pharmacodynamic effect of RSR13 on Hb-O(2) binding affinity was quantified by multipoint tonometry and expressed as an increase in p50, defined as the partial pressure of O(2) that results in 50% SaO(2). The RSR13 dose in the first cohort was 75 mg/kg once a week for two doses; successive cohorts received higher, more frequent doses up to 100 mg/kg/day for 10 days during RT. RESULTS: Twenty patients were enrolled in the study. Repeated daily doses of RSR13 were generally well tolerated. Two adverse events of note occurred: (1) A patient with pre-existing restrictive lung disease had transient persistent hypoxemia after the sixth RSR13 dose; (2) a patient with a recurrent glioma receiving high-dose corticosteroids had edema after the seventh RSR13 dose, likely due to the daily high-volume fluid infusions. Both patients recovered to baseline status with conservative management. Maximum pharmacodynamic effect occurred at the end of RSR13 infusion and was proportional to the RBC RSR13 concentration. After an RSR13 dose of 100 mg/kg, the peak increase in p50 averaged 8.1 mm Hg, consistent with the targeted physiologic effect, and then diminished with a half-life of approximately 5 h. CONCLUSIONS: RSR13 was well tolerated in daily doses up to 100 mg/kg administered for 10 days during RT. The combined administration of RSR13 with 4 L/min supplemental O(2) yielded pharmacodynamic conditions in which hypoxic tumor radiosensitization can occur. Ongoing Phase II and Phase III studies are evaluating the combination of RT and RSR13 for selected indications, including primary brain tumors, brain metastases, and non-small-cell lung cancer.

Cardiac metastasis of cloacagenic carcinoma of the vagina: a case and review of gynecologic malignancies with cardiac metastasis.

We report of a case of a 44-year-old woman with a vaginal cloacagenic carcinoma who initially presented with a hymenal lesion that metastasized first to the perihilar lymph nodes and then consequently to the right ventricle. The embryological tumor is rare with only a few cases of vaginal or vulvar involvement. We present the first case of cloacagenic cancer of the vagina with metastasis to the heart. The lesion was surgically resected after completion of neoadjuvant therapy. Herein we present this unique case and the clinical manifestations of intracardiac and pericardial lesions from gynecologic malignancies.

Evaluation of eye shields made of tungsten and aluminum in high-energy electron beams.

PURPOSE: To protect the lens and cornea of the eye when treating the eyelid with electrons, we designed a tungsten and aluminum eye shield that protected both the lens and cornea, and also limited the amount of backscatter to the overlying eyelid when using electron beam therapy. METHODS AND MATERIALS: Custom curved tungsten eye shields, 2 mm and 3 mm thick, were placed on Kodak XV film on 8 cm polystyrene and irradiated to evaluate the transmission through the shields. To simulate the thickness of the eyelid and to hold the micro-TLDs, an aquaplast mold was made to match the curvature of the eye shields. Backscatter was measured by placing the micro-TLDs on the beam entrance side to check the dose to the underside of the eyelid. Measurements were done with no aluminum, 0.5, and 1.0 mm of aluminum on top of the tungsten eye shields. The measurements were repeated with 2- and 3-mm flat pieces of lead to determine both the transmission and the backscatter dose for this material. RESULTS: Tungsten proved to be superior to lead for shielding the underlying structures and for reducing backscatter. At 6 MeV, a 3-mm flat slab of tungsten plus 0.5 mm of aluminum, resulted in .042 Gy under the shield when 1.00 Gy is delivered to dmax. At 6 MeV for a 3-mm lead plus 0.5-mm aluminum, .046 Gy was measured beneath the shield, a 9.5% decrease with the tungsten. Backscatter was also decreased from 1.17 to 1.13 Gy, a 4% decrease, when using tungsten plus 0.5 mm of aluminum vs. the same thickness of lead. Measurements using 9 MeV were performed in the same manner. With 3 mm tungsten and 0.5 mm of aluminum, at 3 mm depth the dose was .048 Gy compared to .079 Gy with lead and aluminum (39% decrease). Additionally, the backscatter dose was 3% less using tungsten. Simulating the lens dose 3 mm beyond the shield for the 2-mm and 3-mm custom curved tungsten eye shields plus 0.5 mm of aluminum was .030 and .024 Gy, respectively, using 6 MeV (20% decrease). Using 9-MeV electrons, the dose 3 mm beyond the shield was .048 Gy for the 2-mm shield and .029 Gy for the 3-mm shield (40% decrease). Backscatter was not further decreased using thicker tungsten. With a 6-MeV beam, using the 2-mm or 3-mm custom tungsten eye shields plus 0.5 mm of aluminum, the backscattered doses were 1.03 and 1.02 Gy, respectively. The backscatter dose with 9 MeV was 1.06 Gy using the 2-mm custom shield plus 0.5 mm aluminum and 1.05 Gy with a 3-mm custom shield plus 0.5 mm aluminum. There was very little difference in backscatter dosage under the eyelid using 0.5 vs. 1.0 mm of aluminum. Therefore, for patient comfort, we recommend using 0.5 mm of aluminum. CONCLUSIONS: Tungsten is superior to lead as a material for eye shields due to its higher density and lower atomic number (Z). Using 6- and 9-MeV electrons, tungsten provides the necessary protection for the lens and cornea of the eye and decreases the amount of backscatter to the eyelid above the shield.

Unrelated donor bone marrow transplantation for children with acute leukemia.

PURPOSE: To test the use of unrelated donor bone marrow transplantation (URD BMT) to cure children with high-risk acute leukemias. PATIENTS AND METHODS: Between June 1985 and December 1994, 50 children with acute leukemia (15 acute myelogenous leukemia [AML], 35 acute lymphoblastic leukemia [ALL]; 22 greater than second complete remission [CR]) received BMT from a URD at the University of Minnesota. Ages ranged from 0.9 to 17.5 years (median, 8.8). Median follow-up is 2.1 years (range, 1 to 7.3). Thirty patients (60%) received bone marrow fully matched at HLA-A,B and DRB1; 20 (40%) received bone marrow with a major or minor mismatch at a single HLA-A or B locus. RESULTS: The median time to neutrophil engraftment was day 24 (range, 14 to 42 days) in those receiving matched and day 25 (range, 15 to 32 days) in those receiving mismatched marrow (P = .35). The incidence of grades III to IV graft-versus-host disease (GVHD) was 23% (95% confidence interval [CI], 7% to 39%) in matched and 32% (95% CI, 8% to 52%) in HLA-mismatched patients (P = .57). The incidence of chronic GVHD was 50% (95% CI, 28% to 72%) in matched and 57% (95% CI, 23% to 91%) in mismatched patients (P = .80). Disease-free survival for patients with ALL is 37% (95% CI, 21% to 53%) at 1 year and 30% (95% CI, 15% to 46%) at 2 years; for patients with AML, 53% (95% CI, 28% to 78%) at 1 year and 33% (95% CI, 6% to 60%) at 2 years. CONCLUSION: URD BMT is an effective treatment for children with poor-prognosis acute leukemia and should be considered for all high-risk patients. Early referral of patients is strongly recommended.

Autologous bone marrow transplantation in acute myeloid leukemia: the University of Minnesota experience.

PURPOSE: To report the outcome of autologous bone marrow transplantation for patients with acute myeloid leukemia (AML) in first or greater complete remission (CR) treated by autologous bone marrow transplantation using two different preparatory regimens. METHODS AND MATERIALS: Between September 1986 and August 1993, 75 patients with AML ranging in age from 6 months to 58 years underwent autologous bone marrow transplantation using previously harvested and frozen unpurged (n = 6) or 4-hydroperoxycyclophosphamide purged marrows (n = 69). Patients were in first CR (n = 44) or beyond first CR (n = 31). The preparative regimen consisted of 120 mg/kg of cyclophosphamide (CY) and 1320 cGy total body irradiation (TBI) in eight fractions over 4 days (CY/TBI) in 29 patients; and 16 mg/kg of Busulfan (BU) and 200 mg/kg of CY (BU/CY) in 46 patients. Thirty-five of these 75 patients (18 CY/TBI and 17 BU/CY) were part of a randomized trial comparing the two preparative regimens. RESULTS: At 2 years, overall survival and disease-free survival (DFS) were 49% [95% confidence interval (C.I.) 37-61%] and 43% (95% C.I. 32-55%), respectively. Patients in first CR had a significantly better outcome than patients beyond first CR with an estimated 2-year DFS of 59% (95% C.I. 44-74%) vs. 21% (95% C.I. 5-36%, log-rank p = 0.0001), respectively. For patients conditioned with CY/TBI, the estimated 2-year DFS was 52% compared to 39% for BU/CY (log-rank p = 0.35). Estimated 2-year relapse rates were 44% vs. 56% (log-rank p = 0.40), respectively. For patients in first CR, no differences in DFS were observed between the two regimens (2-year estimates 69% vs. 55% log-rank p = 0.52). Patients beyond first CR had a significantly improved DFS with the CY/TBI regimen (2-year estimates of 38% vs. 7%, log-rank p = 0.04). No differences were found between the two regimens in terms of time to WBC engraftment, absolute neutrophil count of > 500, incidence of bacteremias, or median time to hospital discharge. Interstitial pneumonitis developed in two patients (one BU/CY, one CY/TBI) and venoocclusive disease developed in seven BU/CY patients (Fishers exact test p = 0.04). CONCLUSIONS: For patients beyond first CR, the CY/TBI regiment provided a better outcome, with a significantly better disease-free survival and less venoocclusive disease. For patients in first CR, no significant difference between the two regimens was found. The high relapse rate, especially for patients with advanced disease, emphasizes the need for early transplantation and for new strategies to improve outcome.

Malignant neoplasms following bone marrow transplantation.

We undertook an analysis of 2,150 recipients of bone marrow transplant (BMT) at the University of Minnesota to determine the incidence of post-BMT malignant neoplasms (MNs). Fifty-one patients developed 53 MNs, compared with 4.3 expected from general population rates (standardized incidence ratio [SIR], 11.6, 95% confidence interval [CI], 8.2-14.5). These included 22 occurrences of B-cell lymphoproliferative disorder (BLPD), 17 solid nonhematopoietic tumors, 10 myelodysplastic syndromes (MDS), 1 acute myelogenous leukemia (AML), 2 non-Hodgkin's lymphoma (NHL), and 1 Hodgkin's disease (HD). The estimated actuarial incidence of any post-BMT malignancy was 9.9% +/- 2.3% at 13 years posttransplant. The cumulative probability of BLPD plateaued at 1.6% +/- 0.3% by 4 years from transplant and factors independently associated with increased risk included in vitro T-cell depletion of marrow (relative risk (RR) = 11.9, P < .001), HLA mismatch (RR = 8.9, P < .001), use of antithymocyte globulin (ATG) for graft versus host disease (GVHD) prophylaxis (RR = 5.9, P < .001) or in the preparative regimen (RR = 3.1, P = .03) and primary immunodeficiency (RR = 2.5, P = .06). The cumulative probability of developing solid malignancy was 5.6% +/- 2.2% at 13 years from BMT. Malignant melanomas were the most common (SIR, 10.3, 95% CI 1.9 to 25.4). The actuarial incidence of MDS/AML plateaued at 2.1% +/- 0.8% at 9 years and was seen most often in older patients receiving autologous peripheral blood stem cells for HD or NHL. These data document that BMT recipients are at an increased risk of later malignancy, which may add significant morbidity and mortality to the transplant process. Methods for screening and identification of individuals at increased risk need to be addressed in future studies.

Related donor marrow transplant for chronic myeloid leukemia: patient characteristics predictive of outcome.

Pre-transplant characteristics of 137 consecutive patients (including 103 patients with one or more features suggesting advanced disease) undergoing related donor marrow transplant for chronic myeloid leukemia (CML) were analyzed to determine their association with outcome. Multivariate analysis identified increased recipient age (relative risk (RR) for patients over 30 years of relapse or death 2.37; P = 0.004), and longer interval between diagnosis and transplant (RR 1.20; P = 0.0001) as significant adverse influences on disease-free survival (DFS). The 5-year DFS for patients transplanted within 1 year of diagnosis (¿early transplant', n = 71) was significantly higher (51%) than that for patients transplanted beyond 1 year from diagnosis ('delayed transplant', n = 55) (34%; log rank P = 0.02). For early transplant patients, poor prognostic features included myelofibrosis (RR 3.53; P = 0.018), splenomegaly (RR 2.22; P = 0.029) and the use of a female donor (RR 3.16; P = 0.002). The 5-year DFS for patients transplanted within 1 year of diagnosis and without signs of advanced disease was 67%. The presence of increasing numbers of features suggesting acceleration prior to transplant had a cumulative adverse influence of DFS. The risk of relapse (5 year estimate 20%) was also independently and significantly increased in association with a longer interval from diagnosis to transplant (P = 0.012). Early transplant is an important influence on DFS and relapse after related donor transplant therapy for CML, although additional patient characteristics influencing outcome can be identified and may have cumulative adverse effects.

Soft tissue sarcomas: preoperative versus postoperative radiotherapy.

External beam radiation may be given either before or after excision of a primary soft tissue sarcoma. This study was undertaken to determine whether or not the timing of radiotherapy was associated with any difference in either local control, survival, or incidence of complications. The files of 112 patients with a primary, nonmetastatic, extremity soft tissue sarcoma, treated with limb salvage surgery and irradiation were evaluated. Data regarding tumor stage, grade, site, surgical margin, dosage and timing of radiotherapy, treatment complications, disease relapse, and relapse-free survival (RFS) were analyzed. Kaplan-Meier lifetable analysis was used to determine survival estimates. There was no significant difference in the 5-year RFS between patients receiving radiotherapy (RT) preoperatively versus postoperatively; 56 +/- 15% and 67 +/- 12% (P = 0.12, Mantel-Cox), respectively. There was no significant difference in the overall survival between patients receiving RT preoperatively versus postoperatively; 75 +/- 15% and 79 +/- 11% (P = 0.94), respectively. Actuarial local control at 5 years for preoperative versus postoperative RT patients was not statistically different; 83 +/- 12% versus 91 +/- 8% (P = 0.41), respectively. Wound complications were more frequent in preoperative RT patients (31%) compared to postoperative RT patients (8%) (P = 0.0014, chi-square). Preoperative irradiation was not associated with any benefit in terms of relapse-free survival, overall survival or actuarial local control in this series. A higher incidence of major wound complications was found among patients treated with preoperative irradiation. We recommend that patients with a resectable extremity soft tissue sarcoma be treated with postoperative irradiation, reserving preoperative irradiation for those situations in which either the tumor is initially thought to be unresectable or the original tumor boundaries are obscured.

Evaluation of dose variation during total skin electron irradiation using thermoluminescent dosimeters.

PURPOSE: To determine acceptable dose variation using thermoluminescent dosimeters (TLD) in the treatment of Mycosis Fungoides with total skin electron beam (TSEB) irradiation. METHODS AND MATERIALS: From 1983 to 1993, 22 patients were treated with total skin electron beam therapy in the standing position. A six-field technique was used to deliver 2 Gy in two days, treating 4 days per week, to a total dose of 35 to 40 Gy using a degraded 9 MeV electron beam. Thermoluminescent dosimeters were placed on several locations of the body and the results recorded. The variations in these readings were analyzed to determine normal dose variation for various body locations during TSEB. RESULTS: The dose to flat surfaces of the body was essentially the same as the dose to the prescription point. The dose to tangential surfaces was within +/- 10% of the prescription dose, but the readings showed much more variation (up to 24%). Thin areas of the body showed large deviations from the prescription dose along with a large amount of variation in the readings (up to 22%). Special areas of the body, such as the perineum and eyelid, showed large deviations from the prescription dose with very large (up to 40%) variations in the readings. DISCUSSION: The TLD results of this study will be used as a quality assurance check for all new patients treated with TSEB. The results of the TLDs will be compared with this baseline study to determine if the delivered dose is within acceptable ranges. If the TLD results fall outside the acceptable limits established above, then the patient position can be modified or the technique itself evaluated.

Management of pelvic venous stenosis with intravascular stainless steel stents.

Patients with gynecologic malignancies may develop stenosis of the large pelvic veins as a result of their disease or its treatment. The percutaneous insertion of a stainless steel vascular stent is a novel approach to the management of an extrinsically compressed vein. The objective of this study was to review the results of treating lower extremity edema secondary to a pelvic venous stenosis through the percutaneous insertion of a stainless steel vascular stent. A retrospective review was performed on gynecologic oncology patients who presented with an edematous lower extremity and underwent an evaluation to diagnose proximal venous stenosis. The evaluation included sonography, venography, and balloon angioplasty prior to the percutaneous insertion of a stainless steel vascular stent. If a venous thrombosis was documented, thrombolysis with urokinase was performed prior to evaluation for venous stenosis. Records were reviewed for the etiology of the venous stenosis, the location and type of stent inserted, and the ability of the stent to maintain patency and provide symptomatic relief. Patency was evaluated at 1-week and then at 1-, 3-, and 6-month intervals. The probability of vascular stent patency was calculated using life table analysis. Ten patients with cervical (n = 4), corpus (n = 3), ovarian (n = 1), vulvar (n = 1), and vaginal (n = 1) cancer had one or more vascular stents inserted for the treatment of a stenosed pelvic vein. The etiologies of venous stenosis were radiation fibrosis and surgery (n = 5), postoperative fibrosis (n = 3), and metastatic tumor (n = 2). The stented vessels were the left common (n = 5) or left external (n = 4) iliac veins, the right common (n = 1) or right external (n = 3) iliac veins, and the right common femoral vein (n = 1). The median follow-up was 21 months. All patients had subjective resolution of their edematous extremity while the stents were patent. The interval probability of patency of stented veins was greater than 85% at each evaluation interval. Patency was 100% for patients beyond 6 months of follow-up. There were no major complications. The percutaneous intravascular insertion of a stainless steel stent was safe and subjectively effective in the management of venous stenosis associated with a gynecologic cancer. A prospective trial with objective endpoints may be warranted.

Design specifications for a treatment stand used for total body photon irradiation with patients in a standing position.

One total body photon irradiation technique used to treat patients employs a standing treatment position and a horizontally directed high-energy photon field. This standing technique presents special problems, including keeping the patient immobile during treatment and offering protection from injury if the patient develops weakness or loss of consciousness due to either medication (anxiolytics, narcotics, or antiemetics) or other causes. In this article we describe a treatment stand designed to manage these problems and use effectively total body photon irradiation. This stand has been used successfully in our clinic at the University of Minnesota for several years and has met or exceeded the original design expectations.

Randomized comparison of cyclophosphamide-total body irradiation versus busulfan-cyclophosphamide conditioning in autologous bone marrow transplantation for acute myeloid leukemia.

PURPOSE: This prospective trial of autologous bone marrow transplantation for acute myeloid leukemia was undertaken to compare the outcome using two different preparative regimens. METHODS AND MATERIALS: Between October 1987 and April 1993, 35 patients with acute myeloid leukemia in first (n = 12) or greater (n = 23) remission were stratified by remission status and randomized to undergo 4-hydroperoxycyclophosphamide purged autologous bone marrow transplantation after either cyclophosphamide (120 mg/kg) and total body irradiation (1320 Gy in eight fractions over 4 days) (CY/TBI), or busulfan (16 mg/kg) and cyclophosphamide (200 mg/kg) (BU/CY) conditioning. RESULTS: At 2 years, overall survival and disease-free survival were 39% (95% confidence intervals (CI) 22-57%) and 36% (95% CI 19-52%), respectively. Patients in first complete remission had a significantly better outcome with a 2-year disease free survival of 57% (95% CI 28-86%) compared to others at 24% (95% CI 6-43%, log rank p = 0.048). For patients conditioned with CY/TBI, the estimated 2-year disease-free survival was 50% compared to 24% for patients conditioned with BU/CY (log rank p = 0.12). Estimated 2-year relapse rates were 43% vs. 70% (log rank p = 0.17), respectively. For patients in first complete remission no differences in disease-free survival (2-year estimates 67% vs. 50%, log rank p = 0.69), between the two regimens were observed. For patients in greater than first complete remission there was a trend towards improved disease-free survival in the CY/TBI arm (2-year estimates 42% vs. 9%, log rank p = 0.06). There were no differences in time to white blood cell count (WBC) engraftment, absolute neutrophil count of > 500, incidence of bacteremias, or median time to hospital discharge between the two regimens. Acute toxicities were similar. Interstitial pneumonitis developed in two patients (one on each arm), while veno occlusive disease developed in three BU/CY patients, but none of the CY/TBI patients (log rank p = 0.07). CONCLUSIONS: Cyclophosphamide-total body irradiation provided an equivalent or better outcome to BU/CY, particularly in advanced patients, and should remain the standard by which new regimens are judged. The high relapse rate with both regimens, especially patients who were in greater than in first complete remission, emphasizes the need for early transplant and for new strategies to improve outcome.

Erythropoietin increases hemoglobin during radiation therapy for cervical cancer.

PURPOSE: Anemia during radiation therapy independently predicts poor outcome in patients with cervical cancer. Despite a randomized trial demonstrating red cell transfusions improve local control and survival, many patients are not transfused due to toxicity concerns. This study evaluates the efficacy of recombinant human erythropoietin (r-HuEPO) in reversing anemia in patients undergoing radiation therapy. METHODS AND MATERIALS: Twenty patients with criteria of anemia (Hgb < 12.5 g/dL) and surgically staged cervical cancer FIGO stages IB (n = 7), IIA (n = 1), IIB (n = 9), and IIIB (n = 3), ranging in ages from 23-75 years (median 43), were included in this Phase I/II study. Fifteen were treated with r-HuEPO (200 U/kg/day) and ferrous sulfate 5-10 days prior to initiation of external beam radiation therapy, continuing until Hgb was < or = 14 g/dL or completion of radiation therapy. Five patients were treated with ferrous sulfate alone. An additional 61 historical controls meeting eligibility criteria were analyzed. All received external beam radiation therapy and two intracavitary cesium applications. Cisplatinum chemotherapy (20 mg/m2/week) was given as a radiosensitizer in 14 r-HuEPO patients, 4 concurrent controls, and 17 historical controls. RESULTS: A marked reticulocytosis was seen in the r-HuEPO group, but not the study controls. In the r-HuEPO group, the mean +/- SD serum Hgb rose + 30% over the course of radiation therapy from a baseline of 10.3 +/- 1.04 g/dL to 13.2 +/- 1.7 g/dL. Average increase in Hgb was 0.5 g/dL per week. Average Hgb during RT was 13.4 g/dL. In study and historical controls, mean initial Hgb levels were 10.7 +/- 1.04 g/dL and 11.1 +/- 1.3g/dL, respectively, remaining unchanged over the course of radiation therapy. Average Hgb levels during radiation therapy were 11.1 g/dL in study controls and 11.4 g/dL in historical controls, significantly lower than r-HuEPO patients (p = 0.0001). Erythropoietin was well tolerated. There were no significant differences in white blood counts (p = 0.6) or platelet counts (p = 0.4) between r-HuEPO patients and both control groups. No patients had blood pressure changes during r-HuEPO therapy. The only possible side effect was deep venous thrombosis, occurring in two patients who were withdrawn from r-HuEPO therapy. Two additional patients developed deep venous thrombosis 9 and 10 days after radiation therapy and r-HuEPO were completed. CONCLUSION: Erythropoietin appears to be both safe and effective at raising Hgb levels in anemic cervical cancer patients receiving radiation therapy and chemotherapy.