A Prospective Study of Diffusion-weighted Magnetic Resonance Imaging as an Early Prognostic Biomarker in Chemoradiotherapy in Squamous Cell Carcinomas of the Anus.

AIMS: The use of diffusion-weighted magnetic resonance imaging (DW-MRI) as a prognostic marker of treatment response would enable early individualisation of treatment. We aimed to quantify the changes in mean apparent diffusion coefficient (ΔADCmean) between a DW-MRI at diagnosis and on fraction 8-10 of chemoradiotherapy (CRT) as a biomarker for cellularity, and correlate these with anal squamous cell carcinoma recurrence. MATERIALS AND METHODS: This prospective study recruited patients with localised anal cancer between October 2014 and November 2017. DW-MRI was carried out at diagnosis and after fraction 8-10 of radical CRT. A region of interest was delineated for all primary tumours and any lymph nodes >2 cm on high-resolution T2-weighted images and propagated to the ADC map. Routine clinical follow-up was collected from Nation Health Service electronic systems. RESULTS: Twenty-three of 29 recruited patients underwent paired DW-MRI scans. Twenty-six regions of interest were delineated among the 23 evaluable patients. The median (range) tumour volume was 13.6 cm3 (2.8-84.9 cm3). Ten of 23 patients had lesions with ΔADCmean ≤ 20%. With a median follow-up of 41.2 months, four patients either failed to have a complete response to CRT or subsequently relapsed. Three of four patients with disease relapse had lesions demonstrating ΔADCmean <20%, the other patient with persistent disease had ΔADCmean of 20.3%. CONCLUSIONS: We demonstrated a potential correlation between patients with ΔADCmean <20% and disease relapse. Further investigation of the prognostic merit of DW-MRI change is needed in larger, prospective cohorts.

Is There a Role for an 18F-fluorodeoxyglucose-derived Biological Boost in Squamous Cell Anal Cancer?

AIMS: To investigate the potential role for a biological boost in anal cancer by assessing whether subvolumes of high 18F-fluorodeoxyglucose (FDG) avidity, identified at outset, are spatially consistent during a course of chemoradiotherapy (CRT). MATERIALS AND METHODS: FDG-positron emission tomography (FDG-PET) scans from 21 patients enrolled into the ART study (NCT02145416) were retrospectively analysed. In total, 29 volumes including both primary tumours and involved nodes >2 cm were identified. FDG-PET scans were carried out before treatment and on day 8 or 9 of CRT. FDG subvolumes were created using a percentage of maximum FDG avidity at thresholds of 34%, 40%, 50%, on the pre-treatment scans, and 70% and 80% on the subsequent scans. Both FDG-PET scans were deformably registered to the planning computed tomography scan. The overlap fraction and the vector distance were calculated to assess spatial consistency. FDG subvolumes for further investigation had an overlap fraction >0.7, as this has been defined in previous publications as a 'good' correlation. RESULTS: The median overlap fractions between the diagnostic FDG-PET subvolumes 34%, 40% and 50% of maximum standardised uptake value (SUVmax) and subsequent FDG-PET subvolumes of 70% of SUVmax were 0.97, 0.92 and 0.81. The median overlap fraction between the diagnostic FDG-PET subvolumes 34%, 40% and 50% and subsequent FDG-PET subvolumes of 80% were 1.00, 1.00 and 0.92. The median (range) vector distance values between diagnostic FDG-PET subvolumes 34%, 40% and 50% and subsequent FDG-PET subvolumes of 80% were 0.74 mm (0.19-2.94) 0.74 mm (0.19-3.39) and 0.71 mm (0.2-3.29), respectively. Twenty of 29 volumes (69.0%) achieved a threshold > 0.7 between the FDG 50% subvolume on the diagnostic scan and the FDG 80% subvolume on the subsequent scan. CONCLUSION: FDG-avid subvolumes identified at baseline were spatially consistent during a course of CRT treatment. The subvolume of 50% of SUVmax on the pre-treatment scan could be considered as a potential target for dose escalation.

Clustering of pain and its associations with health in people aged 50†years and older: cross-sectional results from the North Staffordshire Osteoarthritis Project.

OBJECTIVE: Most pain in patients aged ≥50 years affects multiple sites and yet the predominant mode of presentation is single-site syndromes. The aim of this study was to investigate if pain sites form clusters in this population and if any such clusters are associated with health factors other than pain. SETTING: Six general practices in North Staffordshire, UK. DESIGN: Cross-sectional, postal questionnaire, study. PARTICIPANTS: Community-dwelling adults aged ≥50 years registered at the general practices. MAIN OUTCOMES MEASURES: Number of pain sites was measured by asking participants to shade sites of pain lasting ≥1 day in the past 4 weeks on a blank body manikin. Health factors measured included anxiety and depression (Hospital and Anxiety Depression Scale), cognitive complaint (Sickness Impact Profile) and sleep. Pain site clustering was investigated using latent class analysis. Association of clusters with health factors, adjusted for age, sex, body mass index and morbidities, was analysed using multinomial regression models. RESULTS: 13 986 participants (adjusted response 70.6%) completed a questionnaire, of whom 12 408 provided complete pain data. Four clusters of participants were identified: (1) low number of pain sites (36.6%), (2) medium number of sites with no back pain (31.5%), (3) medium number of sites with back pain (17.9%) and (4) high number of sites (14.1%). Compared to Cluster 1, other clusters were associated with poor health. The strongest associations (relative risk ratios, 95% CI) were with Cluster 4: depression (per unit change in score) 1.11 (1.08 to 1.14); cognitive complaint 2.60 (2.09 to 3.24); non-restorative sleep 4.60 (3.50 to 6.05). CONCLUSIONS: These results indicate that in a general population aged ≥50 years, pain forms four clusters shaped by two dimensions-number of pain sites (low, medium, high) and, within the medium cluster, the absence or presence of back pain. The usefulness of primary care treatment approaches based on this simple classification should be investigated.