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Purpose: To determine the magnitude of catheter displacement between time of planning and time of treatment delivery for patients undergoing high dose-rate (HDR) brachytherapy, the dosimetric impact of catheter displacement, and the ability to improve dosimetry by catheter readjustment., Methods and Materials: Twenty consecutive patients receiving single fraction HDR brachytherapy underwent kilovoltage cone-beam CT in the treatment room before treatment. If catheter displacement was apparent, catheters were adjusted and imaging repeated. Both sets of kilovoltage cone-beam CT image sets were coregistered off-line with the CT data set used for planning with rigid fusion of anatomy based on implanted fiducials. Catheter displacement was measured on both sets of images and dosimetry calculated., Results: Mean internal displacement of catheters was 11mm. This would have resulted in a decrease in mean volume receiving 100% of prescription dose (V(100)) from the planned 97.6% to 77.3% (p<0.001), a decrease of the mean dose to 90% of the prostate (D(90)) from 110.5% to 72.9% (p<0.001), and increase in dose to 10% of urethra (urethra D(10)) from 118% to 125% (p=0.0094). Each 1cm of catheter displacement resulted in a 20% decrease in V(100) and 36% decrease in D(90). Catheter readjustment resulted in a final treated mean V(100) of 90.2% and D(90) of 97.4%, both less than planned. Mean urethra D(10) remained higher at126% (p=0.0324)., Conclusions: Significantly, internal displacement of HDR catheters commonly occurs between time of CT planning and treatment delivery, even when only a single fraction is used. The adverse effects on dosimetry can be partly corrected by readjustment of catheter position., (Copyright © 2011 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Introduction: Cancer interferes with participation in valued lifestyle activities (illness intrusiveness) throughout post-treatment survivorship. We investigated whether illness intrusiveness differs across life domains among survivors with diverse cancers. Intrusiveness should be highest in activities requiring physical/cognitive functioning (instrumental domain). Intrusiveness into relationship/sexual functioning (intimacy domain) should be higher in prostate, breast, and gastrointestinal cancers than in others., Methods: Cancer outpatients (N = 656; 51% men) completed the Illness Intrusiveness Ratings Scale (IIRS) during follow-up. We compared IIRS Instrumental, Intimacy, and Relationships and Personal Development [RPD] subscale and total scores across gastrointestinal, lung, lymphoma, head and neck, prostate (men), and breast cancers (women), comparing men and women separately., Results: Instrumental subscale scores (M(men) = 3.05-3.80, M(women) = 3.02-3.63) were highest for all groups, except prostate cancer. Men with prostate cancer scored higher on Intimacy (M = 3.40) than Instrumental (M = 2.48) or RPD (M = 1.59), p's < .05; their Intimacy scores did not differ from men with gastrointestinal or lung cancer. Women collectively showed higher Instrumental (M = 3.39) than Intimacy (M = 2.49) or RPD scores (M = 2.27), p's < .001, but not the hypothesized group difference in Intimacy., Conclusions: Post-treatment survivors continue to experience some long-term interference with activities requiring physical and cognitive functioning. Sexual adjustment may be of special concern to men when treatments involve genitourinary functioning., Implications for Cancer Survivors: Ongoing monitoring with the IIRS to detect lifestyle interference throughout survivorship may enhance quality of life. Screening and intervention should target particular life domains rather than global interference.

Objective: Illness- and treatment-related disruptions to valued activities and interests (illness intrusiveness) are central to quality of life in chronic disease and are captured by three subscales of the Illness Intrusiveness Ratings Scale (IIRS): the Instrumental, Intimacy, and Relationships and Personal Development subscales. Using individual (CFA) and multisample confirmatory factor analyses (MSCFA), we evaluated measurement invariance of the IIRS's 3-factor structure in men and women with cancer., Method: Men (n = 210) and women (n = 206) with 1 of 4 cancer diagnoses (gastrointestinal, head and neck, lymphoma, lung) recruited from outpatient clinics completed the IIRS. In the MSCFA, we applied an analysis of means and covariance structures approach to test increasingly stringent equality constraints on factor structure parameters to evaluate weak, strong, and strict measurement invariance of the 3-factor structure between men and women., Results: Individual CFAs demonstrated fit of the hypothesized 3-factor structure for men and women, although more consistently for men. The 3-factor structure was superior to an alternative 1-factor structure. MSCFA results indicated that parameters of the 3-factor structure could be considered equivalent between the sexes up to the level of strong invariance. Strict invariance was not supported., Conclusions: Overall, IIRS scores can be interpreted similarly for men and women with cancer. Illness intrusiveness can be considered as important in the psychosocial adaptation of people with cancer as it is for people affected by other chronic conditions., ((c) 2011 APA, all rights reserved)

The discovery of androgen deprivation therapy (ADT) has been one of the most important advances in the treatment of prostate cancer. Here, the indications for the use of ADT are reviewed, together with the data supporting each indication. The settings for ADT use include cytoreduction; combined ADT and radiotherapy; pathologic node-positive disease; and recurrent, metastatic, or progressive prostate cancer.

Introduction: Wait times for cancer diagnosis and treatment are a significant concern for Canadians. Men with prostate cancer experience longer waiting times for diagnosis and treatment than those observed for other cancers. Longer waits are associated with both patient and family psychosocial distress and may be associated with worse prognosis., Methods: Men referred for treatment of prostate cancer at a single Canadian cancer centre were interviewed. The intervals from suspicion to definitive therapy were calculated, factors associated with delays along this pathway were identified, and common causes of delay identified by patients were described., Results: A total of 41 consecutive patients participated. The median interval from suspicion to the first fraction of radiotherapy for all patients was 247 days (interquartile range [IQR] 168-367 d). The median diagnostic interval was 53 days (IQR 28-166 d). The median treatment interval was 127 days (IQR 100-180 d). Patients under 70 years old and patients with

Purpose: To determine the short- and medium-term effects of a single high-dose-rate brachytherapy fraction of 15 Gy and hypofractionated external beam radiation therapy for prostate cancer., Methods and Materials: Eligible patients had localized prostate cancer with a Gleason score of 7 and a prostate-specific antigen (PSA) concentration of <20 ng/ml or a Gleason score of 6 with a PSA concentration of 10 to 20 ng/ml. Patients received high-dose-rate brachytherapy as a single 15-Gy dose, followed by external beam radiation therapy at 37.5 Gy in 15 fractions, and were followed prospectively for toxicity (using Common Terminology Criteria for Adverse Events version 3.0), urinary symptoms (using the International Prostate Symptom Score [IPSS]), erectile function (with the International Index of Erectile Function [IIEF]), and health-related quality of life (with the Expanded Prostate Cancer Index Composite [EPIC]). Clinical examinations and PSA measurements were performed at every visit, and prostate biopsies were repeated at 2 years. The trial accrued 125 patients, with a median follow-up of 1.14 years., Results: Acute grade 2 and 3 genitourinary toxicity occurred in 62% and 1.6% of patients, respectively, and acute grade 2 gastrointestinal toxicity occurred in 6.5% of patients. No grade 3 late toxicity has occurred: 47% of patients had grade 2 genitourinary and 10% of patients had grade 2 gastrointestinal toxicity. Median IPSSs rose from 5 at baseline to 12 at 1 month and returned to 7 at 3 months. Of the total number of patients who were initially potent (IIEF, >21), 8% of patients developed mild to moderate dysfunction, and 27% of patients developed severe erectile dysfunction. Baseline EPIC bowel, urinary, and sexual bother scores decreased by 9, 7, and 19 points, respectively, at 1 year. No patient has experienced biochemical failure, and 16 of the first 17 biopsy results showed no malignancy., Conclusions: Treatment is well tolerated in the short and medium term, with low toxicity and encouraging early indicators of disease control., ((c) 2010 Elsevier Inc. All rights reserved.)

Purpose: Transrectal ultrasound guided prostate biopsy is widely used to confirm the diagnosis of prostate cancer. The technique has been associated with significant morbidity in a small proportion of patients., Materials and Methods: We conducted a population based study of 75,190 men who underwent a transrectal ultrasound guided biopsy in Ontario, Canada, between 1996 and 2005. We used hospital and cancer registry administrative databases to estimate the rates of hospital admission and mortality due to urological complications associated with the procedure., Results: Of the 75,190 men who underwent transrectal ultrasound biopsy 33,508 (44.6%) were diagnosed with prostate cancer and 41,682 (55.4%) did not have prostate cancer. The hospital admission rate for urological complications within 30 days of the procedure for men without cancer was 1.9% (781/41,482). The 30-day hospital admission rate increased from 1.0% in 1996 to 4.1% in 2005 (p for trend <0.0001). The majority of hospital admissions (72%) were for infection related reasons. The probability of being admitted to hospital within 30 days of having the procedure increased 4-fold between 1996 and 2005 (OR 3.7, 95% CI 2.0-7.0, p <0.0001). The overall 30-day mortality rate was 0.09% but did not change during the study period., Conclusions: The hospital admission rates for complications following transrectal ultrasound guided prostate biopsy have increased dramatically during the last 10 years primarily due to an increasing rate of infection related complications., (2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: Postoperative radiotherapy after radical prostatectomy has been shown to improve numerous outcomes for selected patients in mature randomized controlled trials. During treatment patients usually experience mild to moderate urinary symptoms, lower gastrointestinal symptoms and tiredness. We describe an unusual case of a patient experiencing severe, culture negative urinary symptoms early in a course of salvage radiotherapy., Materials and Methods: A patient's history was retrospectively derived from a single institution., Results: A total radiation dosage of 66 Gy in 33 fractions was to be delivered to the prostate bed by intensity modulated radiation therapy. Urinary symptoms consisting of hematuria, dysuria and urination of cellular debris developed very early during the treatment, were not related to infection and were refractory to breaks from radiation therapy. Computed tomography imaging revealed a 3.5 cm diameter urolith in the posterior bladder. Urinary symptoms resolved after surgical management consisting of, cystolitholapaxy with laser cystoscopy., Conclusions: While rare, urolithiasis should be considered when severe, early, culture negative dysuria develops on radiotherapy for prostate cancer.

Purpose: To determine the efficacy of a combined approach of radiotherapy (RT) plus 2-year androgen suppression (AS) as salvage treatment for prostate-specific antigen (PSA) relapse after radical prostatectomy (RP)., Methods and Materials: Seventy-five patients with PSA relapse after RP were treated with salvage RT plus 2-year AS, as per a pilot, prospective study. AS started within 1 month after completion of salvage RT and consisted of nilutamide for 4 weeks and buserelin acetate depot subcutaneously every 2 months for 2 years. Relapse-free rate including freedom from PSA relapse was estimated using the Kaplan-Meier method. PSA relapse was defined as a PSA rise above 0.2 ng/mL with two consecutive increases over a minimum of 3 months. A Cox regression analysis was performed to evaluate prognostic factors for relapse., Results: Median age of the cohort was 63 years at the time of salvage RT. Median follow-up from salvage RT was 6.4 years. All achieved initially complete PSA response (< 0.2) with the protocol treatment. Relapse-free rate including the freedom from PSA relapse was 91.5% at 5 years and 78.6% at 7 years. Overall survival rate was 93.2% at both 5 and 7 years. On Cox regression analysis, pT3 stage and PSA relapse less than 2 years after RP were significant prognostic factors for relapse., Conclusion: The combined treatment of salvage RT plus 2-year AS yielded an encouraging result for patients with PSA relapse after RP and needs a confirmatory study.

Purpose: Several single nucleotide polymorphisms (SNP) have been associated with the risk of prostate cancer. The clinical utility of using SNPs in the early detection of prostate cancer has not been evaluated., Experimental Design: We examined a panel of 25 SNPs from candidate genes and chromosomal regions in 3,004 unselected men who were screened for prostate cancer using serum prostate-specific antigen (PSA) and digital rectal examination. All underwent a prostate biopsy. We evaluated the ability of these SNPs to help predict the presence of prostate cancer at biopsy., Results: Of the 3,004 patients, 1,389 (46.2%) were found to have prostate cancer. Fifteen of the 25 SNPs studied were significantly associated with prostate cancer (P=0.02-7x10(-8)). We selected a combination of 4 SNPs with the best predictive value for further study. After adjusting for other predictive factors, the odds ratio for patients with all four of the variant genotypes compared with men with no variant genotype was 5.1 (95% confidence interval, 1.6-16.5; P=0.006). When incorporated into a nomogram, genotype status contributed more significantly than PSA, family history, ethnicity, urinary symptoms, and digital rectal examination (area under the curve=0.74). The positive predictive value of the PSA test ranged from 42% to 94% depending on the number of variant genotypes carried (P=1x10(-15))., Conclusions: SNP genotyping can be used in a clinical setting for the early detection of prostate cancer in a nomogram approach and by improving the positive predictive value of the PSA test.

Aims: Most men with low-risk localised prostate cancer prefer treatments with high control rates and minimal disruption to their lives. Hypofractionating external radiation treatments can theoretically maintain high bioequivalent tumour doses, decrease treatment visits and decrease acute and late toxicities. The aim of this study was to assess the toxicity and feasibility of a hypofractionated accelerated regimen for these patients., Materials and Methods: The present study was a phase I/II study in which patients with T1-2b, Gleason < or = 6 and prostate-specific antigen (PSA) < or = 10 ng/ml prostate cancer received 35Gy in five fractions, once a week over 29 days. Treatment was delivered with intensity-modulated radiotherapy on standard linear accelerators, with daily image guidance using gold seed fiducials, and a 4mm clinical target volume to planning target volume margin., Results: As of January 2008, the target accrual of 30 patients had been reached and all had completed treatment and at least 6 months of follow-up. Dose-volume histogram objectives were achievable in all patients. Treatment was very well tolerated with no grade 3 or 4 genitourinary toxicity, gastrointestinal toxicity nor fatigue observed (95% confidence interval 0-12%). As a group, compared with baseline, the following additional grade 2 toxicities were observed: 13% genitourinary, 7% gastrointestinal and 10% fatigue. At 6 months all scores had returned to or improved over baseline. The median PSA before treatment was 6.0 ng/ml. At 6 months, the median PSA was 1.8 ng/ml and 75% had a PSA < or = 3.0 ng/ml., Conclusions: This novel technique using standard linear accelerators seems feasible and is well tolerated. Further follow-up will be carried out to document late toxicity and efficacy.

Purpose: To evaluate the acute and late gastrointestinal (GI) and genitourinary (GU) toxicity of postoperative radiotherapy (RT) after radical prostatectomy (RP)., Methods and Materials: A total of 78 patients with pT3 or positive surgical margins after RP were treated with RT plus 2 years of androgen suppression, according to a Phase II study. Acute and late GI and GU toxicity was prospectively assessed using the National Cancer Institute's Expanded Common Toxicity Criteria, version 2.0. The incidence of late GI and GU toxicity was estimated using a cumulative incidence method. A Cox proportional regression analysis was performed to evaluate the predictive factors for late toxicity., Results: The median patient age was 61 years at RP. The median interval between RP and postoperative RT was 4.2 months. The median follow-up was 42.4 months. Of the 78 patients, 76 and 74 were available for the acute and late toxicity analysis, respectively. Of these patients, 66%, 29%, and 1% experienced Grade 1, 2, and 3 acute GI or GU toxicity, respectively. The cumulative incidence of Grade 2 or greater and Grade 3 or greater late GI toxicity at 36 months was 8.1% and 0%, respectively. The cumulative incidence of Grade 2 or greater and Grade 3 or greater late GU toxicity at 36 months was 16.4% and 2.7%, respectively. None had Grade 4 or greater late toxicity. The severity of acute GU toxicity (less than Grade 2 vs. Grade 2 or greater) was a significant predictor factor for Grade 2 or greater late GU toxicity after adjusting for pre-existing GU dysfunction., Conclusions: Postoperative RT was generally well tolerated. Grade 3 or greater late GI or GU toxicity was uncommon.

Purpose: To evaluate the acute toxicities of hypofractionated accelerated radiotherapy (RT) using a concomitant intensity-modulated RT boost in conjunction with elective pelvic nodal irradiation for high-risk prostate cancer., Methods and Materials: This report focused on 66 patients entered into this prospective Phase I study. The eligible patients had clinically localized prostate cancer with at least one of the following high-risk features (Stage T3, Gleason score >or=8, or prostate-specific antigen level >20 ng/mL). Patients were treated with 45 Gy in 25 fractions to the pelvic lymph nodes using a conventional four-field technique. A concomitant intensity-modulated radiotherapy boost of 22.5 Gy in 25 fractions was delivered to the prostate. Thus, the prostate received 67.5 Gy in 25 fractions within 5 weeks. Next, the patients underwent 3 years of adjuvant androgen ablative therapy. Acute toxicities were assessed using the Common Terminology Criteria for Adverse Events, version 3.0, weekly during treatment and at 3 months after RT., Results: The median patient age was 71 years. The median pretreatment prostate-specific antigen level and Gleason score was 18.7 ng/L and 8, respectively. Grade 1-2 genitourinary and gastrointestinal toxicities were common during RT but most had settled at 3 months after treatment. Only 5 patients had acute Grade 3 genitourinary toxicity, in the form of urinary incontinence (n = 1), urinary frequency/urgency (n = 3), and urinary retention (n = 1). None of the patients developed Grade 3 or greater gastrointestinal or Grade 4 or greater genitourinary toxicity., Conclusion: The results of the present study have indicated that hypofractionated accelerated RT with a concomitant intensity-modulated RT boost and pelvic nodal irradiation is feasible with acceptable acute toxicity.

Aims: We hypothesised that accelerated fractionated radiotherapy may provide a good palliative approach for dysphagia relief in patients with incurable oesophageal cancer, significantly reducing the overall duration of treatment, while providing symptom response with an acceptable toxicity profile. A phase I/II accelerated fractionation study was conducted to evaluate the efficacy and toxicity of this approach., Materials and Methods: Patients with incurable oesophageal cancer, symptomatic with dysphagia, Eastern Cooperative Oncology Group performance statusor=6 h apart), 5 days a week, over 2 weeks., Results: Of the 39 evaluable patients, the dysphagia response rate was 69% (27/39) with a median response duration of 5.5 months. The median time to response was 4 weeks. Twenty-eight per cent (11/39) of patients had transient worsening in their dysphagia scores. Acute toxicity (weeks 1-8) occurred in 41% (16/39) of patients. An improvement in global quality of life by week 8 was seen in 42% of patients. There were no late neurological sequelae. The median overall survival was 8 (range 1.7-58+) months., Conclusion: The ideal palliative regimen should be relatively short, with minimal toxicity, while offering a favourable response profile. Accelerated fractionation fulfils these criteria and is a suitable treatment alternative for the palliation of dysphagia, especially if the goal is to deliver a higher total biological dose within a shorter (2 week) period of time.

We conducted a genome-wide association study of 3090 sporadic prostate cancer patients and controls using the Affymetrix 10 000 SNP GeneChip. Initial screening of 40 prostate cancer cases and 40 non-cancer controls revealed 237 SNPs to be associated with prostate cancer (P<0.05). Among these SNPs, 33 were selected for further association analysis of 2069 men who had undergone a cancer-screening prostate biopsy. Results identified five loci as being significantly associated with increased prostate cancer risk in this larger sample (rs 1930293, OR=1.7, P=0.03; rs 717809-2p12, OR=1.3, P=0.03; rs 494770-4q34, OR=1.3, P=0.01; rs 2348763-7p21, OR=1.5, P=0.01; rs 1552895-9p22, OR=1.5, P=0.002). To validate these association data, 61 additional HapMap tagSNPs spanning the latter five loci were genotyped in this subject cohort and an additional 1021 men (total subject number=3090). This analysis revealed tag SNP rs 4568789 (chromosome 1q25) and tag SNP rs 13225697 (chromosome 7p21) to be significantly associated with prostate cancer (P-values 0.009 and 0.008, respectively). Haplotype analysis revealed significant associations of prostate cancer with two allele risk haplotypes on both chromosome 1q25 (adjusted OR of 2.7 for prostate cancer, P=0.0003) and chromosome 7p21 (adjusted OR of 1.3, P=0.0004). As linkage data have identified a putative prostate cancer gene on chromosome 1q25 (HPC1), and microarray data have revealed the ETV1 oncogene to be overexpressed in prostate cancer tissue, it appears that chromosome 1q25 and 7p21 may be sites of gene variants conferring risk for sporadic and inherited forms of prostate cancer.

The prostate-specific gene, TMPRSS2 is fused with the gene for the transcription factor ERG in a large proportion of human prostate cancers. The prognostic significance of the presence of the TMPRSS2:ERG gene fusion product remains controversial. We examined prostate cancer specimens from 165 patients who underwent surgery for clinically localised prostate cancer between 1998 and 2006. We tested for the presence of TMPRSS2:ERG gene fusion product, using RT-PCR and direct sequencing. We conducted a survival analysis to determine the prognostic significance of the presence of the TMPRSS2:ERG fusion gene on the risk of prostate cancer recurrence, adjusting for the established prognostic factors. We discovered that the fusion gene was expressed within the prostate cancer cells in 81 of 165 (49.1%) patients. Of the 165 patients, 43 (26.1%) developed prostate-specific antigen (PSA) relapse after a mean follow-up of 28 months. The subgroup of patients with the fusion protein had a significantly higher risk of recurrence (58.4% at 5 years) than did patients who lacked the fusion protein (8.1%, P<0.0001). In a multivariable analysis, the presence of gene fusion was the single most important prognostic factor; the adjusted hazard ratio for disease recurrence for patients with the fusion protein was 8.6 (95% CI=3.6-20.6, P<0.0001) compared to patients without the fusion protein. Among prostate cancer patients treated with surgery, the expression of TMPRSS2:ERG fusion gene is a strong prognostic factor and is independent of grade, stage and PSA level.

Purpose: To construct a clinical nomogram instrument to estimate individual risk for having prostate cancer (PC) for patients undergoing prostate specific antigen (PSA) screening, using all risk factors known for PC., Patients and Methods: We conducted a cross-sectional study of 3,108 men who underwent a prostate biopsy, including a subset of 408 volunteers with normal PSA levels. Factors including age, family history of PC (FHPC), ethnicity, urinary symptoms, PSA, free:total PSA ratio, and digital rectal examination (DRE) were incorporated in the model. A nomogram was constructed to assess risk for any and high-grade PC (Gleason score >or= 7)., Results: Of the 3,108 men, 1,304 (42.0%) were found to have PC. Among the 408 men with a normal PSA (< 4.0 ng/mL), 99 (24.3%) had PC. All risk factors were important predictors for PC by multivariate analysis (P, .01 to .0001). The area under the curve (AUC) for the nomogram in predicting cancer, which included age, ethnicity, FHPC, urinary symptoms, free:total PSA ratio, PSA, and DRE, was 0.74 (95% CI, 0.71 to 0.81) and 0.77 (95% CI, 0.74 to 0.81) for high-grade cancer. This was significantly greater than the AUC that considered using the conventional screening method of PSA and DRE only (0.62; 95% CI, 0.58 to 0.66 for any cancer; 0.69; 95% CI, 0.65 to 0.73 for high-grade cancer). From receiver operating characteristic analysis, risk factors including age, ethnicity, FHPC, symptoms, and free:total PSA ratio contributed significantly more predictive information than PSA and DRE., Conclusion: In a PC screening program, it is important to consider age, family history of PC, ethnicity, urinary voiding symptoms, and free:total PSA ratio, in addition to PSA and DRE.

Background: Short-course radiotherapy is a common treatment for the palliation of painful osseous metastases. Pain flare can be problematic, but its incidence has previously not been well-documented. The objectives of this study were to determine (1) the incidence of pain flare after palliative radiation for painful osseous metastases, and (2) whether single-fraction radiotherapy increases the risk of pain flare., Materials and Methods: Patients accrued to a prospective randomized control trial comparing 8 Gy in one fraction to 20 Gy in five fractions (the Canadian Bone Metastasis Study) were approached to fill out a daily pain and analgesia diary for the 7 days post-radiotherapy. Patients assessed their average pain at the index site using the Present Pain Intensity (PPI) scale of the McGill-Melzack pain questionnaire and recorded their daily analgesic medications, which were translated into an analgesic score. Pain flare was defined as a two-point increase in the PPI with no decrease in analgesic score or a 50% increase in analgesic score with no decrease in PPI on at least two consecutive days., Results: Forty-seven patients agreed to fill out the diary and 44 (94%) completed it. Fifteen of 44 (34.1%) patients experienced a pain flare that lasted a median of 3 days. Ten of 23 (43.5%) and 5/21 (23.8%) of patients who received 8 Gy and 20 Gy had a pain flare, respectively., Conclusions: Pain flare is common after palliative radiotherapy for osseous metastases and patients receiving single fraction radiotherapy may be at higher risk. Further study is warranted to determine predictors and preventive interventions.

Aims: To determine the cerebrospinal fluid concentrations and the functional and pain outcomes after a single intravenous infusion of erythropoietin at the start of a standard radiotherapy and steroid protocol., Materials and Methods: Ten paraparetic patients with malignant extradural spinal cord compression who were eligible for radiotherapy, lumbar puncture and intravenous epoetin alpha were enrolled. The patients received epoetin alpha 1500 IU/kg intravenously over 30 min followed by a standardised dexamethasone and radiotherapy protocol. A lumbar puncture and venipuncture were carried out 24-30 h after the epoetin alpha infusion. The patients were followed closely at defined intervals., Results: Erythropoietin was detectable in the cerebrospinal fluid in all eight patients sampled (median 92.5 mIU/ml, range 17.8-214.0 mIU/ml). Before treatment, eight patients were non-ambulatory and two patients were ambulatory with assistance. After treatment, eight (80%, 95% confidence interval [CI] 44-97%) improved at least one functional class and recovered or maintained ambulation. Five of seven patients (71%; 95% CI 29-96%) with objective sensory deficits and one of seven (14%; 95% CI 0-58%) catheter-dependent patients recovered. Overall, 78% (95% CI 40-97%) had a pain response., Conclusions: After an intravenous infusion of epoetin alpha, radiotherapy and steroids, high concentrations of erythropoietin were detectable in the cerebrospinal fluid. Patients with malignant extradural spinal cord compression showed encouraging improvements in neurological function and pain.

Purpose: To examine the effect of salvage radiotherapy (RT) plus 2-year androgen suppression (AS) on quality of life (QOL)., Methods and Materials: A total of 74 patients with biopsy-proven local recurrence or PSA relapse after radical prostatectomy were treated with salvage RT plus 2-year AS, as per a phase II study. Quality of life was prospectively assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30-Item Version 3.0 with the added prostate cancer-specific module at baseline and predefined follow-up visits., Results: Patients experienced a significant increase in bowel dysfunction (23%) by the end of RT (p < 0.0001). This bowel dysfunction improved after RT but remained slightly elevated (5-10%) throughout the 2-year AS period. This extent of residual bowel dysfunction would be considered of minimal clinical importance. A similar, but less pronounced, pattern of change did occur for urinary dysfunction. Erectile function showed no change during RT, but had an abrupt decline (10%) with initiation of AS that was of moderate clinical significance (p < 0.01). None of the other QOL domains demonstrated a persistent, significant change from baseline that would be considered of major clinical significance., Conclusion: The combined treatment with salvage RT plus 2-year AS had relatively minor long-term effects on QOL.

The illness intrusiveness theoretical framework maintains that illness-induced lifestyle disruptions compromise quality of life in chronic life-threatening conditions and that this effect is moderated by social, psychological, and contextual factors. Considerable evidence indicates that lifestyle disruptions compromise quality of life in cancer and other diseases and that the effects differ across life domains. The hypothesis that contextual factors (e.g. age, education, income, stressful life events) moderate these effects has not been tested extensively. We investigated whether age, income, education, and/or recent stressful life events modify the experience of illness intrusiveness across three central life domains (Relationships and Personal Development, Intimacy, and Instrumental life) in six common cancers. A sample of 656 cancer outpatients with one of six common cancers (breast, prostate, lymphoma, lung, head and neck, and gastrointestinal, all n's>100) completed the Illness Intrusiveness Ratings Scale while awaiting follow-up appointments with an oncologist. Results indicated statistically significant (all p's<0.05) interactions involving each of the hypothesized moderator variables and the Life Domain factor. In each case, greatest divergence was evident when illness intrusiveness involved instrumental life domains (e.g. work, finances, health, and active recreation). The findings substantiate the illness intrusiveness theoretical framework and support its relevance for people with cancer. The psychosocial impact of chronic life-threatening disease differs across life domains and depends on the context in which it is experienced.

Within the field of radiation oncology in the last 10 years, there have been two major thematic advances in the understanding and treatment of prostate cancer. Computerized treatment planning and high precision delivery techniques have already revolutionized the treatment of this disease. Three randomized studies have reported improved biochemical disease-free survival rates in patients from low- to high-risk disease with higher radiation doses. When given conformally, the higher doses do not appear to increase severe toxicity. The second important discovery was that prostate cancer reacts differently than other tumors to radiation whereby higher doses of radiation per day ("hypofractionated radiation") seem to be more effective in killing prostate cancer cells. A meta-summary of four reports summarizing 21 studies presented herein produced an alpha/beta ratio of 1.3 Gy. The early experience of two hypofractionated trials in intermediate- and high-risk prostate cancer where the equivalent of > 80 Gy (in 2 Gy per day fractions) delivered in 5-6 weeks is reported. In summary, hypofractionated radiation coupled with high-precision techniques may allow for better prostate cancer control rates, shorter treatment times and less toxicity.

Purpose: The objective of the study was to access toxicities of delivering a hypofractionated intensity-modulated radiotherapy (IMRT) boost with individualized intrafraction planning target volume (PTV) margins and daily online correction for prostate position., Methods and Materials: Phase I involved delivering 42 Gy in 21 fractions using three-dimensional conformal radiotherapy, followed by a Phase II IMRT boost of 30 Gy in 10 fractions. Digital fluoroscopy was used to measure respiratory-induced motion of implanted fiducial markers within the prostate. Electronic portal images were taken of fiducial marker positions before and after each fraction of radiotherapy during the first 9 days of treatment to calculate intrafraction motion. A uniform 10-mm PTV margin was used for the first phase of treatment. PTV margins for Phase II were patient-specific and were calculated from the respiratory and intrafraction motion data obtained from Phase I. The IMRT boost was delivered with daily online correction of fiducial marker position. Acute toxicity was measured using National Cancer Institute Common Toxicity Criteria, version 2.0., Results: In 33 patients who had completed treatment, the average PTV margin used during the hypofractionated IMRT boost was 3 mm in the lateral direction, 3 mm in the superior-inferior direction, and 4 mm in the anteroposterior direction. No patients developed acute Grade 3 rectal toxicity. Three patients developed acute Grade 3 urinary frequency and urgency., Conclusions: PTV margins can be reduced significantly with daily online correction of prostate position. Delivering a hypofractionated boost with this high-precision IMRT technique resulted in acceptable acute toxicity.

Purpose: This systematic review describes the diagnosis and management of adult patients with a suspected or confirmed diagnosis of extradural malignant spinal cord compression (MSCC)., Methods: MEDLINE, CANCERLIT, and the Cochrane Library databases were searched to January 2004 using the following terms: spinal cord compression, nerve compression syndromes, spinal cord neoplasms, clinical trial, meta-analysis, and systematic review., Results: Symptoms for MSCC include sensory changes, autonomic dysfunction, and back pain; however, back pain was not predictive of MSCC. The sensitivity and specificity for magnetic resonance imaging (MRI) range from 0.44 to 0.93 and 0.90 to 0.98, respectively, in the diagnosis of MSCC. The sensitivity and specificity for myelography range from 0.71 to 0.97 and 0.88 to 1.00, respectively. A randomized study detected higher ambulation rates in patients with MSCC who received high-dose dexamethasone before radiotherapy (RT) compared with patients who did not receive corticosteroids before RT (81% v 63% at 3 months, respectively; P = .046). There is no direct evidence that supports or refutes the type of surgery patients should have for the treatment of MSCC, whether surgical salvage should be attempted if patient is progressing on or shortly after RT, and whether patients with spinal instability should be treated with surgery., Conclusion: Patients with symptoms of MSCC should be managed to minimize treatment delay. MRI is the preferred imaging technique. Treatment for patients with MSCC should consider pretreatment ambulatory status, comorbidities, technical surgical factors, the presence of bony compression and spinal instability, potential surgical complications, potential RT reactions, and patient preferences.

Purpose: To develop a clinical practice guideline for the management of men with metastatic, recurrent, or progressive carcinoma of the prostate. The focus of this document is on the use, combinations, and timing of various forms of androgen deprivation therapy (ADT) for the palliation of men with androgen-sensitive disease., Methods: An expert panel and writing committee were formed. The questions to be addressed by the guideline were determined, and a systematic review of the literature was performed, which included a search of online databases, bibliographic review, and consultation with content experts. A priori criteria were used to select studies for analysis and study authors were contacted when necessary., Results: There were 10 randomized controlled trials, six systematic reviews, and one Markov model available to inform the guidelines., Conclusion: A full discussion between practitioner and patient should occur to determine which therapy is best for the patient. Bilateral orchiectomy or luteinizing hormone releasing hormone agonists are the recommended initial treatments. Nonsteroidal antiandrogen therapy may be discussed as an alternative, but steroidal antiandrogens should not be offered as monotherapy. Patients willing to accept the increased toxicity of combined androgen blockage for a small benefit in survival should be offered nonsteroidal antiandrogen in addition to castrate therapy. Until data from studies using modern medical diagnostic/biochemical tests and standardized follow-up schedules become available, no specific recommendations can be issued regarding the question of early versus deferred ADT. A discussion about the pros and cons of early versus deferred ADT should occur.

Measuring patient's satisfaction with their physician is gaining interest but requires a questionnaire that is valid, reliable and acceptable to patients. We previously published a self-administered visit-specific satisfaction with physician questionnaire for cancer patients. Eighty outpatients at a Canadian Cancer Center completed the Princess Margaret Hospital Patient Satisfaction with Doctor Questionnaire and the FACT-G questionnaires along with demographic information just after clinic visit and again 3-5 days later. Exploratory factor analysis extracted two factors, labeled 'physician disengagement' and 'perceived support,' with average coefficient alpha values of 0.93 and 0.90. Test-retest reliability was 0.83 and 0.73, respectively, for the two factors. Confirmatory factor analysis applied to the data from 174 patients in the original study indicated excellent goodness of fit. PMH/PSQ-MD correlated moderately with FACT-G (average r=0.37, p<0.005). The PMH/PSQ-MD questionnaire is a brief, valid and reliable questionnaire that taps two complementary facets of patient satisfaction., (Copyright 2003 John Wiley & Sons, Ltd.)

The interaction of patients with their doctors impacts the experience of disease at many levels. It is thus important to measure patient satisfaction with such interaction as an outcome of care. Our goal was to investigate whether tumor status influences patient satisfaction with interaction with their doctors. Specifically, we investigated whether patients with no evidence of disease (NED), localized, or metastatic cancers seen in routine follow-up differ in their satisfaction with the oncologist. Outpatients attending clinics at a major cancer center completed a battery of questionnaires, including the Patient Satisfaction with Doctor (PSQ-MD) questionnaire, a 24-item, self-report instrument. It taps two facets of the doctor-patient exchange: perceived support and physician disengagement. Data concerning tumor status and satisfaction were obtained for 569 patients, sampled to include equivalent numbers of women and men with breast, head and neck, gastrointestinal, genitourinary, or lung cancer, or lymphoma. Controlling for age, marital status, annual family income, stressful life events, and employment status, patients with metastatic disease felt somewhat less supported by their physicians (mean=3.26+/-0.06) than those with localized disease (mean=3.42+/-0.04) or NED (mean=3.42+/-0.03), (analysis of covariance, p< 0.05). Physician disengagement did not differ across the groups (means=1.54+/-0.06, 1.43+/-0.04, and 1.47+/-0.03 respectively). These findings were consistent across cancer diagnoses. Patients with metastatic disease may feel less physician support than those with less advanced cancers. Increasing attention to satisfaction of different patient groups can pave the way to improved quality of care.

Design: Population-based cohort study., Background: Malignant spinal cord compression (MSCC) has long been recognized as an important complication of cancer, but its incidence is unknown., Objectives: To describe the incidence, the management, and the outcome of MSCC in the cancer population of the Canadian province of Ontario., Methods: Episodes of MSCC, and treatments used for each episode, were identified by linking electronic hospital separation records and cancer centre records to Ontario's population-based cancer registry. The cumulative frequency of MSCC in the last 5 years of life was described in the 121435 patients who died of cancer in Ontario between 1990 and 1995. Survival after the first episode of MSCC, and duration of hospitalization with MSCC, was described., Results: The cumulative probability of experiencing at least one episode of MSCC in the 5 years preceding death from cancer was 2.5% overall, and ranged from 0.2% in cancer of the pancreas to 7.9% in myeloma. Overall, 60.2% of first episodes of MSCC were treated with primary radiotherapy, and 16.1% with surgery +/- postoperative radiotherapy, while in the remaining 23.7%, there was no record of radiotherapy or surgery. Overall, the median survival following the first episode of MSCC was 2.9 months. The diagnosis of MSCC was associated with a doubling of the time spent in hospital in the last year of life., Conclusion: MSCC is a fairly common occurrence among patients dying of cancer. There is a 40-fold variation in the cumulative incidence of MSCC among different types of cancer.

Background: PC-SPES is a herbal remedy gaining acceptance amongst prostate cancer patients and health care providers due to credible laboratory and clinical studies. However, PC-SPES has not been assessed in the standard rigorous approval process mandated for conventional agents., Objectives: To present a case of a patient with prostate cancer who, while using PC-SPES, developed disseminated intravascular coagulation (DIC). A review of the literature was conducted to determine if there is a relationship between PC-SPES and hemorrhagic disorders., Methods: Searches were conducted in MEDLINE (1966-December 2000) and the Cochrane Collaboration's database., Results: There are 116 clinical and laboratory based studies of PC-SPES published to date. There are no randomized controlled trials. Clinical studies have demonstrated a significant reduction in prostate specific antigen (PSA) levels within 6 weeks. Improved quality-of-life, reduction in the volume of tumor deposits and reduction in analgesic use has been demonstrated in hormone refractory patients. Laboratory studies suggest that the beneficial effects of PC-SPES are unrelated to physiologic estrogens. However, PC-SPES has a side-effect profile similar to diethylstilbestrol. There is data demonstrating a <5% risk of thromboembolic events, but this is the first report of DIC., Conclusion: The study of PC-SPES is in its infancy. This case may serve as a cautionary note to health care providers and patients regarding herbal remedies. Those using PC-SPES should have an increased level of surveillance for bleeding disorders.

Purpose: To better define the role of small prostate volume in selecting patients for brachytherapy., Materials and Methods: Thirty patients with a transrectal ultrasound (TRUS)-based prostate volumes less than 20 cc were treated at the University of Washington by permanent isotope implantation for prostatic carcinoma. Preimplant TRUS studies were taken at 0.5-cm intervals from the base of the gland to the apex. Planning margins of 1 to 5 mm were added to the prostatic margins, and sources were routinely planned to be placed as much as 5 mm outside of the prostatic margin. The prescription dose was 144 and 115 Gy for full-dose iodine 125 and palladium 103 monotherapy, respectively. For patients receiving supplemental external-beam irradiation, the implant doses were 120 and 90 Gy for 125I and 103Pd, respectively. The morning following the implant, axial computed tomographic (CT) images of the prostate were obtained at 0.5-cm intervals with patients in the supine position. Follow-up ranged from 11 to 28 months (median 21 months)., Results: The median coverage of the postimplant prostate volume by the prescription dose was 92%. To calculate the incidence of source migration, the number of sources placed at the time of implant was compared with the number identified on postimplant CT scan. The median number of sources implanted was 84 (range 65-103) compared to an average of 82 identified postoperatively, which is consistent with a source migration rate of two. A median of 31 sources appeared to be outside of the prostatic margins, as identified on postimplant CT scan (range 14-53). Of the 23 patients contacted at the time of this report, one had developed acute postimplant urinary retention that resolved within 2 weeks of implantation. At last follow-up, patient pre- and postimplant AUA scores were not substantially different, with the median AUA score increasing from 7 (range 2-21) to 8 (range 1-27)., Conclusions: Patients with small prostate volumes appear to have acceptable morbidity and target coverage with prostate brachytherapy. Based on the data reported here, we do not believe that a small prostate volume in itself is a contraindication to brachytherapy.

Purpose: To develop a psychometrically sound patient-satisfaction-with-physician questionnaire that can be used in an outpatient oncology setting., Patients and Methods: The questionnaire was developed by a four-step process involving a total of 277 cancer patients. The item-generation process utilized input from 95 oncology outpatients, three medical researchers, and the relevant literature. Items were tested by 70 of the above patients. Initial item reduction was achieved by input from another eight patients. Factor analysis and validity testing used data derived from a different group of 174 oncology outpatients. Convergent validity was tested by correlating the Princess Margaret Hospital Patient Satisfaction with Doctor Questionnaire (PMH/PSQ-MD) with Rubin et al's Physician subscale of the Patient's Viewpoint Questionnaire (PS-PVQ) and Smith et al's Patient-Doctor Interaction Scale (PDIS). Divergent validity was tested by comparing these questionnaires with Spitzer's quality of life (QOL) questionnaire., Results: The final PMH/PSQ-MD is a 29-item self-administered questionnaire with four response categories and a "does not apply" category. Four domains were confirmed by factor analysis: (1) information exchange, (2) interpersonal skills, (3) empathy, and (4) quality of time. The questionnaire has an overall Cronbach's alpha of 0.97; the values for each domain are, respectively, 0.92, 0.90, 0. 88, and 0.88. The PMH/PSQ-MD correlated well with both the PDIS and the PS-PVQ (P <.001 for both). Divergent validity was confirmed with Spitzer's QOL questionnaire., Conclusion: The PMH/PSQ-MD is an outpatient satisfaction questionnaire specific to the patient-physician interaction that has shown excellent internal consistency, is feasible, and has strong support for validity in this oncology population.

Since 1989, 17 patients have undergone re-irradiation for locally recurrent nasopharyngeal cancer (NPC). The dose currently administered externally is 39.6 Gy in 36 fractions (BID) followed by an intracavitary boost (15-20 Gy). Disease persisted in five out of five patients treated palliatively. Eleven of 12 patients treated with curative intent achieved local control.

Purpose: To review the literature for malignant extradural spinal cord compression (MSCC), produce evidence-based recommendations based on the criteria used by the Canadian Task Force on the Periodic Health Examination, and make suggestions regarding future research directives., Methods: A systematic review of the literature with explicit study selection and evaluation criteria was performed. Primary outcome measure was posttreatment ambulation rate., Results: There is good evidence to support the use of high-dose dexamethasone (96 mg/d), but inconclusive evidence for the use of moderate-dose steroids (16 mg/d) in conjunction with radiotherapy (RT) for the treatment of MSCC. Fair evidence exists for not using steroids in patients who are nonparetic and ambulatory pretreatment, and to give radiation to patients with subclinical spinal cord compression (SCC). The remainder of the recommendations are based on inconclusive evidence: RT alone should be the first-line treatment for ambulatory patients except when there is spinal instability, bony compression, or paraplegia on presentation, in which case surgery should be performed. Either modality can be used for paraparetic patients who are nonambulatory. Postoperative RT should be considered for tumor in residua. Ambulatory, undiagnosed patients should have needle biopsy attempted first. Patients should be aggressively screened and educated about SCC., Conclusion: In general, there were very few papers of high methodologic quality found in the literature. More studies are needed to satisfy the validity of many of the clinical decisions that are made today with regard to the management of MSCC.