Ethical dilemmas in polio eradication.
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Ethics, Medical↗
Biomedical subjects
M E Taylor
Publications and source records attributed to M E Taylor.
Mechanism of Ca2+ and monosaccharide binding to a C-type carbohydrate-recognition domain of the macrophage mannose receptor.
Site-directed mutagenesis has been used to identify residues that ligate Ca2+ and sugar to the fourth C-type carbohydrate-recognition domain (CRD) of the macrophage mannose receptor. CRD-4 is the only one of the eight CRDs of the mannose receptor to exhibit detectable monosaccharide binding when expressed in isolation, and it is central to ligand binding by the receptor. CRD-4 requires two Ca2+ for sugar binding, like the CRD of rat serum mannose-binding protein (MBP-A). Sequence comparisons between the two CRDs suggest that the binding site for one Ca2+, which ligates directly to the bound sugar in MBP-A, is conserved in CRD-4 but that the auxiliary Ca2+ binding site is not. Mutation of the four residues at positions in CRD-4 equivalent to the auxiliary Ca2+ binding site in MBP-A indicates that only one, Asn728, is involved in ligation of Ca2+. Alanine-scanning mutagenesis was used to identify two other asparagine residues and one glutamic acid residue that are probably involved in ligation of the auxiliary Ca2+ to CRD-4. Sequence comparisons with other C-type CRDs suggest that the proposed binding site for the auxiliary Ca2+ in CRD-4 of the mannose receptor is unique. Evidence that the conserved Ca2+ in CRD-4 bridges between the protein and bound sugar in a manner analogous to MBP-A was obtained by mutation of one of the amino acid side chains at this site. Ring current shifts seen in the 1H NMR spectra of methyl glycosides of mannose, GlcNAc, and fucose in the presence of CRD-4 and site-directed mutagenesis indicate that a stacking interaction with Tyr729 is also involved in binding of sugars to CRD-4. This interaction contributes about 25% of the total free energy of binding to mannose. C-5 and C-6 of mannose interact with Tyr729, whereas C-2 of GlcNAc is closest to this residue, indicating that these two sugars bind to CRD-4 in opposite orientations. Sequence comparisons with other mannose/GlcNAc-specific C-type CRDs suggest that use of a stacking interaction in the binding of these sugars is probably unique to CRD-4 of the mannose receptor.
Alanine↗
Evolution of a family of receptors containing multiple C-type carbohydrate-recognition domains.
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Animals↗
Ethical dilemmas in current planning for polio eradication.
Intensification of polio eradication efforts worldwide raises concerns about costs and benefits for poor countries. A major argument for global funding is the high benefit-cost ratio of eradication; however, financial benefits are greatest for rich countries. By contrast, the greatest costs are borne by poor countries; the Pan American Health Organization has estimated that host countries bore 80% of costs for polio eradication in the Americas. The 1988 World Health Assembly resolution setting up the Polio Eradication Initiative carried the proviso that programs should strengthen health infrastructures. Drastic cuts in donor funding for health make this commitment even more important. Two international evaluations have reported both positive and negative effects of polio and Expanded Programme on Immunization programs on the functioning and sustainability of primary health care. Negative effects were greatest in poor countries with many other diseases of public health importance. If poor countries are expected to divert funds from their own urgent priorities, donors should make solid commitments to long-term support for sustainable health development.
Developed Countries↗
A 47-year-old woman with ductal carcinoma in situ of the breast.
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Breast Neoplasms↗
Brachytherapy or electron beam boost in conservation therapy of carcinoma of the breast: a nonrandomized comparison.
PURPOSE: The results of breast-conservation therapy using breast irradiation and a boost to the tumor excision site with either electron beam or interstitial 192Ir implant are reviewed. METHODS AND MATERIALS: A total of 701 patients with histologically confirmed Stage T1 and T2 carcinoma of the breast were treated with wide local tumor excision or quadrantectomy and breast irradiation. The breast was treated with tangential fields using 4 or 6 MV photons to deliver 48 to 50 Gy in 1.8 to 2 Gy daily dose, in five weekly fractions. In 80 patients the regional lymphatics were irradiated. In 342 patients with Stage T1 and 107 with Stage T2 tumors, boost to the primary tumor excision site was delivered with 9 MeV and, more frequently, with 12 MeV electrons. In 91 patients with Stage T1 and 38 patients with Stage T2 tumors an interstitial 192Ir implant was performed. Tumor control, disease-free survival, cosmesis, and morbidity of therapy are reviewed. Minimum follow-up is 4 years (median 5.6 years; maximum, 24 years). RESULTS: The overall local tumor recurrence rates were 5% in the T1 and 11% in the T2 tumor groups. There was no significant difference in the breast relapse rate in patients treated with either electron beam or interstitial 192Ir boost. Regional lymph node recurrences were 1% in patients with T1 and 5% with T2 tumors. Distant metastases were recorded in 5% of the T1 and 23% of the T2 groups. The 10-year actuarial disease-free survival rates were 87% for patients with T1 and 75% with T2 tumors. Disease-free survival was exactly the same in patients receiving either electron beam or interstitial 192Ir boost. Cosmesis was rated as excellent/good in 84% of patients with T1 tumors treated with electron beam and 81% of patients treated with interstitial implant, and 74 and 79% respectively, in patients with T2 tumors. CONCLUSIONS: Breast-conservation therapy is an effective treatment for patients with T1 and T2 carcinoma of the breast. There is no difference in local tumor control, disease-free survival, cosmesis, or morbidity in patients treated with either electron beam or interstitial 192Ir implant boost. Clinical trials in progress will further elucidate this controversial subject.
Brachytherapy↗
Genetic variants of human T-lymphotrophic virus type II in American Indian groups.
The human T-lymphotropic virus type II (HTLV-II) is found in many New World Indian groups in North and South America and may have entered the New World from Asia with the earliest migration of ancestral Amerindians over 15,000 years ago. To characterize the phylogenetic relationships of HTLV-II strains infecting geographically diverse Indian populations, we used polymerase chain reaction to amplify HTLV-II sequences from lymphocytes of seropositive Amerindians from Brazil (Kraho, Kayapo, and Kaxuyana), Panama (Guaymi), and the United States (the Navajo and Pueblo tribes of the southwestern states and the Seminoles of Florida). Sequence analysis of a 780-base pair fragment (located between the env gene and the second exons of tax/rex) revealed that Amerindian viruses clustered in the same two genetic subtypes (IIa and IIb) previously identified for viruses from intravenous drug users. Most infected North and Central American Indians had subtype IIb, while HTLV-II infected members of three remote Amazonian tribes clustered as a distinct group within subtype IIa. These findings suggest that the ancestral Amerindians migrating to the New World brought at least two genetic subtypes, IIa and IIb. Because HTLV-II strains from Amazonian Indians form a distinct group within subtype HTLV-IIa, these Brazilian tribes are unlikely to be the source of IIa viruses in North American drug users. Finally, the near identity of viral sequences from geographically diverse populations indicate that HTLV-II is a very ancient virus of man.
Amino Acid Sequence↗
Stress and strain distribution within the intact femur: compression or bending?
The aim of this research was to test the hypothesis that the intact femur is loaded predominately in compression. The study was composed of two parts: a finite element analysis of the intact femur to assess if a compressive stress distribution could be achieved in the diaphyseal region of the femur using physiological muscle and joint contact forces; a simple radiological study to assess the in vivo deflections of the femur during one legged stance. The results of this investigation strongly support the hypothesis that the femur is loaded primarily in compression, and not bending as previously thought. The finite element analysis demonstrated that a compressive stress distribution in the diaphyseal femur can be achieved, producing a stress distribution which appears to be consistent with the femoral cross-sectional geometry. The finite element analysis also predicted that for a compressive load case there would be negligible deflections of the femoral head. The radiological study confirmed this, with no measurable in vivo deflection of the femur occurring during one legged stance.
Adult↗
Factors influencing cosmetic results after conservation therapy for breast cancer.
PURPOSE: Host, tumor, and treatment-related factors influencing cosmetic outcome are analyzed for patients receiving breast conservation treatment. METHODS AND MATERIALS: Four-hundred and fifty-eight patients with evaluable records for cosmesis evaluation, a subset of 701 patients treated for invasive breast cancer with conservation technique between 1969 and 1990, were prospectively analyzed. In 243 patients, cosmetic evaluation was not adequately recorded. Cosmesis evaluation was carried out from 3.7 months to 22.3 years, median of 4.4 years. By pathologic stage, tumors were 62% T1N0, 14% T1N1, 15%, T2N0, and 9% T2N1. The majority of patients were treated with 4-6 MV photons. Cosmetic evaluation was rated by both patient and physician every 4-6 months. A logistic regression analysis was completed using a stepwise logistic regression. P-values of 0.05 or less were considered significant. Excellent cosmetic scores were used in all statistical analyses unless otherwise specified. RESULTS: At most recent follow-up, 87% of patients and 81% of physicians scored their cosmetic outcome as excellent or good. Eighty-two percent of physician and patient evaluations agreed with excellent-good vs. fair-poor rating categories. Analysis demonstrated a lower proportion of excellent cosmetic scores when related to patient age > 60 years (p = 0.001), postmenopausal status (p = 0.02), black race (p = 0.0034), and T2 tumor size (p = 0.05). Surgical factors of importance were: volume of resection > 100 cm3 (p = 0.0001), scar orientation compliance with the National Surgical Adjuvant Breast Project (NSABP) guidelines (p = 0.0034), and > 20 cm2 skin resected (p = 0.0452). Extent of axillary surgery did not significantly affect breast cosmesis. Radiation factors affecting cosmesis included treatment volume (tangential breast fields only vs. three or more fields) (p = 0.034), whole breast dose in excess of 50 Gy (p = 0.0243), and total dose to tumor site > 65 Gy (p = 0.06), as well as optimum dose distribution with compensating filters (p = 0.002). Daily fraction size of 1.8 Gy vs. 2.0 Gy, boost vs. no boost, type of boost (brachytherapy vs. electrons), total radiation dose, and use of bolus were not significant factors. Use of concomitant chemotherapy with irradiation impaired excellent cosmetic outcome (p = 0.02). Use of sequential chemotherapy or adjuvant tamoxifen did not appear to diminish excellent cosmetic outcomes (p = 0.31). Logistic regression for excellent cosmetic outcome analysis was completed for age, tumor size, menopausal status, race, type of surgery, volume of breast tissue resected, scar orientations, whole breast radiation dose, total radiation dose, number of radiation fields treated, and use of adjuvant chemotherapy. Significant independent factors for excellent cosmetic outcome were: volume of tissue resected (p = 0.0001), type of surgery (p = 0.0001), breast radiation dose (p = 0.005), race (p = 0.002), and age (p = 0.007). CONCLUSIONS: Satisfactory cosmesis was recorded in 81% of patients. Impaired cosmetic results are more likely with improper orientation of tylectomy and axillary incisions, larger volume of breast resection, radiation dose to the entire breast in excess of 50.0 Gy, and concurrent administration of chemotherapy. Careful selection of treatment procedures for specific patients/tumors and refinement in surgical/irradiation techniques will enhance the cosmetic results in breast conservation therapy.
Adult↗
Viral dynamics in human immunodeficiency virus type 1 infection.
The dynamics of HIV-1 replication in vivo are largely unknown yet they are critical to our understanding of disease pathogenesis. Experimental drugs that are potent inhibitors of viral replication can be used to show that the composite lifespan of plasma virus and virus-producing cells is remarkably short (half-life approximately 2 days). Almost complete replacement of wild-type virus in plasma by drug-resistant variants occurs after fourteen days, indicating that HIV-1 viraemia is sustained primarily by a dynamic process involving continuous rounds of de novo virus infection and replication and rapid cell turnover.
Antiviral Agents↗
Accelerated induction therapy and resection for poor prognosis stage III non-small cell lung cancer.
BACKGROUND: Induction therapy and resection may improve the survival of patients with poor prognosis stage III non-small cell lung cancer, at the cost of significant treatment prolongation. The purpose of this study was to assess toxicity, response, and survival of an accelerated induction regimen and resection in poor prognosis stage III non-small cell lung cancer. METHODS: Forty-two surgically staged patients with poor prognosis stage III non-small cell lung cancer received 11 days of induction treatment consisting of 96 hours of continuous chemotherapy infusions of cisplatin (20 mg.m-2.day-2), 5 fluorouracil (1,000 mg.m-2.day-2), and etoposide (75 mg.m-2.day-2) concurrent with accelerated fractionation radiation therapy (1.5 Gy twice a day, to a dose of 27 Gy). Induction was followed in 4 weeks by resection. Postoperatively, a second course of continuous chemotherapy and concurrent accelerated fractionation radiation therapy (postoperative dose 13 to 36 Gy) was given. RESULTS: Despite some degree of induction toxicity in all patients there was only one induction death (2.4%). A clinical partial response was seen in 24 patients (57%). Thirty-six patients (86%) underwent thoracotomy, and resection was possible in 33 (79%). Pathologic downstaging was seen in 17 patients (40%), and 2 patients (5%) had no residual carcinoma at operation. There were 11 postoperative complications (31%) and 4 postoperative deaths (11%). Thirteen patients (31%) are alive and disease-free, 24 (57%) have persistent disease or have recurred (15 distant, 5 locoregional, 4 both), and 9 patients are alive with disease. The median survival is 21 months and the 2-year Kaplan-Meier survival is 43%, with no differences identified between stages IIIA and IIIB patients (p = 0.63). CONCLUSIONS: We conclude that accelerated induction therapy and resection in poor prognosis stage III non-small cell lung cancer (1) is toxic, with a 12% treatment mortality; (2) is effective with a 79% resection rate and 40% pathologic downstaging rate; (3) provides excellent local control; (4) may prolong survival; and (5) is of value in stage IIIB as well as stage IIIA patients.
Adult↗
Use of a lucite beam spoiler for high-energy breast irradiation.
Treatment planning for breast cancer is a challenge for bridge separations greater than 24 cm. protocols require dose homogeneity to the breast parenchyma to 10% while maintaining good cosmesis (skin sparing). Low-energy beams (6 MV or lower) may not achieve protocol specifications because of lateral or medial hot spots. The buildup region for high-energy beams (i.e., 18 MV) may lead to underdosing in the superficial regions. Adding bolus will pull the isodoses to surface, surrendering skin sparing. A spoiler will increase the contribution of scattered medium energy electrons and photons, thereby increasing superficial dosing and maintaining skin sparing due to displacement of the spoiler from the skin. We chose Lucite as the spoiler material for our 18-MV beam. Buildup measurements were performed with a parallel-plate ionization chamber to find the optimal spoiler thickness of 18 mm at a spoiler-to-skin distance of 22 cm. A breast phantom was designed allowing thermoluminescent dosimeter measurements. The spoiler has increased the percent depth dose from the depths of 0.5 cm to 3.0 cm to mimic those delivered by a 6 MV beam, while the relative skin dose was held to 50%. Our treatment schema is typically 6-MV photons with customized compensation for half or more of the fractions and uncompensated 18-MV photons with the spoiler for the remaining fractions. The spoiler may be used in conjunction with thin bolus (1.0 cm) for therapeutic dosing to the skin (scars, inflammatory disease, etc.). The treatment plans have maintained dose homogeneity for large patients, without consequence of skin reaction.
Breast Neoplasms↗
Characterization of ligand binding to a carbohydrate-recognition domain of the macrophage mannose receptor.
The extracellular portion of the macrophage mannose receptor, an endocytic receptor involved in clearance of glycoconjugates, contains eight domains related to the Ca(2+)-dependent carbohydrate-recognition domains (CRDs) of other C-type animal lectins. The characteristics of ligand binding to an expressed form of one of these CRDs (CRD-4) have been investigated. The expressed domain was found to be a monomer in solution. Results of a solid phase binding assay and a protease resistance assay show that CRD-4 of the mannose receptor undergoes a conformational rearrangement upon binding of Ca2+, correlating with its ability to bind sugar. CRD-4 requires two Ca2+ for sugar binding, even though sequence comparisons with other C-type CRDs suggested that it might bind only one Ca2+. The results are consistent with a ternary complex being formed between CRD-4, sugar, and Ca2+ as is seen in the crystal structure of the CRD of rat mannose-binding protein in complex with an oligosaccharide. The stability of Ca2+ binding is shown to be pH-dependent, a result that is pertinent to release of ligand by the receptor in the endosome. However, CRD-4 retains sugar binding activity at a lower pH than does the whole receptor, suggesting that the conformational change in this CRD alone may not be sufficient to allow release of ligand in the endosomes.
Amino Acid Sequence↗
Aggressive concurrent chemoradiotherapy and surgical resection for proximal esophageal squamous cell carcinoma.
BACKGROUND: Proximal esophageal cancer has been a disease associated with relatively poor treatment success, partly due to advanced disease at presentation and the morbidity of the surgery required. Therefore, most patients receive palliative radiation therapy, and disease control is poor. METHODS: Between July 1990 and December 1992, nine consecutive patients with proximal esophageal squamous cell carcinoma were treated with aggressive concurrent chemoradiotherapy followed by surgical resection. Treatment consisted of cisplatin (20 mg/m2/day) and 5-fluorouracil (1000 mg/m2/day), both given as continuous intravenous infusions over 4 days concurrent with accelerated fractionation external beam radiation therapy (150 cGy twice a day to a dose of 2400 cGy). Three weeks after beginning treatment, a second course of chemotherapy and accelerated fractionation radiation therapy was administered to a total preoperative radiation therapy dose of 4500 cGy. After restaging of their disease, patients next underwent surgical resection. A single postoperative course of chemotherapy and 2400 cGy of concurrent accelerated fractionation radiation therapy was administered to those patients with residual tumor in the resection specimen. Two of these nine patients also were given 4-day etoposide infusions (75 mg/m2/day) as part of their chemotherapy and received lower induction radiation therapy doses. RESULTS: Although significant toxicity was experienced, there were no deaths attributable to the chemoradiotherapy and only one perioperative death. All nine patients underwent surgery; five required pharyngolaryngoesophagectomy. No residual tumor was found in the resection specimen in three of the nine patients. Continuous locoregional tumor control was achieved in all patients. Only two developed distant metastases. CONCLUSIONS: These results, using aggressive multimodality treatment, suggest that excellent locoregional control and long term, disease free survival can be achieved in selected patients with proximal esophageal cancer.
Adult↗
Management of locally advanced carcinoma of the breast. I. Noninflammatory.
BACKGROUND: The treatment of patients with locally advanced noninflammatory breast cancer has evolved substantially over the past 30 years. From 1968 to 1989, 281 women were treated at Mallinckrodt Radiation Oncology Center with four different treatment methods. Median follow-up was 6.2 years (range 3-22 years); no patient was lost to follow-up. METHODS: Retrospective review of records and analysis of data on a computer file were carried out. Thirty-five patients were treated with irradiation alone, 33 with irradiation and adjuvant chemotherapy, 81 with mastectomy and irradiation, and 132 with mastectomy, irradiation, and chemotherapy (triple-modality). RESULTS: Actuarial 5- and 10-year disease free survival (DFS) rates were 45% and 36%, respectively, with triple-modality therapy, 31% and 10% with irradiation and chemotherapy, 32% and 19% with irradiation and mastectomy, and 19% and 11% with irradiation alone. Cause specific survival (CSS) paralleled DFS in the four groups. Locoregional tumor control at 5 years was 91% for irradiation, mastectomy, and chemotherapy, 80% for irradiation and mastectomy, 54% for irradiation and chemotherapy, and 31% for irradiation alone. Systemic therapy and/or irradiation given before mastectomy yielded better locoregional tumor control, DFS, and CSS (not statistically significant). No difference in results was noted with radical, modified radical, or total mastectomy. In the triple-modality group, no chest wall failures occurred with chest wall doses greater than 5040 cGy. Grade 2 or higher treatment sequelae were noted in 10-42% of patients, depending on treatment modality. CONCLUSIONS: Triple-modality therapy yielded improved locoregional tumor control, DFS, and CSS compared with other modalities. Patients treated with surgery had better locoregional tumor control than those who received irradiation alone or in combination with chemotherapy, but the impact on DFS and CSS was less impressive. Additional clinical trials are needed to define further the role and optimal use of the various therapeutic modalities in the management of locally advanced breast cancer.
Adult↗
Management of locally advanced carcinoma of the breast. II. Inflammatory carcinoma.
BACKGROUND: Inflammatory carcinoma of the breast has been associated with a poor prognosis. Several therapeutic approaches have been under investigation in an effort to improve outcome. METHODS: This is a retrospective analysis of 179 patients with histologically confirmed inflammatory carcinoma of the breast: 33 treated with irradiation alone, 35 with combined irradiation and chemotherapy, 25 with irradiation and surgery, and 86 with a combination of three modalities. RESULTS: The 5-year disease free survival (DFS) rates were 40% for patients treated with three modalities, 24% for those treated with irradiation and surgery, and 6% for those treated with irradiation alone or in combination with chemotherapy without a surgical procedure. The 10-year DFS rates were 35%, 24%, and 0%, respectively. Cause specific survival (CSS) curves closely follow the same trends. A clearly superior locoregional tumor control was observed in patients who underwent a surgical procedure: 79% with three modalities, 76% with irradiation and surgery, and only 30% with irradiation alone or in combination with chemotherapy. Distant metastasis occurred in 57% of the group treated with triple-modality therapy, 60% of those treated with irradiation plus surgery, and 85% of the patients treated with irradiation alone or in combination with chemotherapy. There was no significant correlation between the type of mastectomy or doses of irradiation and locoregional tumor control or survival. The significant morbidity of the trimodal therapy (10%), although somewhat higher than that of other modalities (3.2%), was acceptable. CONCLUSIONS: The addition of mastectomy to irradiation significantly improved locoregional tumor control, DFS, and CSS; differences were statistically significant. The combination of chemotherapy, surgery, and irradiation had a significant impact on locoregional tumor control and incidence of distant metastases compared with surgery plus irradiation, and a lesser impact, although still statistically significant, on DFS and CSS. Further clinical trials are needed to optimize the management of patients with inflammatory breast cancer.
Adenocarcinoma↗
Endobronchial radiation therapy with or without neodymium yttrium aluminum garnet laser resection for managing malignant airway obstruction.
BACKGROUND: Previous reports have shown low-dose-rate (LDR) afterloading Ir-192 endobronchial radiation therapy (EnBRT) to effectively palliate symptoms in patients with malignant airway obstruction. The authors retrospectively assessed the consequences of LDR EnBRT with or without neodymium yttrium aluminum garnet (Nd:YAG) laser resection in 37 patients. METHODS: Between February 1986 and June 1991, 37 patients with malignant airway obstruction were treated with LDR EnBRT at The Cleveland Clinic Foundation. Inclusion criteria for LDR EnBRT with or without Nd:YAG laser resection were patients with recurrent, symptomatic endobronchial lesions treated previously with external beam irradiation. Of the 37 patients, 21 patients with endobronchial lesions underwent Nd:YAG laser resection; 16 patients with mainly extrinsic lesions received EnBRT only. Before EnBRT, selected patients (7 of 16 in the nonlaser-treatment group and 14 of 21 in the laser-treatment group) received additional external beam treatments of 2000 cGy/10 fractions. The LDR afterloading Ir-192 technique was used to deliver approximately 30 Gy to a 1.0-cm radius target. RESULTS: All patients had one or more of the following symptoms: 1) dyspnea, 2) fever, 3) cough, and 4) hemoptysis. Good-to-excellent symptom relief was apparent in 16 of 21 (76.2%) laser-treated patients and in 12 of 16 (75%) nonlaser-treated patients. Follow-up bronchoscopy in 28 patients revealed tumor regression in 22 (79%). Median survival time was 16.3 weeks in the laser group and 11.7 weeks in the nonlaser group (P = 0.36). Longer median survival times were noted in laser-treated (22.8 weeks) and nonlaser-treated (16.4 weeks) patients receiving additional external beam treatments. Exsanguination occurred in 7 of 21 (33.3%) laser-treated patients and in 4 of 16 (25%) nonlaser-treated patients. The only factor affecting the exsanguination rate was implant location: 6 of 11 (54.5%) patients had lesions in the right or left upper lobe. CONCLUSIONS: EnBRT alone or with Nd:YAG laser resection provided good-to-excellent symptom palliation in these patients although a high rate of exsanguination occurred in both groups.
Adult↗
Photon versus fast neutron external beam radiotherapy in the treatment of locally advanced prostate cancer: results of a randomized prospective trial.
PURPOSE: To evaluate the effectiveness of fast neutron radiation therapy in treatment of locally advanced carcinomas of the prostate. METHODS AND MATERIALS: From April 1986 to October 1990, 178 patients were entered on a prospective, multi-institutional randomized study of the NCI-sponsored Neutron Therapy Collaborative Working Group. This trial compared external beam photon irradiation (7000-7020 cGy) with external beam neutron irradiation (2040 ncGy) for patients with high-grade T2 or T3-4, N0-1, M0 adenocarcinomas of the prostate. Eighty-nine patients were randomized to each treatment. Six patients were subsequently judged to be ineligible, leaving 85 photon and 87 neutron randomized patients eligible for analysis. RESULTS: With a follow-up time ranging from 40 to 86 months (68 months median follow-up) the 5-year actuarial clinical local-regional failure rate for patients treated with neutrons was 11%, vs. 32% for photons (p < 0.01). Incorporating the results of routine posttreatment prostate biopsies, the resulting "histological" local-regional tumor failure rates were 13% for neutrons vs. 32% for photons (p = 0.01). To date, actuarial survival and cause-specific survival rates are statistically indistinguishable for the two patient cohorts, with 32% of the neutron-treated patient deaths and 41% of the photon-treated patient deaths caused by prostate cancer (p = n.s.). Prostate specific antigen (PSA) values were elevated in 17% of neutron-treated patients and 45% of photon-treated patients at 5 years (p < 0.001). Severe late complications of treatment were higher for the neutron-treated patients (11% vs. 3%), and were inversely correlated with the degree of neutron beam shaping available at the participating institutions. Neutron treatment delivery utilizing a fully rotational gantry and multileaf collimator did not result in an increase in severe late effects when compared to photon treatment. CONCLUSION: High energy fast neutron radiotherapy is safe and effective when adequate beam delivery systems and collimation are available, and it is significantly superior to external beam photon radiotherapy in the local-regional treatment of large prostate tumors.
Adenocarcinoma↗