Staff Publication

ARISTOTLE: Mature results of a phase 3 trial evaluating the addition of irinotecan to capecitabine chemoradiation in locally advanced rectal cancer (2025)

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Type of publication:

Conference abstract

Author(s):

Sebag-Montefiore D.; Samuel L.; *Gollins S.; Glynne-Jones R.; Harte R.; West N.; Quirke P.; Myint A.S.; Bach S.; Falk S.; Parsons P.; Dhadda A.; Misra V.; Brown G.; Harrison M.; White L.; Duggan M.; Begum R.; Chang E.; Musleh R.; Lopes A.; Adams R.

Citation:

Radiotherapy and Oncology. Conference: ESTRO 2025. Vienna Austria. 206(Supplement 1) (pp S1192-S1194), 2025. Date of Publication: 01 May 2025

Abstract:

Purpose/Objective: To determine if the addition of irinotecan to capecitabine chemoradiation (CRT) improves disease-free survival in MRI-defined locally advanced rectal cancer (LARC). Material/Methods: ARISTOTLE (ISRCTN:09351447) is a phase III, multi-centre, open-label trial that randomly assigned (1:1) patients with MRI-defined LARC threatening or involving resection margins without metastases to pre-operative radiotherapy:45Gy/25 fractions combined with either capecitabine 900mg/m2 (CRT) or 650 mg/m2 bd weekdays with Irinotecan iv once-weekly 60mg/m2 (IrCRT) weeks 1-4. The primary endpoint is disease-free survival (DFS). Result(s): 75 UK sites randomised 564 eligible patients from 10/2011 to 07/2018; 284 to CRT and 280 to IrCRT. 66% male; median age 61 years (range:24-83). Radiological staging in both arms was similar:mrT3(77%), mrT4(16%); mrCRM involved(49%);resection margin threatened <=1mm(38%). Median follow-up is 62.1 months.Compared with CRT, IrCRT patients were less likely to receive 45Gy RT: 208(75%) vs 251(89%), p < 0.001; or receive >=90% capecitabine dose:187(68%) in IrCRT vs 253(89%) CRT, p < 0.001. 205(74%) IrCRT patients received >=90% irinotecan dose. >=Gd 3 non-haematological adverse events included fatigue 17(6%) vs 8(3%) p=0.06; diarrhoea:14% vs 4% p<0.001; abdominal pain 5% vs <1% p=0.001 for IrCRT and CRT respectively. >=Gd 3 haematological adverse events included leucopaenia: 9% vs 2%, p<0.001; neutropaenia: 10% vs 1%,p<0.001; and febrile neutropaenia: 1% vs <1% for IrCRT and CRT respectively. 5 patients had a grade 5 adverse event (3 lrCRT,2 CRT). The median time from the end of RT to surgery was 10.6 weeks. 238(85%) and 243(86%) patients underwent surgery in the IrCRT and CRT arms. The R0 resection rate was 90% vs 89% p=0.75 for IrCRT and CRT respectively. The pCR rate was 20% for IrCRT vs 18% for CRT p = 0.52. The rate of any post-surgical complications was similar in both arms:94(39%) for IrCRT and 91(37%) for CRT p=0.65). There is no evidence of a difference in loco-regional failure free (HR 0.94 [0.46-1.90]p=0.86, distant metastasis free (HR 0.89 [0.63-1.25] p=0.51), disease free HR 0.87 [0.64-1.18] p=0.37) or overall survival (HR 0.91[0.63-1.30],p=0.59) when IrCRT is compared with CRT. Conclusion(s): For patients with MRI-defined high risk LARC, low rates of CRM involvement and 36 month loco-regional failure were observed.The addition of irinotecan to CRT was associated with decreased radiotherapy and chemotherapy compliance and a higher rate of adverse events.There is no evidence of a difference in the pCR rate,36 month locoregional recurrence free or disease-free survival.

DOI: 10.1016/S0167-8140%2825%2900901-6

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Simultaneous integrated boost and organ at risk constraints in the APHRODITE trial (2024)

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Type of publication:

Conference abstract

Author(s):

Iddenden J.; Howard D.; Hudson E.; Teo M.; Diez P.; Miles E.; Turtle L.; Patel R.; Appelt A.; *Gollins S.

Citation:

Radiotherapy and Oncology. Conference: ESTRO 2024. Glasgow United Kingdom. 194(Supplement 1) (pp S5977-S5980), 2024. Date of Publication: 01 May 2024.

Abstract:

Purpose/Objective: APHRODITE (ISRCTN16158514), funded by Yorkshire Cancer Research, is a phase II randomised controlled trial comparing radical (chemo)radiotherapy (CRT) alone versus dose-escalated CRT with a simultaneous integrated boost (SIB). Patients with early stage rectal cancer, who are considered by their multidisciplinary team as unsuitable for radical total mesorectum excision or have a strong preference for organ preservation, will all receive 50.4Gy in 28 fractions to a small mesorectal-only planning target volume (PTV). Those in the experimental dose-escalation arm also receive up to 62Gy SIB to the primary tumour volume (PTVp). The trial is currently in active recruitment with a target sample size of 104 patients. Few studies exist detailing dose-volume constraints applied in this setting and none which examine the frequency to which they are achieved1. Anonymised trial plans were retrospectively reviewed to determine if the optimal organ at risk (OAR) dose-volume constraints as set out in the trial protocol are achievable. The conformity of the target volumes coverage was also assessed. Material/Methods: All centres completed the pre-trial radiotherapy quality assurance programme prior to recruiting. Radiotherapy planning data was requested for all patients. To date, 8 centres have recruited patients, with plan data for 46 out of 73 trial patients available at the time of analysis. Radiotherapy was planned according to their randomisation following APHRODITE dose-volume constraints. All plans were retrospectively reviewed on Velocity version 4.1 (Varian Medical Systems, Inc.) and dose-volume constraints extracted from DVH data. Conformity indices, as defined by RTOG (95% isodose volume/volume of PTV), were calculated for all PTVs. The standard deviation was calculated for optimal OAR dose-volume constraints and target volume conformity. Mann-Whitney U tests (two-tailed) were performed to test differences between the standard and dose-escalated arms. Result(s): Dose-volume constraints for the APHRODITE trial were developed from a retrospective mesorectum only planning study for a cohort of early-stage rectal cancer patients2. All constraints were considered optimal, rather than mandatory, due to the paucity of data on normal tissue dose limits in the setting of rectal cancer organ preservation. In all cases, the V95% >= 99% for both PTV and PTVp (dose-escalated arm only) were achieved. Table 1 demonstrates that centres were able to meet the optimal OAR dose-volume constraints in both trial arms in the majority of cases. Randomisation to receive a 62Gy boost did not have a statistically significant impact on achieving optimal OAR dosevolume constraints when compared to the standard arm dose. Evaluation of conformity indices in Table 2 suggested that there was a negligible difference in the conformity of PTV coverage between standard and dose-escalated patients. Mean conformity index for the mesorectal PTV was 1.15 for standard arm patients and 1.16 for patients in the escalated arm (p=0.67). For comparison, mean conformity index for the boost PTVp in the escalated arm was 1.18. The analysis of the target volume conformity test showed that 95% dose conformity is widely achievable across both trial arms in this multi-centre study. Table 2: Conformity indices of target volume and standard deviation Target Volume Mean Conformity Index Standard Deviation Standard (PTV) 1.15 0.06 Escalated (PTV) 1.16 0.05 Escalated (PTVp) 1.18 0.11 Conclusion(s): Delivering a SIB dose of up to 62.0Gy to the primary tumour volume does not have a statistically significant impact on the achievability of optimal OAR dose-volume constraints set out in the APHRODITE trial. Retrospective analysis of available plan data has shown that highly conformal SIB plans can be produced in a multi-centre setting, with resulting dose distributions being comparable to those in the standard arm.

DOI: 10.1016/S0167-8140%2824%2902083-8

Optimisation of the DLG in Mobius3D independent verification software for Ethos and TrueBeam linacs (2025)

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Type of publication:

Conference abstract

Author(s):

*Patel A.; Albaladejo M.M.; Puchades V.P.; Amores D.R.; Arteaga J.S.; Gonzalez A.O.; Berna A.S.

Citation:

Radiotherapy and Oncology. Conference: ESTRO 2024. Glasgow United Kingdom. 194(Supplement 1) (pp S4770-S4773), 2024. Date of Publication: 01 May 2024.

Abstract:

Purpose/Objective: The purpose of this study is to demonstrate the experience in commissioning and optimising Varian's Mobius3D secondary dosimetry software for IMRT/VMAT patient specific QA using Varian TrueBeam HD-MLC and Ethos linacs, performed in the radiotherapy department at Complejo Hospitalario Universitario de Cartagena (CHUC). Material/Methods: Mobius3D provides an independent plan check against the TPS using a separate beam model and dose algorithm. This can be quantified with a 3D gamma pass rate (3%, 3mm threshold at CHUC), as well as point dose differences of seven positions within a Mobius Verification Phantom (MVP), which can be practically verified using a Semiflex 3D ionisation chamber (PTW 31021). For every plan at CHUC, this is initially done in the phantom's central position. Mobius3D was commissioned following Varian's guide for Ethos (energy 6FFF) and TrueBeam (energies 6X and 6FFF) linacs, which included a reference point dose calculation, and verification of the PDD curves, output factors, wedge factors, off-axis ratios, and the CT electron density table. The system was then evaluated against simple conformal plans, followed by more complex clinical VMAT/SBRT/SRS plans. As per the Mobius3D commissioning guidance provided by Varian, if plans are systematically returned with target volumes too hot or too cold with respect to the TPS then it is recommended that the model's dosimetric leaf gap (DLG) correction value is adjusted, which may be different for VMAT and IMRT techniques. For optimisation, Varian recommends using a small ionization chamber within an MVP insert to measure the delivered point dose from 5-10 clinical plans and comparing against the values returned by Mobius3D. This was performed on 8 IMRT plans over a range of DLG correction values. However, as the 3D gamma pass rate metric is generally more often used for comparing dose distributions, it may be more beneficial to optimise against this rather than the point dose difference. This was therefore also performed following the point dose optimisation. Result(s): The results following commissioning from plans on the Ethos linac were promising; for the default DLG values the target volume doses agreed to a sufficient degree, the 3D gamma pass rate (3%, 3mm) had a median of 99.5%, and the point dose difference had a median of -0.1%, as shown in Figure 1 (left and centre) for approximately 200 plans. This was also similar for VMAT plans on the TrueBeam linac. However, the Mobius3D results for IMRT treatments on the TrueBeam model gave target dose distributions which were consistently lower than those provided by the Eclipse TPS (AcurosXB v16). Additionally, the 3D gamma pass rates (3%, 3mm) were below the tolerance of 95%, with a median of 83.1% (n = 21), also shown in Figure 1 (right side). This therefore required optimisation of the DLG values. In this last scenario, the average point-dose difference between the plans was found for each DLG value. A trendline was plotted using linear regression, as depicted in Figure 2, and the DLG corresponding to a 0% point-dose difference was found to be 1.48 +/- 0.05mm. Similarly, the 3D gamma (3%, 3mm) pass rates were also found for each DLG value. Polynomial regression was performed to fit a cubic function to this data, also depicted in Figure 2, which gave a maximum corresponding to a DLG of 1.25 +/- 0.4mm. Considering the results from both methods, the DLG correction on the Mobius3D system for this TrueBeam and both energies was set as the average 1.4mm for IMRT, and 0mm for both VMAT and Ethos. This first value aligns closely with the value used for TrueBeam plans on the Eclipse TPS. From analysing plans following this optimisation, it was observed that the gamma3D (3%, 3mm) pass rates significantly improved, with a new higher median of 96.5% (n = 28, p < 0.001), as shown in Figure 1 (right). Conclusion(s): There is the need to optimize the DLG value for IMRT treatment plans on TrueBeam HD-MLC. Following this adjustment, the Mobius3D software gave satisfactory agreements to the TPS dose distribution for TrueBeam IMRT plans, with a substantial increase in 3D gamma (3%, 3mm) median pass rates. Ethos plans gave strong agreements without the need for optimisation, as did TrueBeam VMAT plans for the software default DLG values. It can therefore be concluded that the Mobius3D software offers a rigorous independent dose check against the TPS and is suitable for clinical use on Ethos and TrueBeam platforms, provided that a proper verification and optimization process has been previously performed.

DOI: 10.1016/S0167-8140%2824%2901289-1

Mitral Valve-in-Ring Approach for High-Risk Pannus-Related Mitral Stenosis (2025)

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Type of publication:

Journal article

Author(s):

*Yera, Hassan O; Azam, Ziyad; *Azam, Najeeb M.

Citation:

Cureus. 17(10):e94204, 2025 Oct.

Abstract:

A male patient under follow-up for degenerative mitral regurgitation, treated with a Physio annuloplasty ring two decades earlier, developed progressive shortness of breath and fluid overload, corresponding to New York Heart Association (NYHA) class III/IV. A transoesophageal echocardiogram revealed significant mitral stenosis, with a mean gradient of 11.8 mmHg due to pannus formation around the annuloplasty ring. Surgical repair posed a mortality risk of 25%-35% because of the combined risks of redo surgery, reduced left ventricular systolic function and chronic kidney disease. A transcatheter mitral valve-in-ring (TMViR) procedure was the only feasible option. A 29 mm Sapien 3 valve (Edwards Lifesciences, Irvine, CA) was successfully implanted within the mitral ring. Four months following the procedure, the patient reported significant symptom relief and an improved quality of life (QOL), with a shift to NYHA class I/II. Follow-up echocardiography demonstrated a stable valve position, a mean gradient of 4 mmHg and mild mitral regurgitation. This case highlights TMViR as a viable option for high-risk patients with pannus-related mitral stenosis.

DOI: 10.7759/cureus.94204

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Missed on X-ray, Found on CT: A Retrospective Study on the Diagnostic Yield and Clinical Consequences of Occult Posterior Malleolus Fractures in Tibial Shaft Fractures (2025)

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Type of publication:

Journal article

Author(s):

Kanesan, Hariprasath; Choudhary, Zain; Singal, Sachin; *Kanesan, Mahesh; Hang-Kin Nam, Ronald; Radhamony, Niranj Ganeshan; Hamadto, Mohamed.

Citation:

Cureus. 17(10):e94260, 2025 Oct.

Abstract:

Background Posterior malleolus fractures (PMFs) are common in distal tibial shaft fractures yet are frequently occult on plain radiographs. Accurate preoperative characterization on CT may improve surgical planning and functional recovery. Methods We conducted a retrospective cohort study of consecutive adults (>=18 years) with mid- or distal tibial shaft fractures treated at a major trauma center (January 2022-December 2024). Demographics, imaging, fracture characteristics, management, and outcomes were abstracted. PMF detection was compared across radiography, CT, and intraoperative findings. Predictors of a posterior malleolus (PM) fragment being missed on radiography were evaluated with multivariable logistic regression. Among operatively treated cases, the effect of fixation strategy on postoperative full weight-bearing (FWB) was analyzed with a logistic model including fixation, PM status, and their interaction; pairwise, covariate-adjusted contrasts (emmeans with Tukey correction) compared strategies. An exploratory random forest provided permutation-importance rankings. Findings PMFs were present in 147/387 fractures (38.0%), more often in women (60.5%), closed injuries (76.9%), and distal fractures (98.0%). Radiography identified 116/147 PMFs (78.9%), and CT 120/147 (81.6%); 29/147 (19.7%) fragments were missed on radiographs but detected on CT or intraoperatively. Missed fragments were most frequent in undisplaced and intermediate-sized (33-50%) fragments; CT identified all posteromedial and >50% fragments. In adjusted analyses, fracture morphology was the principal correlate of radiographic omission: oblique patterns were less likely to be missed (adjusted odds ratio 0.18, 95% CI 0.04-0.60), whereas other demographic and injury variables were not significant. Among operatively managed fractures, intramedullary nailing was associated with the highest likelihood of achieving FWB and was statistically superior to plate and external fixation in pairwise, covariate-adjusted comparisons; the relative ranking of fixation methods did not differ by PM involvement. Neither PMF location (posteromedial, posterolateral, or undisplaced) nor fragment size independently predicted FWB, infection, or mal-/non-union. Conclusions Approximately two in five distal tibial shaft fractures harbour a PM fragment, and nearly one in five PMFs are occult on initial radiographs, particularly when undisplaced or of intermediate size. CT modestly increases detection and ensures complete characterisation of posteromedial and large fragments, supporting a low threshold for pre-operative CT in distal tibial fractures.

DOI: 10.7759/cureus.94260

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A Diagnostic Challenge: Sclerosed Hepatic Haemangioma Mimicking Malignancy (2025)

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Type of publication:

Journal article

Author(s):

*Lakhani, Umar A.

Citation:

Cureus. 17(10):e94449, 2025 Oct.

Abstract:

A 75-year-old lady presented to Accident and Emergency (A&E) with acute worsening shortness of breath and new palpitations. On assessment, she was found to have fast atrial fibrillation, signs of heart failure, and bilateral peripheral oedema. Investigations revealed pulmonary embolism and an incidental hepatic lesion on CT imaging, suspicious for malignancy. Multidisciplinary discussion led to liver biopsy, which confirmed a benign sclerosed haemangioma. The patient was managed conservatively for cardiac and thromboembolic complications. This case highlights the difficulty in differentiating sclerosed haemangiomas from malignant liver lesions on imaging alone and underscores the importance of biopsy and multidisciplinary decision-making in elderly patients with comorbidities. Learning points include diagnostic vigilance, safe management of anticoagulation, and avoidance of unnecessary surgery.

DOI: 10.7759/cureus.94449

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Long-Term Outcomes of Coronary Artery Aneurysms in Children With Kawasaki Disease: A Systematic Review (2025)

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Type of publication:

Systematic Review

Author(s):

Shafy, Shoaib Syed Mohammed; Salavarria, Karla Andrea Calderon; Saleh, Sara; *Cuino, Ingrid; Nadeem, Sadaf; Perez, Rebeca Cristina Romero; Shetty, Arushi; Adhikari, Kedar; Khatter, Tanya; Arasada, Chinmayee; Moussa, Naji; Mbaekwe, Eziamaka; Horsaengchai, Panchanit; Ali, Ramsha.

Citation:

Cureus. 17(10):e94418, 2025 Oct.

Abstract:

Kawasaki disease (KD) is a systemic inflammation of the blood vessels seen in children. It is the leading cause of acquired heart disease. Coronary artery aneurysm (CAA) is the most concerning complication, associated with long-term morbidity and mortality. This systematic review examined long-term outcomes of CAAs in KD, with emphasis on regression, complications, and the role of medical and surgical interventions. A total of 21 studies involving 10,922 patients were reviewed. The incidence of CAAs ranged from 3%-27%, mostly affecting infants under 6 months. Small and moderate aneurysms regressed in the majority of cases (>80%), whereas giant aneurysms were less likely to regress. Complications included thrombosis, myocardial infarction, major adverse cardiac events, and cardiac death. Early treatment with intravenous immunoglobulin (IVIG) enhanced the likelihood of regression. Aneurysms in the left anterior descending artery were less likely to regress, suggesting an anatomical influence. Coronary artery bypass grafting was the most common surgical intervention. Early and aggressive management with IVIG, with escalation to steroids or biologics when required, remains the preferred approach. Surgical intervention is sought for giant or persistent aneurysms. These findings emphasize the importance of timely diagnosis, risk stratification, and the establishment of standardized guidelines to optimize long-term care and surveillance of patients with KD.

DOI: 10.7759/cureus.94418

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IUGA Opinion Paper on Obstructed Defecation: Management of Clinical and Proctographic Rectoceles (2025)

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Type of publication:

Journal article

Author(s):

*Rachaneni, Suneetha; Dietz, Hans Peter; Latthe, Pallavi; Sirany, Annie; Spivak, Anna; Dua, Anupreet.

Citation:

International Urogynecology Journal.  2025 Nov 11.

Abstract:

INTRODUCTION AND HYPOTHESIS: Obstructed defecation syndrome (ODS) is a defecatory abnormality with a sensation of incomplete evacuation, the need to strain at stool, the need for digitation in the vagina, the anus, or the perineum. Anterior rectocele and rectal intussusception are the frequent pathologies behind ODS. The review focuses on the assessment and treatment of obstructed defecation in women with rectocele, recto-enterocele and rectal intussusception in the remit of a urogynecologist.

METHODS: A working subcommittee from the International Urogynecology Association (IUGA) Research and Development (R&D) Committee was formed with colorectal surgeons from the American Society of Colon & Rectal Surgeons (ASCRS). An initial document was drafted based on a literature review. The review focused on the treatment options of women with presenting with obstructed defecation and posterior compartment prolapse either on clinical examination or on imaging. After evaluation by the
entire IUGA R&D Committee revisions were made. The quality of the evidence was graded and used to form consensus recommendations.

RESULTS: Ultrasound and dynamic MRI are helpful imaging modalities in triaging patients. A defecating proctogram to evaluate the size of rectal intussusception and enterocele is the standard investigation. Conservative therapies are effective first-line management options. The transvaginal native tissue rectocele repair is a safe and effective first-line surgical treatment in women with obstructed defecation.

CONCLUSIONS: When evaluating patients with obstructive defecation, it is important to address anatomy as well as function. In the absence of a clinically significant rectocele or enterocele during vaginal examination, in women with obstructed defecation, referral to a gastroenterologist or colorectal surgeon for further evaluation and management is recommended.

DOI: 10.1007/s00192-025-06288-7

CT guided percutaneous lung biopsy - self-audit (2025)

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Type of publication:

Audit

Author(s):

*Abayaratne, Chulangani

Citation:

Shrewsbury and Telford Hospital NHS Trust, 2025

Abstract:

CT-guided percutaneous lung biopsy is a widely practiced interventional radiology procedure for
obtaining tissue samples from pulmonary lesions. Regular self-audit of such procedures is good
clinical practice and is recommended to ensure high diagnostic adequacy and low complication
rates, in line with national benchmarks.

In the UK, the British Thoracic Society (BTS) and the Royal College of Radiologists (RCR)
recommend regular audits to evaluate local diagnostic yield and complication rates and compare
them with national standards.

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A survey of the current state of training in inflammatory disease (IBD) surgery in the United Kingdom (UK) (2025)

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Type of publication:

Conference abstract

Author(s):

Argyriou O.; *El-Sayed C.; Drami I.; Celentano V.; Reza L.

Citation:

Colorectal Disease. Conference: 20th Scientific and Annual Conference of the European Society of Coloproctology, ESCP 2025. Paris France. 27(Supplement 1) (no pagination), 2025. Date of Publication: 01 Aug 2025.

Abstract:

Aim: Inflammatory Bowel Disease (IBD) surgery demands advanced technical skills due to the complexity and variability of procedures. High-quality training is essential, not only for the management of acute IBD-related emergencies but also for the development of a specialist IBD practice. This survey, developed by the Dukes' Club for UK colorectal surgery trainees and the IBD Subcommittee of the Association of Coloproctology of Great Britain and Ireland (ACPGBI), aims to evaluate the current state of IBD surgical training in the UK and to identify key areas and potential interventions for improvement. Method(s): An electronic survey was designed by members of the Dukes' Club executive committee and the ACPGBI IBD subcommittee, followed by dissemination via various professional networks, between September 2024 and April 2025.The survey investigated a number of key domains, including exposure to IBD procedures (routine/complex), participation in multidisciplinary team (MDT) meetings and joint surgical-gastroenterological clinics, career and fellowship intentions, as well as access to training resources. Result(s): The survey was completed by 103 participants (70% in training, 30% early years consultants).Senior trainees (ST6-ST8) represented 58.4% of the trainee participants.58.4% of trainees reported lack of exposure to IBD MDTs, with only 5.6% undertaking an active role in the MDT.Trainees reported minimal exposure to ileoanal pouch surgery and complex procedures such as strictureplasties and Kono-S anastomosis. In contrast, higher levels of exposure were noted for subtotal colectomies, ileo-caecal resections for Crohn's Disease, and IBD-related perianal fistula procedures. Conclusion(s): The survey demonstrated a lack of focus in IBD surgical training. Apart from high-quality educational activities that are delivered by the Dukes' Club and ACPGBI, a structured approach to ensure better exposure, through the training curriculum, is called for.

DOI: 10.1111/codi.70174

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