Coincidental splenic irradiation and risk of functional hyposplenism in oesophageal cancer treatment.

INTRODUCTION: Definitive chemoradiotherapy (dCRT) and radical radiotherapy are central to the management of distal oesophageal carcinoma. This study sought to establish whether the spleen receives a significant incidental radiation dose when treating distal oesophageal carcinoma with the standardised dCRT or radical radiotherapy doses. METHODS: In this single-centre retrospective study, all patients (n = 34) with distal oesophageal cancer, treated with either dCRT or radical radiotherapy over an 18-month period using a volumetric modulated arc therapy (VMAT) planning technique, were included. The median age was 74 years old: 56% were male; 50% (n = 17) had adenocarcinoma and 41% (n = 14) had squamous carcinoma. The majority (79%) received dCRT with a prescribed dose of 50 Gy in 25 fractions while the other 21% of patients were treated with radical radiotherapy alone (55 Gy in 20 fractions). The spleen was retrospectively contoured by one physician, and the V10 Gy and mean splenic dose (MSD) were calculated using Eclipse planning software. RESULTS: The median MSD was 14.4 Gy with a range of 0.75-28.3 Gy. The median V10 Gy was 62.7%. Of the cohort, 67.6% received an MSD of more than 10 Gy. CONCLUSIONS: Two-thirds of the patients received a dose of more than the 10 Gy. A review of the literature suggests that higher splenic radiation doses may increase the long-term risk of infection and impact on other outcomes. This study provides important evidence that the spleen receives a significant dose of radiation when treating distal oesophageal cancer and should be considered as an organ at risk.

A pilot study of patient reported outcomes evaluating treatment related symptoms and quality of life for men receiving high dose rate brachytherapy combined with hypo-fractionated radiotherapy or hypo-fractionated radiotherapy alone for the treatment of localised prostate cancer.

Patient Reported Outcome Measures (PROMS) are useful metrics in evidence-based clinical care and translational research. Recording treatment-related symptoms and Quality of Life (QoL) can provide information in counselling patients to aid decision-making. This prospective study tested the feasibility of radiographer-led collection of multiple validated PROMS from Prostate Cancer (PCa) patients comparing High Dose Rate Brachytherapy combined with hypo-fractionated external beam radiotherapy (hEBRT) and hEBRT alone. From June to August 2017, 20 men with localised PCa (T1-T3aN0M0) consented to participate in the study. Ten patients received combination treatment (37.5 Gray/15 fractions followed by a 15 Gray implant), and ten patients received monotherapy (60 Gray/20 fractions). PROMS were collected at four time-points (1) at baseline, (2) final fraction of hEBRT, (3) 8 weeks after commencing radiotherapy and (4) 12 weeks after commencing radiotherapy. The PROMS used were EPIC-26, IPSS, IIEFF-5 and SF-12. The difference between the two groups were tested using Mann-Whitney U test and Wilcoxon Signed-Rank Test. All participants completed all PROMS (100% response-rate). The Monotherapy group reported a higher incidence of bowel symptoms compared to the combination group and at Week 12, EPIC-26 bowel summary score demonstrated a statistically significant difference (p = 0.005). The prevalence of erectile dysfunction increased within both groups. Maintenance of QoL was reported throughout treatment. This small study demonstrated feasibility of radiographer-led PROMS collection by 100% completion rate. Streamlining of these tools into integrated technology applications and real time PROMS measurement has the ability to benefit patients and guide clinicians in adapting therapies based on individual need.

Fiducial markers visibility and artefacts in prostate cancer radiotherapy multi-modality imaging.

BACKGROUND: In this study, a novel pelvic phantom was developed and used to assess the visibility and presence of artefacts from different types of commercial fiducial markers (FMs) on multi-modality imaging relevant to prostate cancer. METHODS AND MATERIALS: The phantom was designed with 3D printed hollow cubes in the centre. These cubes were filled with gel to mimic the prostate gland and two parallel PVC rods were used to mimic bones in the pelvic region. Each cube was filled with gelatine and three unique FMs were positioned with a clinically-relevant spatial distribution. The FMs investigated were; Gold Marker (GM) CIVCO, GM RiverPoint, GM Gold Anchor (GA) line and ball shape, and polymer marker (PM) from CIVCO. The phantom was scanned using several imaging modalities typically used to image prostate cancer patients; MRI, CT, CBCT, planar kV-pair, ExacTrac, 6MV, 2.5MV and integrated EPID imaging. The visibility of the markers and any observed artefacts in the phantom were compared to in-vivo scans of prostate cancer patients with FMs. RESULTS: All GMs were visible in volumetric scans, however, they also had the most visible artefacts on CT and CBCT scans, with the magnitude of artefacts increasing with FM size. PM FMs had the least visible artefacts in volumetric scans but they were not visible on portal images and had poor visibility on lateral kV images. The smallest diameter GMs (GA) were the most difficult GMs to identify on lateral kV images. CONCLUSION: The choice between different FMs is also dependent on the adopted IGRT strategy. PM was found to be superior to investigated gold markers in the most commonly used modalities in the management of prostate cancer; CT, CBCT and MRI imaging.

Schneider's first rank symptoms and continuous performance disturbance as indices of dysconnectivity of left- and right-hemispheric components of language in schizophrenia.

BACKGROUND: Here we investigate pathophysiological dimensions (language disturbance, negative symptoms, lateralisation and the continuous performance test) in relation to ICD-10 and DSM-IV concepts of diagnosis. METHODS: A total of 32 consecutive psychotic patients with at least one Schneider's first rank symptom (SFRS), 15 depressed patients without SFRS and 17 normal volunteers were assessed with the Clinical Language Disorder Rating Scale (CLANG), SFRS, "pure defect" Huber's basic symptoms (HBS), handedness (Annett's pegboard task), and the A-X Continuous Performance Test (AX-CPT). RESULTS: CLANG total score (an index of severity of language disorder) was correlated with the severity of SFRS, a higher leftward shift of handedness, and poorer performance on AX-CPT. Receiver operating characteristic (ROC) analysis showed that only CLANG and AX-CPT variables had adequate predictive validity in separating cases of ICD-10 schizophrenia from other diagnoses. The logistic regression model predicting the presence of ICD-10 schizophrenia was statistically significant using CLANG and AX-CPT variables, but not SFRS or other variables. HBS did not correlate with other variables and did not predict ICD-10 diagnosis. CONCLUSIONS: A cross-sectional diagnosis based on language disturbance and CPT performance yields a diagnostic construct largely overlapping with the ICD-10 definition of schizophrenia. We suggest that Schneider's first rank symptoms (that play a large role in the DSM-IV concept) can be considered an index of left hemisphere dysconnectivity for language whereas CPT dysfunction reflects dysconnectivity of the right hemisphere for those remoter ("spatial") associations that are closer to Bleuler's core defect and to the chronicity implicit in the ICD definition. Thus the dimensions of language disturbance in psychosis can be traced to specific cortico-cortical dysconnectivities.

Prostate cancer treated with brachytherapy; an exploratory study of dose-dependent biomarkers and quality of life.

BACKGROUND: Low-dose-rate permanent prostate brachytherapy (PPB) is an attractive treatment option for patients with localised prostate cancer with excellent outcomes. As standard CT-based post-implant dosimetry often correlates poorly with late treatment-related toxicity, this exploratory (proof of concept) study was conducted to investigate correlations between radiation - induced DNA damage biomarker levels, and acute and late bowel, urinary, and sexual toxicity. METHODS: Twelve patients treated with 125I PPB monotherapy (145Gy) for prostate cancer were included in this prospective study. Post-implant CT based dosimetry assessed the minimum dose encompassing 90% (D90%) of the whole prostate volume (global), sub-regions of the prostate (12 sectors) and the near maximum doses (D0.1cc, D2cc) for the rectum and bladder. Six blood samples were collected from each patient; pre-treatment, 1 h (h), 4 h, 24 h post-implant, at 4 weeks (w) and at 3 months (m). DNA double strand breaks were investigated by staining the blood samples with immunofluorescence antibodies to γH2AX and 53BP1 proteins (γH2AX/53BP1). Patient self-scored quality of life from the Expanded Prostate Cancer Index Composite (EPIC) were obtained at baseline, 1 m, 3 m, 6 m, 9 m, 1 year (y), 2y and 3y post-treatment. Spearman's correlation coefficients were used to evaluate correlations between temporal changes in γH2AX/53BP1, dose and toxicity. RESULTS: The minimum follow up was 2 years. Population mean prostate D90% was 144.6 ± 12.1 Gy and rectal near maximum dose D0.1cc = 153.0 ± 30.8 Gy and D2cc = 62.7 ± 12.1 Gy and for the bladder D0.1cc = 123.1 ± 27.0 Gy and D2cc = 70.9 ± 11.9 Gy. Changes in EPIC scores from baseline showed high positive correlation between acute toxicity and late toxicity for both urinary and bowel symptoms. Increased production of γH2AX/53BP1 at 24 h relative to baseline positively correlated with late bowel symptoms. Overall, no correlations were observed between dose metrics (prostate global or sector doses) and γH2AX/53BP1 foci counts. CONCLUSIONS: Our results show that a prompt increase in γH2AX/53BP1foci at 24 h post-implant relative to baseline may be a useful measure to assess elevated risk of late RT - related toxicities for PPB patients. A subsequent investigation recruiting a larger cohort of patients is warranted to verify our findings.