The Christie School of Oncology: Christie Research Publications Repository
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Reference dosimetry for MRI-Linacs: an addendum to the 2020 IPEM code of practice for high-energy photon therapy dosimetry
No full textThe 2020 Institute of Physics and Engineering in Medicine code of practice (COP) for megavoltage dosimetry (Eaton et al2020Phys. Med. Biol.65195006) provides standardised and practical methods for measurement of absorbed dose to water, linked to calibration by the National Physical Laboratory. This report extends the use of that COP to MRI-Linacs through the addition of two correction factors: (1) to account for the influence of the magnetic field on the absorbed dose and model-specific chamber response; and (2) to account for differences in chamber response in the beam spectrum of the MRI-Linac and the Linac where the cross-calibration is performed. Guidance is provided on practical aspects of chamber calibration and dose measurement in MRI-Linac beams, including the use of liquid water, consistent chamber orientation and corrections for other influence quantities. Using this approach uncertainties are similar to other applications of the COP
Quality of life after radiotherapy treatment for patients with stage IV non-small cell Lung cancer: QUARTZ LUNG a candidate-specific trial within the TOURIST platform
No full textDevelopment of lattice radiotherapy methodology as preparatory work for phase I clinical trial
No full textAdenoviral Retinitis: A Rare Case Presentation of a Common Virus
No full textPURPOSE: To report a rare case of bilateral necrotising retinitis caused by a potentially novel human adenovirus D (HAdV-D) in a post-bone marrow transplant patient and to highlight the diagnostic challenges and therapeutic role of intravenous cidofovir, alongside a review of previously reported cases of human adenovirus (HAdV) retinitis. METHODS: Retrospective case report. RESULTS: A 60-year-old man with a history of acute myeloid leukaemia, in remission post-bone marrow transplant, presented with bilateral hypertensive granulomatous panuveitis and necrotising retinitis. Repeated aqueous polymerase chain reaction (PCR) testing for herpes simplex virus, varicella-zoster virus, cytomegalovirus, syphilis and Toxoplasma gondii was negative and the patient showed a poor response to multiple empirical antiviral therapies. This led to expanded PCR testing which detected high HAdV loads in both aqueous and vitreous samples. Genomic sequencing confirmed the presence of a potentially novel HAdV-D. The patient received intravenous cidofovir with close renal monitoring. Serial aqueous PCR demonstrated a substantial reduction in HAdV load, with corresponding clinical improvement and complete resolution of active retinitis, replaced by retinal scarring. Final best-corrected visual acuities were 0.4 LogMAR in the right eye and hand movements in the left eye. CONCLUSION: HAdV retinitis, though rare, should be considered in immunocompromised patients with progressive necrotising retinitis that is unresponsive to conventional antivirals, particularly when associated with repeatedly negative PCR for herpes viruses, syphilis and Toxoplasma gondii. Intravenous cidofovir may be an effective off-label treatment. A multidisciplinary approach is essential, and serial aqueous PCR is useful for monitoring treatment response
Efficacy/safety of the BTK degrader NX-5948 in chronic lymphocytic leukemia: an ongoing phase 1a/b study
No full textDevelopment and validation of a rapid and simple LC-MS/MS method for quantification of the anti-microtubule, anti-cancer agent ABT-751 in human and mouse plasma and mouse tissues
No full textA rapid and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for quantifying ABT-751, an anticancer agent targeting microtubules. Sample preparation involved protein precipitation using acetonitrile and formic acid (100:1, v/v), providing efficient ABT-751 extraction with minimal ion suppression. Buparlisib (BKM-120) served as the internal standard. Chromatographic separation was achieved on a Zorbax Extend C18 column, with gradient elution from 20 to 95% methanol in 0.1% (v/v) formic acid in water, and MS/MS detection was performed in positive ionization mode. This assay was validated for human plasma, mouse plasma, and various mouse tissues, including brain, liver, lung, and kidney homogenates. Calibrants were prepared in each respective blank biological matrix, except for mouse tumor tissue, and curves were fitted by quadratic regression from 5 to 10,000 nM. For mouse tumor tissue we used human plasma as surrogate matrix for calibrants. Precision and accuracy for intra-day and inter-day measurements were within acceptable limits across low, medium, and high concentrations for all matrices. Stability concerns with ABT-751 in mouse plasma and tissue homogenate samples that were stored for more than 8 months were identified and addressed. A pilot pharmacokinetic study in mice demonstrated the applicability of this validated LC-MS/MS method
Stereotactic body radiation therapy for oligoprogressive disease in androgen-suppressed prostate cancer: primary endpoint analysis of the TRAP trial
No full textPURPOSE: Optimal management of oligoprogressive prostate cancer while on androgen receptor pathway inhibitors (ARPIs) is not known. The TRAP trial tests the role of stereotactic body radiation therapy (SBRT) in this setting. The objective of this phase 2 prospective, nonrandomized, single-arm trial was to determine if local control of oligoprogressive disease with SBRT can delay further progression by >4 months, postponing time to next therapy. METHODS AND MATERIALS: Men with castration-resistant prostate cancer with ≤2 oligoprogressive sites developing on treatment with an ARPI, after initial response to therapy, were recruited. All patients were treated to a dose of 30 Gy in 5 fractions (alternate days) or 36 Gy in 6 fractions weekly (prostate only). RESULTS: Eighty-six men were recruited between October 2018 and February 2023. SBRT was delivered to 81 men. Mean age was 74 years. Most patients (67%) had 1 oligoprogressive disease lesion. Sites irradiated were bone (59%), lung (1%), lymph node (32%), and prostate (7%). Median follow-up was 22.9 months at the time of analysis. Fifty-five (68%) patients had progressed, 33 (41%) of patients progressed within 6 months of radiation therapy. Median progression-free survival (PFS) was 6.4 months (95% CI, 5.9-11.4). An estimated 39% (95% CI, 29-49) of patients have a prolonged PFS of > 12 months. Thirty-three (41%) of patients had started new treatment or died. Median time to either next treatment or death was 27.0 months (95% CI, 14.9-29.6). Median overall survival was 27.2 months (95% CI, 24.7-36.6). Four deaths occurred within 6 months of SBRT; none were related to radiation therapy treatment. CONCLUSIONS: The TRAP trial has demonstrated a median PFS of 6.4 months after SBRT for oligoprogression of prostate cancer, meeting the primary endpoint. Further analysis of biomarker panel including circulating DNA and whole-body magnetic resonance imaging will promote better patient selection
The landscape of prostate tumour methylation
No full textProstate cancer is characterized by profound clinical and molecular heterogeneity. While its genomic heterogeneity is well-characterized, its epigenomic heterogeneity remains less understood. We therefore created a compendium of 3,001 multi-ancestry prostate methylomes spanning normal tissue through localized disease of all grades to poly-metastatic disease. A subset of 884 samples had multi-omic DNA and/or RNA characterization. We identify four epigenomic subtypes that risk-stratify patients and reflect distinct evolutionary trajectories. We demonstrate extensive regulatory interplay between DNA ploidy and DNA methylation, with transcriptional consequences that vary across genes and disease stages. We define the epigenetic dysregulation signatures of the 15 most important clinico-molecular features, creating predictive models for each. For example, we identify specific epigenetic features that predict patient outcome and that are synergistic with clinico-genomic prognostic features. These results define a complex interplay between tumour genetics and epigenetics that converges to modify gene-expression programs and clinical presentation
Novel technique in intraoperative localisation of skin cancer metastasis using ultrasound guidance: a case report
No full textBACKGROUND: Localisation of metastatic squamous cell carcinoma (SCC) often poses intraoperative challenges. There is limited description of surgical practices to address these difficulties in the literature. Low-frequency ultrasound use intraoperatively may enhance tumour detection and facilitate complete resection. CASE PRESENTATION: We present the case of a 78-year-old male with right-sided intra-parotid metastatic SCC requiring surgical excision. This was completed under intraoperative ultrasound scan guidance. Preoperative whole-body PET-CT and MRI of the head were inadequate for confirming accurate lesion localisation regarding the depth of invasion and facial nerve involvement. Intraoperative ultrasound performed by a consultant radiologist guided the metastasectomy by confirming lesion boundaries, navigating safe excision by sparing the facial nerve branches and facilitating the avoidance of more radical resection. Full resection with no residual disease was confirmed intraoperatively with the ultrasound. CONCLUSION: We propose using ultrasound guidance intraoperatively to aid localisation and excision of metastatic disease in anatomically challenging sites