Yuvnik Trada

Background: To systematically review and meta-analyse the prognostic value of quantitative mid-treatment imaging biomarkers for predicting locoregional tumour control in patients undergoing definitive radiotherapy for mucosal head and neck squamous cell carcinoma. Main body: A systematic literature search (2005–2023) was conducted in PubMed, EMBASE, Scopus, and Cochrane databases according to a pre-registered PROSPERO protocol. Studies evaluating quantitative imaging features derived from CT, MRI, or PET during radiotherapy were included. Imaging features were grouped as baseline, absolute mid-treatment, or relative mid-treatment (delta) parameters. A random-effects meta-analysis was performed on studies reporting receiver operating characteristic (ROC)-based area under the curve (AUC) values. Forty-one studies encompassing 1654 patients were included. Seventeen studies (n = 612 patients) reported sufficient data for meta-analysis. The pooled AUC for relative mid-treatment parameters was 0.796 (95% CI: 0.762–0.831), demonstrating higher predictive performance than absolute mid-treatment parameters (AUC 0.686; 95% CI: 0.628–0.745). Baseline parameters showed moderate predictive ability (AUC 0.736; 95% CI: 0.688–0.785), and while numerically lower than relative mid-treatment parameters, this difference did not reach statistical significance. Diffusion-weighted MRI (ΔADCmean) and FDG-PET (ΔMTV, ΔTLG) emerged as the most consistently predictive modalities. Relative measures offer practical advantages, including internal self-normalisation and improved reproducibility across imaging platforms. Conclusions: Relative mid-treatment imaging biomarkers demonstrate superior predictive performance compared to baseline and absolute measures, supporting their potential role in adaptive radiotherapy strategies. Further prospective multi-centre studies with standardised imaging protocols and external validation are essential for clinical translation.

Background: Oral mucositis is a debilitating yet potentially modifiable toxicity frequently encountered in patients receiving head and neck radiotherapy. This study aimed to evaluate mid-treatment functional changes in the oral cavity using fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) and correlate these early imaging findings with moderate-severe mucositis at the completion of radiotherapy in patients with mucosal head and neck squamous cell carcinoma (HNSCC). Methods: A total of 54 patients with newly diagnosed mucosal HNSCC without distant metastases from two prospective imaging biomarker studies received FDG-PET/CT imaging at baseline and mid-treatment (week 3). The oral cavity was volumetrically segmented at baseline on the CT component of the CT-PET, with this volume transferred to mid-treatment imaging. The median standardised uptake value (SUV_median) on FDG-PET was measured at these timepoints. Absolute values and relative change (Δ) in SUV_median were correlated with the development of moderate-to-severe mucositis at treatment completion. Four predictive models, including a reference clinical model, were developed using multivariable logistic regression incorporating clinical and radiotherapy dosimetric parameters. Results: Forty-six patients (82.1%) developed moderate-severe [Common Terminology Criteria for Adverse Events (CTCAE) grade ≥2] mucositis at completion of treatment. The average oral cavity SUV_median (g/mL) increased from baseline to mid-treatment. Change in oral cavity SUV_median from baseline to mid-treatment was associated with mucositis (CTCAE grade ≥2) on univariate (P=0.04) and multivariate analysis (P=0.049). The reference ‘clinical model’ correlated with mucositis [area under the curve (AUC) 0.784, P=0.003]. Addition of oral cavity ΔSUV_median to the clinical model resulted in the highest correlation to mucositis at completion of treatment (AUC 0.855, PConclusions: Our study demonstrated that functional changes in the oral cavity as seen on mid-treatment FDG-PET/CT correlate with development of moderate-severe mucositis at completion of radiotherapy. Integration of this imaging data with clinical variables may enhance mucositis risk prediction, with potential application in the individualisation of head and neck radiotherapy.

Background: Hepatocellular carcinoma (HCC) often develops in the setting of chronic liver disease, making preservation of hepatic function central to treatment decisions. Despite this, the temporal change on liver function caused by stereotactic body radiation therapy (SBRT), particularly using objective measures such as the albumin–bilirubin (ALBI) score, remains poorly defined. This retrospective study aimed to measure temporal changes in liver function in patients with HCC treated with SBRT. Comparable data was also obtained from patients treated with microwave ablation (MWA), a liver-directed therapy with negligible impact on hepatic function, acting as a control cohort for estimating changes attributable to underlying cirrhosis rather than treatment. Methods: A total of 126 patients with HCC were included, 72 in the SBRT and 54 in the control cohorts respectively. Biochemical data was extracted before and at 3, 6 and 12 months post-treatment for calculation of albumin-bilirubin (ALBI) and Child-Pugh (CP) scores. Clinical and dosimetric data was obtained for assessment of factors associated with change in liver function following SBRT. Results: Baseline liver function was similar between the SBRT and control cohorts (ALBI score, −2.30 vs. −2.27, P=0.68). The median lesion size was significantly larger in the SBRT group (37 vs. 20 mm, PConclusions: Liver function as measured by ALBI score gradually declines following SBRT for HCC, with larger lesion size associated with greater change. However, this change is only significant in a minority of our cohort with added contributions from non-treatment-related factors including co-existing cirrhosis.

Background: To systematically review and meta-analyse the prognostic value of quantitative mid-treatment imaging biomarkers for predicting locoregional tumour control in patients undergoing definitive radiotherapy for mucosal head and neck squamous cell carcinoma. Main body: A systematic literature search (2005–2023) was conducted in PubMed, EMBASE, Scopus, and Cochrane databases according to a pre-registered PROSPERO protocol. Studies evaluating quantitative imaging features derived from CT, MRI, or PET during radiotherapy were included. Imaging features were grouped as baseline, absolute mid-treatment, or relative mid-treatment (delta) parameters. A random-effects meta-analysis was performed on studies reporting receiver operating characteristic (ROC)-based area under the curve (AUC) values. Forty-one studies encompassing 1654 patients were included. Seventeen studies (n = 612 patients) reported sufficient data for meta-analysis. The pooled AUC for relative mid-treatment parameters was 0.796 (95% CI: 0.762–0.831), demonstrating higher predictive performance than absolute mid-treatment parameters (AUC 0.686; 95% CI: 0.628–0.745). Baseline parameters showed moderate predictive ability (AUC 0.736; 95% CI: 0.688–0.785), and while numerically lower than relative mid-treatment parameters, this difference did not reach statistical significance. Diffusion-weighted MRI (ΔADCmean) and FDG-PET (ΔMTV, ΔTLG) emerged as the most consistently predictive modalities. Relative measures offer practical advantages, including internal self-normalisation and improved reproducibility across imaging platforms. Conclusions: Relative mid-treatment imaging biomarkers demonstrate superior predictive performance compared to baseline and absolute measures, supporting their potential role in adaptive radiotherapy strategies. Further prospective multi-centre studies with standardised imaging protocols and external validation are essential for clinical translation.

Background: This study evaluated mid-treatment changes in intra-tumoural metabolic heterogeneity and quantitative FDG-PET/CT imaging parameters and correlated the changes with treatment outcomes in oropharyngeal squamous cell cancer (OPSCC) patients. 114 patients from two independent cohorts underwent baseline and mid-treatment (week 3) FDG-PET. Standardized uptake value maximum (SUV_max), standardized uptake value mean (SUV_mean), metabolic tumour volume (MTV), and total lesional glycolysis (TLG) were measured. Intra-tumoural metabolic heterogeneity was quantified as the area under a cumulative SUV-volume histogram curve (AUC-CSH). Baseline and relative change (%∆) in imaging features were correlated to locoregional recurrence free survival (LRRFS) using multivariate Cox regression analysis. Patients were stratified into three risk groups utilising ∆AUC-CSH and known prognostic features, then compared using Kaplan-Meier analysis. Results: Median follow up was 39 months. 18% of patients developed locoregional recurrence at 2 years. A decrease in heterogeneity (∆AUC-CSH: 24%) was observed mid-treatment. There was no statistically significant difference in tumour heterogeneity (AUC-CSH) at baseline (p = 0.134) and change at week 3 (p = 0.306) between p16 positive and p16 negative patients. Baseline imaging features did not correlate to LRRFS. However, ∆MTV (aHR 1.04; 95% CI 1.03–1.06; p < 0.001) and ∆AUC-CSH (aHR 0.96; 95% CI 0.94–0.98; p = 0.004) were correlated to LRRFS. Stratification using ∆AUC-CSH and p16 status into three groups showed significant differences in LRR (2 year LRRFS 94%, 79%, 17%; log rank p < 0.001). Stratification using ∆AUC-CSH and ∆MTV into three groups showed significant differences in LRR (2 year LRRFS 93%, 70%, 17%; log rank p < 0.001). Conclusion: Mid-treatment changes in intra-tumoural FDG-PET/CT heterogeneity correlated with treatment outcomes in OPSCC and may help with response prediction. These findings suggest potential utility in designing future risk adaptive clinical trials.

Introduction: The aim of this study was to evaluate and compare the spatial pattern of locoregional recurrences in patients diagnosed with HPV‐associated and HPV‐non‐associated oropharyngeal SCC (OPSCC) treated with definitive radiotherapy.Methods and materials: Patients who had locoregional recurrence following definitive intensity‐modulated radiation therapy were identified at a single tertiary institution. Target volumes were delineated according to the latest consensus international guidelines. Recurrences were classified into five categories based on radiotherapy dose distribution and target volume, using a previously validated methodology; type A (central high dose), type B (peripheral high dose), type C (central elective dose), type D (peripheral elective dose), and type E (extraneous dose). The types of failure were compared between p16‐positive and p16‐negative tumors using the Pearson chi‐square test.Results: Fifty‐eight locoregional recurrences were observed in 36 patients. The majority of recurrences were in nodal locations (66%, 38/58). Among these, 34 (59%) were classified as type A, 6 (10%) as type B, 9 (15%) as type C, 5 (9%) as type D, and 4 (7%) as type E failure. A significant difference was found in the types of failure between p16‐positive and p16‐negative tumors (X² 9.52, p = 0.044). p16‐negative tumors were more likely to have recurrences in a peripheral location compared to p16‐positive tumors (32% vs. 7%). p16‐positive tumor were more likely to have extraneous recurrences (17% vs. 0%).Conclusion: Our study results identified a significant difference in patterns of locoregional failure among patients diagnosed with oropharyngeal cancer following consensus‐based tumor delineation and modern radiotherapy. Further confirmatory pattern of failure studies are required to enable greater individualization of radiotherapy for patients diagnosed with oropharyngeal malignancy in the future.

Objectives: To test if tumour changes measured using combination of diffusion-weighted imaging (DWI) MRI and FDG-PET/CT performed serially during radiotherapy (RT) in mucosal head and neck carcinoma can predict treatment response. Methods: Fifty-five patients from two prospective imaging biomarker studies were analysed. FDG-PET/CT was performed at baseline, during RT (week 3), and post RT (3 months). DWI was performed at baseline, during RT (weeks 2, 3, 5, 6), and post RT (1 and 3 months). The ADC_mean from DWI and FDG-PET parameters SUV_max, SUV_mean, metabolic tumour volume (MTV), and total lesion glycolysis (TLG) were measured. Absolute and relative change (%∆) in DWI and PET parameters were correlated to 1-year local recurrence. Patients were categorised into favourable, mixed, and unfavourable imaging response using optimal cut-off (OC) values of DWI and FDG-PET parameters and correlated to local control. Results: The 1-year local, regional, and distant recurrence rates were 18.2% (10/55), 7.3% (4/55), and 12.7% (7/55), respectively. ∆Week 3 ADC_mean (AUC 0.825, p = 0.003; OC ∆ > 24.4%) and ∆MTV (AUC 0.833, p = 0.001; OC ∆ > 50.4%) were the best predictors of local recurrence. Week 3 was the optimal time point for assessing DWI imaging response. Using a combination of ∆ADC_mean and ∆MTV improved the strength of correlation to local recurrence (p ≤ 0.001). In patients who underwent both week 3 MRI and FDG-PET/CT, significant differences in local recurrence rates were seen between patients with favourable (0%), mixed (17%), and unfavourable (78%) combined imaging response. Conclusions: Changes in mid-treatment DWI and FDG-PET/CT imaging can predict treatment response and could be utilised in the design of future adaptive clinical trials. Clinical relevance statement: Our study shows the complementary information provided by two functional imaging modalities for mid-treatment response prediction in patients with head and neck cancer. Key Points: •FDG-PET/CT and DWI MRI changes in tumour during radiotherapy in head and neck cancer can predict treatment response. •Combination of FDG-PET/CT and DWI parameters improved correlation to clinical outcome. •Week 3 was the optimal time point for DWI MRI imaging response assessment.

Original Article Impact of tumour region of interest delineation method for mid-treatment FDG-PET response prediction in head and neck squamous cell carcinoma undergoing radiotherapy Yuvnik Trada, Peter Lin, Mark T. Lee, Michael G. Jameson, Phillip Chlap, Paul Keall, Daniel Moses, Allan Fowler

Prostate cancer (PC) is the most common malignancy in men. Internal radiotherapy (brachytherapy) has been used to treat PC successfully for over a century. In particular, there is level-one evidence of the benefits of using brachytherapy to escalate the dose of radiotherapy compared with standard external beam radiotherapy approaches. However, the use of PC brachytherapy is declining, despite strong evidence for its improved cancer outcomes. A method using external beam radiotherapy known as virtual high-dose-rate brachytherapy boost (vHDRB) aims to noninvasively mimic a brachytherapy boost radiation dose plan. In this review, we consider the evidence supporting brachytherapy boosts for PC and the continuing evolution of vHDRB approaches, culminating in the current generation of clinical trials, which will help define the role of this emerging modality.