The Christie School of Oncology: Christie Research Publications Repository
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Neurocognitive concerns and neurocognitive impairment in long-term survivors of oropharyngeal cancer post (chemo)radiotherapy
No full textBACKGROUND: Little is known about neurocognitive concerns (NCC) and neurocognitive function (NCF) in survivors of oropharyngeal cancer (OPC) following (chemo)radiotherapy. METHODS: A multicentre cross-sectional study was conducted in non-surgically treated OPC. Using the Medical Outcomes Study Cognitive Functioning Scale (MOS-Cog), NCC were classed as having concerns at least some of the time (MOS-Cog score of ≤ 60 across all items). Patients were also invited to complete an online cognitive test battery (Amsterdam Cognition Scan; ACS) to assess NCF. Using norm scores from 708 individuals from the UK general population, significant NCF impairment was defined as Z score ≤ - 2 in one domain or ≤ - 1.5 in at least two domains. Regression analysis was performed to identify factors associated with NCC/NCF. RESULTS: Three hundred thirty-eight patients treated for OPC, with median age at treatment of 58.6 years and median follow-up of 6 years (IQR 4-8) post-treatment, were recruited. NCC were present in 14.8% of patients. Amongst 93 patients who completed the ACS, 33% demonstrated significant impairment in NCF. Memory and attention were the most affected domains in NCC and NCF. On multivariable regression analysis, mental fatigue, mood, general fatigue, and physical fatigue significantly predicted NCC. Multivariate analysis revealed a small but statistically significant negative association between mood and NCF. No statistically significant correlations were found between NCC/NCF impairment and radiation dose received by the posterior fossa. CONCLUSION: NCC and NCF impairment affects a substantial proportion of long-term survivors of OPC. Assessment of NCC and NCF is essential for a comprehensive understanding of cognitive health in this population. IMPLICATIONS FOR CANCER SURVIVORS: This study highlights that a substantial proportion of long-term oropharyngeal cancer survivors experience both subjective NCC and objective NCF impairment. The findings underscore the need for neurocognitive screening and a multidisciplinary approach to survivorship care, incorporating psychological and cognitive support alongside traditional follow-up
Cognitive Outcomes in Children Treated for Ependymoma Diagnosed Under 36 Months: A Systematic Review
No full textIt is crucial to understand the morbidity associated with treatments for young children with ependymoma given this is a high incidence age group also known to be at risk of poorer cognitive outcomes. This review aimed to identify the quality of existing evidence describing cognitive outcomes in children treated for ependymoma under 36 months of age with a particular focus on the impact of radiotherapy. Eight studies were identified. Given the quality and heterogeneity of methodology, studies were only suitable for qualitative synthesis, as the majority included small numbers of participants with multiple confounding factors. Whilst some studies reported poor cognitive outcomes, the only large study reporting planned irradiation reported outcomes below the population mean but still broadly in the average range. This was consistent with a further study of interest that did not meet inclusion criteria but reported outcomes for children treated under five years old, many of whom were likely in the target population age for this review. Overall, the length of follow-up was often limited, and further research to monitor long-term impact, including photon and proton irradiation protocols on cognitive development, is required. Importantly, there is an urgent need to agree homogeneous methodology and achieve international consensus for cognitive assessment protocols to interrogate cognitive outcomes in this vulnerable population
Quality of life and toxicity in patients with pancreatic ductal adenocarcinoma treated with online adaptive stereotactic magnetic resonance guided radiation therapy
No full textPURPOSE: Online adaptive magnetic resonance guided radiation therapy (MRgRT) using a hybrid magnetic resonance imaging and linear accelerator enables stereotactic ablative radiation doses to pancreatic tumors. We evaluated patient-reported quality of life (QoL) and clinician-reported toxicity in patients with pancreatic ductal adenocarcinoma after stereotactic MRgRT. METHOD: Patients with nonmetastatic pancreatic ductal adenocarcinoma treated with stereotactic MRgRT on a 1.5-Tesla magnetic resonance imaging and linear accelerator according to local standard practices between May 2019 and December 2023 were identified using the international, prospective observational Multi-OutcoMe EvaluatioN of radiation Therapy Using the MR-Linac study (MOMENTUM, NCT04075305). Patient-reported QoL and clinician-reported toxicity were assessed using the European Organization for Research and Treatment of Cancer Core Quality-of-Life Questionnaires and National Cancer Institute Common Terminology Criteria for Adverse Events at baseline, 3, 6, and 12 months of follow-up. Patients with new systemic therapy or resection were censored. Patients with disease progression were additionally censored for a sensitivity analysis. Mean difference (MD) QoL scores from baseline were estimated using a linear mixed model, which were evaluated for clinical relevance (MD ≥ 10) and statistical significance (P ≤ .05). Acute (≤3 months follow-up) and late (3-12 months follow-up) toxicity was captured if grade ≥3. RESULTS: A total of 127 patients were included from 8 centers. Treatment dose ranged from 30 to 50 Gy in 5 fractions. Functional QoL domains remained stable over time. A statistically significant and clinically relevant improvement was found for nausea and vomiting (MD -10; 95% CI, -17 to -3; P < .001), and in the sensitivity analysis for nausea and vomiting (MD -11; 95% CI -18 to -3; P < .001) and appetite (MD -14; 95% CI -28 to 0; P = .05), all at 6 months follow-up. No clinically relevant and statistically significant deterioration was found in other domains. New-onset acute and late grade 3 toxicity occurred in 2 patients and 1 patient, respectively. CONCLUSION: Stereotactic MRgRT for patients with nonmetastatic pancreatic ductal adenocarcinoma was associated with stable functioning, improved disease-related symptoms, and minimal toxicity up to 12 months after treatment
UK-PeCan survey: current practices for venous thromboembolism (VTE) prophylaxis in penile cancer surgery across the UK
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Establishing measurement traceability for quantitative SPECT imaging
No full textBACKGROUND: Single Photon Emission Computed Tomography (SPECT) is increasingly used as a quantitative modality, especially in the context of Molecular Radiotherapy, where the measurements are used as input to absorbed dose calculations for patient-specific dosimetry. Establishing measurement traceability is an essential step in providing confidence in quantitative measurements. This requires an unbroken chain of calibrations where uncertainties must be reported in all stages of calibration and for the final measurement result. Traceability ensures that a measurement result can be related to an underlying standard, allowing harmonisation of data, and facilitating comparison of results between sites. METHODS: The process of establishing measurement traceability for quantitative SPECT is demonstrated for the therapeutic radionuclide (177)Lu using a common, phantom based, calibration method. Phantoms with activities of (177)Lu, measured using a traceably calibrated radionuclide calibrator, were used to perform the calibration. The calibration was validated using 3D-printed anthropomorphic organ phantom inserts mimicking clinically relevant geometries. For all measurements, traceability to primary standards for radioactivity is demonstrated along with an accompanying calibration chain and statement of uncertainty. RESULTS: For all activity measurements the dominant component in the activity uncertainty budget was the uncertainty on the radionuclide calibrator calibration factor, resulting in an average combined standard uncertainty of 1.57%. The resulting uncertainty on the SPECT Image Calibration Factor was 1.6%. An optional additional correction was included in the calibration to provide volume-based partial volume correction (PVC). Measurement traceability was extended for measurands using this additional correction. The activity recovery in the organ phantoms with PVC applied was 96(7)% for both the kidney and spleen. CONCLUSIONS: A manufacturer independent methodology for establishing measurement traceability for quantitative SPECT is demonstrated for (177)Lu, using a radionuclide calibrator previously calibrated against national standards. The ability to establish measurement traceability for quantitative SPECT using standard clinical equipment, and the limitations of traceability are presented
Panorama of chromosomal instability in lung cancer
No full textLung cancer is a highly heterogeneous disease primarily driven by tobacco smoking. About 20% of lung cancers occur among patients who have never smoked (LCINS) with differences in patient ancestry, sex, tumor histology, and clinical features. Our understanding of chromosomal instability in lung cancer, especially LCINS, is still limited. Here, we perform a comprehensive study of 182,429 somatic structural variations (SVs) detected in 1,209 whole-genome sequenced lung cancers, of which 864 LCINS. SVs are more abundant in tumors from patients who have smoked (LCSS); however, they are more complex and play more important roles in tumorigenesis in LCINS. EGFR mutations and KRAS mutations profoundly and independently shape the SV landscape. EGFR-mutant tumors have higher SV burden and more cancer-driving SVs. In contrast, KRAS mutations are associated with lower SV burden and less driver SVs. We decompose 16 SV signatures for both complex and simple SVs that likely represent divergent molecular mechanisms. The SV breakpoints have distinct distributions across the genome depending on the signatures due to mutagenic mechanisms and positive selection. Many established cancer-driving genes are recurrently rearranged by multiple SV signatures suggesting functional convergence of these genome instability mechanisms
Conventional Versus High-Complexity Total Pelvic Exenteration For Locally Advanced and Locally Recurrent Rectal Cancer: An International Multicenter Study
No full textBACKGROUND: Pelvic exenteration is the treatment of choice for selected patients with locally advanced primary and recurrent rectal cancer. Involvement of major pelvic neurovascular structures and bone were historically considered contraindications due to unacceptably high rates of morbidity and low R0 resection rates. OBJECTIVE: To compare the outcomes of these 'high-complexity' exenterative resections to those of 'conventional' pelvic exenteration. DESIGN: International multicenter retrospective cohort study. SETTINGS: Sixteen specialized exenteration centers. PATIENTS: Those who underwent total pelvic exenteration for locally advanced primary and recurrent rectal cancer between 2018 and 2023 at participating centers. MAIN OUTCOME MEASURES: Perioperative resource utilization, morbidity, mortality and R0 resection rates were reported. RESULTS: 763 patients underwent total pelvic exenteration, of which 478 (63%) and 285 patients (37%) required conventional and high-complexity procedures, respectively. High-complexity pelvic exenteration was associated with longer operating time (600 vs 480 mins, p < 0.001 for locally advanced primary rectal cancer, 623 vs 480 mins, p < 0.001 for locally recurrent rectal cancer), intensive care stay (2 vs 1 day, p < 0.001 and 3 vs 1 day, p < 0.001), hospital stay (19 vs 15 days, p = 0.008 and 23 vs 15 days, p < 0.001) and higher blood loss (2000 vs 1236 mL, p < 0.001 and 3000 vs 1600 mL, p < 0.001). Morbidity and mortality outcomes, and R0 resection rates were similar between the groups. LIMITATIONS: Generalizability of findings outside of expert units. CONCLUSIONS: High-complexity pelvic exenteration for the treatment of rectal cancer is associated with similar morbidity, mortality, and R0 resection rates, but significantly higher operative time, blood loss, and hospital resource utilization compared to conventional pelvic exenteration. In high volume, specialized centers, these techniques are considered the standard of care for appropriately selected patients with tumors that involve major pelvic bone or neurovascular structures. See Video Abstract
Patient-specific HLA-I subtypes predict response to immune checkpoint blockade
No full textSpecific shared HLA-I alleles were linked to the response to immune checkpoint blockade (ICB). We aimed to identify the HLA-A subtypes associated with maximum benefit from ICB. We compiled a clinical dataset of patients who underwent a CLIA-approved germline HLA status testing as part of various advanced immune and cell therapy trials undertaken at the Christie NHS Foundation Trust. A total of 285 patients were eligible for final analysis. We identified 15 HLA-A subtypes, the most common alleles being HLA-A02, HLA-A01, and HLA-A03. A02:01 showed a tumor lineage-specific distribution. One hundred and forty patients received ICB and had evaluable response status. Patients with A01 were associated with better clinical outcomes. No significant associations were observed between HLA-A subtypes and the incidence of immune-related adverse effects. HLA genotyping should be incorporated early in the diagnostic work-up of patients with solid cancers as a predictive and selective biomarker