Dosimetric comparison of proton therapy and CyberKnife in stereotactic body radiation therapy for liver cancers.

Stereotactic body radiation therapy (SBRT) has been increasingly used for the ablation of liver tumours. CyberKnife and proton beam therapy (PBT) are two advanced treatment technologies suitable to deliver SBRT with high dose conformity and steep dose gradients. However, there is very limited data comparing the dosimetric characteristics of CyberKnife to PBT for liver SBRT. PBT and CyberKnife plans were retrospectively generated using 4DCT datasets of ten patients who were previously treated for hepatocellular carcinoma (HCC, N = 5) and liver metastasis (N = 5). Dose volume histogram data was assessed and compared against selected criteria; given a dose prescription of 54 Gy in 3 fractions for liver metastases and 45 Gy in 3 fractions for HCC, with previously published consensus-based normal tissue dose constraints. Comparison of evaluation parameters showed a statistically significant difference for target volume coverage and liver, lungs and spinal cord (p < 0.05) dose, while chest wall and skin did not indicate a significant difference between the two modalities. A number of optimal normal tissue constraints was violated by both the CyberKnife and proton plans for the same patients due to proximity of tumour to chest wall. PBT resulted in greater organ sparing, the extent of which was mainly dependent on tumour location. Tumours located on the liver periphery experienced the largest increase in organ sparing. Organ sparing for CyberKnife was comparable with PBT for small target volumes.

Overall survival and treatment modalities in pancreatic adenocarcinoma: a retrospective analysis of a single centre in Western Australia.

Background: Pancreatic ductal adenocarcinoma (PDAC) has a 5-year survival rate of approximately 10.7% in Australia. It is becoming an increasingly common cause of cancer mortality. The therapeutic model for PDAC remains limited, especially for those with metastatic disease on presentation. Methods: We completed a retrospective cohort study including all patients with PDAC presenting between April 2008 and October 2021 to St. John of God Subiaco Hospital in Western Australia. Overall survival (OS) was calculated via Kaplan-Meier method. Results: We identified 251 patients treated for PDAC. Of these, 134 patients (53%) had resectable, borderline resectable or locally advanced (LA) disease at diagnosis and 117 patients (47%) had metastatic disease. The median age of all patients was 66 years (range, 25-87 years). OS in PDAC was 26 months [95% confidence interval (CI): 23-30]. In the non-metastatic group OS was 34 months (95% CI: 30-39). In the metastatic group OS was 19 months (95% CI: 14-22). Treatment modalities varied between patients. Overall 123 patients were treated with chemotherapy alone, 55 patients had chemoradiotherapy, 34 patients had chemotherapy and surgery and 37 had tri-modality treatment including chemotherapy, surgery and radiotherapy. Two patients received cyberknife radiation alone. Conclusions: This retrospective study shows a significant prolonged survival for PDAC patients. Further studies are needed to validate second- and third-line regimens in PDAC.

Pembrolizumab with Chemoradiation as Treatment for Muscle-invasive Bladder Cancer: Analysis of Safety and Efficacy of the PCR-MIB Phase 2 Clinical Trial (ANZUP 1502).

BACKGROUND: Radiation may improve the efficacy of immune checkpoint inhibition. This study investigates the combination of pembrolizumab and chemoradiation (CRT) for muscle-invasive bladder cancer (MIBC). OBJECTIVE: To assess the feasibility and safety of pembrolizumab combined with CRT for MIBC. DESIGN, SETTING, AND PARTICIPANTS: A single-arm phase 2 trial was performed with 28 participants having cT2-T4aN0M0 MIBC (Eastern Cooperative Oncology Group performance status 0-1; estimated glomerular filtration rate ≥40 ml/min; no contraindications to pembrolizumab) suitable for CRT. INTERVENTION: Whole bladder radiation therapy (RT; 64 Gy in 32 daily fractions, over 6.5 wk, combined with cisplatin (35 mg/m2 intravenously [IV] weekly, six doses) and pembrolizumab (200 mg IV q3 weeks, seven doses), both starting with RT. Surveillance cystoscopy/biopsy and computerised tomography scans performed 12 and 24 wk after CRT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was feasibility, determined by a prespecified satisfactory low rate of grade 3 or worse nonurinary toxicity or completion of planned CRT according to defined parameters. Secondary endpoints were complete cystoscopic response, locoregional progression-free survival (LRPFS), distant metastasis-free survival (DMFS), and overall survival (OS). RESULTS AND LIMITATIONS: Twenty-eight patients were enrolled with a 31-mo median follow-up. Six had Grade >3 nonurinary adverse events during/within 12 wk after treatment; three had more than one cisplatin dose reduction. The 24-wk post-CRT complete response (CR) rate was 88%. Eight patients developed metastatic disease, and three had nonmetastatic progression. The DMFS at 2 yr is 78% (95% confidence interval [CI] 54-90%), with LRPFS at 2 yr of 87% (95% CI 64-96%) and median OS of 39 mo (95% CI 17.1-not evaluable). Limitations are the single-arm design and sample size. CONCLUSIONS: Combining pembrolizumab with CRT for MIBC was feasible, with manageable toxicity and promising CR rates. PATIENT SUMMARY: Immunotherapy treats nonmetastatic/metastatic bladder cancer effectively. We combined pembrolizumab with chemotherapy and radiation to assess its safety and impact on treatment delivery. The combination was feasible with encouraging early activity. Further larger trials are warranted.

Reporting Attendance and Resistance Exercise Compliance in Men with Localized Prostate Cancer.

PURPOSE: Resistance exercise is a well-established intervention to counteract musculoskeletal and metabolic toxicities from prostate cancer treatment. In this study, we reported resistance exercise attendance and compliance, and examined if these variables can influence changes in outcomes of interest in men with localized or locally advanced prostate cancer. METHODS: A total of 83 prostate cancer patients (age, 68.2 ± 7.0 yr; body mass index, 27.7 ± 3.8 kg·m -2 ) who had undergone 6 months of resistance-based exercise and had data available on exercise training from logbook records were examined. Attendance outcomes such as missed sessions, interruptions and permanent discontinuation, and metrics such as dosage completed (sessions × number of exercises × sets × repetitions × external load), compliance, tolerance, reductions, and escalations were assessed. Outcomes assessed were body composition, physical function, and muscle strength. RESULTS: Median resistance exercise attendance was 80.6%, with a median resistance exercise compliance of 88.5% (interquartile range [IQR], 61.1%-107.1%) per participant. A median of 11 (IQR, 1-26) and 0 (IQR, 0-2) sessions were escalated or reduced, respectively. Significant improvements were observed in whole-body lean mass, 400-m walk, repeated chair rise, leg press, and chest press strength after 6 months of intervention ( P < 0.05) regardless of resistance exercise compliance ( Ptrend = 0.199-0.950). Participants with higher levels of resistance exercise compliance presented greater improvements in trunk fat mass ( Ptrend = 0.026) and appendicular lean mass ( Ptrend = 0.047). CONCLUSIONS: A higher resistance exercise compliance led to greater improvements in regional fat and lean mass, whereas physical function and muscle strength improvements were achieved with lower compliance. In addition, patients experienced a high number of dose escalations during the intervention. These findings are important to improve the reproducibility/precision of exercise medicine prescription.

Evaluation of a Clinic-Based Exercise Program in Patients with Pancreatic Cancer Undergoing Nonsurgical Treatment.

INTRODUCTION: Evidence regarding the role of exercise in pancreatic cancer (PanCa) is limited and is derived exclusively under tightly controlled research conditions. This study aimed to quantify adherence, adverse events, and changes in physical and psychological outcomes in any patients with PanCa referred to undertake exercise during nonsurgical treatment. METHODS: The study involved 22 patients with localized or metastatic PanCa undertaking a clinic-based exercise program during chemotherapy or chemoradiotherapy. The program included supervised aerobic and resistance exercise undertaken twice weekly for 12 wk and a 12-wk follow-up with supervised exercise optional dependent on patient preference and condition. Patients were monitored for adherence and adverse events. Objective and patient-reported outcomes were assessed at baseline, 12 wk, and 24 wk. RESULTS: A total of 251 sessions were attended by 19 patients over the first 12 wk (attendance rate, 55%). Complete case analyses indicated significant ( P < 0.05) improvements in functional ability (5.2%-17.2%), muscle strength (16.9%-25.1%), and static balance (6.8%). There were no significant changes in body composition or patient-reported outcomes except for sleep quality, which deteriorated; however, at an individual level, several patients had clinically relevant improvements in cancer-related fatigue and quality of life. Patients who continued with supervised exercise to week 24 largely preserved improvements in functional ability, muscle strength, and static balance. No serious adverse events resulted from the exercise program. CONCLUSIONS: Individualized, supervised aerobic and resistance exercise in a clinic-based setting appears to be safe and may improve or maintain physical and psychological health in patients with PanCa undergoing nonsurgical treatment.

Early results from implementation of a 'watch and wait' protocol for complete clinical response following chemoradiotherapy for rectal cancer.

BACKGROUND: Neoadjuvant long course chemoradiotherapy (NLCRT) for rectal cancer can result in complete pathological response (pCR). In 2017, we started offering patients who had a complete clinical response (cCR), a choice between total mesorectal excision (TME) and an intensive surveillance or 'watch and wait' (W&W) program. We report the early outcomes of this prospective study. METHODS: All patients undergoing NLCRT from 2017 to 2019 were included. All patients were restaged at 8 weeks, and those who had a cCR were offered TME or W&W. RESULTS: Of 59 patients who underwent NLCRT, 55 had restaging. Eleven of these patients had a cCR (20%). Three chose to have TME and all had a pCR. Eight were enrolled in W&W. Two patients were diagnosed with local regrowth and underwent TME at 7 and 17 months after NLCRT. A further nine patients, who were surgically unfit or refused TME, and had an excellent response to NLCRT, but one that did not reach criteria for a cCR, were also managed with W&W. Of these, two patients developed regrowth with distant metastases. From 2017 to 2019, of the 17 patients who were managed with a W&W approach, 13 patients have remained regrowth free after a median of 28 (13-58) months of W&W. CONCLUSION: Preliminary findings suggest management with W&W, following cCR, may be a safe alternative to TME. There have so far been no instances of distant failure, and those with cCR that had regrowth, were identified early and successfully managed with salvage TME.

Weight loss for overweight and obese patients with prostate cancer: a study protocol of a randomised trial comparing clinic-based versus Telehealth delivered EXercise and nutrition intervention (the TelEX trial).

INTRODUCTION: Obese men with prostate cancer have an increased risk of biochemical recurrence, metastatic disease and mortality. For those undergoing androgen deprivation therapy (ADT), substantial increases in fat mass are observed in the first year of treatment. Recently, we showed that a targeted supervised clinic-based exercise and nutrition intervention can result in a substantial reduction in fat mass with muscle mass preserved in ADT-treated patients. However, the intervention needs to be accessible to all patients and not just those who can access a supervised clinic-based programme. The purpose of this study was to evaluate the efficacy of telehealth delivered compared with supervised clinic-based delivered exercise and nutrition intervention in overweight/obese patients with prostate cancer. METHODS AND ANALYSIS: A single-blinded, two-arm parallel group, non-inferiority randomised trial will be undertaken with 104 overweight/obese men with prostate cancer (body fat percentage ≥25%) randomly allocated in a ratio of 1:1 to a telehealth-delivered, virtually supervised exercise and nutrition programme or a clinic-based, face-to-face supervised exercise and nutrition programme. Exercise will consist of supervised resistance and aerobic exercise performed three times a week plus additional self-directed aerobic exercise performed 4 days/week for the first 6 months. Thereafter, for months 7-12, the programmes will be self-managed. The primary endpoint will be fat mass. Secondary endpoints include lean mass and abdominal aortic calcification, anthropometric measures and blood pressure assessment, objective measures of physical function and physical activity levels, patient-reported outcomes and blood markers. Measurements will be undertaken at baseline, 6 months (post intervention), and at 12 months of follow-up. Data will be analysed using intention-to-treat and per protocol approaches. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the Edith Cowan University Human Research Ethics Committee (ID: 2021-02157-GALVAO). Outcomes from the study will be published in academic journals and presented in scientific and consumer meetings. TRIAL REGISTRATION NUMBER: ACTRN12621001312831.

Nationwide Industry-Led Community Exercise Program for Men With Locally Advanced, Relapsed, or Metastatic Prostate Cancer on Androgen-Deprivation Therapy.

PURPOSE: Androgen-deprivation therapy in patients with prostate cancer (PCa) is associated with considerable side effects and secondary comorbidities such as overweight/obesity and cardiovascular disease. The aim of this study was to investigate the effectiveness of an industry-led, treatment-integrated, community-based exercise program on outcomes of body weight, cardiovascular health, and physical function. PATIENTS AND METHODS: PCa patients with locally advanced, relapsed, or metastatic disease receiving leuprorelin acetate were enrolled across multiple sites in Australia and assigned supervised group exercise undertaken weekly or biweekly (ie, 16 exercise sessions in total) for 10-18 weeks, consisting of aerobic and resistance training performed at moderate-to-vigorous intensity. RESULTS: Between 2014 and 2020, 760 participants completed the baseline and follow-up assessment. Participants were age 48-94 years, and most were either overweight (42.1%) or obese (38.1%). Program compliance was high, with 90% of participants completing all 16 exercise sessions. There was a small but significant reduction in waist circumference (-0.9 cm; 95% CI [-1.2 to -0.5]; P < .001) and no change in weight or body mass index. Systolic (-3.7 mmHg; 95% CI [-4.8 to -2.6]; P < .001) and diastolic (-1.7 mmHg; 95% CI [-2.3 to -1.0]; P < .001) blood pressure were significantly lower after the program. Furthermore, significant improvements were seen in cardiorespiratory fitness and muscle strength (P < .001). For most of the investigated outcomes, participants with poorer initial measures had the greatest benefit from participating in the program. CONCLUSION: The community exercise program was feasible and effective in preventing weight gain, reducing blood pressure, and improving physical function in patients with PCa on androgen-deprivation therapy.

Evaluating the utility of knowledge-based planning for clinical trials using the TROG 08.03 post prostatectomy radiation therapy planning data.

Background and purpose: Poor quality radiotherapy can detrimentally affect outcomes in clinical trials. Our purpose was to explore the potential of knowledge-based planning (KBP) for quality assurance (QA) in clinical trials. Materials and methods: Using 30 in-house post-prostatectomy radiation treatment (PPRT) plans, an iterative KBP model was created according to the multicentre clinical trial protocol, delivering 64 Gy in 32 fractions. KBP was used to replan 137 plans. The KB (knowledge based) plans were evaluated for their ability to fulfil the trial constraints and were compared against their corresponding original treatment plans (OTP). A second analysis between only the 72 inversely planned OTPs (IP-OTPs) and their corresponding KB plans was performed. Results: All dose constraints were met in 100% of KB plans versus 69% of OTPs. KB plans demonstrated significantly less variation in PTV coverage (Mean dose range: KB plans 64.1 Gy-65.1 Gy vs OTP 63.1 Gy-67.3 Gy, p < 0.01). KBP resulted in significantly lower doses to OARs. Rectal V60Gy and V40Gy were 17.7% vs 27.7% (p < 0.01) and 40.5% vs 53.9% (p < 0.01) for KB plans and OTP respectively. Left femoral head (FH) V45Gy and V35Gy were 0.4% vs 7.4% (p < 0.01) and 7.9% vs 34.9% (p < 0.01) respectively. In the second analysis plan improvements were maintained. Conclusions: KBP created high quality PPRT plans using the data from a multicentre clinical trial in a single optimisation. It is a powerful tool for utilisation in clinical trials for patient specific QA, to reduce dose to surrounding OARs and variations in plan quality which could impact on clinical trial outcomes.

Event-free survival after radical prostatectomy according to prostate-specific membrane antigen-positron emission tomography and European Association of Urology biochemical recurrence risk groups.

OBJECTIVE: To assess European Association of Urology (EAU) risk groups for biochemical recurrence (BCR) of prostate cancer relative to prostate-specific membrane antigen-positron emission tomography (PSMA-PET) status and oncological outcomes. PATIENTS AND METHODS: A retrospective analysis of a study that incorporated PSMA-PET for men with BCR after radical prostatectomy (RP) was undertaken. EAU risk groups were considered relative to clinical variables, PSMA-PET findings, and deployment of salvage radiotherapy (SRT). The primary oncological outcome was event-free survival (EFS) and this was analysed relative to clinical and imaging variables. An 'event' occurred if prostate-specific antigen (PSA) level rose >0.2 ng/mL above nadir or additional therapies were introduced. RESULTS: A total of 137 patients were included, most of whom had EAU high-risk disease (76%) and/or low PSA levels (80% <0.5 ng/mL) at the time of PSMA-PET. EAU risk group was not associated with regional nodal/distant metastasis on PSMA-PET. Regional nodal/distant metastasis on PSMA PET (compared to negative/local recurrence: hazard ratio [HR] 2.2; P = 0.002) and SRT use (vs no SRT: HR 0.44; P = 0.004) were associated with EFS. EAU high-risk status was not significantly associated with worse EFS (HR 1.7, P = 0.12) compared to EAU low-risk status. Among patients who received SRT, both regional/distant metastasis on PSMA-PET (HR 3.1; P < 0.001) and EAU high-risk status (HR 2.9; P = 0.04) were independently associated with worse EFS, which was driven by patients in the EAU high-risk group with regional/distant metastases (38%; HR 3.1, P = 0.001). CONCLUSIONS: In patients with post-RP BCR, PSMA-PET findings and receipt of SRT predicted EFS. In patients receiving SRT, PSMA status combined with EAU risk grouping was most predictive of EFS. These findings suggest that the EAU risk groups could be improved with the addition of PSMA-PET.

Long-Term Results of Triple Immunosuppression With Tacrolimus Added to Mycophenolate and Corticosteroids in the Treatment of Lupus Nephritis.

Introduction: Addition of a calcineurin inhibitor (CNI) to corticosteroids and mycophenolate increased the renal response rate in lupus nephritis (LN) because of proteinuria reduction, but there is little long-term efficacy and safety data on this triple immunosuppressive regimen. Methods: This is a cohort study of patients with class III/IV/V LN whose proteinuria persisted despite initial standard therapy with mycophenolate mofetil (MMF) and prednisolone (PRED), in whom tacrolimus (TAC) was added (target 12-hour trough TAC plasma levels of 4-6 µg/l). Results: A total of 22 patients with LN treated with triple immunosuppression were included, with follow-up of 61.1 ± 28.1 months. Achieved trough levels of TAC and mycophenolic acid (MPA) were 3.8 to 5.7 µg/l and 1.3 to 2.1 mg/l respectively. Significant proteinuria reduction occurred after 6 months and was sustained up to 5 years. Complete response (CR) and partial response (PR) rates at 12, 24, and 36 months was 59.1%, 72.7%, and 77.3% respectively. The slope of estimated glomerular filtration rate (eGFR) over time did not change after TAC was added. A total of 7 patients (31.8%) showed progressive chronic kidney disease (CKD). Two patients reached end-stage kidney disease during follow-up. Renal survival rate at -, 3, and 5 years was 100.0%, 95.0%, and 88.7% respectively. Two patients (9.1%) had renal relapse after 8.5 ± 0.7 months. A total of 5 patients (22.7%) showed worsening of hypertension, and 3 (13.6%) had worsened hyperlipidemia. Other key adverse events included infection (n = 16, 1 in 7 patient-years) and gastrointestinal upset (n = 6). Conclusion: Triple immunosuppression with the addition of TAC to mycophenolate and PRED resulted in further proteinuria reduction and sustained disease quiescence in patients with LN whose proteinuria did not respond optimally to standard therapy.

Randomised controlled trial on the effect of simethicone bowel preparation on rectal variability during image-guided radiation therapy for prostate cancer (SPoRT study).

INTRODUCTION: The purpose of this study was to assess whether simethicone reduces the rectal volume (RV) and gas volume (GV), to increase treatment accuracy and to decrease toxicity of prostate radiation therapy. METHODS: 30 patients were randomised to simethicone or no intervention. Cone-beam computed tomography (CBCT) scans were performed on Days 1-3 and weekly until completion of radiation. RV and GV were measured using volume delineation. Toxicity data were collected. RESULTS: 264 CBCTs were analysed. RV and GV were not significantly different in the simethicone group compared with the control group at each time point (P >0.05) after adjusting for Week 0 values as a covariate. The simethicone group showed an average reduction in RV and GV of 10% and 21%, respectively, compared with the control group (P >0.05). Standard deviations were calculated over 10 time points, which were grouped to represent the first 2-3 weeks of radiation therapy versus subsequent weeks. These were not significantly different between the simethicone and control group. However, there was a statistically significant decrease in the variability of RV at time points 6-10 compared with time points 1-5 within the simethicone group (P = 0.012), but no significant difference was found between these grouped time points in the control group (P = 0.581). The toxicity questionnaires showed no significant difference between the groups. CONCLUSIONS: Simethicone did not decrease the RV or GV overall. However, simethicone appeared to significantly decrease the RV variability from Week three onwards. This suggests that taking simethicone two to three weeks before starting radiation therapy may reduce RV variability, although a larger study is needed to confirm this.

Associations of fat and muscle mass with overall survival in men with prostate cancer: a systematic review with meta-analysis.

BACKGROUND: To systematically review and analyse the associations between fat and muscle mass measures with overall survival in men with prostate cancer. METHODS: A systematic search was conducted in CINAHL, Cochrane Library, EMBASE, PubMed, and Web of Science databases from inception to December 2020, while abstracts from the American Society of Clinical Oncology (ASCO), Clinical Oncology Society of Australia (COSA), and the American College of Sports Medicine (ACSM) conferences were searched from 2014 to 2020. Eligible articles examined the association of body composition measures, such as fat mass (e.g., fat mass, visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and VAT/SAT) and muscle mass measures, with overall survival in prostate cancer patients at any treatment stage. The primary endpoint was overall survival. Random-effect meta-analysis was conducted for studies reporting multivariable or univariable analysis assessing the associations of fat mass measures (i.e., fat mass, VAT, SAT, VAT/SAT) and muscle mass measures with overall survival. RESULTS: Sixteen cohort studies that comprised 4807 men with prostate cancer were included. Total adiposity (hazard ratio (HR) 0.98, 95% CI: 0.75-1.28, p = 0.888) and VAT (HR 1.03, 95% CI: 0.74-1.43, p = 0.873) were not significantly associated with overall survival, while higher subcutaneous adipose tissue levels were associated with higher survival (HR 0.68, 95% CI: 0.54-0.84, p = 0.001). Greater mortality risk was found in patients with localised (HR 1.91, 95% CI: 1.40-2.62, p < 0.001) and advanced disease (HR 1.43, 95% CI: 1.07-1.92, p = 0.020) presenting with low levels of muscle mass compared to those presenting with high levels. DISCUSSION: These results indicate that although overall adiposity should be cautiously interpreted in regards to survival, high muscle mass and SAT, and low VAT/SAT ratio values are associated with overall survival in men with prostate cancer.

GCN2 kinase activation by ATP-competitive kinase inhibitors.

Small-molecule kinase inhibitors represent a major group of cancer therapeutics, but tumor responses are often incomplete. To identify pathways that modulate kinase inhibitor response, we conducted a genome-wide knockout (KO) screen in glioblastoma cells treated with the pan-ErbB inhibitor neratinib. Loss of general control nonderepressible 2 (GCN2) kinase rendered cells resistant to neratinib, whereas depletion of the GADD34 phosphatase increased neratinib sensitivity. Loss of GCN2 conferred neratinib resistance by preventing binding and activation of GCN2 by neratinib. Several other Food and Drug Administration (FDA)-approved inhibitors, such erlotinib and sunitinib, also bound and activated GCN2. Our results highlight the utility of genome-wide functional screens to uncover novel mechanisms of drug action and document the role of the integrated stress response (ISR) in modulating the response to inhibitors of oncogenic kinases.

Interventions for Improving Body Composition in Men with Prostate Cancer: A Systematic Review and Network Meta-analysis.

PURPOSE: To perform a systematic review and network meta-analysis to investigate the most effective intervention for improving body composition outcomes in prostate cancer patients during or after treatment. METHODS: A systematic search was undertaken in multiple databases from inception to December 2020. Randomized clinical trials examining the effects of exercise/physical activity and/or nutrition interventions on body composition and body weight measures in prostate cancer patients were included. The primary endpoints were both whole-body and regional fat mass and lean mass measures, with body weight and BMI as secondary outcomes. A frequentist random-effects network meta-analysis was undertaken to examine the clustering effect of intervention modalities or control groups on the outcomes of interest. The study protocol is publicly available on PROSPERO (CRD42020202339). RESULTS: Fifty articles describing 47 trials (n = 3207) were included. Resistance training and combined resistance and aerobic exercise were the most effective interventions to reduce body fat percentage (-0.9%; 95% confidence interval [CI], -1.4% to -0.3%) and fat mass (-0.5 kg; 95% CI, -0.9 to -0.1 kg), respectively. For whole-body and regional lean mass, combined resistance and aerobic exercise + healthy diet (0.6 kg; 95% CI, 0.1 to 1.0 kg) and resistance training alone (0.7 kg, 95% CI: 0.4 to 1.0 kg) were the best intervention, respectively. A low-fat diet was the most effective for reducing body weight immediately after or at follow-up, while no intervention promoted significant reductions in BMI. CONCLUSIONS: These results indicate that a resistance-based exercise program alone or combined with a general healthy diet are the most effective interventions for improving overall body composition in men with prostate cancer.

Effects of Exercise During Radiation Therapy on Physical Function and Treatment-Related Side Effects in Men With Prostate Cancer: A Systematic Review and Meta-Analysis.

PURPOSE: Radiation therapy is a commonly used treatment for prostate cancer; however, the side effects may negatively affect quality of life and cause patients to be less physically active. Although exercise has been shown to mitigate radiation therapy-related fatigue in men with prostate cancer during radiation therapy, other adverse effects of treatment such as physical deconditioning, urinary symptoms, or sexual dysfunction have not been systematically reviewed in this patient population. Thus, the purpose of this review was to investigate the effect of exercise on physical function and treatment-related side effects in men with prostate cancer undergoing radiation therapy. METHODS: A systematic literature search was conducted in the PubMed, Embase, CINAHL Plus, SPORTDiscus, and Web of Science databases in December 2020. Included studies were randomized controlled trials examining the effects of aerobic and/or resistance exercise interventions on measures of physical function and treatment-related side effects in prostate cancer patients undergoing radiation therapy. Meta-analysis was performed on outcomes that were reported in 2 or more studies. RESULTS: Seven publications from 6 randomized controlled trials involving 391 prostate cancer patients were included. Patients had stage I to IV cancer with a Gleason score of ≤6 to 10. Exercise resulted in consistent significant benefits for physical function in terms of cardiovascular fitness (standardized mean difference [SMD], 0.83; 95% confidence interval [CI], 0.31-1.36; P < .01) and muscle function (SMD, 1.30; 95% CI, 0.53-2.07; P < .01). Furthermore, there was a significant positive effect of exercise on urinary toxicity (SMD, -0.71; 95% CI, -1.25 to -0.18; P < .01), but not on intestinal (P = .21) or hormonal toxicity (P = .41), depression (P = .45), or sleep symptoms (P = .88). CONCLUSION: Based on the current evidence, exercise in men with prostate cancer undergoing radiation therapy improves physical function and mitigates urinary toxicity. The effect of exercise on other treatment-related side effects are less clear and require further investigation.

Feasibility and efficacy of a multicomponent exercise medicine programme in patients with pancreatic cancer undergoing neoadjuvant therapy (the EXPAN trial): study protocol of a dual-centre, two-armed phase I randomised controlled trial.

INTRODUCTION: Exercise is emerging as a therapy in oncology for its physical and psychosocial benefits and potential effects on chemotherapy tolerability and efficacy. However, evidence from randomised controlled trials (RCTs) supporting exercise in patients with borderline resectable or locally advanced pancreatic cancer (PanCa) undergoing neoadjuvant therapy (NAT) are lacking. METHODS AND ANALYSIS: The EXPAN trial is a dual-centre, two-armed, phase I RCT. Forty patients with borderline resectable or locally advanced PanCa undergoing NAT will be randomised equally to an exercise intervention group (individualised exercise+standard NAT) or a usual care control group (standard NAT). The exercise intervention will be supervised and consist of moderate to vigorous intensity resistance and aerobic-based training undertaken two times a week for 45-60 min per session for a maximum period of 6 months. The primary outcome is feasibility. Secondary outcomes are patient-related and treatment-related endpoints, objectively measured physical function, body composition, psychological health and quality of life. Assessments will be conducted at baseline, prior to potential alteration of treatment (~4 months postbaseline), at completion of the intervention (maximum 6 months postbaseline) and 3-month and 6-month postintervention (maximum 9 and 12 months postbaseline). ETHICS AND DISSEMINATION: The EXPAN trial has been approved by Edith Cowan University (reference no.: 2020-02011-LUO), Sir Charles Gairdner Hospital (reference no.: RGS 03956) and St John of God Subiaco Hospital (reference no.: 1726). The study results will be presented at national/international conferences and submitted for publications in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ACTRN12620001081909.

Exercise Medicine in the Management of Pancreatic Cancer: A Systematic Review.

ABSTRACT: The aim of this study was to examine the health-related effects of exercise in patients with pancreatic cancer (PanCa) through a systematic review of current evidence. Studies were obtained through searching PubMed, Web of Science, PsycINFO, Embase, CINAHL Plus, and Cochrane Library databases with additional hand searches. All intervention-based studies were included if it involved (1) adult patients with PanCa, (2) exercise training, and (3) findings in quality of life, cancer-related fatigue, psychological distress, and physical function. The review protocol was registered in PROSPERO: CRD42020154684. Seven trials described in 9 publications were included consisting of 201 patients with early-stage and advanced PanCa. Participants were required to perform supervised and/or home-based, low- to moderate-intensity resistance and/or aerobic exercise for 12 to 35 weeks or duration of neoadjuvant therapy. There were no exercise-related adverse events with a reported retention rate of 71% to 90% and exercise attendance of 64% to 96%. The programs were consistently associated with improvements in cancer-related fatigue, psychological distress, and physical function, with mixed effects on quality of life. Exercise training seems to be safe and feasible and may have a beneficial effect on various physical and psychological outcomes in patients with PanCa. Further work with rigorous study designs is required to consolidate and advance current findings.

Clinico-pathological associations of serum VCAM-1 and ICAM-1 levels in patients with lupus nephritis.

OBJECTIVE: We investigated the clinico-pathological associations of serum VCAM-1 and ICAM-1 levels in patients with biopsy-proven Class III/IV±V lupus nephritis (LN). METHODS: Serum VCAM-1 and ICAM-1 levels were determined by ELISAs. Sera from patients with non-renal SLE or non-lupus chronic kidney disease (CKD), and healthy subjects served as controls. RESULTS: Seropositivity rate for VCAM-1 and ICAM-1 was 93.10% and 37.93% respectively at the time of nephritic flare, and 44.83% and 13.79% respectively at remission, with both showing higher levels during flare (P < 0.05, for both). VCAM-1 level correlated with proteinuria, serum creatinine, and anti-dsDNA antibodies, and inversely correlated with C3. VCAM-1 level also correlated with leukocyte infiltration and fibrinoid necrosis/karyorrhexis scores in active LN kidney biopsies. ICAM-1 level correlated with proteinuria, but not anti-dsDNA or C3, nor histopathological features. VCAM-1 level increased 4.5 months before renal flare, while ICAM-1 increase coincided with flare, and both decreased after treatment. ROC analysis showed that VCAM-1 distinguished active LN from healthy subjects, LN in remission, active non-renal lupus, and CKD (ROC AUC of 0.98, 0.86, 0.93 and 0.90 respectively). VCAM-1 level in combination with either proteinuria or C3 was superior in distinguishing active LN from remission compared to the measurement of individual markers. Serum ICAM-1 level distinguished active LN from healthy subjects and LN patients in remission (ROC AUC of 0.75 and 0.66 respectively), but did not distinguish between renal versus non-renal lupus. ICAM-1 level in combination with markers of endothelial cell activation (syndecan-1, hyaluronan and thrombomodulin) was superior to proteinuria, anti-dsDNA, or C3 in distinguishing active LN from quiescent disease. CONCLUSION: Our findings suggest potential utility of serum VCAM-1 and ICAM-1 in clinical management. Monitoring VCAM-1 may facilitate early diagnosis of flare. Combining selected biomarkers may be advantageous in diagnosing active LN. VCAM-1 may have a pathogenic role in renal parenchymal inflammation in active LN.