Three-dimensional conformal therapy (3D-CRT) for prostate cancer.
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Computer Simulation↗
Biomedical subjects
A T Porter
Publications and source records attributed to A T Porter.
RBE variation between fast neutron beams as a function of energy. Intercomparison involving 7 neutrontherapy facilities.
In fast neutron therapy, the relative biological effectiveness (RBE) of a given beam varies to a large extent with the neutron energy spectrum. This spectrum depends primarily on the energy of the incident particles and on the nuclear reaction used for neutron production. However, it also depends on other factors which are specific to the local facility, eg, target, collimation system, etc. Therefore direct radiobiological intercomparisons are justified. The present paper reports the results of an intercomparison performed at seven neutrontherapy centres: Orléans, France (p(34)+Be), Riyadh, Saudi Arabia (p(26)+Be), Ghent, Belgium (d(14.5)+Be), Faure, South Africa (p(66)+Be), Detroit, USA (d(48)+Be), Nice, France (p(65)+Be) and Louvain-la-Neuve, Belgium (p(65)+Be). The selected radiobiological system was intestinal crypt regeneration in mice after single fraction irradiation. The observed RBE values (ref cobalt-60 gamma-rays) were 1.79 +/- 0.10, 1.84 +/- 0.07, 2.24 +/- 0.11, 1.55 +/- 0.04, 1.51 +/- 0.03, 1.50 +/- 0.04 and 1.52 +/- 0.04, respectively. When machine availability permitted, additional factors were studied: two vs one fraction (Ghent, Louvain-la-Neuve), dose rate (Detroit), influence of depth in phantom (Faure, Detroit, Nice, Louvain-la-Neuve). In addition, at Orléans and Ghent, RBEs were also determined for LD50 at 6 days after selective abdominal irradiation and were found to be equal to the RBEs for crypt regeneration. The radiobiological intercomparisons were always combined with direct dosimetric intercomparisons and, when possible in some centres, with microdosimetric investigations.
Abdomen↗
Recommendations of the first Michigan conference on prostate cancer.
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Forecasting↗
The current role of radiotherapy in the treatment of invasive bladder cancer.
Invasive bladder cancer remains a therapeutic challenge. Approximately 50% of patients treated with radical cystectomy die of metastatic disease. External beam radiation therapy when given alone has results inferior to that of surgery, and although it has shown some benefit when given in the preoperative setting, this was not verified by randomized trials. Altered fractionation radiation schemes and combined modality using a cisplatin-based combination chemotherapy with radiation have resulted in up to 60% bladder preservation.
Brachytherapy↗
Localization of potential tumor suppressor loci to a < 2 Mb region on chromosome 17q in human prostate cancer.
We recently demonstrated a high frequency of loss of heterozygosity (LOH) at the D17S856 and D17S855 (within the BRCA1 gene) loci in primary prostate cancer, suggesting that the BRCA1 gene and/or other tumor suppressor gene(s) located within the interval of the D17S856 and D17S855 loci and/or within the vicinity of this interval may be important in prostate cancer (Cancer Res., 55: 1002-1005, 1995). To further define the exact boundary of the deleted region (i.e., D17S856/D17S855) and to detect other possible LOH regions on the long arm of chromosome 17, we analysed 23 matched normal and tumor DNAs with 15 polymorphic microsatellite markers spanning chromosome 17q12-21. Eleven of 22 (50%) informative tumors showed allelic deletion at one or more of the loci studied. A minimal area of LOH was identified to extend from the proximal boundary at the D17S776 locus to the distal boundary at the D17S855 locus, spanning an estimated < 2 Mb segment on chromosome 17q21. Our results suggest that a potential tumor suppressor gene(s) may reside in the < 2 Mb region centromeric (inclusive) to the BRCA1 gene and that this tumor suppressor gene(s) may be involved in the formation of prostate cancer.
Aged↗
Somatic mutations of the WAF1/CIP1 gene in primary prostate cancer.
The WAF1/CIP1 gene, a potential tumor suppressor gene, has recently been cloned and identified as a p53 mediator and an inhibitor for G1 cyclin-dependent kinases (CDKs). We undertook this study to investigate the possible role of the WAF1/CIP1 gene in human prostatic carcinoma. Matched normal and cancer tissues from 18 patients with prostate cancer were screened for WAF1/CIP1 mutation by nested reverse transcription-polymerase chain reaction/single strand conformational polymorphism (RT-PCR/SSCP) and DNA sequencing. Shifted bands from three tumor, but not the matched normal specimens, were observed. Subsequent direct DNA sequencing of the PCR fragments identified four sequence alterations including a cytosine (C) to adenine (A) transversion and a guanine (G) to A transition and two A insertions. Our results demonstrated that mutations of the WAF1/CIP1 gene occur and may be important during the pathogenesis of human prostate cancer. This is the first report of WAF1/CIP1 mutation in a primary human cancer.
Base Sequence↗
Recent trends in incidence and treatment of prostate cancer among elderly men.
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Aged↗
Loss of heterozygosity of the BRCA1 and other loci on chromosome 17q in human prostate cancer.
A putative tumor suppressor gene, the BRCA1 gene, on chromosome 17q21 has recently been identified and shown to be mutated in breast and ovarian cancers. We have undertaken the present study to explore the possible involvement of the BRCA1 and/or other potential genes on chromosome 17q in prostate cancer. Twenty-three patients were screened by PCR for loss of heterozygosity at five microsatellite loci spanning the region of 17q12-21. One of the loci (i.e., D17S855) studied is intragenic to the BRCA1. Forty-four and 40% of the informative cases showed loss of heterozygosity at the BRCA1 (D17S855) and D17S856 loci, respectively, whereas 10%, 10%, and 11% of the informative cases were positive for loss of heterozygosity at the D17S250, D17S579, and D17S588 loci, respectively. Overall, 52% (11/21) of the informative cases have allelic loss of at least one locus on chromosome 17q. Our data suggest that the BRCA1 and/or other genes within the interval between BRCA1 and D17S856 on 17q21 may be important in the pathogenesis of prostate cancer.
Adenocarcinoma↗
Elevated 12-lipoxygenase mRNA expression correlates with advanced stage and poor differentiation of human prostate cancer.
OBJECTIVES: Prostate cancer is the most frequently diagnosed cancer and the second leading cause of cancer death in males in the United States. The mortality is due mainly to distant metastasis. Therefore, predicting the prognosis of prostate cancer patients is an important clinical problem. Previously, we demonstrated that a 12-lipoxygenase (12-LOX) metabolite of arachidonic acid, 12(S)-hydroxyeicosatetraenoic acid, enhances the invasiveness of prostate cancer cells and that a 12-LOX-selective inhibitor [N-benzyl-N-hydroxy-5-phenylpentanamide] reduces experimental metastasis in animal model systems. In this study, we investigated the potential of 12-LOX as a predictor for the aggressiveness of prostate cancer. METHODS: The mRNA expression level of 12-LOX in 122 matching prostate normal and cancerous tissues were measured by quantitative reverse transcription- polymerase chain reaction. Possible association between 12-LOX expression and histologic grade, pathologic and clinical stage, margin positivity, age, and race was analyzed. RESULTS: 12-LOX mRNA levels were elevated in cancer cells and the expression associated with poor differentiation and invasiveness of prostate cancer. Overall, 46 (38%) of 122 evaluable patients showed elevated levels of 12-LOX mRNA in prostate cancer tissues compared with the matching normal tissues. A statistically significantly greater number of cases were found to have an elevated level of 12-LOX among T3, high grade, and surgical margin-positive than T2, intermediate, and low grade, and surgical margin-negative prostatic adenocarcinomas. CONCLUSIONS: Our data suggest that elevation of 12-LOX mRNA expression occurs more frequently in advanced stage, high-grade prostate cancer and that 12-LOX may serve as an indicator for progression and prognosis of prostate cancer. This enzyme also may be a novel target for the development of anti-invasive and antimetastatic agents.
Adenocarcinoma↗
Alternating conformal neutron and photon irradiation for locally advanced adenocarcinoma of the prostate.
The substantial local failure rate for patients with locally advanced carcinoma of the prostate (LACaP) following photon irradiation, the association of local failure with a poor prognosis, and the promising results of mixed neutron/photon (40%/60%) radiotherapy supplied the rationale for this study. The purpose of this study was to evaluate the combined advantages of mixed neutron/photon (75%/25%) irradiation, 3D treatment planning, as well as fully conformal beam shaping capabilities in reducing the morbidity associated with neutron irradiation. The first 35 patients treated with this technique are the basis for this analysis. After CT stimulation and treatment planning, the normal tissue and target structures were entered into the 3D planning system. The neutron dose was delivered in 15 fractions at 1.0 Gy/fraction (NGy) to the prostate and seminal vesicles (PSV) and 0.6 NGy/fraction to the pelvic lymph nodes (LN). The photon dose was given in 10 fractions of 1.8 Gy each to both the PSV and LN volumes. Neutron and photon dose-volume histograms (DVHs) were generated in each patient for the prostate, seminal vesicles, lymph nodes, bladder, and rectum. The adequacy of the neutron and photon components of the treatment were compared with respect to target volume and normal tissue irradiation. Based on the DVH analysis, the prostate and seminal vesicles received the prescribed dose with both neutrons (99% +/- 2%) and photons (99% +/- 2%). There was no significant difference in the dose to the bladder and rectum for both the neutrons and photons. The acute treatment related reactions have been mild, with only one grade III bladder reaction. The 3D conformal technology utilized in this study has been shown to allow for the delivery of neutron irradiation with no increase in dose to the adjacent normal tissues compared with that achieved with conformal photon treatment. Further follow-up will reveal whether the dosimetric advantage demonstrated by this technique translates into an improved therapeutic ratio.
Adenocarcinoma↗
A direct measurement of strontium-89 activity in bone metastases.
The total absorbed dose after systemic administration of 89Sr has been determined by measuring directly its activity in bone metastases. Autoradiography was performed on sections of bones obtained from patients treated with 89Sr to study the pattern of deposition. Discs of 5 and 8 mm diameter were cut from metastatic sites and normal bone. The beta-ray activity was determined with a scintillation counter, which was calibrated using similar bovine cancellous bone discs, onto which a known activity of 89Sr was transferred by pipette. From the activity measured, the initial activity (at the time of 89Sr administration) was calculated. The absorbed dose was estimated using the methodology described in NCRP Report No. 58. The estimated initial activity of 89Sr in the bone metastases varied from 2.3 to 240 MBq kg-1, with a mean value of 31 +/- 27 MBq kg-1. The total absorbed dose ranged from 1.3 to 64 Gy, with a mean of 18 +/- 16 Gy. The average total dose to normal bone sites was 1.1 +/- 0.4 Gy. The metastases to normal bone dose ratio in individual samples varied from 8 +/- 4 to 40 +/- 25. These estimates are in agreement with those obtained previously by indirect methods.
Autoradiography↗
Selective accumulation of strontium-89 in metastatic deposits in bone: radio-histological correlation.
The systemic administration of 89Sr has proven effective in the palliation of painful osseous metastases. Biodistribution studies with the gamma-emitter 85Sr suggest that both its uptake and retention are increased in bone metastases, where increased mineral turnover takes place. To study the pattern and nature of this process further, bones containing metastatic deposits were obtained from three patients who had previously been treated with 148 MBq of 89Sr. The bones were cut into 0.5-1.0 cm sections. The cut surfaces which faced together were marked with India ink, and adjacent sections were submitted for histology and autoradiography. Strontium deposition and retention were observed in regions which exhibited significant osteoblastic activity, mostly in areas adjacent to metastatic deposits, but also in subchondral and endosteal locations, as well as in an area corresponding to a pathological fracture with callus formation. With these exceptions, strontium deposition was not observed in histologically normal bone or within the marrow. Our findings demonstrate directly the selective nature of accumulation and retention of 89Sr and confirm previous clinical impressions.
Adenocarcinoma↗
Neoadjuvant hormonal downsizing of localized carcinoma of the prostate: effects on the volume of normal tissue irradiation.
A prospective evaluation of neoadjuvant hormonal downsizing in patients with localized carcinoma of the prostate was undertaken to assess its effect on normal tissue irradiation. Twenty patients with stage T1 or T2 (A, B) carcinoma of the prostate received 3 months of Lupron prior to definitive radiotherapy. The volumes of the prostate, seminal vesicles, bladder, and rectum from both the pre- and posthormone treatment planning CT were entered onto a 3-D treatment-planning system. The treatment planning parameters were standardized to facilitate comparison of the pre- and posthormonal volumes. Following the three monthly injections of Lupron, the average volume of the prostate was reduced by 37%. As a consequence, the volume of the bladder receiving at least 40, 52, and 64 Gy was reduced by an average of 15, 18, and 20%, respectively. In addition, the volume of the rectum receiving at least 40, 52, and 64 Gy was reduced by an average of 13, 20, and 34%, respectively. In conclusion, in patients with localized prostate cancer, downsizing of the prostate resulted in a reduction in the volume of bladder and rectum receiving high radiation doses. This approach may result in an improvement in the therapeutic ratio by reducing the morbidity of treatment.
Adenocarcinoma↗
Strontium 89 in the treatment of bony metastases.
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Bone Neoplasms↗
Topical application of WR-2721 achieves high concentrations in the rectal wall.
Rectal wall injury is an important treatment-related morbidity in patients treated with radiation for prostate cancer. We have undertaken this study to investigate the merits of topical intrarectal application of the radioprotective compound WR-2721. Male Copenhagen rats were injected intrarectally with 2% WR-2721 gel. At 10, 20, 30 and 40 min after application, a laparotomy was performed, and the rectum and prostate were removed. Concentrations of total WR-1065 (the active metabolite of WR-2721) were determined in these samples by an HPLC assay. While the concentration in the rectal wall tended to increase with time, it did not change substantially in the prostate. The concentration in the rectal wall was found to be significantly higher at all times. We conclude that preferential accumulation of WR-2721 in the rectal wall can be achieved by topical application. This is a promising approach to modifying rectal wall tolerance that deserves more study.
Administration, Topical↗
Radiotherapy of T1c prostate cancer.
With a 10-year local control rate of 85% to 100% and a low complication rate, radiotherapy is an effective treatment option for T1c prostate cancer. Controversial topics, such as treatment volumes and dose-response, are critically reviewed. New investigational approaches will be discussed.
Humans↗
Afterloading high dose rate intracavitary vaginal cylinder.
PURPOSE: To design an afterloading vaginal cylinder application appropriate to treat the vault with high dose rate (HDR) brachytherapy after prior total abdominal hysterectomy. METHODS AND MATERIALS: A vaginal cylinder was designed and built using nylon and source loading channels positioned for source movement for HDR vault and vaginal brachytherapy. The channels are positioned to treat a broader isodose surface and to avoid the "end" effects of linear source brachytherapy. The central channel allows an applicator tube to be advanced beyond the end of the cylinder to treat a "tented" vault or a cervical stump (or uterus). Additional peripheral sources can be added to allow vaginal wall plaque therapy. RESULTS: The application allows vault, vault plus proximal vagina, or vault plus entire vagina therapy using HDR. The isodose surface treated is controlled by source positioning and dwell times. CONCLUSION: The HDR cylinder has wide potential usability for uterus or cervix therapy as both low stage and operable endometrial carcinomas are now usually treated by surgery.
Brachytherapy↗