Study protocol: multi-parametric magnetic resonance imaging for therapeutic response prediction in rectal cancer.

BACKGROUND: Response to neoadjuvant chemoradiotherapy (CRT) of rectal cancer is variable. Accurate imaging for prediction and early assessment of response would enable appropriate stratification of management to reduce treatment morbidity and improve therapeutic outcomes. Use of either diffusion weighted imaging (DWI) or dynamic contrast enhanced (DCE) imaging alone currently lacks sufficient sensitivity and specificity for clinical use to guide individualized treatment in rectal cancer. Multi-parametric MRI and analysis combining DWI and DCE may have potential to improve the accuracy of therapeutic response prediction and assessment. METHODS: This protocol describes a prospective non-interventional single-arm clinical study. Patients with locally advanced rectal cancer undergoing preoperative CRT will prospectively undergo multi-parametric MRI pre-CRT, week 3 CRT, and post-CRT. The protocol consists of DWI using a read-out segmented sequence (RESOLVE), and DCE with pre-contrast T1-weighted (VIBE) scans for T1 calculation, followed by 60 phases at high temporal resolution (TWIST) after gadoversetamide injection. A 3-dimensional voxel-by-voxel technique will be used to produce colour-coded ADC and Ktrans histograms, and data evaluated in combination using scatter plots. MRI parameters will be correlated with surgical histopathology. Histopathology analysis will be standardized, with chemoradiotherapy response defined according to AJCC 7th Edition Tumour Regression Grade (TRG) criteria. Good response will be defined as TRG 0-1, and poor response will be defined as TRG 2-3. DISCUSSION: The combination of DWI and DCE can provide information on physiological tumour factors such as cellularity and perfusion that may affect radiotherapy response. If validated, multi-parametric MRI combining DWI and DCE can be used to stratify management in rectal cancer patients. Accurate imaging prediction of patients with a complete response to CRT would enable a 'watch and wait' approach, avoiding surgical morbidity in these patients. Consistent and reliable quantitation from standardised protocols is essential in order to establish optimal thresholds of ADC and Ktrans and permit the role of multi-parametric MRI for early treatment prediction to be properly evaluated. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) number ACTRN12616001690448 (retrospectively registered 8/12/2016).

The Population Benefit of Radiotherapy for Malignant Brain Tumors: Local Control and Survival Estimates for Guideline-Based Use.

OBJECTIVE: To estimate the population benefit of radiotherapy (RT) for primary malignant brain tumors if evidence-based guidelines were routinely followed. METHODS: This study investigated 5-year local control (LC) and 2- and 5-year overall survival (OS) benefits. RT benefit was the absolute proportional benefit of RT alone over no RT for radical indications, and over surgery alone for adjuvant indications. Chemoradiotherapy (CRT) benefit was the absolute incremental benefit of concurrent chemotherapy and RT over RT alone. Decision tree models were adapted to define the incidence of each indication. Citation databases were systematically queried for the highest level of evidence defining indication benefits. Meta-analysis was performed if there were multiple sources of the same evidence level, and deterministic and probabilistic sensitivity analysis was also performed. RESULTS: Among all patients with malignant brain tumors, 82% had indications for curative- or adjuvant-intent RT. The magnitude of benefit was based on level I or II evidence in 44% of all patients. A total of 25 relevant studies were used to quantify indication benefits. All RT benefit included in the model was irreplaceable. For malignant brain tumors, the estimated population benefit for RT alone was 9% for 5-year LC (95% CI, 7%-10%), 9% for 2-year OS (95% CI, 8%-11%), and 5% for 5-year OS (95% CI, 4%-5%). The incremental benefit of CRT was 1% for 5-year LC (95% CI, 0%-2%), 7% for 2-year OS (95% CI, 4%-11%), and 3% for 5-year OS (95% CI, 1%-5%). The model was robust in sensitivity analysis. CONCLUSIONS: When optimally used, RT provides an important benefit for many patients with malignant brain tumors. The model provided a robust means for estimating the magnitude of this benefit.