Infectious exposure in the first years of life and risk of central nervous system tumours in children: analysis of birth order, childcare attendance and seasonality of birth.

BACKGROUND: An infective, mostly viral basis has been found in different human cancers. To test the hypothesis of a possible infectious aetiology for central nervous system (CNS) tumours in children, we investigated the associations with proxy measures of exposure to infectious disease. METHODS: In a large case-control study nested in the populations of Denmark, Norway, Sweden, and Finland of 4.4 million children, we studied the association of birth order and seasonal variation of birth with subsequent risk for CNS tumours. We identified 3983 children from the national cancer registries, and information on exposure was obtained from the high-quality national administrative health registries. We investigated the association between childcare attendance during the first 2 years of life and the risk for CNS tumours in a subset of Danish children with CNS tumours, using information from the Danish Childcare database. RESULTS: We observed no association between birth order and risk of CNS tumours overall (odds ratio (OR) for second born or later born vs first born, 1.03; 95% confidence interval (CI), 0.96-1.10) or by histological subgroup, and children with CNS tumours did not show a seasonal variation of birth that was distinct from that of the background population. Childcare attendance compared with homecare showed a slightly increased OR (1.29; 95% CI, 0.90-1.86) for CNS tumours, with the highest risk observed in children attending a crèche. The strongest association was observed for embryonal CNS tumours. We found no effect of age at enrolment or duration of enrolment in childcare. CONCLUSION: These results do not support the hypothesis that the burden of exposure to infectious disease in early childhood has an important role in the aetiology of paediatric CNS tumours.

Infant crying and adults' anticipated caregiving responses: acoustic and contextual influences.

These studies assessed adults' latencies to signal that they would respond to infant crying as functions of (1) the degree of infant distress they perceived in the cry, and (2) contextual information relevant to caregiving. In the first study (N = 34), listeners waited longer to respond to cries that they had earlier rated as sounding less distressed than when they heard cries of higher distress. Further, those who had been told that the infant needed sleep waited longer to respond than those without this information. This effect of context information, however, was limited to the latencies; in another study (N = 50), listeners' ratings of distress were not affected. Several acoustic features of the cries correlated with distress ratings and with latencies to signal a caregiving response. Taken together, the results suggest that adults' responses to crying are influenced both by acoustic gradations in the cry itself and by the caregiving context. Ratings of degree of distress manifest in the cry, in other words, may be highly predictive of caregiving behavior but not wholly so. Finally, although certain acoustic variations related to greater perceived distress and speed of response, differences were apparent between infants in the magnitude of these variations. The implication that the general process of cry perception may be calibrated, or fine tuned, to the range of acoustic variation provided by individual infants is discussed.

An opportunity for HMOs to use marketing to increase enrollee satisfaction.

PURPOSE: To identify the combination of marketing components (i.e., service, price, access, and promotion) of commercial health maintenance organizations (HMOs) that are related to overall enrollee satisfaction. The researchers focus on factors that commercial HMOs control directly--specifically, health care organization and financing. DESIGN: Descriptive (mail order). METHODOLOGY: This study uses national data provided by a major health benefits consulting firm, which collected data from a 1997 calendar year mail survey of HMO administrators. The administrators responded to an extensive survey, which tapped selected HMO marketing-mix components and the percentage of surveyed members who indicated satisfaction with their HMOs. To test hypotheses, researchers treated marketing-mix components as independent variables and enrollee satisfaction as the dependent variable. PRINCIPAL FINDINGS: This study found statistically significant relationships between overall satisfaction and HMO providers' quality; access, particularly to specialists and out-of-network providers; waiting times for physician services; customer service; and disease prevention/health promotion programs. The researchers did not find significant relationships between overall satisfaction and accreditation by the National Committee for Quality Assurance (NCQA), the presence of physician gatekeepers, numbers of providers, or financial indicators. The relationship between overall satisfaction and utilization was mixed. This study's findings are largely consistent with the literature, consumer- and professional-group position papers, and the President's Advisory Commission on Consumer Protection and Quality in the Health Care Industry. CONCLUSIONS: HMOs can use marketing as a way to address problems and pursue opportunities identified by enrollees. As these findings demonstrate, certain features of HMO design are more appealing to patients. By focusing on these preferences, HMOs can adopt a responsive market orientation that gives rise to more effective marketing mixes and hence improves enrollee satisfaction. With improved satisfaction, enrollees generate less need for government intervention through regulation or legislation.

Phase II prospective study of the use of conformal high-dose-rate brachytherapy as monotherapy for the treatment of favorable stage prostate cancer: a feasibility report.

PURPOSE: To evaluate the technical feasibility and tolerance of image-guided transperineal conformal high-dose-rate (C-HDR) brachytherapy as the sole treatment modality for favorable, localized cancer of the prostate, and to analyze possible intrafraction and interfraction volume changes in the prostate gland which may affect dosimetric quality. METHODS AND MATERIALS: Patients were eligible for this prospective Phase II trial if they had biopsy proven adenocarcinoma of the prostate with favorable prognostic factors (Gleason score < or =7, PSA < or =10 ng/ml and Stage < or =T2a). The technique consisted of a transperineal implant procedure using a template with transrectal ultrasound (TRUS) guidance. An interactive on-line real-time planning system was utilized with geometric optimization. This allowed dosimetry to be generated and modified as required intraoperatively. Prescription was to the minimum dose point in the implanted volume, assuring conformal coverage of the prostate at its widest dimension with no margin. Total dose was 3800 cGy in 4 fractions of 950 cGy each, delivered twice a day over 2 days. The dose to any segment of rectum and urethra was limited to < or =75% and < or =125% of the prescription dose, respectively. Before each fraction, needle positions were verified under fluoroscopy and adjusted as required. For the last 10 patients, the adjustments required were measured in a prospective fashion in representative extrema of the gland. TRUS images were recorded for all patients before any needle manipulation, again just before delivering the first fraction and immediately after the last fraction. This typically meant approximately 36 h to pass between the first and last measurements. Implant quality was assessed via dose-volume histograms (DVH). RESULTS: Between 3/99 and 6/00, 41 patients received C-HDR interstitial brachytherapy as their only treatment for prostate cancer at our institution. Median age was 64 years (range 51-79). Stage distribution was 27 T1c patients and 14 T2a patients. Three patients had Gleason score (GS) of 5; 34 had GS of 6; 4 patients had GS of 7. Median pretreatment PSA was 4.7 ng/ml (range 0.8-13.3). All patients tolerated the treatment well with minimal discomfort. For 23 patients, data on volume changes in the gland during the implant were tabulated. They demonstrated a mean prostate volume of 30.7 cc before any manipulation with needles, 37.0 cc at the end of fraction 1, and 38.2 cc at the end of fraction 4. In addition, for those 10 patients prospectively evaluated for required adjustments, the overall mean adjustment between fraction 1 and fraction 2 was 2.0 cm, between fraction 2 and 3 was 0.4 cm, and between fractions 3 and 4 was 0.4 cm. For 10 consecutive patients, the average prescriptions dose -D90 for fractions 1 and 4 were 104% and 100%, respectively. The corresponding average urethral D10 for fractions 1 and 4 were 122% and 132%. CONCLUSION: Our protocol using C-HDR interstitial brachytherapy as monotherapy for early cancer of the prostate was feasible and well tolerated by 41 patients treated. Changes in interfraction prostate volume do not appear to be significant enough to warrant modification of dosimetry for each fraction. Both excellent dose coverage of the prostate gland and low urethral dose are achieved as measured by DVH. However, paramount attention should be given to needle displacement before each fraction. Needle movement is most significant between fractions 1 and 2. Acute toxicity (RTOG) has been modest. Late toxicity and tumor control rates will be reported as longer follow-up allows.

Wear of ultra-high molecular weight polyethylene and polytetrafluoroethylene in a hip simulator: a dose-response study of protein concentration.

Charnley's laboratory wear studies of non-gamma sterilized polytetrafluoroethylene (PTFE) and polyethylene (PE) found that the PTFE to PE wear-rate ratio of 250:1 was much higher than the in-vivo wear ratio of 20:1. Tests of PTFE and PE in our laboratory showed a wear ratio of 150:1, using bovine serum as the lubricant and 190:1 with water as the lubricant. Our hypothesis was that the wear-rates of PTFE and PE cup materials were related to the concentration of protein in the serum. We studied the wear behavior of PTFE and PE cups in varied protein concentrations, using 4 femoral head sizes to validate the clinical range reported by Charnley. The PTFE wear-rates increased with increasing protein concentration and conversely, PE wear-rates decreased with increasing protein concentration. This inverse relationship made it possible to bring the wear ratio closer to the desired clinical wear ratio. We found that the clinically relevant PTFE/PE wear ratio corresponded to 3-10 mg/mL of protein in bovine serum.

Ultra-low wear rates for rigid-on-rigid bearings in total hip replacements.

With the increased clinical interest in metal-on-metal and ceramic-on-ceramic total-hip replacements (THRs), the objective of this hip simulator study was to identify the relative wear ranking of three bearing systems, namely CoCr-polyethylene (M-PE), CoCr-CoCr (M-M) and ceramic-on-ceramic (C-C). Volumetric wear rates were used as the method of comparison. The seven THR groupings included one M-PE study, two M-M studies and four C-C studies. Special emphasis was given to defining the 'run-in' phase of accelerated wear that rigid-on-rigid bearings generally exhibit. The hypothesis was that characterization of the run-in and steady state wear phases would clarify not only the tribological performance in vitro but also help correlate these in vitro wear rates with the 'average' wear rates measured on retrieved implants. The implant systems were studied on multichannel hip simulators using the Paul gait cycle and bovine serum as the lubricant. With 28 mm CoCr heads, the PE (2.5 Mrad/N2) wear rates averaged 13 mm3/10(6) cycles duration. This was considered a low value compared with the clinical model of 74 mm3/year (for 28 mm heads). Our later studies established that this low laboratory value was a consequence of the serum parameters then in use. The mating CoCr heads (with PE cups) wore at the steady state rate of 0.028 mm3/10(6) cycles. The concurrently run Metasul M-M THRs wore at the steady state rate of 0.119 mm3/10(6) cycles with high-protein serum. In the second Metasul M-M study with low-protein serum, the THR run-in rate was 2.681 mm3/10(6) cycles and steady state was 0.977 mm3/10(6) cycles. At 10 years, these data would predict a 70-fold reduction in M-M wear debris compared with the clinical PE wear model. All M-M implants exhibited biphasic wear trends, with the transition point at 0.5 x 10(6) cycles between run-in and steady state phases, the latter averaging a 3-fold decrease in wear rate. White surface coatings on implants (coming from the serum solution) were a confounding factor but did not obscure the two orders of magnitude wear performance improvement for CoCr over PE cups. The liners in the alumina head-alumina cup combination wore at the steady state rate of 0.004 mm3/10(6) cycles over 14 x 10(6) cycles duration (high-protein serum). The zirconia head-alumina cup THR combination wore at 0.174 and 0.014 mm3/10(6) cycles for run-in and steady state rates respectively (low-protein serum). The zirconia head and cup THR combination wore slightly higher initially with 0.342 and 0.013 mm3/10(6) cycles for run-in and steady state rates respectively. Other wear studies have generally predicted catastrophic wear for such zirconia-ceramic combinations. It was noted that the zirconia wear trends were frequently masked by the effects of tenacious white surface coatings. It was possible that these coatings protected the zirconia surfaces somewhat in this simulator study. The experimental ceramic Crystaloy THR had the highest ceramic run-in wear at 0.681 mm3/10(6) cycles and typical 0.016 mm3/10(6) cycles for steady state. Since these implants represented the first Crystaloy THR sets made, it was likely that the surface conditions of this high-strength ceramic could be improved in the future. Overall, the ceramic THRs demonstrated three orders of magnitude wear performance improvement over PE cups. With zirconia implants, while the cup wear was sometimes measurable, head wear was seldom discernible. Therefore, we have to be cautious in interpreting such zirconia wear data. Identifying the run-in and steady state wear rates was a valuable step in processing the ceramic wear data and assessing its reliability. Thus, the M-M and C-C THRs have demonstrated two to three orders of reduction in volumetric wear in the laboratory compared with the PE wear standard, which helps to explain the excellent wear performance and minimal osteolysis seen with such implants at retrieval operations.

Integration of nurse executives into executive level administration in Utah hospitals.

Nurse executives (NEs) in Utah acute care hospitals perceive that they are integrated into executive level administration. This perception is shared by NEs' career supporters and hinderers. To integrate NEs, influential colleagues used active methods, especially involvement. NEs add value to the administrative team by combining clinical and managerial expertise. NE integration is manifest in decision making, participation and interaction. Continued integration depends upon commitment from the chief executive officer (CEO), leadership in organizational change, addressing "glass ceiling" issues, and NEs' continuous demonstration of competence.

Matched-pair analysis of conformal high-dose-rate brachytherapy boost versus external-beam radiation therapy alone for locally advanced prostate cancer.

PURPOSE: We performed a matched-pair analysis to compare our institution's experience in treating locally advanced prostate cancer with external-beam radiation therapy (EBRT) alone to EBRT in combination with conformal interstitial high-dose-rate (HDR) brachytherapy boosts (EBRT + HDR). MATERIALS AND METHODS: From 1991 to 1998, 161 patients with locally advanced prostate cancer were prospectively treated with EBRT + HDR at William Beaumont Hospital, Royal Oak, Michigan. Patients with any of the following characteristics were eligible for study entry: pretreatment prostate-specific antigen (PSA) level of >/= 10.0 ng/mL, Gleason score >/= 7, or clinical stage T2b to T3c. Pelvic EBRT (46.0 Gy) was supplemented with three (1991 through 1995) or two (1995 through 1998) ultrasound-guided transperineal interstitial iridium-192 HDR implants. The brachytherapy dose was escalated from 5.50 to 10.50 Gy per implant. Each of the 161 EBRT + HDR patients was randomly matched with a unique EBRT-alone patient. Patients were matched according to PSA level, Gleason score, T stage, and follow-up duration. The median PSA follow-up was 2.5 years for both EBRT + HDR and EBRT alone. RESULTS: EBRT + HDR patients demonstrated significantly lower PSA nadir levels (median, 0.4 ng/mL) compared with those receiving EBRT alone (median, 1.1 ng/mL). The 5-year biochemical control rates for EBRT + HDR versus EBRT-alone patients were 67% versus 44%, respectively (P <.001). On multivariate analyses, pretreatment PSA, Gleason score, T stage, and the use of EBRT alone were significantly associated with biochemical failure. Those patients in both treatment groups who experienced biochemical failure had a lower 5-year cause-specific survival rate than patients who were biochemically controlled (84% v 100%; P <.001). CONCLUSION: Locally advanced prostate cancer patients treated with EBRT + HDR demonstrate improved biochemical control compared with those who are treated with conventional doses of EBRT alone.

Interim report of image-guided conformal high-dose-rate brachytherapy for patients with unfavorable prostate cancer: the William Beaumont phase II dose-escalating trial.

PURPOSE: We analyzed our institution's experience treating patients with unfavorable prostate cancer in a prospective Phase II dose-escalating trial of external beam radiation therapy (EBRT) integrated with conformal high-dose-rate (HDR) brachytherapy boosts. This interim report discusses treatment outcome and prognostic factors using this treatment approach. METHODS AND MATERIALS: From November 1991 through February 1998, 142 patients with unfavorable prostate cancer were prospectively treated in a dose-escalating trial with pelvic EBRT in combination with outpatient HDR brachytherapy at William Beaumont Hospital. Patients with any of the following characteristics were eligible: pretreatment prostate-specific antigen (PSA) >/= 10.0 ng/ml, Gleason score >/= 7, or clinical stage T2b or higher. All patients received pelvic EBRT to a median total dose of 46.0 Gy. Pelvic EBRT was integrated with ultrasound-guided transperineal conformal interstitial iridium-192 HDR implants. From 1991 to 1995, 58 patients underwent three conformal interstitial HDR implants during the first, second, and third weeks of pelvic EBRT. After October 1995, 84 patients received two interstitial implants during the first and third weeks of pelvic EBRT. The dose delivered via interstitial brachytherapy was escalated from 5.50 Gy to 6.50 Gy for each implant in those patients receiving three implants, and subsequently, from 8.25 Gy to 9.50 Gy per fraction in those patients receiving two implants. To improve implant quality and reduce operator dependency, an on-line, image-guided interactive dose optimization program was utilized during each HDR implant. No patient received hormonal therapy unless treatment failure was documented. The median follow-up was 2.1 years (range: 0.2-7.2 years). Biochemical failure was defined according to the American Society for Therapeutic Radiology and Oncology Consensus Panel definition. RESULTS: The pretreatment PSA level was >/= 10.0 ng/ml in 51% of patients. The biopsy Gleason score was >/= 7 in 58% of cases, and 75% of cases were clinical stage T2b or higher. Despite the high frequency of these poor prognostic factors, the actuarial biochemical control rate was 89% at 2 years and 63% at 5 years. On multivariate analysis, a higher pretreatment PSA level, higher Gleason score, higher PSA nadir level, and shorter time to nadir were associated with biochemical failure. In the entire population, 14 patients (10%) experienced clinical failure at a median interval of 1.7 years (range: 0.2-4.5 years) after completing RT. The 5-year actuarial clinical failure rate was 22%. The 5-year actuarial rates of local failure and distant metastasis were 16% and 14%, respectively. For all patients, the 5-year disease-free survival, overall survival, and cause-specific survival rates were 89%, 95%, and 96%, respectively. The 5-year actuarial rate of RTOG Grade 3 late complications was 9% with no patient experiencing Grade 4 or 5 acute or late toxicity. CONCLUSION: Pelvic EBRT in combination with image-guided conformal HDR brachytherapy boosts appears to be an effective treatment for patients with unfavorable prostate cancer with minimal associated morbidity. Our dose-escalating trial will continue.

Enrollee satisfaction with HMOs and its relationship with disenrollment.

Relying on 1997 data from a universe of 740 HMOs, this study uniquely documented, from the perspective of health plan administrators, rates of enrollee satisfaction and disenrollments. On the basis of various reporting totals per variable or indicator, the average level of satisfaction was 83.9%; the average number of disenrollments was 20,996 per plan. Among different datasets, an average of 18.9% members disenrolled per plan; an average of 10.2% were voluntary disenrollments; and an average of 18.3% were involuntary disenrollments. Plans with higher satisfaction enrollees had predominantly lower disenrollment rates, more enrollees likely to recommend plans to family or friends, fewer older enrollees, fewer male enrollees, and higher overall plan performance. To enhance the gaining and retaining of enrollees, plan administrators should closely monitor the various dimensions of satisfaction, such as services complement, quality of care, administrative efficiency, care management, enrollees' complaints, plan performance, appointment convenience, and waiting times.

3-O-Desacyl monophosphoryl lipid A derivatives: synthesis and immunostimulant activities.

The synthesis of a series of novel analogues of lipid A, the active principle of lipopolysaccharide, is reported. In these compounds, the 1-O-phosphono and (R)-3-hydroxytetradecanoyl moieties of native Salmonella minnesota R595 lipid A have been replaced with hydrogen and the length of the normal fatty acyl residues has been systematically varied. Normal fatty acid chain length in the 3-O-desacyl monophosphoryl lipid A (MLA) series is shown to be a critical determinant of iNOS gene expression in activated mouse macrophages and the induction of proinflammatory cytokines in human peripheral monocytes. Examination of pyrogenicity in rabbits and lethal toxicity in D-galactosamine-treated mice shows that toxic effects in the MLA series can be ameliorated by modifying fatty acid chain length. When used as an adjuvant for tetanus toxoid vaccines, certain MLA derivatives enhance the production of tetanus toxoid-specific antibodies in mice.

Effectiveness of nurse executives: measurement of role factors and attitudes.

This article describes the outcome of a survey of 40 nurse executives and 56 influential colleagues. Both groups agreed that leadership was the most important quality for the executive role. The nurses' primary focus was resolution of patient care problems. Influential colleagues stated resource allocation and initiation of change were two qualities needing improvement. The nurses rated themselves high in confidence about their job responsibilities, scored relationships as the most satisfying attribute, and cited provision of quality health care as the greatest advantage of their position. The greatest disadvantage was lack of administrative support. The results suggest the educational preparation needed for nurse executives.

Biological effects of a bifunctional DNA crosslinker. I. Generation of triradial and quadriradial chromosomes.

Interduplex crosslinks by a bifunctional anthramycin DNA crosslinker produced triradial and quadriradial chromosomes. The crosslinker alkylates guanine at N-2. Bovine chromosomes contain GC-rich density satellite DNAs at the centromeric heterochromatin and is the basis for the formation of triradial and quadriradial chromosomes at the centromeres. The in situ crosslinking of interphase chromosomes indicates that the distance between centromeres is 17.5 A. We conclude that the nuclear matrix associated DNA in the centromeric heterochromatin of interphase chromosomes are positioned close enough for crosslinking to occur. We propose a model for the generation of triradial and quadriradial chromosomes based upon the number of interduplex crosslinks between two chromosomes.

Biological effects of a bifunctional DNA cross-linker. II. Generation of micronuclei and attached micronuclear-like structures.

Madin-Darby bovine kidney (MDBK) cells were treated with the bifunctional DNA cross-linker, L-7, to examine the generation of micronuclei and other nuclear abnormalities. The preceding paper demonstrates that L-7 treatment induces the formation of triradial and quadriradial chromosomes in MDBK cells. These chromosomes are believed to result from interduplex DNA cross-links formed between G-C rich centromeric satellite DNA regions on non-sister chromatids. Treatment produces a majority of centromere-positive micronuclei. In addition, many daughter cells remain attached by chromatin bridges which are sometimes beaded with micronuclei. Up to 15% of cell nuclei become lobular and fused with numerous micronuclear-like structures attached to their membranes. These attached structures are classified as attached micronuclear-like structures (AMNLS). Fluorescence in situ hybridization (FISH) using a centromeric satellite sequence was performed on treated cells. Hybridization reveals that intercellular bridges are composed of centromeric sequences and initiate at centromeric foci in daughter cells. Furthermore, the majority of junctions between AMNLS and nuclei contain an enhancement of centromeric signal. The frequency of AMNLS appears dependent on the concentration of L-7 and the duration of treatment. Similar results were found for the generation of cross-linked chromosome products in the previous paper. We suggest that AMNLS result from the abnormal mitotic segregation of cross-linked chromosome products.

A comprehensive review of prostate cancer brachytherapy: defining an optimal technique.

PURPOSE: A comprehensive review of prostate cancer brachytherapy literature was performed to determine if an optimal method of implantation could be identified, and to compare and contrast techniques currently in use. METHODS AND MATERIALS: A MEDLINE search was conducted to obtain all articles in the English language on prostate cancer brachytherapy from 1985 through 1998. Articles were reviewed and grouped to determine the primary technique of implantation, the method or philosophy of source placement and/or dose specification, the technique to evaluate implant quality, overall treatment results (based upon pretreatment prostate specific antigen, (PSA), and biochemical control) and clinical, pathological or biochemical outcome based upon implant quality. RESULTS: A total of 178 articles were identified in the MEDLINE database. Of these, 53 studies discussed evaluable techniques of implantation and were used for this analysis. Of these studies, 52% used preoperative ultrasound to determine the target volume to be implanted, 16% used preoperative computerized tomography (CT) scans, and 18% placed seeds with an open surgical technique. An additional 11% of studies placed seeds or needles under ultrasound guidance using interactive real-time dosimetry. The number and distribution of radioactive sources to be implanted or the method used to prescribe dose was determined using nomograms in 27% of studies, a least squares optimization technique in 11%, or not stated in 35%. In the remaining 26%, sources were described as either uniformly, differentially, or peripherally placed in the gland. To evaluate implant quality, 28% of studies calculated some type of dose-volume histogram, 21% calculated the matched peripheral dose, 19% the minimum peripheral dose, 14% used some type of CT-based qualitative review and, in 18% of studies, no implant quality evaluation was mentioned. Six studies correlated outcome with implant dose. One study showed an association of implant dose with the achievement of a PSA nadir < or = 0.5. Two studies showed an improvement in biochemical control with a D90 (dose to 90% of the prostate volume) of 120 to 140 Gy or higher, and 2 additional studies found an association of clinical outcome with implant dose. One study correlated implant quality with biopsy results. Of the articles, 33 discussed evaluable treatment results, but only 16 reported findings based upon pretreatment PSA and biochemical control. Three- to 5-year biochemical control rates ranged from 48% to 100% for pretreatment PSAs < or = 4, 55% to 90% for PSAs between 4 and 10, 30% to 89% for PSAs > 10, < or = 20 and < 10% to 100% for PSAs > 20. Due to substantial differences in patient selection criteria (e.g., median Gleason score, clinical stage, pretreatment PSA), number of patients treated, median follow-up, definitions of biochemical control, and time points for analysis, no single technique consistently produced superior results. CONCLUSIONS: Our comprehensive review of prostate cancer brachytherapy literature failed to identify an optimal treatment approach when studies were analyzed for treatment outcome based upon pretreatment PSA and biochemical control. Although several well-designed studies showed an improvement in outcome with total dose or implant quality, the numerous techniques for implantation and the varied and inconsistent methods to specify dose or evaluate implant quality suggest that standardized protocols should be developed to objectively evaluate this treatment approach. These protocols have recently been suggested and, when implemented, should significantly improve the reporting of treatment data and, ultimately, the efficacy of prostate brachytherapy.

Iridium-192 transperineal interstitial brachytherapy for locally advanced or recurrent gynecological malignancies.

PURPOSE: To assess treatment outcome for patients with locally advanced or recurrent gynecological malignancies treated with continuous low-dose-rate (LDR) remote afterloading brachytherapy using the Martinez Universal Perineal Interstitial Template (MUPIT). MATERIALS AND METHODS: Between 7/85 and 6/94, 69 patients with either locally advanced or recurrent malignancies of the cervix, endometrium, vagina, or female urethra were treated by 5 different physicians using the MUPIT with (24 patients) or without (45 patients) interstitial hyperthermia. Fifty-four patients had no prior treatment with radiation and received a combination of external beam irradiation (EBRT) and an interstitial implant. The combined median dose was 71 Gy (range 56-99 Gy), median EBRT dose was 39 Gy (range 30-74 Gy), and the median implant dose was 32 Gy (range 17-40 Gy). Fifteen patients with prior radiation treatment received an implant alone. The total median dose including previous EBRT was 91 Gy (range 70-130 Gy) and the median implant dose was 35 Gy (range 25-55 Gy). RESULTS: With a median follow-up of 4.7 yr in survivors, the 3-yr actuarial local control (LC), disease-specific survival (DSS), and overall survival (OS) for all patients was 60%, 55%, and 41% respectively. The clinical complete response rate was 78% and in these patients the 3-year actuarial LC, DSS, and OS was 78%, 79%, and 63% respectively. On univariate analysis for local control, disease volume and hemoglobin were found to be statistically significant. On multivariate analysis, however, only disease volume remained significant (p = 0.011). There was no statistically significant difference in local control whether patients had received any prior treatment with radiation (p = 0.34), had recurrent disease (p = 0.13), or which physician performed the implant (p = 0.45). The grade 4 complication rate (small bowel obstruction requiring surgery, fistulas, soft tissue necrosis) for all patients was 14%. With a dose rate less than 70 cGy/hour, the grade 4 complication rate was 3% vs. 24% with dose rate > or = 70 cGy/hour (p = 0.013). CONCLUSION: Patients with locally advanced or recurrent gynecological malignancies treated with the remote afterloader LDR MUPIT applicator can expect reasonable rates of local control that are not operator-dependent. Complication rates with this approach are acceptable and appear to be related to the dose rate.

Use of three-dimensional radiation therapy planning tools and intraoperative ultrasound to evaluate high dose rate prostate brachytherapy implants.

PURPOSE: We performed a pilot study to evaluate the quality of high dose rate (HDR) prostate implants using a new technique combining intraoperative real-time ultrasound images with a commercially available 3-dimensional radiation therapy planning (3D RTP) system. METHODS AND MATERIALS: Twenty HDR prostate implants performed by four different physicians on a phase I/II protocol were evaluated retrospectively. Radiation therapy (RT) consisted of pelvic external beam RT (EBRT) to a dose of 46 Gy in 2-Gy fractions over 5 weeks and 2 HDR implants (prescribed dose of 950 cGy per implant). Our in-house real-time geometric optimization technique was used in all patients. Each HDR treatment was delivered without moving the patient. Ultrasound image sets were acquired immediately after needle placement and just prior to HDR treatment. The ultrasound image sets, needle and source positions and dwell times were imported into a commercial computerized tomography (CT) based 3D RTP system. Prostate contours were outlined manually caudad to cephalad. Dose-volume histograms (DVHs) of the prostate were evaluated for each implant. RESULTS: Four patients with stage T2a carcinoma, 4 with stage T2b, and 3 with stage T1c were studied. The median number of needles used per implant was 16 (range 14-18). The median treated volume of the implant (volume of tissue covered by the 100% isodose surface) was 82.6 cc (range 52.6-96.3 cc). The median target volume based on the contours entered in the 3D RTP system was 44.83 cc (range 28.5-67.45 cc). The calculated minimum dose to the target volume was 70% of the prescribed dose (range 45-97%). On average 92% of the target volume received the prescribed dose (range 75-99 %). The mean homogeneity index (fraction of the target volume receiving between 1.0 to 1.5 times the prescribed dose) was 80% or 0.8 (range 0.55-0.9). These results compare favorably to recent studies of permanent implants which report a minimum target volume dose of 43% (range 29-50%) and an average of 85% of the target volume (range 76-92%) receiving the prescribed dose. CONCLUSIONS: The feasibility of evaluating HDR prostate implants using ultrasound images (acquired immediately prior to treatment) with a commercially available 3D RTP system was established. The dosimetric characteristics of these HDR implants appear to be substantially different compared to permanent implants. These developments allow quantitative evaluation of the dosimetric quality of HDR prostate treatments. Future studies will examine any correlation between the dosimetric quality of the implant and clinical/biochemical outcomes.

Irradiation of the tumor bed alone after lumpectomy in selected patients with early-stage breast cancer treated with breast conserving therapy.

BACKGROUNDS AND OBJECTIVES: We present the interim findings of our in-house protocol treating the tumor bed alone after lumpectomy with low-dose-rate (LDR) interstitial brachytherapy in selected patients with early-stage breast cancer treated with breast conserving therapy (BCT). METHODS: From 1 March 1993 through 1 January 1995, 50 women with early-stage breast cancer were entered into a protocol of tumor bed irradiation alone using an interstitial LDR implant. Patients were eligible if their tumor was an infiltrating ductal carcinoma < or =3 cm in diameter, surgical margins were clear by at least 2 mm, the tumor did not contain an extensive intraductal component, the axilla was surgically staged with < or =3 nodes involved with cancer, and a postoperative mammogram was performed. Implants were positioned using a template guide delivering 50 Gy over 96 hr to the lumpectomy bed plus a 1-2-cm margin. Local control, cosmetic outcome, and complications were assessed. RESULTS: Patients ranged in age from 40 to 84 years (median, 65). The median tumor size was 10 mm (range, 1-25). Seventeen of 50 patients (34%) had well-differentiated tumors, 22 (44%) had moderately differentiated tumors, and in 11 (22%) the tumor was poorly differentiated. Forty-five patients (90%) were node-negative while five (10%) had 1-3 positive nodes. A total of 23 (46%) patients were placed on tamoxifen and 3 (6%) received adjuvant systemic chemotherapy. No patient was lost to follow-up. The median follow-up for surviving patients is 47 months (range, 37-59). No patient has experienced a local, regional, or distant failure. Three patients have died at 19, 33, and 39 months after treatment. All were without clinical evidence of recurrent disease and all deaths were unrelated to treatment. Good-to-excellent cosmetic results have been observed in 49 of 50 patients (98%) (median cosmetic follow-up was 44 months with a range of 19-59). No patient has experienced significant sequelae related to their implant. CONCLUSIONS: Interim results with treatment of the tumor bed alone with an LDR interstitial implant appear promising. Long-term follow-up of these patients and additional studies will be necessary to establish the equivalence of this treatment approach compared to standard BCT.