High-intensity focused ultrasound for prostate cancer: a practice guideline

Objective:

The aim of this practice guideline was to develop evidence-based recommendations for clinicians on the use of high-intensity focused ultrasound (HIFU) in patients with localized prostate cancer.

Methods:

The guideline was developed using the methods of Cancer Care Ontario’s Program in Evidence-Based Care (PEBC). The core methodology of the PEBC’s guideline development process is systematic review. A comprehensive literature search was undertaken to identify high-quality studies, reviews and other practice guidelines on the use of HIFU in prostate cancer. The evidence formed the basis of the recommendations, which were reviewed and amended where necessary, by clinical experts in medical and radiation oncology and urology.

Results:

The literature review yielded limited evidence. No randomized controlled trials or meta-analyses comparing HIFU with currently accepted management approaches were identified. The body of evidence is primarily based on data from case series. Internal feedback was provided by the PEBC Genitourinary Disease Site Group membership and the Report Approval Panel. External peer review included targeted review by clinical experts specifically requested to comment on the guideline, and professional consultation through an online survey of health care professionals.

Conclusion:

HIFU is currently not recommended as an alternative to accepted curative treatment approaches for localized prostate cancer.     

MRI simulation: effect of gradient distortions on three-dimensional prostate cancer plans

PURPOSE: To quantify the dosimetric consequences of external patient contour distortions produced on low-field and high-field MRIs for external beam radiation of prostate cancer. METHODS AND MATERIALS: A linearity phantom consisting of a grid filled with contrast material was scanned on a spiral CT, a 0.23 T open MRI, and a 1.5 T closed bore system. Subsequently, 12 patients with prostate cancer were scanned on CT and the open MRI. A gradient distortion correction (GDC) program was used to postprocess the MRI images. Eight of the patients were also scanned on the 1.5 T MRI with integrated GDC correction. All data sets were fused according to their bony landmarks using a chamfer-matching algorithm. The prostate volume was contoured on an MRI image, irrespective of the apparent prostate location in those sets. Thus, the same target volume was planned and used for calculating the anterior-posterior (AP) and lateral separations. The number of monitor units required for treatment using a four-field conformal technique was compared. Because there are also setup variations in patient outer contours, two different CT scans from 20 different patients were fused, and the differences in AP and lateral separations were measured to obtain an estimate of the mean interfractional separation variation. RESULTS: All AP separations measured on MRI were statistically indistinguishable from those on CT within the interfractional separation variations. The mean differences between CT and low-field MRI and CT and high-field MRI lateral separations were 1.6 cm and 0.7 cm, respectively, and were statistically significantly different from zero. However, after the GDC was applied to the low-field images, the difference became 0.4 +/- 0.4 mm (mean +/- standard deviation), which was statistically insignificant from the CT-to-CT variations. The mean variations in the lateral separations from the low-field images with GDC would result in a dosimetric difference of <1%, assuming an equally weighted four-field 18-MV technique for patient separations up to approximately 40 cm. CONCLUSIONS: For patients with lateral separations <40 cm, a homogeneous calculation simulated using a 1.5 T MRI or a 0.23 T MRI with a gradient distortion correction will yield a monitor unit calculation indistinguishable from that generated using CT simulation.     

Apolipoprotein E polymorphism, serum lipids and occurrence of "double pre-betalipoproteinemia' (DPBL) in subjects from two different populations

The association between apolipoprotein E phenotype and the presence of 2 electrophoretic populations of very low density (VLDL) lipoproteins from human sera, double pre-beta(VLDL)lipoproteinemia (DPBL), was studied in 2 groups of subjects, one from Italy and one from Finland. In both populations the prevalence of DPBL was significantly higher in subjects with E4/4 and E4/3 phenotypes than in the other phenotypes not containing the E4 isoprotein. This finding suggests that the presence of a structural variant of the apo E protein, the isoprotein E4, may be causally related to the appearance of DPBL phenomenon.     

Antifilaggrin antibodies in recent-onset arthritis

We evaluated the sensitivity and prognostic value of an enzyme-linked immunosorbent assay (ELISA) for the measurement of antifilaggrin antibodies (AFA), using filaggrin purified from human skin as an antigen. The AFA test was applied to a series of 306 patients with various recent-onset inflammatory joint diseases. The results were compared to those of the conventional immunofluorescence tests for antikeratin antibody (AKA) and antiperinuclear factor (APF) and of the rheumatoid factor (RF) tests from a previous study. There was a very good agreement between the results of the tests for APF and AFA (kappa-value 0.79 in patients with peripheral poly/oligoarthritis). The agreement between the tests for AKA and AFA was significant but less pronounced (kappa-value 0.50). The AFA test detected 10/22 of the RF-negative erosive cases, particularly those with a large number of erosive joints. Thus, the test for AFA supplements RF in the prediction of erosiveness.     

Controversies in prostate cancer radiotherapy: consensus development

The GU Radiation Oncologists of Canada (GUROC) had a consensus meeting in November 2000 to discuss and develop consensus on four controversial areas: risk assessment of localized prostate cancer, conformal radiotherapy, role of brachytherapy in prostate cancer and combined hormonal therapy and radiotherapy for prostate cancer. The meeting was a success and resulted in consensus being achieved on a number of areas. The group agreed on three risk groupings: low risk, intermediate risk and high risk localized prostate cancer based on clinical stage, Gleason score and PSA level. The participants agreed that based on available toxicity data from randomized controlled trials, conformal treatment techniques should be offered to patients receiving prostatic radiotherapy. Consensus was reached on the role of dose escalation in each of the three risk groups and is summarized in the article. At present there is insufficient evidence from randomized clinical trials to recommend the use of brachytherapy over current other standard therapy (radical prostatectomy or external beam radiotherapy). Non randomized published studies show promising short and intermediate term results. Where ever possible patients should be approached about participation in ongoing RCT's evaluating brachytherapy versus current other standard therapy. Outside a clinical trial the participants felt permanent seed implants should be considered an acceptable treatment option for appropriate patients with low risk prostate cancer. Based on randomized controlled trials the group agreed that patients with high risk disease should be treated with prolonged (up to 2-3 years) adjuvant hormonal therapy. Part of this hormonal treatment may be given in a neoadjuvant fashion. The group agreed that adjuvant hormones should not be routinely used in low and intermediate risk patients. Neoadjuvant hormones have been demonstrated to improve outcome in patients with bulky tumors. The role of neoadjuvant hormones in other patients with intermediate and low risk prostate cancer is unclear and will be clarified with the publication of recently completed studies. The consensus meeting strongly endorsed continued accrual to current studies investigating clinically relevant questions.     

Improved separation of PCR amplified VNTR alleles by a vertical polyacrylamide gel electrophoresis

Summary The effect of a stacking gel, the pH and cross-linking agent concentration on the resolution and sharpness of PCR amplified VNTR alleles in a vertical discontinuous polyacrylamide gel electrophoresis system was investigated. The experiments show that the use of a low crosslinking agent concentration, a stacking gel and a wide pH difference between the gel buffer and the electrophoresis buffer at the beginning of the electrophoresis resulted in reduced band width and increasing resolution in silver-stained polyacrylamide gels. The importance of sharp DNA fragments is especially emphasized when analyzing multi-allelic DNA loci, that exhibit alleles differing from only few by to few dozen by in length, such as variable number of tandem repeat (VNTR) or short tandem repeat (STR) loci.     

Primitive neuroectodermal tumors of the uterus: a report of four cases.

Four cases of primitive neuroectodermal tumor (PNET) of the uterine corpus are reported, bringing the total number of reported PNETs in this site to seven. The four women were in their seventh decade of life and presented with abnormal vaginal bleeding and, in two cases, an enlarged uterus. The patients underwent total or subtotal abdominal hysterectomy and bilateral salpingo-oophorectomy and, in one patient, pelvic lymphadenectomy. Three patients received postoperative radiation therapy, chemotherapy, or both. Gross examination revealed fleshy polypoid masses filling the endometrial cavity and, in two cases, deeply invading the myometrium. Histologic, immunohistochemical, and, in two cases, ultrastructural examination revealed typical PNETs that exhibited variable degrees of neural, glial, ependymal, and medulloepithelial differentiation. Two PNETs were admixed with other neoplasms: in one case a grade I endometrial adenocarcinoma and in the other a low-grade endometrial stromal sarcoma. The prognosis of the tumors was related to their stage: two patients with stage I tumor were alive with no evidence of disease at 5 and 6 years, whereas two patients with stage III or IV tumor died of tumor at 6 and 12 months. Although it has been suggested that uterine PNETs may be derived from displaced germ cells or implanted fetal tissues, evidence provided by this study, including the advanced ages of the patients and an admixture with neoplasms of unquestioned müllerian origin, suggests a müllerian origin for these tumors in at least some cases.     

The relationship between the bladder and the cervix in patients undergoing intracavitary therapy

Previous studies have shown a poor correlation between bladder damage and bladder dosage in patients treated with radiation therapy, including intracavitary therapy for uterine tumours. This study was undertaken to investigate prospectively the relationship between the cervical os and the bladder in patients undergoing intracavitary treatment. The computed tomography scans of 59 patients undergoing intracavitary treatment were analysed. The upper limit of the undistended bladder relative to the os extended from 5.5 cm cephalic to the cervix to 4.0 cm below it. The distance from the central tube to the posterior bladder wall at the level of the cervix ranged from 1.5 cm to 4.2 cm. This was positively associated with size of ovoid (p = 0.022), though with considerable individual variation. A separate analysis failed to show a consistent correlation with age or stage of disease. Thirty-nine of the 59 patients (65.5%) had asymmetrical bladders. Of these, half had "slight" asymmetry and the others had "marked" asymmetry. The thickness of the vesico-vaginal septum varied from 0.5 cm to 2.9 cm but was difficult to assess in some patients. In patients treated with medium-sized ovoids and those with Stage IB and IIB disease, the distance to the bladder base is greatest, though there is marked individual variation. These investigations reveal a marked variation in bladder position relative to the cervix in patients undergoing intracavitary therapy. The position of the bladder cannot be accurately predicted by any of these clinical criteria and requires to be defined by a radiological technique in the individual patient.     

Non-hormonal systemic therapy in men with hormone-refractory prostate cancer and metastases: a systematic review from the Cancer Care Ontario Program in Evidence-based Care's Genitourinary Cancer Disease Site Group

Background

Prostate cancer that has recurred after local therapy or disseminated distantly is usually treated with androgen deprivation therapy; however, most men will eventually experience disease progression within 12 to 20 months. New data emerging from randomized controlled trials (RCTs) of chemotherapy provided the impetus for a systematic review addressing the following question: which non-hormonal systemic therapies are most beneficial for the treatment of men with hormone-refractory prostate cancer (HRPC) and clinical evidence of metastases?

Methods

A systematic review was performed to identify RCTs or meta-analyses examining first-line non-hormonal systemic (cytotoxic and non-cytotoxic) therapy in patients with HRPC and metastases that reported at least one of the following endpoints: overall survival, disease control, palliative response, quality of life, and toxicity. Excluded were RCTs of second-line hormonal therapies, bisphosphonates or radiopharmaceuticals, or randomized fewer than 50 patients per trial arm. MEDLINE, EMBASE, the Cochrane Library, and the conference proceedings of the American Society of Clinical Oncology were searched for relevant trials. Citations were screened for eligibility by four reviewers and discrepancies were handled by consensus.

Results

Of the 80 RCTs identified, 27 met the eligibility criteria. Two recent, large trials reported improved overall survival with docetaxel-based chemotherapy compared to mitoxantrone-prednisone. Improved progression-free survival and rates of palliative and objective response were also observed. Compared with mitoxantrone, docetaxel treatment was associated with more frequent mild toxicities, similar rates of serious toxicities, and better quality of life. More frequent serious toxicities were observed when docetaxel was combined with estramustine. Three trials reported improved time-to-disease progression, palliative response, and/or quality of life with mitoxatrone plus corticosteroid compared with corticosteroid alone. Single trials reported improved disease control with estramustine-vinblastine, vinorelbine-hydrocortisone, and suramin-hydrocortisone compared to controls. Trials of non-cytotoxic agents have reported equivocal results.

Conclusion

Docetaxel-based chemotherapy modestly improves survival and provides palliation for men with HRPC and metastases. Other than androgen deprivation therapy, this is the only other therapy to have demonstrated improved overall survival in prostate cancer in RCTs. Further investigations to identify more effective therapies for HRPC including the use of systemic therapies earlier in the natural history of prostate cancer are warranted.