Brachytherapy for high grade prostate cancer induces distinct changes in circulating CD4 and CD8 T cells - Implications for systemic control.

This exploratory study is a follow up to our previous investigation of immune response in the circulation of high-grade Gleason 9 prostate cancer patients treated with EBRT + BT compared to EBRT alone. Notably, EBRT + BT demonstrates the potential to elicit an effect on CD4/CD8 ratio which may have attributed to improved clinical response to therapy. Our findings show promise for leveraging circulating immune cells as predictive biomarkers for radiotherapy response.

Multimodal Biomarkers That Predict the Presence of Gleason Pattern 4: Potential Impact for Active Surveillance.

PURPOSE: Latent grade group ≥2 prostate cancer can impact the performance of active surveillance protocols. To date, molecular biomarkers for active surveillance have relied solely on RNA or protein. We trained and independently validated multimodal (mRNA abundance, DNA methylation, and/or DNA copy number) biomarkers that more accurately separate grade group 1 from grade group ≥2 cancers. MATERIALS AND METHODS: Low- and intermediate-risk prostate cancer patients were assigned to training (n=333) and validation (n=202) cohorts. We profiled the abundance of 342 mRNAs, 100 DNA copy number alteration loci, and 14 hypermethylation sites at 2 locations per tumor. Using the training cohort with cross-validation, we evaluated methods for training classifiers of pathological grade group ≥2 in centrally reviewed radical prostatectomies. We trained 2 distinct classifiers, PRONTO-e and PRONTO-m, and validated them in an independent radical prostatectomy cohort. RESULTS: PRONTO-e comprises 353 mRNA and copy number alteration features. PRONTO-m includes 94 clinical, mRNAs, copy number alterations, and methylation features at 14 and 12 loci, respectively. In independent validation, PRONTO-e and PRONTO-m predicted grade group ≥2 with respective true-positive rates of 0.81 and 0.76, and false-positive rates of 0.43 and 0.26. Both classifiers were resistant to sampling error and identified more upgrading cases than a well-validated presurgical risk calculator, CAPRA (Cancer of the Prostate Risk Assessment; P < .001). CONCLUSIONS: Two grade group classifiers with superior accuracy were developed by incorporating RNA and DNA features and validated in an independent cohort. Upon further validation in biopsy samples, classifiers with these performance characteristics could refine selection of men for active surveillance, extending their treatment-free survival and intervals between surveillance.

Absolute Percentage of Pattern 4 Disease as a Prognostic Measure for Intermediate-risk Prostate Cancer Treated with Stereotactic Body Radiotherapy.

AIMS: Intermediate-risk prostate cancer is heterogenous. The absolute percentage of biopsied tissue positive for Gleason pattern 4 disease (APP4) is a possible prognostic measure. Here we sought to determine the impact of APP4 in a prospective multi-institutional pooled analysis of men with intermediate-risk prostate cancer treated with stereotactic body radiotherapy (SBRT). MATERIALS AND METHODS: Patients with intermediate-risk prostate cancer treated with SBRT (40 Gy in five fractions or 26 Gy in two fractions) with or without androgen deprivation therapy treated on prospective clinical trials were included. Pathology reports were queried to obtain APP4, calculated as the percentage of Gleason pattern 4 disease within the tumour(s) multiplied by the percentage of total biopsied tissue positive for disease divided by 100. The optimal APP4 cut-off points for biochemical failure and distant metastasis were calculated and used as a stratification in the cumulative incidence of biochemical failure and distant metastasis. Multivariable competing risk models were developed. RESULTS: In tota, 227 patients were included. The median follow-up was 56.5 months. The optimal APP4 cut-off points were 5% for biochemical failure and 20% for distant metastasis. At 4 years, the cumulative incidence of biochemical failure was 23.6% and 2.3% for APP4 >5% and ≤ 5%, respectively (P < 0.0001). The cumulative incidence of distant metastasis was 12.5% for APP4 >20% and 1% for APP4 ≤ 20% (P = 0.02). APP4 sub-stratified favourable intermediate-risk prostate cancer and unfavourable intermediate-risk prostate cancer into groups at similarly low and similarly high risk of biochemical failure and distant metastasis. On multivariable competing risk analysis, APP4 >5% (P = 0.0004) was significantly associated with biochemical failure, but APP4 (log) was not for distant metastasis (P = 0.08). CONCLUSION: APP4 may be an easily accessible promising prognostic measure for patients with intermediate-risk prostate cancer treated with SBRT. Incorporation of APP4 into prospective trials will help to determine its value.

Four-year Prostate-specific Antigen Response Rate as a Predictive Measure in Intermediate-risk Prostate Cancer Treated With Ablative Therapies: The SPRAT Analysis.

AIMS: There is a lack of early predictive measures of outcome for patients with intermediate-risk prostate cancer (PCa) treated with stereotactic body radiotherapy (SBRT). The aim of the present study was to explore 4-year prostate-specific antigen response rate (4yPSARR) as an early predictive measure. MATERIALS AND METHODS: Individual patient data from six institutions for patients with intermediate-risk PCa treated with SBRT between 2006 and 2016 with a 4-year (42-54 months) PSA available were analysed. Cumulative incidences of biochemical failure and metastasis were calculated using Nelson-Aalen estimates and overall survival was calculated using the Kaplan-Meier method. Biochemical failure-free survival was analysed according to 4yPSARR, with groups dichotomised based on PSA <0.4 ng/ml or ≥0.4 ng/ml and compared using the Log-rank test. A multivariable competing risk analysis was carried out to predict for biochemical failure and the development of metastases. RESULTS: Six hundred and thirty-seven patients were included, including 424 (67%) with favourable and 213 (33%) with unfavourable intermediate-risk disease. The median follow-up was 6.2 years (interquartile range 4.9-7.9). The cumulative incidence of biochemical failure and metastasis was 7 and 0.6%, respectively; overall survival at 6 years was 97%. The cumulative incidence of biochemical failure at 6 years if 4yPSARR <0.4 ng/ml was 1.7% compared with 27% if 4yPSARR ≥0.4 ng/ml (P < 0.0001). On multivariable competing risk analysis, 4yPSARR was a statistically significant predictor of biochemical failure-free survival (subdistribution hazard ratio 15.3, 95% confidence interval 7.5-31.3, P < 0.001) and metastasis-free survival (subdistribution hazard ratio 31.2, 95% confidence interval 3.1-311.6, P = 0.003). CONCLUSION: 4yPSARR is an encouraging early predictor of outcome in patients with intermediate-risk PCa treated with SBRT. Validation in prospective trials is warranted.

Multiparametric Magnetic Resonance Imaging in the Diagnosis of Clinically Significant Prostate Cancer: an Updated Systematic Review.

There has been growing utilisation of multiparametric magnetic resonance imaging (MPMRI) as a non-invasive tool to diagnose and localise clinically significant prostate cancer (CSPCa). This updated systematic review examines the use of MPMRI in patients with an elevated risk of CSPCa who have had a prior negative transrectal ultrasound systematic biopsy (TRUS-SB) and who were biopsy naïve. MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews were searched for existing systematic reviews published up to September 2020. The literature search of the electronic databases combined disease-specific terms (prostate cancer, prostate carcinoma, etc.) and treatment-specific terms (magnetic resonance, etc.). Studies were included if they were randomised controlled trials (RCTs) comparing MPMRI to template transperineal mapping biopsy (TPMB) or to TRUS-SB. Thirty-six RCTs were eligible. For biopsy-naïve men, accuracy of diagnosis of CSPCa showed sensitivities from 87 to 96% and specificities ranging from 29 to 45%. Meta-analyses for CSPCa showed increased detection favouring MPMRI-targeted biopsy over TRUS-SB by 3% (95% confidence interval 0-7%, P = 0.03) and decreased detection of clinically insignificant prostate cancer (CISPCa) favouring MPMRI by 8% (95% confidence interval -11 to 5%, P < 0.00001). Accuracy of MPMRI for men with prior negative biopsy showed sensitivities of 78-100% and specificities of 30-100%. Meta-analyses comparing MPMRI to TRUS-SB showed increased detection of 5% (95% confidence interval 3-7%, P < 0.0001) with a reduction of CISPCa detection of 7% (95% confidence interval 4-9%, P < 0.00001). The growing acceptance of MPMRI utilisation internationally and the recent publication of several RCTs regarding MPMRI in reducing CISPCa detection rates, particularly in biopsy-naïve men, without loss of sensitivity for CSPCa necessitates the synthesis of updated evidence examining MPMRI in the diagnosis of CSPCa.

Immune cell profiling in Gleason 9 prostate cancer patients treated with brachytherapy versus external beam radiotherapy: An exploratory study.

This exploratory study evaluates immunological changes in high-risk Gleason 9 prostate cancer patients treated with EBRT+BT compared to EBRT alone. Notably, BT demonstrates the potential to elicit a T cell response which may support further investigation using circulating immune cells as predictive and prognostic biomarkers for radiotherapy response.

Surgical and Radiotherapeutic Management of Malignant Extradural Spinal Cord Compression.

Malignant spinal cord compression is one of the most dreaded complications of advanced malignancy, with patients presenting with progressive paralysis, paresthesia and/or autonomic dysfunction. The choice of management should be guided by the expected prognosis and outcome, not just from a neurological function point-of-view but also from the metastatic cancer itself. The main indications for surgery are: impending cord compression, spinal instability from tumour progression, bony retropulsion, for tissue diagnosis and for pain resistant to conventional therapies. Here, surgical principles, traditional and novel techniques and complications will be reviewed. For radiotherapy, multiple randomised studies have shown that for most patients a single fraction of external radiation has the same functional outcomes compared with multi-fractionation protocols. The experience of a specialised centralised interdisciplinary team will also be discussed.

Complex surgery and perioperative systemic therapy for genitourinary cancer of the retroperitoneum.

Objective: The purpose of the present guideline is to recommend surgical or systemic treatment for metastatic testicular cancer; T3b or T4, or node-positive, and metastatic renal cell cancer (rcc); and T3, T4, or node-positive upper tract urothelial (utuc) cancer. Methods: Draft recommendations were formulated based on evidence obtained through a systematic review of randomized controlled trials, comparative retrospective studies, and guideline endorsement. The draft recommendations underwent an internal review by clinical and methodology experts, and an external review by clinical practitioners. Results: The primary literature search yielded eight guidelines, five systematic reviews, and twenty-seven primary studies that met the eligibility criteria. Conclusions: Cytoreductive nephrectomy should no longer be considered the standard of care in patients with T3b or T4, or node-positive, and metastatic rcc. Eligible patients should be treated with systemic therapy and have their primary tumour removed only after review at a multidisciplinary case conference (mcc). Adjuvant sunitinib after surgery is not recommended. Patients with venous tumour thrombus should be considered for surgical intervention. Patients with T3, T4, or node-positive utuc should have their tumour removed without delay. Decisions concerning lymph node dissection should be done at a mcc and be based on stage, expertise, and imaging. Adjuvant systemic treatment is recommended for resected high-risk utuc. Patients with metastasis-positive testicular cancer with residual tumour after systemic treatment should be treated at specialized centres. For all complex retroperitoneal surgeries, the evidence shows that higher-volume centres are associated with lower rates of procedure-related mortality, and patients should be referred to higher-volume centres for surgical resection.

Elective Pelvic Nodal Irradiation With a Simultaneous Hypofractionated Integrated Prostate Boost for Localised Prostate Cancer: Ready for Prime Time?

External beam radiotherapy is a standard treatment option for localised prostate cancer and hypofractionation has become an alternative to conventionally fractionated radiotherapy. In patients who receive external beam radiotherapy, elective pelvic nodal irradiation is sometimes delivered, especially in patients with unfavourable disease who are at risk of micrometastatic spread of cancer into the regional nodes. One elegant approach to combine prostate hypofractionation with elective pelvic nodal irradiation is with a simultaneous integrated boost technique, where a radical hypofractionated dose is delivered to the prostate while the regional pelvic nodes receive a lower microscopic dose simultaneously in a single radiotherapy plan over the same number of treatment fractions. This article reviews the existing published literature evaluating such an approach.

Results of 15 Gy HDR-BT boost plus EBRT in intermediate-risk prostate cancer: Analysis of over 500 patients.

PURPOSE/OBJECTIVE: To report biochemical control associated with single fraction 15 Gy high-dose-rate brachytherapy (HDR-BT) boost followed by external beam radiation (EBRT) in patients with intermediate-risk prostate cancer. MATERIALS AND METHODS: A retrospective chart review of all patients with intermediate-risk disease treated with a real-time ultrasound-based 15 Gy HDR-BT boost followed by EBRT between 2009 and 2016 at a single quaternary cancer center was performed. Freedom from biochemical failure (FFBF), cumulative incidence of androgen deprivation therapy use for biochemical or clinical failure post-treatment (CI of ADT) and metastasis-free survival (MFS) outcomes were measured. RESULTS: 518 patients met the inclusion criteria for this study. Median age at HDR-BT was 67 years (IQR 61-72). 506 (98%) had complete pathologic information available. Of these, 146 (28%) had favorable (FIR) and 360 (69%) had unfavorable (UIR) intermediate-risk disease. 83 (16%) received short course hormones with EBRT + HDR. Median overall follow-up was 5.2 years. FFBF was 91 (88-94)% at 5 years. Five-year FFBF was 94 (89-99)% and 89 (85-94)% in FIR and UIR patients, respectively (p = 0.045). CI of ADT was 4 (2-6)% at 5 years. Five-year CI of ADT was 1 (0-3)% and 5 (2-8)% in FIR and UIR patients, respectively (p = 0.085). MFS was 97 (95-98)% at 5 years. Five-year MFS was 100 (N/A-100)% and 95 (92-98)% in FIR and UIR patients, respectively (p = 0.020). CONCLUSION: In this large cohort of intermediate-risk prostate cancer patients, 15 Gy HDR-BT boost plus EBRT results in durable biochemical control and low rates of ADT use for biochemical failure.

Prostate-specific Antigen Bounce After Stereotactic Body Radiotherapy for Prostate Cancer: A Pooled Analysis of Four Prospective Trials.

AIMS: We conducted a pooled analysis of four prospective stereotactic body radiotherapy (SBRT) trials of low- and intermediate-risk prostate cancer to evaluate the incidence of prostate-specific antigen (PSA) bounce and its correlation with the time-dose-fraction schedule. The correlation between bounce with PSA response at 4 years (nadir PSA < 0.4 ng/ml) and biochemical failure-free survival (BFFS) was also explored. MATERIALS AND METHODS: The study included four treatment groups: 35 Gy/five fractions once per week (QW) (TG-1; n = 84); 40 Gy/five fractions QW (TG-2; n = 100); 40 Gy/five fractions every other day (TG-3; n = 73); and 26 Gy/two fractions QW (TG-4; n = 30). PSA bounce was defined as a rise in PSA by 0.2 ng/ml (nadir + 0.2) or 2 ng/ml (nadir + 2.0) above nadir followed by a decrease back to nadir. Patients with fewer than three follow-up PSA tests were excluded from the pooled analysis. RESULTS: In total, 287 patients were included, with a median follow-up of 5.0 years. The pooled 5-year cumulative incidence of bounce by nadir + 2.0 was 8%. The 2-year cumulative incidences of PSA bounce by nadir + 0.2 were 28.9, 21, 19.6 and 16.7% (P = 0.12) and by nadir + 2.0 were 7.2, 8, 2.7 and 6.7% (P = 0.32) for TG-1 to TG-4, respectively. Multivariable analysis revealed that for nadir + 2.0, pre-treatment PSA (odds ratio 0.49; 95% confidence interval 0.26-0.97) correlated with PSA bounce. Although PSA bounce by nadir + 0.2 (odds ratio 0.10; 95% confidence interval 0.04-0.24) and nadir + 2.0 (odds ratio 0.29; 95% confidence interval 0.09-0.93) was associated with a lower probability of PSA response at 4 years, there was no association between bounce by nadir + 0.2 (hazard ratio 0.36; 95% confidence interval 0.08-1.74) or nadir + 2 (hazard ratio 1.77; 95% confidence interval 0.28-11.07) with BFFS. CONCLUSION: The incidence of PSA bounce was independent of time-dose-fraction schedule for prostate SBRT. One in 13 patients experienced a bounce high enough to be misinterpreted as biochemical failure, and clinicians should avoid early salvage interventions in these patients. There was no association between PSA bounce and BFFS.

Absolute percentage of biopsied tissue positive for Gleason pattern 4 disease (APP4) appears predictive of disease control after high dose rate brachytherapy and external beam radiotherapy in intermediate risk prostate cancer.

BACKGROUND AND PURPOSE: To identify if, in intermediate risk prostate cancer (IR-PCa), the absolute percentage of biopsied tissue positive for pattern 4 disease (APP4) may be a predictor of outcome. MATERIALS AND METHODS: 411 patients with IR-PCa were retrospectively reviewed. APP4 was calculated based on biopsy reports. Multivariable competing risk analysis was then performed on optimized APP4 cutpoints to predict for biochemical failure (BF), androgen deprivation use for BF (ADT-BF) and development of metastases (MD). RESULTS: Median follow-up for the cohort was 5.2 (Inter Quartile Range: 2.9-6.6) years. Median baseline PSA was 7.3 (5.3-9.8) ng/mL. 234 (56.9%) patients had T1 and 177 (43.1%) had T2 disease. Median APP4 was 2.00 (0.75-7.50)%. 38 (9.3%) patients experienced BF. The optimal cutpoint of APP4 for BF was >3.3% with an area under the curve (AUC) of 0.66. 17 (4.1%) received ADT-BF. The ADT-BF cutpoint was >6.6% with an AUC of 0.72. Eight (2.0%) developed MD. The MD cutpoint was >17.5% with an AUC of 0.86. Using APP4 >3.3 vs ≤ 3.3, log-transformed baseline PSA ln(PSA) (HR 2.5, 1.1-6.1; p = 0.037) and APP4 (HR 2.3, 1.1-4.7; p = 0.031) predicted for BF. Using APP4 >6.6 vs ≤ 6.6, ln(PSA) (HR 4.2, 1.4-12.4; p = 0.010) and APP4 (HR 3.7, 1.4-10.0; p = 0.009) were predictive of ADT-BF. APP4 >17.5 vs ≤ 17.5 alone was predictive of MD (HR 25.7, 4.9-135.3; p < 0.001). CONCLUSION: APP4 cutpoints of >3.3%, >6.6% and >17.5% were strongly associated with increased risk of BF, ADT-BF and developing MD respectively. These findings may inform future practice when treating IR-PCa but require external validation.

Randomised Phase II Feasibility Trial of Image-guided External Beam Radiotherapy With or Without High Dose Rate Brachytherapy Boost in Men with Intermediate-risk Prostate Cancer (CCTG PR15/ NCT01982786).

AIMS: We conducted a multicentre feasibility study to assess the ability to randomise patients between image-guided radiotherapy (IGRT) and IGRT + high dose rate (HDR) brachytherapy boost and to adhere to appropriate radiation quality assurance standards. MATERIALS AND METHODS: The primary end point was to determine the ability to randomise 60 patients over an 18 month period. Arm 1 (IGRT) patients received 78 Gy in 39 fractions or 60 Gy in 20 fractions (physician's preference), whereas arm 2 (IGRT + HDR) received 37.5 Gy in 15 fractions with HDR boost of 15 Gy. The secondary end points included >grade 3 acute genitourinary and gastrointestinal toxicity, using Common Terminology Criteria for Adverse Events version 4.0 at 3 months, validation of a prospectively defined radiation oncology quality assurance to assess treatment compliance. All analyses were descriptive; no formal comparisons between treatment arms were carried out. RESULTS: Between April 2014 and September 2015, 57 National Comprehensive Cancer Network (NCCN)-defined intermediate-risk prostate cancer patients were randomised between IGRT alone (arm 1; n = 29) and IGRT plus HDR brachytherapy boost (arm 2; n = 28). Overall, 93% received the treatment as randomised. There were four patients (one on IGRT arm 1 and three patients on the IGRT + HDR arm 2) who were treated differently from randomisation assignment. For the 29 patients receiving IGRT (arm 1), there were 14 cases reported with minor deviations and three with major deviations. For patients on IGRT + HDR (arm 2), there were 18 cases reported with minor deviations and two with major deviations. At 3 months in the IGRT group (arm 1), one patient reported grade 3 diarrhoea, whereas in the IGRT + HDR group (arm 2), two patients reported grade 3 haematuria. No other gastrointestinal and genitourinary toxicities were reported. CONCLUSION: The pilot study showed the feasibility of randomisation between treatment with IGRT alone versus IGRT + HDR boost. Treatment compliance was good, including adherence to quality assurance standards.

Follow-up Care for Survivors of Prostate Cancer - Clinical Management: a Program in Evidence-Based Care Systematic Review and Clinical Practice Guideline.

AIMS: This clinical practice guideline was developed to provide evidence-based guidance on the frequency by which prostate-specific antigen (PSA) levels should be tested in men after curative-intent treatment for prostate cancer and to define the most appropriate diagnostic testing if biochemical recurrence occurs. MATERIALS AND METHODS: An electronic search using OVID was used to systematically search the MEDLINE and EMBASE databases for systematic reviews and primary literature. A systematic review and practice guideline was written, reviewed and approved by the Guideline Development Group (GDG) and Program in Evidence-Based Care Report Approval Panel. External review by three prostate experts was completed, as well as an online consultation with healthcare professionals who were intended users of the guideline. RESULTS: Three systematic reviews and seven primary studies were included in the evidence base. All identified literature reported on diagnostic imaging properties of diagnostic tests following biochemical recurrence. CONCLUSIONS: Due to a lack of empirical research, few evidenced-based recommendations could be made with respect to a follow-up schedule of PSA testing for prostate cancer survivors following curative-intent treatment, or detailing diagnostic testing upon detection of biochemical recurrence. Accordingly, the GDG focused substantial effort on critical examination of the identified evidence, existing clinical practice guidelines and on obtaining clinical expertise consensus using a modified Delphi method. Overall, the recommendations embedded in this guideline reflect the best practice to date for the efficient and effective clinical follow-up care of prostate cancer survivors.

Exercise for people with cancer: a systematic review.

BACKGROUND: This systematic review was completed by the Exercise for People with Cancer Guideline Development Group, a group organized by Cancer Care Ontario's Program in Evidence-Based Care (pebc). It provides background and guidance for clinicians with respect to exercise for people living with cancer in active and post treatment. It focuses on the benefits of specific types of exercise, pre-screening requirements for new referrals, safety concerns, and delivery models. METHODS: Using the pebc's standardized approach, medline and embase were systematically searched for existing guidelines, systematic reviews, and primary literature. RESULTS: The search identified two guidelines, eighteen systematic reviews, and twenty-nine randomized controlled trials with relevance to the topic. The present review provides conclusions about the duration, frequency, and intensity of exercise appropriate for people living with cancer. CONCLUSIONS: The evidence shows that exercise is safe and provides benefit in quality of life and in muscular and aerobic fitness for people with cancer both during and after treatment. The evidence is sufficient to support the promotion of exercise for adults with cancer, and some evidence supports the promotion of exercise in group or supervised settings and for a long period of time to improve quality of life and muscular and aerobic fitness. Exercise at moderate intensities could also be sustainable for longer periods and could encourage exercise to be continued over an individual's lifetime. It is important that a pre-screening assessment be conducted to evaluate the effects of disease, treatments, and comorbidities.

Stereotactic Body Radiotherapy versus Low Dose Rate Brachytherapy for Localised Prostate Cancer: a Cost-Utility Analysis.

AIMS: To conduct a cost-utility analysis comparing stereotactic body radiotherapy (SBRT) with low dose rate brachytherapy (LDR-BT) for localised prostate cancer (PCa). MATERIALS AND METHODS: A decision-analytic Markov model was developed from the healthcare payer perspective to simulate the history of a 66-year-old man with low-risk PCa. The model followed patients yearly over their remaining lifetimes. Health states included 'recurrence-free', 'biochemical recurrence' (BR), 'metastatic' and 'death'. Transition probabilities were based on a retrospective cohort analysis undertaken at our institution. Utilities were derived from the literature. Costs were assigned in 2015 Canadian dollars ($) and reflected Ontario's health system and departmental costs. Outcomes included quality-adjusted life years (QALYs), costs and incremental cost-effectiveness ratios. A willingness-to-pay threshold of $50 000/QALY was used. RESULTS: SBRT was the dominant strategy with 0.008LYs and 0.029QALYs gained and a reduction in cost of $2615. Under base case conditions, our results were sensitive to the BR probability associated with both strategies. LDR-BT becomes the preferred strategy if the BR with SBRT is 1.3*[baseline BR_SBRT] or if the BR with LDR-BT is 0.76*[baseline BR_LDR-BT]. When assuming the same BR for both strategies, LDR-BT becomes marginally more effective with 0.009QALYs gained at a cost of $272 848/QALY. CONCLUSIONS: SBRT represents an economically attractive radiation strategy. Further research should be carried out to provide longer-term follow-up and high-quality evidence.

Exercise for people with cancer: a clinical practice guideline.

BACKGROUND: Development of this guideline was undertaken by the Exercise for People with Cancer Guideline Development Group, a group organized by Cancer Care Ontario's Program in Evidence-Based Care (pebc). The purpose of the guideline was to provide guidance for clinicians with respect to exercise for patients living with cancer, focusing on the benefits of specific types of exercise, recommendations about screening requirements for new referrals, and safety concerns. METHODS: Consistent with the pebc's standardized approach, a systematic search was conducted for existing guidelines, and systematic literature searches were performed in medline and embase for both systematic reviews and primary literature. Content and methodology experts performed an internal review, which was followed by an external review by targeted experts and intended users. RESULTS: The search identified three guidelines, eighteen systematic reviews, and twenty-nine randomized controlled trials with relevance to the topic. The present guideline provides recommendations for the duration, frequency, and intensity of exercise appropriate for people living with cancer. It also provides recommendations for pre-exercise assessment, safety concerns, and delivery models. CONCLUSIONS: There is sufficient evidence to show that exercise provides benefits in quality of life and muscular and aerobic fitness for people with cancer both during and after treatment, and that it does not cause harm. The present guideline is intended to support the Canadian Society for Exercise Physiology's Canadian physical activity guidelines. The recommendations are intended for clinicians and institutions treating cancer patients in Ontario, and for policymakers and program planners involved in the delivery of exercise programs for cancer patients.