Stereotactic Ablative Radiotherapy Versus Low Dose Rate Brachytherapy or External Beam Radiotherapy: Propensity Score Matched Analyses of Canadian Data.

AIMS: To compare biochemical failure-free survival (BFFS) and overall survival for prostate cancer treated with stereotactic ablative radiotherapy (SABR), low dose rate (LDR) brachytherapy or external beam radiotherapy (EBRT) using a large Canadian multi-institutional database. MATERIALS AND METHODS: Patients with low risk localised prostate cancer treated with SABR, LDR or EBRT and no androgen deprivation therapy were selected. Propensity score matching was used to create two sets of matched cohorts with LDR and EBRT serving as control groups. Kaplan-Meier survival analysis and Cox proportional hazards regression were used to compare differences in BFFS and overall survival between treatment groups. RESULTS: The pre-matched cohort contained 602 patients; the median follow-up was >5.0 years. There were no significant differences in BFFS before or after matching for SABR versus LDR but the prostate-specific antigen (PSA) nadir was lower after LDR. For the SABR versus EBRT, SABR had a BFFS trend before matching (P = 0.08), which became significant after matching (P < 0.001). CONCLUSIONS: Using the Genitourinary Radiation Oncologists of Canada Prostate Cancer Risk Stratification database, low risk prostate cancer patients receiving SABR had similar BFFS compared with patients receiving LDR but better BFFS than EBRT patients. Further comparative studies of efficacy, quality of life and economic outcomes using a broader risk of patients are warranted.

Development & validation of a quantitative anti-protective antigen IgG enzyme linked immunosorbent assay for serodiagnosis of cutaneous anthrax.

BACKGROUND & OBJECTIVES: Anthrax caused by Bacillus anthracis is primarily a disease of herbivorous animals, although several mammals are vulnerable to it. ELISA is the most widely accepted serodiagnostic assay for large scale surveillance of cutaneous anthrax. The aims of this study were to develop and evaluate a quantitative ELISA for determination of IgG antibodies against B. anthracis protective antigen (PA) in human cutaneous anthrax cases. METHODS: Quantitative ELISA was developed using the recombinant PA for coating and standard reference serum AVR801 for quantification. A total of 116 human test and control serum samples were used in the study. The assay was evaluated for its precision, accuracy and linearity. RESULTS: The minimum detection limit and lower limit of quantification of the assay for anti-PA IgG were 3.2 and 4 µg/ml, respectively. The serum samples collected from the anthrax infected patients were found to have anti-PA IgG concentrations of 5.2 to 166.3 µg/ml. The intra-assay precision per cent CV within an assay and within an operator ranged from 0.99 to 7.4 per cent and 1.7 to 3.9 per cent, respectively. The accuracy of the assay was high with a per cent error of 6.5 - 24.1 per cent. The described assay was found to be linear between the range of 4 to 80 ng/ml (R [2] = 0.9982; slope = 0.9186; intercept = 0.1108). INTERPRETATION & CONCLUSIONS: The results suggested that the developed assay could be a useful tool for quantification of anti-PA IgG response in human after anthrax infection or vaccination.

Serodiagnosis of human cutaneous anthrax in India using an indirect anti-lethal factor IgG enzyme-linked immunosorbent assay.

Anthrax, caused by Bacillus anthracis, is primarily a zoonotic disease. Being a public health problem also in several developing countries, its early diagnosis is very important in human cases. In this study, we describe the use of an indirect enzyme-linked immunosorbent assay (ELISA) for detection of anti-lethal factor (anti-LF) IgG in human serum samples. A panel of 203 human serum samples consisting of 50 samples from patients with confirmed cutaneous anthrax, 93 samples from healthy controls from areas of India where anthrax is nonendemic, 44 samples from controls from an area of India where anthrax is endemic, and 16 patients with a disease confirmed not to be anthrax were evaluated with an anti-LF ELISA. The combined mean anti-LF ELISA titer for the three control groups was 0.136 ELISA unit (EU), with a 95% confidence interval (CI) of 0.120 to 0.151 EU. The observed sensitivity and specificity of the ELISA were 100% (95% CI, 92.89 to 100%) and 97.39% (95% CI, 93.44 to 99.28%), respectively, at a cutoff value of 0.375 EU, as decided by receiver operating characteristic (ROC) curve analysis. The likelihood ratio was found to be 49.98. The positive predictive value (PPV), negative predictive value (NPV), efficiency, and Youden's index (J) for reliability of the assay were 92.5%, 100%, 98.02%, and 0.97, respectively. The false-positive predictive rate and false-negative predictive rate of the assay were 2.61% and 0%. The assay could be a very useful tool for early diagnosis of cutaneous anthrax cases, as antibodies against LF appear much earlier than those against other anthrax toxins in human serum samples.

High-intensity focused ultrasound for prostate cancer: a systematic review.

High-intensity focused ultrasound (HIFU) has recently been promoted as a non-invasive treatment option for prostate cancer. This systematic review sought to evaluate the evidence comparing it with standard treatment in patients with localised prostate cancer. The literature review included searches of MEDLINE, EMBASE, the Cochrane Library, annual meetings' abstracts and websites of evidence-based practice guideline producers. Studies were included if they were randomised controlled trials comparing HIFU with current management approaches, or were meta-analyses, systematic reviews or practice guidelines addressing HIFU. No randomised controlled trials or meta-analyses were identified. Seven systematic reviews and two practice guidelines were identified; neither contained randomised controlled trials. Adjusting the selection criteria to include case series found 34 clinical studies of HIFU. Twenty-nine evaluated HIFU as the primary treatment and five examined HIFU as salvage treatment for recurrence after radiotherapy. In most studies the outcomes used to determine efficacy were negative biopsy rates or prostate-specific antigen (PSA) levels. Among the 29 studies of HIFU as the primary treatment, negative biopsy rates ranged from 35 to 95% in 21 studies, a PSA nadir of ≤0.5 ng/ml ranged from 55 to 91% in 10 studies and mean PSA nadirs ranged from 0 to 1.9 ng/ml in 17 studies. Five studies reported 5-year disease-free survival rates ranging from 55 to 95%. Among five studies of HIFU as salvage treatment, negative biopsy rates ranged from 73 to 84% in four studies, a PSA nadir of ≤0.5 ng/ml ranged from 57 to 66% in three studies and mean PSA nadirs were 1.97 and 2.38 ng/ml in two studies, respectively. Current evidence on HIFU use in prostate cancer patients is of low quality, rendering it difficult to draw conclusions about its efficacy. Until results from case series are confirmed in prospective studies, the widespread use of HIFU is not supported.

Management of stage I seminomatous testicular cancer: a systematic review.

The treatment options available for the management of stage I seminoma consist of either a surveillance strategy or adjuvant therapy after orchidectomy. A systematic review was undertaken to identify the optimal management strategy. The MEDLINE and EMBASE databases, in addition to the American Society of Clinical Oncology Meeting Proceedings, were searched for the period 1981 to May 2007. Studies were eligible for inclusion if they discussed at least one of survival, recurrence, second malignancy, cardiac toxicity, or quality of life for patients with stage I seminoma. A search update was carried out in June 2009. Fifty-four reports satisfied the eligibility criteria, including seven clinical practice guidelines, one systematic review, three randomised controlled trials focused on treatment options, 26 non-randomised studies of treatment options, and 15 non-randomised long-term toxicity studies. The existing data suggest that virtually all patients with stage I testicular seminoma are cured regardless of the post-orchidectomy management. The 5-year survival reported in all the studies identified in this systematic review was over 95%, regardless of the management strategy, including surveillance alone with no adjuvant therapy. In conclusion, to date, the optimal management of stage I seminoma remains to be defined. Surveillance seems to be the preferable option, as this strategy minimises the toxicity that might be associated with adjuvant treatment, while preserving high long-term cure rates. The currently available evidence should be presented to patients in order to select the most appropriate option for the individual.

Adjuvant external beam radiotherapy in the treatment of endometrial cancer (MRC ASTEC and NCIC CTG EN.5 randomised trials): pooled trial results, systematic review, and meta-analysis.

BACKGROUND: Early endometrial cancer with low-risk pathological features can be successfully treated by surgery alone. External beam radiotherapy added to surgery has been investigated in several small trials, which have mainly included women at intermediate risk of recurrence. In these trials, postoperative radiotherapy has been shown to reduce the risk of isolated local recurrence but there is no evidence that it improves recurrence-free or overall survival. We report the findings from the ASTEC and EN.5 trials, which investigated adjuvant external beam radiotherapy in women with early-stage disease and pathological features suggestive of intermediate or high risk of recurrence and death from endometrial cancer. METHODS: Between July, 1996, and March, 2005, 905 (789 ASTEC, 116 EN.5) women with intermediate-risk or high-risk early-stage disease from 112 centres in seven countries (UK, Canada, Poland, Norway, New Zealand, Australia, USA) were randomly assigned after surgery to observation (453) or to external beam radiotherapy (452). A target dose of 40-46 Gy in 20-25 daily fractions to the pelvis, treating five times a week, was specified. Primary outcome measure was overall survival, and all analyses were by intention to treat. These trials were registered ISRCTN 16571884 (ASTEC) and NCT 00002807 (EN.5). FINDINGS: After a median follow-up of 58 months, 135 women (68 observation, 67 external beam radiotherapy) had died. There was no evidence that overall survival with external beam radiotherapy was better than observation, hazard ratio 1.05 (95% CI 0.75-1.48; p=0.77). 5-year overall survival was 84% in both groups. Combining data from ASTEC and EN.5 in a meta-analysis of trials confirmed that there was no benefit in terms of overall survival (hazard ratio 1.04; 95% CI 0.84-1.29) and can reliably exclude an absolute benefit of external beam radiotherapy at 5 years of more than 3%. With brachytherapy used in 53% of women in ASTEC/EN.5, the local recurrence rate in the observation group at 5 years was 6.1%. INTERPRETATION: Adjuvant external beam radiotherapy cannot be recommended as part of routine treatment for women with intermediate-risk or high-risk early-stage endometrial cancer with the aim of improving survival. The absolute benefit of external beam radiotherapy in preventing isolated local recurrence is small and is not without toxicity.

Maximal androgen blockade for the treatment of metastatic prostate cancer--a systematic review.

INTRODUCTION: Maximal androgen blockade (MAB) versus castration alone in patients with metastatic prostate cancer has been extensively evaluated in randomized trials. The inconsistent results have led to the publication of multiple meta-analyses. The present review examines the evidence from meta-analytic reports to determine whether MAB using agents such as flutamide, nilutamide, and cyproterone acetate (CPA) is associated with a survival advantage. METHODS: We conducted a systematic review of the literature (MEDLINE, EMBASE, and the Cochrane Library through July 2004; CANCERLIT through October 2002) for meta-analyses that compared MAB with castration alone in previously untreated men with metastatic prostate cancer (D1 or D2, N+/M0 or M1). Two reviewers selected papers for eligibility; disagreement was resolved by all the authors through consensus. RESULTS: The literature search identified six meta-analyses that met the eligibility criteria of the review. Two of those reports were based on individual patient data (IPD), and four were based on data from the published literature. All six meta-analyses pooled data on overall survival. The best evidence came from the largest meta-analysis, conducted by the Prostate Cancer Trialists Collaborative Group and based on IPD (8725 patients) from 27 trials. That analysis detected no difference in overall survival between mab and castration alone at 2 or 5 years. However, a subgroup analysis showed that MAB with nonsteroidal anti-androgens (NSAAS) was associated with a statistically significant improvement in 5-year survival over castration alone (27.6% vs. 24.7%; p = 0.005). The combination of MAB with CPA, a steroidal anti-androgen, was associated with a statistically significant increased risk of death (15.4% vs. 18.1%; p = 0.04). Compared with castration alone, MAB was associated with more side effects (that is, gastrointestinal, endocrine function) and reduced quality of life in domains related to treatment symptoms and emotional functioning. CONCLUSIONS: The small survival benefit conferred by MAB with NSAA is of questionable clinical significance given the added toxicity and concomitant decline in quality of life observed in patients treated with MAB. Therefore, combined treatment with flutamide or nilutamide should not be routinely offered to patients with meta-static prostate cancer beyond the purpose of blocking testosterone flare. Monotherapy, consisting of orchiectomy or the administration of a luteinizing hormone-releasing hormone agonist is recommended as standard treatment.

Combined gamma-irradiation and subsequent cisplatin treatment in human squamous carcinoma cell lines sensitive and resistant to cisplatin.

PURPOSE: To investigate the effects of combined radiation and subsequent cisplatin treatment on the human squamous carcinoma cell line SCC-25 and its cisplatin-resistant derivative SCC-25/CP. MATERIALS AND METHODS: SCC-25 and SCC-25/CP cells were treated with various gamma-ray doses (5 cGy-7 Gy) followed 60 min later by cisplatin treatment and subsequently assayed for survival using a conventional colony assay. For SCC-25, the subsequent cisplatin treatment was 0.1, 1, 10 and 20 microM for 1 h. For the more cisplatin-resistant SCC-25/CP cells, the subsequent cisplatin treatment was 10 and 50 microM for 1 h. RESULTS: The cisplatin-resistant SCC-25/CP cells were not cross-resistant to gamma-irradiation. Subsequent treatment with an LD50 concentration of cisplatin (10 and 50 microM for SCC-25 and SCC-25/CP, respectively) resulted in radiosensitization for SCC-25/CP but not for SCC-25 cells. Gamma-irradiation of SCC-25/CP cells followed by treatment with 10 and 50 microM cisplatin for 1 h resulted in radiation survival curves displaying a significant low-dose hypersensitive region followed by increased radioresistance at higher doses. A total of 10 microM cisplatin resulted in radiosensitization confined to the low-dose region (0.05 and 0.25 Gy), whereas the higher cisplatin treatment of 50 microM resulted in the appearance of a hypersensitive region together with a reduction of the increased radioresistance region. In contrast, cisplatin treatment (0.1, 1, 10 and 20 microM for 1 h) of SCC-25 cells had no significant effect on survival following 2.5 or 7.0 Gy and actually resulted in an increased low-dose radiation survival (0.05, 0.25 and 1 Gy) when survival was corrected for cisplatin treatment (p<0.01 for all cisplatin concentrations tested). CONCLUSIONS: The significant radiosensitization for SCC-25/CP given subsequent treatment with 50 microM cisplatin indicates cisplatin can inhibit the increased radioresistance response in SCC-25/CP cells. In contrast, the subsequent cisplatin treatment of SCC-25 cells can enhance their survival following low radiation doses.

Concurrent cisplatin-based chemotherapy plus radiotherapy for cervical cancer--a meta-analysis.

PURPOSE: To evaluate the role of concurrent cisplatin plus radiotherapy in the treatment of cervical cancer. METHODS: A systematic review of randomized trials of cisplatin administered concurrently with external beam radiotherapy versus radiotherapy without cisplatin for cervical cancer was combined with a meta-analysis of results abstracted from published reports of the trials. RESULTS: Pooled survival rates from eight randomized trials that evaluated the role of cisplatin, alone or in combination with other chemotherapy agents, administered concurrently with external beam radiotherapy to patients with cervical cancer demonstrated a statistically significant effect in favour of cisplatin-based chemotherapy plus radiotherapy compared with radiotherapy without cisplatin (relative risk [RR] of death, 0.74; 95% confidence interval [CI], 0.64 to 0.86). The pooled RR of death among the six trials that enrolled only women with locally advanced cervical cancer was 0.78 (95% CI, 0.67 to 0.90). The pooled relative risk for the two trials in high-risk early-stage disease also demonstrated a statistically significant benefit for the addition of cisplatin-based chemotherapy to radiotherapy (RR=0.56; 95% CI, 0.41 to 0.77). CONCLUSION: This meta-analysis confirms that treatment with concurrent cisplatin-based chemotherapy plus radiotherapy improves overall survival over various controls in women with locally advanced cervical cancer, large stage IB tumours (prior to surgery) and high-risk early-stage disease (following surgery). The variation in control treatments and the quality of their delivery among the randomized trials makes interpretation difficult. Nonetheless, the meta-analysis supports the use of concurrent cisplatin with radical radiotherapy in the treatment of cervical cancer.

Phase III trial comparing radical radiotherapy with and without cisplatin chemotherapy in patients with advanced squamous cell cancer of the cervix.

PURPOSE: To test the hypothesis that cisplatin (CDDP) administered concurrently with standard radiotherapy (RT) would improve pelvic control and survival in patients with advanced squamous cell cancer of the cervix. PATIENTS AND METHODS: A total of 259 patients with International Federation of Gynecology and Obstetrics stage IB to IVA squamous cell cervical cancer with central disease greater-than-or-equal 5 cm or histologically confirmed pelvic lymph node involvement were randomized to receive RT (external-beam RT plus brachytherapy) plus weekly CDDP chemotherapy (40 mg/m(2)) (arm 1) or the same RT without chemotherapy (arm 2). RESULTS: A total of 253 patients were available for analysis. Median follow-up was 82 months. No significant difference was found in progression-free survival (P =.33). No significant difference in 3- and 5-year survival rates was found (69% v 66% and 62% v 58%, respectively; P =.42). The hazard ratio for survival (arm 2 to arm 1) was 1.10 (95% confidence interval, 0.75 to 1.62). CONCLUSION: This study did not show a benefit to either pelvic control or survival by adding concurrent weekly CDDP chemotherapy in a dose of 40 mg/m(2) to radical RT as given in this trial. Careful attention to RT details is important for achieving optimum outcome for patients with this disease.

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.

Cutaneous metastasis of papillary serous uterine cancer.

BACKGROUND: Cutaneous metastases from uterine cancer are uncommon. They usually indicate the aggressive nature of the underlying disease. CASE: A 65-year-old patient presented with stage 3 papillary serous carcinoma of the uterus. Eight months after surgery and pelvic radiation therapy, this patient presented with cutaneous metastases. A single cobalt field was used on three occasions over the next 9 months to provide symptomatic control of the abdominal and vulvar cutaneous metastases. CONCLUSIONS: This is the first case report of cutaneous metastases from papillary serous cancer of the uterus. Cutaneous metastases were the first indication of unsuspected occult disease. Palliative local radiation has a useful role in controlling symptoms like pruritus.

Systematic overview of the evidence for brachytherapy in clinically localized prostate cancer.

BACKGROUND: Brachytherapy (permanent implantation of radioactive seeds) has emerged as an alternative to existing standard therapy with radical prostatectomy or external beam radiotherapy in the treatment of clinically localized (T1 and T2) prostate cancer. The Genitourinary Cancer Disease Site Group of the Cancer Care Ontario Practice Guidelines Initiative examined the role of brachytherapy in treating clinically localized prostate cancer. METHODS: A systematic review of articles published from 1988 to April 1999, retrieved through a search of MEDLINE and CANCERLIT databases, was combined with a consensus interpretation of the evidence in the context of conventional practice. RESULTS: Although there were no randomized trials comparing brachytherapy with standard treatment, evidence was available from 13 case series and 3 cohort studies. Rates of freedom from biochemical failure (biochemically no evidence of disease [bNED]) varied considerably from one series to another and were highly dependent on tumour stage, grade and pretreatment serum prostate-specific antigen (PSA) levels. Results in patients with favourable tumours (T1 or T2 tumour, Gleason score of 6 or lower, serum PSA level of 10 ng/mL [microgram/L] or less) were comparable to those in patients undergoing radical prostatectomy. Acute urinary retention was reported in 1%-14% of patients. Long-term sequelae occurred in less than 5% of patients and included urinary incontinence, cystitis, urethral strictures and proctitis. Sexual potency was maintained after implantation in 86%-96% of patients. INTERPRETATION: At present, there is insufficient evidence to recommend the use of brachytherapy over current standard therapy for localized prostate cancer. Brachytherapy using transrectal ultrasound guidance for seed implantation is promising in terms of freedom from biochemical failure in selected patients with early-stage prostate cancer. Brachytherapy is currently available outside of clinical trials, but whenever possible patients should be asked to participate in randomized trials comparing brachytherapy and current standard therapy. Brachytherapy should be available to selected patients (those with T1c or T2a tumours, a Gleason score of 6 or lower and a serum PSA level of 10 micrograms/L or less), after discussion of the available data and potential adverse effects.

Surveillance programs for early stage non-seminomatous testicular cancer: a practice guideline.

BACKGROUND AND PURPOSE: To identify an appropriate surveillance program for men with clinical stage I non-seminomatous germ cell tumors of the testis (NSGCT). MATERIALS AND METHODS: A systematic review of the published literature was combined with a consensus process, around the interpretation of the evidence in the context of conventional practice, to develop an evidence-based practice guideline. RESULTS: No randomized controlled trials (RCTs) comparing surveillance schedules were found, but data from 12 case series and one RCT which compared radiotherapy with surveillance were reviewed. Variations in the schedules were not associated with observed variations in relapse, salvage, or survival rates. CONCLUSIONS: Men with clinical stage I testicular cancer, as defined by a normal physical examination, normal radiological scans (computed tomography [CT]) and serum markers (alpha-fetoprotein [AFP] and beta-subunit of human chorionic gonadotropin (betaHCG) which are normal or fall within normal limits during their expected half-lives, are eligible for surveillance. A recommended surveillance schedule is as follows: 1) Physical examination, blood serum marker tests (AFP and HCG), and chest x-rays should be conducted every month in the first year, every 2 months in the second year, every 3 months in the third year, and every 6 months in the fourth and fifth years; and 2) CT scans of the abdomen and pelvis should be conducted every 3 months in the first year, every 4 to 6 months in the second year and every 6 months in the third year, and once a year in the fourth and fifth year.

Pre-exposure of human squamous carcinoma cells to low-doses of gamma-rays leads to an increased resistance to subsequent low-dose cisplatin treatment.

PURPOSE: To investigate low-dose hypersensitivity to cisplatin and increased resistance at higher doses of cisplatin for the human squamous carcinoma cell line SCC-25 and its cisplatin-resistant derivative SCC-25/CP, and to examine the effects of pre- and post-treatment of SCC-25 cells with low-doses of gamma-rays on their resistance to cisplatin. MATERIALS AND METHODS: SCC-25 and SCC-25/CP cells were treated with various cisplatin concentrations (0.1 to 20 microM for 1 h) and assayed for survival using a conventional colony assay. For SCC-25, various doses of gamma-rays (5 cGy to 2.5 Gy) were given either 10 or 60 min before the cisplatin challenge dose as well as either 10 or 60 min after the cisplatin challenge dose. RESULTS: Low-dose (0.5, 0.75 and 1 microM for 1 h) hypersensitivity to cisplatin and increased resistance at higher doses was detected for the SCC-25 cell line, but not for its cisplatin-resistant derivative, SCC-25/CP. Pretreatment of SCC-25 cells with an acute low-dose of 5, 25 cGy or 1 Gy gamma-rays given 60 min before a low-dose cisplatin challenge (0.1 and 1 microM for 1 h) resulted in a significant increase in resistance (p=0.2, 0.01 and <0.001 respectively). For pretreatment of SCC-25 cells with similar low-doses of gamma-rays 10 min before the challenge cisplatin dose, the increased resistance was reduced or absent and was only significantly increased for pretreatment with 25 cGy and a challenge cisplatin dose of 0.1 microM for 1 h (p = 0.02). Similar acute low-doses of y-rays given either 10 or 60 min after the challenge cisplatin dose did not increase resistance. CONCLUSIONS: The human squamous carcinoma cell line SCC-25 showed a low-dose hypersensitivity to cisplatin followed by increased resistance at higher doses. Treatment of SCC-25 cells with low-doses of gamma-rays can induce a protective effect to a subsequent low-dose cisplatin challenge.

Use of strontium-89 in endocrine-refractory prostate cancer metastatic to bone. Provincial Genitourinary Cancer Disease Site Group.

GUIDELINE QUESTION: What is the role of strontium-89 in effective palliative care of patients with stage D endocrine-refractory prostate cancer and multiple sites of painful bone metastases? OBJECTIVE: To make recommendations about the routine use of 89Sr in this clinical setting. OUTCOMES: Effective palliation is the primary outcome of interest. Patient survival and toxic effects of treatment are also considered. PERSPECTIVE (VALUES): Evidence was selected and reviewed by 3 members of the Genitourinary Cancer Disease Site Group (Genitourinary Cancer DSG) of the Cancer Care Ontario Practice Guidelines Initiative. Earlier drafts of the guideline were circulated and reviewed by members of the DSG. The Genitourinary Cancer DSG comprises medical oncologists, radiation oncologists, urologists, a pathologist and a community representative. Guideline approval requires input from community representatives. QUALITY OF EVIDENCE: Three randomized controlled trials (RCTs) were available for evaluation. Two compared 89Sr with placebo, and one RCT compared 89Sr with conventional radiation (either hemibody or involved-field radiotherapy, as determined before randomization). BENEFITS: One of the 2 studies comparing 89Sr with placebo demonstrated the palliative efficacy of the intervention (p < 0.01); the other showed no benefit. The third study, comparing 89Sr with conventional radiation, concluded that all treatments provided equally effective pain relief and that improvement was sustained for at least 3 months in similar proportions of patients. The difference in the median duration of patient survival between groups in this study was neither clinically nor statistically significant. HARMS: The use of 89Sr may cause bone marrow suppression, but clinically significant sequelae are uncommon. The use of 89Sr may preclude further systemic chemotherapy or eligibility for clinical trials of systemic therapy. Symptoms other than those due to bone marrow suppression are rare. PRACTICE GUIDELINE: 89Sr is recommended for use in patients with endocrine-refractory prostate cancer who have multiple uncontrolled painful sites of bone metastases on both sides of the diaphragm not adequately controlled with conventional analgesic therapy, and in whom the use of multiple single fields of external beam radiation is not possible. 89Sr has proven to be efficacious in the palliation of hormone-refractory painful bone metastases from prostate cancer. It has not been shown to lengthen the average duration of patient survival. There is limited evidence on the relative efficacy of 89Sr compared with wide-field radiotherapy. 89Sr is the treatment of choice given all the following specific indications: Established diagnosis of prostate cancer metastatic to bone. Metastatic disease refractory to hormone therapy. Progressive sites of pain poorly controlled with conventional narcotics. Painful sites of disease on both sides of the diaphragm (otherwise, hemibody radiotherapy is equally efficacious). Patient or tumour factors (number of involved sites, location of involved sites or level of pain control) that are relative contraindications to the use of multiple single fields of radiation as an alternative. No evidence of impending spinal cord compression. Adequate bone marrow reserve. Evidence from a diagnostic bone scan of radionuclide concentration in painful bone lesions. PRACTICE GUIDELINE DATE: Nov. 23, 1997. Part 2. GUIDELINE QUESTION: What is the role of 89Sr in effective palliative care of patients with stage D hormone-refractory prostate cancer receiving involved-field radiotherapy for isolated painful bone metastases? OBJECTIVE: To make recommendations about the routine use of 89Sr in this clinical setting. OUTCOMES: Effective palliation is the primary outcome of interest. Patient survival and toxic effects of treatment are also considered. PERSPECTIVE (VALUES): As described in preceding abstract (Part 1). QUALITY OF EVIDENCE: One RCT was available for evaluati

A phase II study of leuprolide in advanced/recurrent endometrial cancer.

In order to determine the efficacy and toxicity of the gonadotrophin-releasing hormone agonist Leuprolide in the management of patients with recurrent or metastatic endometrial cancer, we performed a phase II study. Patients were included if there was clinical or radiological documentation of bidimensionally measurable recurrent or metastatic endometrial cancer that was deemed incurable. Treatment was 7.5 mg i.m. every 28 days, and was to continue for at least 2 courses until evidence of disease progression, patient requested withdrawal, or unacceptable toxicity. Twenty-five patients received Leuprolide for recurrent or metastatic endometrial cancer. The median age at study entry was 62 years, and the median time from initial diagnosis to first course of Leuprolide was 25 months. Six patients had received no systemic or radiotherapy prior to study entry, and 2 of these had not previously undergone hysterectomy. Fifteen patients received prior pelvic radiotherapy and 3 patients received prior whole abdominal radiotherapy. Nine of the 25 patients had received prior progestational agents, and 2 had received prior systemic chemotherapy. There were no responders, 8 patients had stable disease for a median 5 months (range 1-8), 14 patients progressed on therapy, and 3 patients were not evaluable for response due to receiving only 1 treatment. One patient experienced a grade 3 toxicity that was possibly attributable to Leuprolide (deep venous thrombosis). The median survival from study entry was 6 months. Twelve patients received progesterone after discontinuing this study, and none responded. Leuprolide does not appear to be a clinically active agent in the treatment of recurrent or metastatic endometrial cancer.