Variations in Demand across England for the Magnetic Resonance-Linac Technology, Simulated Utilising Local-level Demographic and Cancer Data in the Malthus Project.

AIMS: Cancer incidence varies across England, which affects the local-level demand for treatments. The magnetic resonance-linac (MR-linac) is a new radiotherapy technology that combines imaging and treatment. Here we model the demand and demand variations for the MR-linac across England. MATERIALS AND METHODS: Initial clinical indications were provided by the MR-linac consortium and introduced into the Malthus radiotherapy clinical decision trees. The Malthus model contains Clinical Commissioning Group (CCG) population, cancer incidence and stage presentation data (for lung and prostate) and simulated the demand for the MR-linac for all CCGs and Radiotherapy Operational Delivery Networks (RODN) across England. RESULTS: Based on the initial target clinical indications, the MR-linac could service 16% of England's fraction burden. The simulated fractions/million population demand/annum varies between 3000 and 10 600 fractions/million at the CCG level. Focussing only on the cancer population, the simulated fractions/1000 cancer cases demand/annum ranges from 1028 to 1195 fractions/1000 cases. If a national average for fractions/million demand was then used, at the RODN level, the variation from actual annual demand ranges from an overestimation of 8400 fractions to an underestimation of 5800 fractions. When using the national average fractions/1000 cases, the RODN demand varies from an overestimation of 3200 fractions to an underestimation of 3000 fractions. CONCLUSIONS: Planning cancer services is complex due to regional variations in cancer burden. The variations in simulated demand of the MR-linac highlight the requirement to use local-level data when planning to introduce a new technology.

Selecting Patients with Favorable Risk, Grade Group 2 Prostate Cancer for Active Surveillance-Does Magnetic Resonance Imaging Have a Role?

PURPOSE: The National Comprehensive Cancer Network® recommends that selected men with grade group 2 prostate cancer be considered for active surveillance. However, selecting which patients with grade group 2 disease can be safely managed by active surveillance remains controversial. The aim of this study was to evaluate the association of multiparametric magnetic resonance imaging with adverse pathology in the radical prostatectomy specimen of men with favorable risk grade group 2 prostate cancer, which could help select patients for active surveillance. MATERIALS AND METHODS: We retrospectively analyzed a cohort of patients with favorable grade group 2 disease who underwent radical prostatectomy between 2010 and 2019. Preoperative multiparametric magnetic resonance imaging was scored as negative (no identifiable lesion), positive (identifiable lesion) or equivocal. We defined a multivariable logistic regression model with multiparametric magnetic resonance imaging score as the predictor and adverse pathology (up staging to T3a/b disease, upgrading to ≥grade group 3 or lymph node invasion) as the outcome, adjusting for preoperative prostate specific antigen, biopsy Gleason grade, clinical stage, and number of negative and positive prostate biopsy cores. Secondary outcomes of biochemical recurrence, grade group upgrading alone and the added value of incorporating multiparametric magnetic resonance imaging data into the nomogram were also investigated. RESULTS: We identified 1,117 patients with favorable risk grade group 2 disease who underwent radical prostatectomy. Positive multiparametric magnetic resonance imaging was associated with higher rates of adverse pathology (OR 2.55, 95% CI 1.75-3.40, p <0.0001) and upgrading (OR 3.89, 95% CI 2.00-7.56, p <0.0001). However, as our study included only grade group 2 patients who underwent radical prostatectomy, our cohort may represent a higher risk group than grade group 2 patients as a whole. Adding multiparametric magnetic resonance imaging results to a standard prediction model led to higher net benefit on decision curve analysis. An identifiable lesion on multiparametric magnetic resonance imaging was associated with an increased risk of aggressive pathological features in the radical prostatectomy specimen of patients with favorable risk grade group 2 prostate cancer who were potential active surveillance candidates. This information could be used to inform biopsy strategy, counsel patients on treatment options and guide strategies for those on active surveillance. CONCLUSIONS: Combining multiple magnetic resonance imaging modalities (multiparametric magnetic resonance imaging) provides a more accurate prediction of the risk presented by prostate cancer than current prediction methods. In this study, positive magnetic resonance imaging results approximately doubled the chances that a patient with favorable risk prostate cancer would be found to have adverse pathology when their prostate was removed. Thus, multiparametric magnetic resonance imaging could help select patients with favorable risk cancer who may be good candidates for active surveillance, and help guide biopsy and surveillance strategies for such patients.

External Evaluation of a Novel Prostate Cancer Risk Calculator (ProstateCheck) Based on Data from the Swiss Arm of the ERSPC.

PURPOSE: We externally validated a novel prostate cancer risk calculator based on data from the Swiss arm of the ERSPC and assessed whether the risk calculator (ProstateCheck) is superior to the PCPT-RC and SWOP-RC in an independent Swiss cohort. MATERIALS AND METHODS: Data from all men who underwent prostate biopsy at an academic tertiary care center between 2004 and 2012 were retrospectively analyzed. The probability of having any prostate cancer or high grade prostate cancer (Gleason score 7 or greater) on prostate biopsy was calculated using the ProstateCheck. Risk calculator performance was assessed using calibration and discrimination, and additionally compared with the PCPT-RC and SWOP-RC by decision curve analyses. RESULTS: Of 1,615 men 401 (25%) were diagnosed with any prostate cancer and 196 (12%) with high grade prostate cancer. Our analyses of the ProstateCheck-RC revealed good calibration in the low risk range (0 to 0.4) and moderate overestimation in the higher risk range (0.4 to 1) for any and high grade prostate cancer. The AUC for the discrimination of any prostate cancer and high grade prostate cancer was 0.69 and 0.72, respectively, which was slightly but significantly higher compared to the PCPT-RC (0.66 and 0.69, respectively) and SWOP-RC (0.64 and 0.70, respectively). Decision analysis, taking into account the harms of transrectal ultrasound measurement of prostate volume, showed little benefit for ProstateCheck-RC, with properties inferior to those of the PCPT-RC and SWOP-RC. CONCLUSIONS: Our independent external evaluation revealed moderate performance of the ProstateCheck-RC. Its clinical benefit is limited, and inferior to that of the PCPT-RC and SWOP-RC.

Accuracy of the EORTC risk tables and of the CUETO scoring model to predict outcomes in non-muscle-invasive urothelial carcinoma of the bladder.

BACKGROUND: The European Organization for Research and Treatment of Cancer (EORTC) risk tables and the Spanish Urological Club for Oncological Treatment (CUETO) scoring model are the two best-established predictive tools to help decision making for patients with non-muscle-invasive bladder cancer (NMIBC). The aim of the current study was to assess the performance of these predictive tools in a large multicentre cohort of NMIBC patients. METHODS: We performed a retrospective analysis of 4689 patients with NMIBC. To evaluate the discrimination of the models, we created Cox proportional hazard regression models for time to disease recurrence and progression. We incorporated the patients calculated risk score as a predictor into both of these models and then calculated their discrimination (concordance indexes). We compared the concordance index of our models with the concordance index reported for the models. RESULTS: With a median follow-up of 57 months, 2110 patients experienced disease recurrence and 591 patients experienced disease progression. Both tools exhibited a poor discrimination for disease recurrence and progression (0.597 and 0.662, and 0.523 and 0.616, respectively, for the EORTC and CUETO models). The EORTC tables overestimated the risk of disease recurrence and progression in high-risk patients. The discrimination of the EORTC tables was even lower in the subgroup of patients treated with BCG (0.554 and 0.576 for disease recurrence and progression, respectively). Conversely, the discrimination of the CUETO model increased in BCG-treated patients (0.597 and 0.645 for disease recurrence and progression, respectively). However, both models overestimated the risk of disease progression in high-risk patients. CONCLUSION: The EORTC risk tables and the CUETO scoring system exhibit a poor discrimination for both disease recurrence and progression in NMIBC patients. These models overestimated the risk of disease recurrence and progression in high-risk patients. These overestimations remained in BCG-treated patients, especially for the EORTC tables. These results underline the need for improving our current predictive tools. However, our study is limited by its retrospective and multi-institutional design.

A four-kallikrein panel for the prediction of repeat prostate biopsy: data from the European Randomized Study of Prostate Cancer screening in Rotterdam, Netherlands.

BACKGROUND: Most men with elevated levels of prostate-specific antigen (PSA) do not have prostate cancer, leading to a large number of unnecessary biopsies. A statistical model based on a panel of four kallikreins has been shown to predict the outcome of a first prostate biopsy. In this study, we apply the model to an independent data set of men with previous negative biopsy but persistently elevated PSA. METHODS: The study cohort consisted of 925 men with a previous negative prostate biopsy and elevated PSA (>or=3 ng ml(-1)), with 110 prostate cancers detected (12%). A previously published statistical model was applied, with recalibration to reflect the lower positive biopsy rates on rebiopsy. RESULTS: The full-kallikrein panel had higher discriminative accuracy than PSA and DRE alone, with area under the curve (AUC) improving from 0.58 (95% confidence interval (CI): 0.52, 0.64) to 0.68 (95% CI: 0.62, 0.74), P<0.001, and high-grade cancer (Gleason >or=7) at biopsy with AUC improving from 0.76 (95% CI: 0.64, 0.89) to 0.87 (95% CI: 0.81, 0.94), P=0.003). Application of the panel to 1000 men with persistently elevated PSA after initial negative biopsy, at a 15% risk threshold would reduce the number of biopsies by 712; would miss (or delay) the diagnosis of 53 cancers, of which only 3 would be Gleason 7 and the rest Gleason 6 or less. CONCLUSIONS: Our data constitute an external validation of a previously published model. The four-kallikrein panel predicts the result of repeat prostate biopsy in men with elevated PSA while dramatically decreasing unnecessary biopsies.

Unconventional therapies for cancer and cancer-related symptoms.

A significant proportion of cancer patients try unconventional therapies and many use 'complementary' therapies, as adjuncts to mainstream care, for management of symptoms and to improve quality of life. A smaller proportion use 'alternative' therapies, which are typically invasive, biologically active, and commonly promoted as replacements for, rather than adjuncts to, mainstream therapy. Many alternative therapies, including high-dose vitamin C, the Di Bella regimen, and laetrile have been shown not to be effective. For others, such as metabolic therapy, evidence is extremely limited. Conversely, most complementary therapies are well studied and of proven benefit. There is evidence from randomised trials supporting the value of hypnosis for cancer pain and nausea; relaxation therapy, music therapy, and massage for anxiety; and acupuncture for nausea. Such complementary therapies are increasingly provided at mainstream cancer centres.

Homeopathic Arnica 30x is ineffective for muscle soreness after long-distance running: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To determine whether homeopathic Arnica 30X can reduce muscle soreness following long-distance running more than a placebo. DESIGN: Randomized, double-blind placebo-controlled trial. SETTING: Long-distance runs taking place in the community. SUBJECTS: A total of 519 runners anticipating delayed-onset muscles soreness after long-distance races. INTERVENTIONS: A homeopathic medicine (Arnica 30x) and an indistinguishable placebo. OUTCOME MEASURES: Subjects completed a visual analog scale and Likert scale of muscle soreness every morning and evening for the 5 days following their race. Race time was also recorded. The main outcome measure was mean 2-day visual analog scores. RESULTS: Results were obtained from 400 subjects. Groups were well matched at baseline. Mean 2-day visual analog soreness scores for Arnica and placebo were 45.2 mm and 41.0 mm, respectively. The 95% confidence interval was between 8.81 mm in favor of placebo and 0.51 mm in favor of Arnica. No differences were found for Likert scores or race time. CONCLUSION: Homeopathic Arnica 30x is ineffective for muscle soreness following long-distance running.

Can acupuncture have specific effects on health? A systematic review of acupuncture antiemesis trials.

The effects of acupuncture on health are generally hard to assess. Stimulation of the P6 acupuncture point is used to obtain an antiemetic effect and this provides an excellent model to study the efficacy of acupuncture. Thirty-three controlled trials have been published worldwide in which the P6 acupuncture point was stimulated for treatment of nausea and/or vomiting associated with chemotherapy, pregnancy, or surgery. P6 acupuncture was equal or inferior to control in all four trials in which it was administered under anaesthesia; in 27 of the remaining 29 trials acupuncture was statistically superior. A second analysis was restricted to 12 high-quality randomized placebo-controlled trials in which P6 acupuncture point stimulation was not administered under anaesthesia. Eleven of these trials, involving nearly 2000 patients, showed an effect of P6. The reviewed papers showed consistent results across different investigators, different groups of patients, and different forms of acupuncture point stimulation. Except when administered under anaesthesia, P6 acupuncture point stimulation seems to be an effective antiemetic technique. Researchers are faced with a choice between deciding that acupuncture does have specific effects, and changing from 'Does acupuncture work?' to a set of more practical questions; or deciding that the evidence on P6 antiemesis does not provide sufficient proof, and specifying what would constitute acceptable evidence.