Xenon: effect on radiation sensitivity of HeLa cells.

HeLa cells, plated onto plastic petri dishes, were exposed to various atmospheres composed of air and carbon dioxide; helium, oxygen, and carbon dioxide; and xenon, oxygen, and carbon dioxide in a pressure vessel. Survival curves with x-rays, 280 kilovolts (peak), show that air and helium have the same effect, but that xenon potentiates x-irradiation to the extent that the dose to produce a given level of survival with xenon is 0.58 of the dose required with air.

Estimation of tumor growth fraction in murine tumors by the primer-available DNA-dependent DNA polymerase assay.

The tumor growth fraction measured by the percentage labeled mitoses method has been determined in transplantable solid and ascites murine tumors, the latter being measured at different times after transplantation. These values were compared to an in vitro, autoradiographic assay that determines the fraction of cells in a given population (primer-available DNA-dependent DNA polymerase index) that have both nuclear DNA-dependent DNA polymerase and DNA capable of acting as primer-template. It appears that almost all cells with a short G1 phase duration (less than 19 hr) that are within the proliferative cycle are primer-available DNA-dependent DNA polymerase positive. The results of the comparison indicate that the primer-available DNA-dependent DNA polymerase index estimation of growth fraction is very nearly identical to the growth fraction measured by the percentage labeled mitoses method.

Synergistic antitumor activity of cisplatin and interleukin 1 in sensitive and resistant solid tumors.

The antitumor activity of cis-diamminedichloroplatinum(II) (cP) and human recombinant interleukin-1 alpha (IL-1 alpha) was studied in RIF-1 and SC VII solid tumor models and in a cP-resistant subline of RIF-1 designated RIF-R1cP. In RIF-1 tumors, clonogenic cell survival after cP plus IL-1 alpha combinations was highly schedule and IL-1 alpha dose dependent. More than additive clonogenic cell kill was seen when cP was given 6 h before, but not 8 h before or at 2-6 h after IL-1 alpha. Time course studies indicated that maximal clonogenic cell killing was achieved within 4-6 h after the cP plus IL-1 alpha combination, with little or no recovery for up to 24 h. In vivo dose-response studies indicated that cP plus IL-1 alpha combinations induced more clonogenic cell kill than cP alone in all three tumor models, and analysis by the median effect principle indicated highly synergistic antitumor activity. Dexamethasone but not indomethacin inhibited the synergistic interaction. IL-1 alpha had no effect on the cytotoxicity of cP in SCC VII cells in vitro, and neither in vitro hypoxia nor in vivo ischemia, induced by clamping tumor blood supply, significantly affected cP clonogenic cell killing. Increased clonogenic cell killing was seen, however, after removal of the clamp, implicating reperfusion events, such as oxyradical stress, as a potential mechanism for increased cP cytotoxicity in SCC VII solid tumors. The data from our model systems provide a rationale for additional work to define the mechanisms of the synergistic antitumor activity of the cP plus IL-1 alpha combination and indicate that IL-1 alpha might be a useful adjunct to increase the clinical efficacy of cP-containing strategies for both sensitive and cP-resistant cancers.

A quantitative assessment of standard vs. customized midline shield construction for invasive cervical carcinoma.

PURPOSE: An individualized midline shield (MLS) has been advocated for delivering homogeneous radiotherapy for patients with invasive cervical carcinoma. Yet, many radiation oncologists continue to employ a standard block. In the latter instance, any deviation of the cranial-caudal central axis of he tandem from the patient's midline could result in dose inhomogeneity to tumor. A retrospective review of a single university medical center's experience with constructing the MLS was initiated to determine the outcome of using a standard block vs. a customized block that conforms to the "Point A" isodose line. In addition, participating radiation oncologists associated with the Gynecologic Oncology Group (GOG) were polled to assess if there exists a consensus regarding midline block utilization in the management of cervical cancer patients which could be compared to the institutional study. METHODS AND MATERIALS: From January 1, 1990 through December 31, 1992, 32 patients with invasive cervical carcinoma who underwent low dose rate brachytherapy at a single institution were identified. Patients were grouped as having a standard block (18 cases), customized block (5 cases), or no block (9 cases). The "Point A" isodose distribution from the implant was superimposed onto the whole pelvic simulation film and quantitatively compared to the actual or a hypothetical standard block outlined on the same radiograph. In September of 1995, 56 member and affiliated institutions in the GOG were surveyed concerning their use of a MLS, and the results were tabulated in December of 1995. RESULTS: Approximately 72% of all cases (23 out of 32) at the single institution had tandem deviation ranging from 0-230 with a median of 50. This translated into a median percent overdosage to "Point A" Right of 15% and "Point A" Left of 12.5%. Although overall survival and incidence of chronic complications have not been affected by type of shielding, patient follow-up is limited with a median of 17.7 months (range: 4.2-58.9 months). Of the 56 surveyed radiation facilities in the GOG, 34 (61%) responded. One center was subsequently excluded as it performs only high dose rate brachytherapy. Of the evaluable respondents, 88% (29 out of 33) utilize a MLS in treating their patients with invasive cervical carcinoma. Of the latter group, 76% (22 out of 29), 21% (6 out of 29), and 3% (1 out of 29) employ a standard block, customized block, and a "step-wedge," respectively. For those using a standard block, 77% (17 out of 22) align the central cranial-caudal axis of the MLS along the corresponding midplane of the patient's pelvis on an anteroposterior radiograph rather than along the superior-inferior central axis of the tandem. CONCLUSIONS: This study suggests that the use of a standard midline shield could result in potential tumor dose inhomogeneity and should be avoided. A national survey of major academic centers further suggests that the majority of these facilities also utilize a rectangular central block that is not positioned with respect to possible tandem deviation. Further investigation concerning the techniques of midline shield construction should be considered.

Analysis of treatment results in 36 children with retinoblastoma treated by scleral plaque irradiation.

This is a retrospective analysis of treatment results in 36 patients with retinoblastoma treated by the Radiation Oncology Department of Hahnemann University Hospital and the Division of Oncology of Wills Eye Hospital between January 1975 and December 1986. There were 14 females and 22 males; ages ranged from 2 months to 4 1/2 years of age at presentation. Leukocoria was the most common clinical sign of presentation. These patients were treated with external beam radiation therapy in combination with scleral plaque irradiation in 20 patients and with scleral plaque alone in 16 patients. Cobalt-60, Iodine-125, Iridium-192, and Ruthenium-106, scleral plaques were used. The dose delivered to the mid plane of the globe was 40 Gy and the scleral dose adjacent to the plaque was in the range of 180-200 Gy. The treatment was successful in 30 of 36 patients. Complications of radiation therapy were minimal in patients treated by scleral plaque alone. The advantages of this treatment modality are discussed.

External beam radiation for retinoblastoma: results, patterns of failure, and a proposal for treatment guidelines.

PURPOSE: To analyze treatment results and patterns of failure following external beam radiation for retinoblastoma and propose treatment guidelines according to specific clinical variables. METHODS AND MATERIALS: We analyzed 27 patients (34 eyes) with retinoblastoma who received external beam radiation as initial treatment at Hahnemann University Hospital from October 1980 to December 1991 and have been followed for at least 1 year. Of the 34 eyes, 14 were Groups I-II (Reese-Ellsworth classification), 7 were Group III, and 13 were Groups IV-V. Doses ranged from 34.5-49.5 Gy (mean 44.3 Gy, median 45 Gy) in 1.5-2.0 Gy fractions generally delivered through anterior and lateral wedged pair fields. RESULTS: At a mean follow up of 35.2 months (range 12-93 months), local tumor control was obtained in 44% (15 out of 34) of eyes with external beam radiation alone. Salvage therapy (plaque brachytherapy, cryotherapy, and/or photocoagulation) controlled an additional 10 eyes (29.5%), so that overall ocular survival has been 73.5%. Local tumor control with external beam radiotherapy alone was obtained in 78.5% (11 out of 14) of eyes in Groups I-II, but in only 20% (4 out of 20) of eyes in Groups III-V. A total of 67 existing tumors were identified prior to treatment in the 34 treated eyes and local control with external beam radiation alone was obtained in 87% (46 out of 53) of tumors measuring 15 mm or less and in 50% (7 out of 14) of tumors measuring more than 15 mm. When analyzing patterns of failure in the 19 eyes that relapsed, a total of 28 failure sites were identified and consisted of progression of vitreous seeds in seven instances (25% of failure sites) recurrences from previously existing tumors in 10 instances (36% of failure sites) and development of new tumors in previously uninvolved retina in 11 instances (39% of failure sites). CONCLUSIONS: 1) We find that external beam radiation to a dose of 45 Gy in fractions of 1.5 to 2.0 Gy provides adequate tumor control in retinoblastoma eyes Groups I-II (Reese-Ellsworth classification) or tumors measuring 15 mm in diameter or less. Eyes in more advanced group staging or containing tumors larger than the 15 mm seem to require higher radiation doses. We propose treatment guidelines for external beam radiation of retinoblastoma that specifically take into account the important clinical variables of tumor stage and patient age. 2) External beam radiation does not prevent the appearance of new tumors in clinically uninvolved retina. Therefore, the traditional belief that external beam radiation can treat the retina "prophylactically" should be seriously questioned. Due to this finding and their significant less morbidity, focal treatment modalities (plaque brachytherapy, photocoagulation, and/or cryotherapy), when clinically feasible, should be considered the treatment of choice for intraocular retinoblastoma. External beam radiation should be considered only when focal treatment modalities are not clinically indicated.

The treatment of primary intraocular malignancy.

This paper will summarize much of the information derived in an association between The Department of Radiation Oncology of Hahnemann University Hospital and the Oncology Service of Wills Eye Hospital of Thomas Jefferson University, a collaborative effort for the treatment of primary intraocular malignancies that has spanned the last dozen years. In that time we have treated malignant intraocular melanoma by radioactive eyeplaque brachytherapy and have begun to develop a similar program for treatment of recurring retinoblastoma. These experiences will be described.

Dose determination in high dose-rate brachytherapy.

Although high dose-rate brachytherapy with a single, rapidly moving radiation source is becoming a common treatment modality, a suitable formalism for determination of the dose delivered by a moving radiation source has not yet been developed. At present, brachytherapy software simulates high dose-rate treatments using only a series of stationary sources, and consequently fails to account for the dose component delivered while the source is in motion. We now describe a practical model for determination of the true, total dose administered. The algorithm calculates both the dose delivered while the source is in motion within and outside of the implanted volume (dynamic component), and the dose delivered while the source is stationary at a series of fixed dwell points. It is shown that the dynamic dose element cannot be ignored because it always increases the dose at the prescription points and, in addition, distorts the dose distribution within and outside of the irradiated volume. Failure to account for the dynamic dose component results in dosimetric errors that range from significant (> 10%) to negligible (< 1%), depending on the prescribed dose, source activity, and source speed as defined by the implant geometry.

Optimization of high dose-rate cervix brachytherapy; Part I: Dose distribution.

Computer controlled high dose-rate (HDR) brachytherapy afterloading machines are equipped with a single, miniaturized, high activity Ir-192 source that can be rapidly moved in fine increments among several channels. Consequently, by appropriate programming of source dwell positions and times, the dose distribution can be optimized as desired. We have explored the optimization potential of this new technology for two applications: (a) cervix brachytherapy, and (b) transvaginal irradiation. Cervix brachytherapy with a gynecologic ring applicator was simulated by 48 sources of relative activities ranging from 0.17 to 1.00 that were equally distributed between the tandem and the ring. The results confirmed that the optimized distribution of physical doses are superior to those achievable with standard brachytherapy sources and applicators. For example, with five-point optimization, the relative dose-rate in the rectum was only 47% of that in point A; for standard application the dose rate was 47% higher. For transvaginal application 27 sources of relative activities between 0.07-0.79 were placed in the ring and a single source of unit strength in the tandem. Using dose distribution homogeneity as an optimization criterion, the results (+/- 2.5%) were again superior to those obtained for commonly used double ovoid (+/- 15%), linear cylinder (+/- 27%), or a "T" source (31%).

Computer controlled stereotaxic radiotherapy system.

A computer-controlled stereotaxic radiotherapy system based on a low-frequency magnetic field technology integrated with a single fixation point stereotaxic guide has been designed and instituted. The magnetic field, generated in space by a special field source located in the accelerator gantry, is digitized in real time by a field sensor that is six degree-of-freedom measurement device. As this sensor is an integral part of the patient stereotaxic halo, the patient position (x, y, z) and orientation (azimuth, elevation, roll) within the accelerator frame of reference are always known. Six parameters--three coordinates and three Euler space angles--are continuously transmitted to a computer where they are analyzed and compared with the stereotaxic parameters of the target point. Hence, the system facilitates rapid and accurate patient set-up for stereotaxic treatment as well as monitoring of patient during the subsequent irradiation session. The stereotaxic system has been developed to promote the integration of diagnostic and therapeutic procedures, with the specific aim of integrating CT and/or MR aided tumor localization and long term (4- to 7-week) fractionated radiotherapy of small intracranial and ocular lesions.

Preliminary report of toxicity following 3D radiation therapy for prostate cancer on 3DOG/RTOG 9406.

PURPOSE: A prospective Phase I dose escalation study was conducted to determine the maximally-tolerated radiation dose in men treated with three-dimensional conformal radiation therapy (3D CRT) for localized prostate cancer. This is a preliminary report of toxicity encountered on the 3DOG/RTOG 9406 study. METHODS AND MATERIALS: Each participating institution was required to implement data exchange with the RTOG 3D quality assurance (QA) center at Washington University in St. Louis. 3D CRT capabilities were strictly defined within the study protocol. Patients were registered according to three stratification groups: Group 1 patients had clinically organ-confined disease (T1,2) with a calculated risk of seminal vesicle invasion of < 15%. Group 2 patients had clinical T1,2 disease with risk of SV invasion > or = 15%. Group 3 (G3) patients had clinical local extension of tumor beyond the prostate capsule (T3). All patients were treated with 3D techniques with minimum doses prescribed to the planning target volume (PTV). The PTV margins were 5-10 mm around the prostate for patients in Group 1 and 5-10 mm around the prostate and SV for Group 2. After 55.8 Gy, the PTV was reduced in Group 2 patients to 5-10 mm around the prostate only. Minimum prescription dose began at 68.4 Gy (level I) and was escalated to 73.8 Gy (level II) and subsequently to 79.2 Gy (level III). This report describes the acute and late toxicity encountered in Group 1 and 2 patients treated to the first two study dose levels. Data from RTOG 7506 and 7706 allowed calculation of the expected probability of observing a > or = grade 3 late effect more than 120 days after the start of treatment. RTOG toxicity scores were used. RESULTS: Between August 23, 1994 and July 2, 1997, 304 Group 1 and 2 cases were registered; 288 cases were analyzable for toxicity. Acute toxicity was low, with 53-54% of Group 1 patients having either no or grade 1 toxicity at dose levels I and II, respectively. Sixty-two percent of Group 2 patients had either none or grade 1 toxicity at either dose level. Few patients (0-3%) experienced a grade 3 acute bowel or bladder toxicity, and there were no grade 4 or 5 toxicities. Late toxicity was very low in all patient groups. The majority (81-85%) had either no or mild grade 1 late toxicity at dose level I and II, respectively. A single late grade 3 bladder toxicity in a Group 2 patient treated to dose level II was recorded. There were no grade 4 or 5 late effects in any patient. Compared to historical RTOG controls (studies 7506, 7706) at dose level I, no grade 3 or greater late effects were observed in Group 1 and Group 2 patients when 9.1 and 4.8 events were expected (p = 0.003 and p = 0.028), respectively. At dose level II, there were no grade 3 or greater toxicities in Group 1 patients and a single grade 3 toxicity in a Group 2 patient when 12.1 and 13.0 were expected (p = 0.0005 and p = 0.0003), respectively. Multivariate analysis demonstrated that the relative risk of developing acute bladder toxicity was 2.13 if the percentage of the bladder receiving > or = 65 Gy was more than 30% (p = 0.013) and 2.01 if patients received neoadjuvant hormonal therapy (p = 0.018). The relative risk of developing late bladder complications also increased as the percentage of the bladder receiving > or = 65 Gy increased (p = 0.026). Unexpectedly, there was a lower risk of late bladder complications as the mean dose to the bladder and prescription dose level increased. This probably reflects improvement in conformal techniques as the study matured. There was a 2.1 relative risk of developing a late bowel complication if the total rectal volume on the planning CT scan exceeded 100 cc (p = 0.019). CONCLUSION: Tolerance to high-dose 3D CRT has been better than expected in this dose escalation trial for Stage T1,2 prostate cancer compared to low-dose RTOG historical experience. With strict quality assurance standards and review, 3D CRT can be safely studied in a co

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.

Biodistribution and pharmacokinetics of S-35-labeled 5-thio-D-glucose in hamsters bearing pancreatic tumors.

5-thio-D-glucose (5-TDG) exerts profound effects on rapidly metabolizing tissues. We have used liquid scintillation counting to study the tissue distribution and pharmacokinetics of S-35-labeled 5-TDG in hamster models of pancreatic tumors. In the normal hamster, initial uptake of S-35 activity into kidney, liver, and blood was high, but rapidly decreased with time. The pancreatic uptake (% dose/g) never exceeded 0.75%. This level occurred only at the earliest times after administration. Uptake in all three tumor models exceeded that in pancreatic tissue within 15 min of injection. The highest tumor-to-pancreas ratio was seen in the duct-tumor model, which also exhibited the most favorable tumor-to-tissue ratio when compared with kidney, liver and muscle. Favorable ratios were most pronounced at 6 and 24 hr after injection. These studies provide impetus for the use of 5-TDG as a model compound for the synthesis of potentially useful agents for clinical detection of pancreatic tumors.

Local carboplatin and radiation therapy in the treatment of murine transgenic retinoblastoma.

BACKGROUND: Combined modality therapy in the treatment of retinoblastoma may decrease treatment-related morbidity and second tumor-associated mortality, while maintaining excellent tumor control rates. OBJECTIVE: To evaluate tumor control and potential synergy between intravitreally delivered carboplatin and external beam radiation therapy (EBRT), using a transgenic murine model of spontaneous heritable retinoblastoma. METHODS: Sixty-six mouse eyes from 4-week-old transgenic mice positive for the simian virus 40 large T antigen were evaluated. Thirty-three mice were treated with 5 intravitreal injections of carboplatin (ranging from 0.1-4.0 micrograms) combined with concurrent bilateral EBRT (ranging from 10-30 Gy) delivered in twice daily 5-Gy fractions. All eyes were followed up for treatment complications. Twelve weeks following final treatment, all eyes were enucleated, serial histologic sections obtained, and the eyes examined for the presence of retinoblastoma. RESULTS: No eye treated with 0.1 microgram of carboplatin and EBRT exhibited tumor control. Three (75%) of 4 mice receiving 1.0 microgram of carboplatin combined with 10-Gy EBRT had complete tumor control. Four (100%) of 4 mice receiving 1.0 microgram of carboplatin combined with 30-Gy EBRT had complete tumor control. Nine (100%) of 9 mice receiving 4.0 micrograms of carboplatin in combination with EBRT had complete tumor control. The chemotherapeutic enhancement ratio ranged from 1.07 to 3.24. CONCLUSIONS: Combined administration of intravitreal carboplatin and EBRT enhances local tumor control in murine retinoblastoma. Combining these treatment modalities may allow tumor control in selected patients with retinoblastoma while decreasing treatment-related morbidity and the mutagenic risks associated with radiation and systemic chemotherapy.

Computed tomography of posterior uveal melanomas.

Computed tomographic (CT) scans were obtained from 48 patients with posterior uveal melanoma. The CT measurements of maximal and minimal basal diameters and thickness of each tumor were compared with the assessments of these tumor dimensions obtained by ophthalmoscopic estimation (basal diameters only) and standardized A-scan ultrasonography (thickness only) and with the gross pathologic measurements of these tumors. The correlation between measurements of tumor thickness by CT scanning, standardized A-scan ultrasonography, and gross pathologic analysis was substantially better than that between the CT, ophthalmoscopic, and gross pathologic measurements of tumor basal diameters. Computed tomographic scanning appears to be a good method for determining the in vivo size of choroidal and ciliary body melanomas.

External beam radiotherapy in retinoblastoma: tumor control and comparison of 2 techniques.

OBJECTIVE: To investigate eye conservation, local control, and complication rates among children with retinoblastoma treated with 2 different external beam radiotherapy (EBR) techniques. METHODS: Fifty-eight eyes in 42 patients received EBR as the primary treatment modality for retinoblastoma (median follow-up, 37 months). The EBR technique was relative lens-sparing (RLS) in 26 eyes and modified lateral beam (MLB) in 32 eyes. Both groups were comparable in Reese-Ellsworth retinoblastoma classification. If necessary, patients received focal salvage therapy. RESULTS: At 24 months, eye conservation rates were 88.5% and 89.1% among eyes treated with RLS and MLB, respectively (P = .40); tumor control rates without salvage therapy were 84.6% and 53.3% (P = .02), respectively. Among eyes with Reese-Ellsworth stage IV and V disease, eye conservation rates were 88%+/-8% and 83%+/-9% at 36 months in the RLS and MLB groups, respectively, and local tumor control rates were 81%+/-10% and 51%+/-12%. Percentages of eyes without cataract at 36 months were 83.1% and 63.0%, respectively (P = .40). Among patients observed for at least 18 months, midfacial hypoplasia developed in 38.5% and 29.4%, respectively (P = .70). CONCLUSIONS: The EBR technique was associated with high eye conservation and local control rates. Salvage therapy was performed significantly less frequently in the RLS group compared with the MLB group, and complication rates in both groups were similar.

Radiation therapy and ferromagnetic hyperthermia in the treatment of murine transgenic retinoblastoma.

BACKGROUND: Combined modality therapy for childhood retinoblastoma holds the potential of decreasing treatment-related morbidity while maintaining excellent tumor control rates. OBJECTIVE: To evaluate the efficacy of external beam radiation therapy (EBRT), ferromagnetic hyperthermia (FMH), and the combination of both modalities in the control of ocular tumors in a transgenic murine model of retinoblastoma. METHODS: One hundred sixty-six mouse eyes from 4-week-old animals transgenically positive for simian virus 40 large T antigen were treated with a total dose of 10, 15, 20, 30, 40, 45, or 50 Gy of EBRT in 5-Gy fractions twice daily, with 48 degrees C or 54 degrees C FMH for 20 minutes, or with combined EBRT at 10 or 30 Gy and 48 degrees C or 54 degrees C FMH for 20 minutes. Serial histologic sections, obtained 8 weeks after treatment, were examined for the presence of tumor. RESULTS: The tumor control dose for 50% of eyes (TCD50) treated with EBRT occurred at 27.6 Gy. Ferromagnetic hyperthermia at 48 degrees C cured 30% (6/20) of eyes, while 54 degrees C FMH resulted in a 100% (20/20) cure rate. Combined treatment with 48 degrees C FMH and EBRT exhibited a TCD50 at 3.3 Gy. The thermal enhancement ratio was 8.4. Ferromagnetic hyperthermia at 54 degrees C exhibited tumor cure in all animals, but 25% of eyes were lost owing to secondary treatment complications. CONCLUSIONS: This represents the first documentation of tumor control via EBRT, ocular FMH, and a combination of these treatment modalities in this murine transgenic retinoblastoma model. The extent of treatment synergy in this model suggests that combined treatment application may allow a reduction in total ocular and periocular radiation dose while maintaining excellent local tumor control.

Radioresistance in murine solid tumors induced by interleukin-1.

Interleukin-1 (IL-1) has radioprotective activity in hematopoietic lineages and in other normal cell renewal systems, but little is known about the effects of IL-1 alpha on the radiosensitivity of tumor cell populations. The present studies were conducted to investigate the effects of IL-1 alpha on the radiosensitivity of clonogenic cells in RIF-1 and SCC-7 tumors. Radioresistance was detected within 2-4 after administration of IL-1 alpha (0.5 micrograms/mouse, ip) and characterized by increases in D(o), Dq, alpha/beta and SF2. This radioresistance was similar to that seen in tumors rendered totally hypoxic before X irradiation. Tirapazamine, a hypoxic cell cytotoxin, and IL-1 alpha had synergistic schedule-dependent antitumor activity in vivo, suggesting that IL-1-induced radioresistance in vivo is due to hypoxia. Radioresistance induced by IL-1 alpha was transient, and the data suggested reoxygenation within 12 h. In vitro, IL-1 alpha had no direct effect on the radiosensitivity of SCC-7 cells in tissue culture under aerobic conditions. However, an increase in D(o), alpha/beta and SF2 was seen in clonogenic tumor cells from primary cultures treated with IL-1 alpha under aerobic conditions. Superoxide dismutase and catalase prevented the induction of radioresistance by IL-1 alpha in vitro, suggesting that oxidative responses from tumor macrophages after administration of IL-1 alpha may be responsible for induced radioresistance by IL-1 in vitro. Although oxidant stress induced by IL-1 and in vitro in our models, the mechanisms by which such responses modulate tumor radiosensitivity in vivo and in vitro are likely quite different.

Intraoperative echographic localization of iodine-125 episcleral plaque for brachytherapy of choroidal melanoma.

PURPOSE: To report intraoperative echographic localization of iodine-125 episcleral plaque for brachytherapy of choroidal melanoma. METHODS: In a retrospective study, 117 eyes with medium-sized choroidal melanoma in 117 patients not participating in the Collaborative Ocular Melanoma Study underwent iodine-125 episcleral plaque radiotherapy with intraoperative echographic verification of plaque placement between January 1992 and December 1998 at the Bascom Palmer Eye Institute. RESULTS: After initial plaque placement using standard localization techniques, intraoperative echography demonstrated satisfactory tumor-plaque apposition in 76% of eyes (89 of 117). In the 28 eyes (28 of 117, 24%) that required repositioning of the plaque, the extent of misplacement was less than 1 mm in 10 eyes, 1.1 to 3.0 mm in six eyes, and greater than 3 mm in eight eyes. Two eyes had tilting of the plaque, and in two additional eyes, although the plaque covered all tumor margins, the centration was considered suboptimal. Repositioning was necessary in 1 eye with an anteriorly located tumor (1 of 13, 7.7%) and in 20 eyes with peripapillary or posterior pole tumors (20 of 67, 26.3%). Anteriorly located tumors required plaque repositioning significantly less frequently than did posteriorly located tumors (P = .041). Misalignment involved one tumor margin in 23 eyes and two margins in five eyes. The most commonly misaligned margins were the lateral (35%) and posterior margins (26%). In no case was an anterior marginal misalignment documented. At a mean follow-up of 37 months, no tumor-related death or metastatic disease was noted. Two of the 117 patients (1.7%) had local tumor recurrence and underwent enucleation. CONCLUSIONS: Intraoperative echography is an effective adjunct for localization and confirmation of tumor-plaque relationship. This technique facilitates the identification and correction of suboptimal plaque placement at the time of surgery, potentially minimizing treatment failures.

Radiation therapy for adjunctive treatment of adrenal cortical carcinoma.

Adrenocortical carcinoma is a rare disease which is primarily approached surgically. There have been few reports of the efficacy of radiation therapy and, for the most part, these have been anecdotal. This paper reports on the potential adjuvant role of radiation therapy after surgical excision of primary adrenal cortical carcinoma and also comments about the efficacy of palliative radiation therapy for metastases. We have identified eight patients treated for adrenal cortical carcinomas at Hahnemann University Hospital (HUH) from 1962 until the present and have also identified five patients with the same diagnosis at Philadelphia General Hospital (PGH) from 1962 until its close in 1975. These two groups are examined separately. In the PGH group, in which two patients were diagnosed at autopsy and only one patient was treated by radiation therapy, the median survival was between 0 and 1 month for Stage IV disease with the only patient surviving to 6 months being that patient receiving radiation therapy. In the HUH group, five of eight patients were treated adjunctively after diagnosis, one was not and two received palliative therapy. The median survival for treated Stage III patients was between 34 months and 7 years. The suggestion, based on a limited patient series, is that patients treated postoperatively to the tumor bed and nodal areas in Stage III disease may have improved survival over historic series and improved local control.