Quality of life 2 years after salvage cryosurgery for the treatment of local recurrence of prostate cancer after radiotherapy.

PURPOSE: Previous research has raised concerns that although salvage cryosurgery may be an effective treatment to prevent the progression of prostate cancer after radiotherapy failure, the quality of life cost many be so severe as to prevent its acceptance as a viable treatment. The present study's purpose was to further the understanding of the quality of life outcomes of salvage cryosurgery. MATERIALS AND METHODS: A total of 46 men with locally recurrent prostate cancer after radiotherapy were recruited to participate in a prospective Phase II clinical trial using salvage cryosurgery. There were 2 questionnaires (i.e., the European Organization of Research and Treatment of Cancer QLQ C30 and the Prostate Cancer Index) administered before cryosurgery, and at 1.5, 3, 6, 12, 18, and 24 months after treatment. RESULTS: Quality of life returned to preoperative levels by 24 months after cryosurgery in all domains, with the exception of urinary and sexual functioning. At 24 months, 29% of men reported urinary bother as a moderate-to-big problem, and 56% reported sexual bother as a moderate-to-big problem. CONCLUSIONS: To our knowledge, this is the first study to evaluate prospectively men's quality of life for 2 years after salvage cryosurgery for locally recurrent prostate cancer after radiotherapy. Long-term impairments in quality of life appear to be limited to the sexual and urinary function domains. Overall quality of life appears to be high. These results support salvage cryosurgery as a viable treatment option.

Abbreviated course of radiation therapy in older patients with glioblastoma multiforme: a prospective randomized clinical trial.

PURPOSE: To prospectively compare standard radiation therapy (RT) with an abbreviated course of RT in older patients with glioblastoma multiforme (GBM). PATIENTS AND METHODS: One hundred patients with GBM, age 60 years or older, were randomly assigned after surgery to receive either standard RT (60 Gy in 30 fractions over 6 weeks) or a shorter course of RT (40 Gy in 15 fractions over 3 weeks). The primary end point was overall survival. The secondary end points were proportionate survival at 6 months, health-related quality of life (HRQoL), and corticosteroid requirement. HRQoL was assessed using the Karnofsky performance status (KPS) and Functional Assessment of Cancer Therapy-Brain (FACT-Br). RESULTS: All patients had died at the time of analysis. Overall survival times measured from randomization were similar at 5.1 months for standard RT versus 5.6 months for the shorter course (log-rank test, P =.57). The survival probabilities at 6 months were also similar at 44.7% for standard RT versus 41.7% for the shorter course (lower-bound 95% CI, -13.7). KPS scores varied markedly but were not significantly different between the two groups (Wilcoxon test, P =.63). Low completion rates of the FACT-Br (45%) precluded meaningful comparisons between the two groups. Of patients completing RT as planned, 49% of patients (standard RT) versus 23% required an increase in posttreatment corticosteroid dosage (chi(2) test, P =.02). CONCLUSION: There is no difference in survival between patients receiving standard RT or short-course RT. In view of the similar KPS scores, decreased increment in corticosteroid requirement, and reduced treatment time, the abbreviated course of RT seems to be a reasonable treatment option for older patients with GBM.

Role of transrectal ultrasound guided salvage cryosurgery for recurrent prostate carcinoma after radiotherapy.

Despite improvements in treatment of localized prostate cancer, local recurrence remains a significant problem. A total of 46 patients with proven local cancer recurrence following external beam radiotherapy entered a prospective clinical trial using ultrasound-guided cryosurgery to ablate the residual prostate gland. Persistent complications included one urethra-rectal fistula, incontinence (2), retention (3), and treatment induced erectile dysfunction (7). Using the PSA definitions for biochemical failure as PSA>or=0.3 ng/ml, the Kaplan-Meier plots showed the incidence of patients to be free of biochemical recurrence at 51 and 44% at 1 and 2 y, respectively. For a PSA>or=1.0, the values at 1 and 2 y were 72 and 58%.

How often are nonenhancing supratentorial gliomas malignant? A population study.

The presence of contrast enhancement in a brain tumor is often regarded as a sign of malignancy. The authors identified 314 patients with malignant and low-grade supratentorial glial neoplasms in an unselected population, 58 of which lacked contrast enhancement on preoperative neuroimaging. Nonenhancing gliomas were malignant in approximately one third of cases, especially in older patients. Histologic confirmation of the diagnosis is therefore important in all patients suspected of harboring a primary glial neoplasm.

Does the new generation of high-flex knee prostheses improve the post-operative range of movement?: a meta-analysis.

A new generation of knee prostheses has been introduced with the intention of improving post-operative knee flexion. In order to evaluate whether this goal has been achieved we performed a systematic review and meta-analysis. Systematic literature searches were conducted on MEDLINE and EMBASE from their inception to December 2007, and proceedings of scientific meetings were also searched. Only randomised, clinical trials were included in the meta-analysis. The mean difference in the maximum post-operative flexion between the 'high-flex' and conventional types of prosthesis was defined as the primary outcome measure. A total of five relevant articles was identified. Analysis of these trials suggested that no clinically relevant or statistically significant improvement was obtained in flexion with the 'high-flex' prostheses. The weighted mean difference was 2.1° (95% confidence interval -0.2 to +4.3; p = 0.07).

Comparative study of the ThinPrep Pap test and conventional cytology results in a Canadian cohort.

OBJECTIVE: To compare the frequency of Pap test results in a prospective series of direct to vial ThinPrep tests to a cohort of conventionally prepared tests. To follow-up all test results for a minimum of 2 years and assess performance based on this outcome. METHODS: All women presenting for either routine screening or colposcopic examination in 2001 were enrolled in the ThinPrep cohort. A similar, population of conventionally prepared tests was extracted from the year 2000 laboratory data. Information on all concurrent and follow-up cervical specimens over the ensuing 2 years was retrieved. RESULTS: The ThinPrep cohort comprised 2288 Pap tests and the conventional, 2211. The frequency of normal [within normal limits (WNL) and benign cellular changes (BCC)] results in the ThinPrep cohort was 6% lower and the frequency of abnormal [> or =atypical squamous cells of undetermined significance (ASCUS)] results was 6.8% higher. Respective ThinPrep and conventional cohort results were 1156 (51%) and 1291 (58%) WNL, 625 (27%) and 561 (25%) BCC, 101 (4%) and 65 (3%) ASCUS, 21 (1%) and 2 (0.1%) atypical glandular cells of undetermined significance, 301 (13%) and 224 (10%) low-grade squamous intraepithelial lesion (LSIL), and 74 (3%) and 40 (2%) high-grade SIL (HSIL) (P < 0.0001). Follow-up was available for nearly 80% of each cohort. LSIL or higher was confirmed in 57.5% (n = 266) of the abnormal ThinPrep and 60.9% (n = 190) of the abnormal conventional tests. The ThinPrep yield of confirmed tests however was almost 50% higher than the conventional test. CONCLUSION: In this population, ThinPrep was superior to the conventional Pap test.

A phase II study of carboplatin and chronic high-dose tamoxifen in patients with recurrent malignant glioma.

PURPOSE: To determine the response rate, time to disease progression, survival, and toxicity of intravenous carboplatin and chronic oral high-dose tamoxifen in patients with recurrent malignant gliomas. PATIENTS AND METHODS: Patients with histological confirmation of recurrent malignant gliomas were eligible for this multicenter phase II trial. Treatment consisted of 400 mg/m2 carboplatin intravenously every 4 weeks and oral high dose chronic tamoxifen (80 mg bid in women and 100 mg bid in men). RESULTS: Twenty seven patients met the eligibility criteria and were evaluable for response. The histological subtypes were: 16 (59%) glioblastoma multiforme (GBM), malignant astrocytoma (5 patients), malignant mixed glioma (5 patients), and glioblastoma/gliosarcoma (1 patient). Twenty-two patients (82%) had an ECOG performance status of 0 or 1. No complete responses were observed, 4 patients (15%) achieved a partial response, and 14 patients (52%) had stable disease. Median time to progression was 3.65 months (95%CI 2.56, 4.83). Median overall survival was 14.09 months (95%CI 7.06, 19.91). One patient with a recurrent GBM had a sustained partial response and is progression free 81 months since starting treatment. Another patient with mixed malignant oligoastrocytoma also had a prolonged partial response (lasting 63 months) and is alive 84 months after treatment for recurrence. The most frequently reported grade 3 or 4 toxicities were fatigue (19%), nausea (11%) and anorexia (11%). CONCLUSIONS: Carboplatin and high dose tamoxifen has similar response rates to other regimens for recurrent malignant gliomas and are probably equivalent to those found using tamoxifen as monotherapy. Long-lasting periods of disease free survival in some patients (particularly those with malignant mixed oligo astrocytomas) were found.

Prospective trial of cryosurgical ablation of the prostate: five-year results.

OBJECTIVES: To determine in a prospective pilot study the safety and efficacy of cryosurgical ablation for localized prostate carcinoma. METHODS: A total of 87 cryosurgical procedures were performed on 76 consecutive patients between December 1994 and February 1998. All patients had histologically proved adenocarcinoma of the prostate, with prostate-specific antigen (PSA) readings of less than 30 ng/mL. Clinical evaluations, PSA determinations, and patient self-reported quality-of-life questionnaires (functional assessment of cancer treatment-prostate; FACT-P) were used to determine biochemical and clinical disease-free status and complications. Patients had a mean follow-up of 50 months (minimum 36). RESULTS: Follow-up biopsies were performed in 73 patients, and 72 were negative for malignancy after one or more treatments. Ten patients required two treatments and 1 patient required three treatments. The 5-year overall and cancer-specific survival rate was 89% (95% confidence interval, 83% to 97%) and 98.6% (95% confidence interval, 96% to 100%), respectively. The undetectable PSA rate (less than 0.3 ng/mL) for low-risk patients (n = 13) was 60% at 5 years; for moderate-risk patients (n = 23), it was 77%, and for high-risk patients (n = 40), 48%. The corresponding percentage of patients with a PSA level less than 1.0 ng/mL at 5 years was 75%, 89%, and 76%. Sloughing occurred in 3 patients (3.9%), incontinence in 1 (1.3%), and testicular abscess in 1 (1.3%). At 3 years, 18 (47%) of 38 patients capable of unassisted intercourse at the time of cryosurgery had resumed sexual intercourse, 5 spontaneously and 13 with sildenafil or prostaglandin. CONCLUSIONS: The results of this prospective evaluation show cryosurgery to be both a safe and an effective option in the treatment of localized prostate cancer.

Postoperative chemotherapy in advanced ovarian granulosa cell tumors.

The objective of this research is to assess the use of first-line postoperative chemotherapy in patients with advanced ovarian granulosa cell tumor (GCT). A retrospective population-based case series identified 60 women with stage IC or greater ovarian GCT over a 25-year period. Five patients were excluded because of incomplete information. None of the patients had received chemotherapy or radiotherapy prior to the diagnosis of advanced GCT. All patients had, at a minimum, a total abdominal hysterectomy and bilateral salpingo-oophorectomy. Pathology was centrally reviewed and the diagnosis confirmed. Of the 55 eligible patients, the 21 women with stage III and IV disease were the main focus of the study. Clinical outcomes and survival were compared between 13 women who received combination chemotherapy and eight who did not. Univariate analysis was conducted to assess the impact of age at diagnosis, size of residual disease, and adjuvant use of radiation therapy on prognosis. For the 55 patients, median age at diagnosis was 54 years (range 22-79). Median length of follow-up was 4.4 years (range 0.3-23.3). Median time to progression was 2.3 years (range 0.3-5.3). Sixty percent of those with no macroscopic disease after primary surgery recurred within 4.5 years of diagnosis. All patients with gross residual disease (>2 cm) were dead within 4 years of diagnosis. Overall 5 years survival rate was 61.6% (95% CI (49.3-76.9)). Among stage III and IV patients, there were no differences with respect to age at diagnosis and use of radiation therapy between those who did and did not receive chemotherapy. The only statistically significant difference was the presence of macroscopic residual disease (82% vs. 22%). Although there was no statistical significant difference in overall survival, there was a trend toward a poorer outcome in the group that received chemotherapy. Survival of patients with macroscopic residual disease was not influenced by use of chemotherapy (P = 0.976). We conclude that the presence of macroscopic residual disease after primary surgery was the most important prognostic factor. Although these patients were more likely to receive postoperative chemotherapy, there was no evidence to document a beneficial effect of systemic therapy in this group of women.

Reovirus as an experimental therapeutic for brain and leptomeningeal metastases from breast cancer.

Brain and leptomeningeal metastases are common in breast cancer patients and our current treatments are ineffective. Reovirus type 3 is a replication competent, naturally occurring virus that usurps the activated Ras-signaling pathway (or an element thereof) of tumor cells and lyses them but leaves normal cells relatively unaffected. In this study we evaluated reovirus as an experimental therapeutic in models of central nervous system (CNS) metastasis from breast cancer. We found all breast cancer cell lines tested were susceptible to reovirus, with > 50% of these cells lysed within 72 h of infection. In vivo neurotoxicity studies showed only mild local inflammation at the injection site and mild communicating hydrocephalus with neither diffuse encephalitis nor behavioral abnormalities at the therapeutically effective dose of reovirus (intracranial) (ie 10(7) plaque-forming units) or one dose level higher. In vivo, a single intratumoral administration of reovirus significantly reduced the size of tumors established from two human breast cancer cell lines and significantly prolonged survival. Intrathecal administration of reovirus also remarkably prolonged survival in an immunocompetent racine model of leptomeningeal metastases. These data suggest that the evaluation of reovirus as an experimental therapeutic for CNS metastases from breast cancer is warranted.