The Christie School of Oncology: Christie Research Publications Repository
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Pathological & radiological variables in the diagnosis of bronchopulmonary carcinoids (BPCs) with a focus on Antigen Kiel 67 (Ki-67) proliferation index
No full textBACKGROUND: Bronchopulmonary carcinoids (BPCs) are classified into typical carcinoids (TC) and atypical carcinoids (AC), based on the mitotic count and absence/presence of necrosis on pathology specimens. There are limitations to accurate measurement of these criteria. It important to study other markers like Ki-67, to enhance the diagnostic accuracy of lung carcinoids. OBJECTIVE AND METHODOLOGY: Retrospective analysis of BPCs treated with surgery between 2012-2022, to examine the accuracy of Ki-67 on the diagnostic specimen, concordance of diagnostic and resection specimens, diagnostic accuracy of Positron Emission Tomography (PET) and concordance of clinical and pathological staging. RESULTS: 205 patients were included in the analysis (final diagnosis TC 180, AC 25). Mean age 60.5 years and 68 % female. Ki-67 (<5% vs. 5-30 %) on diagnostic biopsy, available in 64 % (n = 131) of the cohort, had specificity (diagnose TC correctly) of 89.4 % (95 %CI 80.4 %-94.7 %) and sensitivity (diagnose AC correctly) of 77.8 % (40.2 %-96.1 %). This compared to 97.5 % (90.3 %-99.6 %) and 36.4 % (12.4 %-68.4 %) for mitotic count (<2mitoses/2mm(2) vs. 2-10mitoses/2mm(2)) and 100 % (94.4 %-100 %) and 21.4 % (5.7 %-51.2 %) for necrosis (absence vs. presence). A pre-resection diagnosis of TC (including surgical biopsy) shows better concordance with final diagnosis on resection specimen (94.9 %, 95 %CI 88.7 %-97.9 %, n = 117) as compared to the diagnosis of AC 83.3 % (95 %CI 50.9 %-97.1 %, n = 12). Concordance for AC appears higher with image guided lung biopsy 80 % (95 % CI, 29.9 %-98.9 %) than bronchoscopy 50 % (9.5 %-90.5 %). SUVmax on 18FDG-PET was a modest predictor of BPC sub-type with an AUC of 0.684 (95 % CI: 0.545,0.823). The clinical and pathological staging were concordant in 46 % (85/184) cases. However, 27 % (50/184) were upstaged and 13 % (23/172) found to have occult nodal metastases on pathology review of the surgical specimens. CONCLUSION: The diagnosis and sub-typing of BPCs on diagnostic specimens is challenging. Our data suggest Ki-67 could increase diagnostic accuracy, but further research is needed to confirm this
Patient and clinician engagement to develop GastroSCOPE-a proposed phase 2 UK study of high dose radiotherapy for inoperable gastric cancer
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The genomic and clinical consequences of replacing procarbazine with dacarbazine in escalated BEACOPP for hodgkin lymphoma: a retrospective, observational study
No full textBACKGROUND: Procarbazine-containing chemotherapy regimens are associated with cytopenias and infertility, suggesting stem-cell toxicity. When treating Hodgkin lymphoma, procarbazine in escalated-dose bleomycin-etoposide-doxorubicin-cyclophosphamide-vincristine-procarbazine-prednisolone (eBEACOPP) is increasingly replaced with dacarbazine (eBEACOPDac) to reduce toxicity. We aimed to investigate the impact of this drug substitution on the mutation burden in stem cells, patient survival, and toxicity. METHODS: In this two-part retrospective, observational study, we first compared mutational landscapes in haematopoietic stem and progenitor cells (HSPCs) from patients with advanced-stage Hodgkin lymphoma in remission for at least 6 months who had been treated with eBEACOPDac (eBEACOPDac cohort), eBEACOPP (real-world eBEACOPP cohort), or doxorubicin-bleomycin-vinblastine-dacarbazine (ABVD); in buccal DNA from five children of a female patient with classical Hodgkin lymphoma treated with eBEACOPP before conceiving the third child; in sperm DNA from a patient with mild oligospermia treated with eBEACOPP; and in caecal adenocarcinoma and healthy colon tissue from a survivor of Hodgkin lymphoma treated with chlorambucil-vinblastine-procarbazine-prednisolone. For the second part, we analysed efficacy and toxicity data from adult patients (aged >16 years) treated with first-line eBEACOPDac (eBEACOPDac cohort) at 25 centres across UK, Ireland, and France; efficacy was compared with the German HD18 eBEACOPP trial data and toxicity with a UK real-world dataset. Participants in the German HD18 and UK real-world datasets were adults (aged >16 years) with previously untreated Hodgkin lymphoma, treated with first-line eBEACOPP. We had two co-primary objectives: to define the comparative stem-cell mutation burden and mutational signatures after treatment with or without procarbazine-containing chemotherapy (first study part); and to determine progression-free survival of patients with Hodgkin lymphoma treated with eBEACOPP or eBEACOPDac (second study part). Secondary objectives included overall survival and explored differences in specific toxicity outcomes, including transfusion requirements and measures of reproductive health (second study part). FINDINGS: In the first part of the study (mutational analysis), patients treated with eBEACOPP (n=5) exhibited a higher burden of point mutations in HSPCs compared with those treated with eBEACOPDac (n=4) or ABVD (n=3; excess mutations 1150 [95% CI 934-1366] vs 290 [241-339] vs 186 [116-254]). Two novel mutational signatures, SBSA (SBS25-like) and SBSB, were identified in HSPCs and in a single neoplastic and healthy colon sample from patients who received procarbazine-containing chemotherapy. SBSB was also identified in germline DNA of three children conceived after eBEACOPP and in sperm of a male patient treated with eBEACOPP. SBSC was detected in patients treated with either ABVD or eBEACOPDac. In the second part of the study (efficacy and toxicity analysis), dacarbazine substitution did not appear to compromise efficacy or safety. 312 patients treated with eBEACOPDac (eBEACOPDac cohort; treated 2017-22, 186 [60%] male, median follow-up 36·0 months [IQR 25·2-50·1]) had a 3-year progression-free survival of 93·3% (95% CI 90·3-96·4), which was similar to the 93·3% [95% CI 92·1-94·4]) progression-free survival seen in 1945 patients in the German HD18 eBEACOPP trial (treated 2008-14, 1183 [61%] male, median follow-up 57·0 months [35·4-64·7]). Patients treated with eBEACOPDac required fewer blood transfusions (mean 1·70 units [SD 2·77] vs 3·69 units [3·89]; p<0·0001), demonstrated higher post-chemotherapy sperm concentrations (median 23·4 million per mL [IQR 11·0-632·3] vs 0·0 million per mL [0·0-0·001]; p=0·0040), and had earlier resumption of menstrual periods (mean 5·04 months [SD 3·07] vs 8·77 months [5·57]; p=0·0036) compared with 73 patients treated with eBEACOPP in the UK real-world dataset. INTERPRETATION: Procarbazine induces a higher mutation burden and novel mutational signatures in patients with Hodgkin lymphoma treated with eBEACOPP and their germline DNA, raising concerns for the genomic health of survivors of Hodgkin lymphoma and hereditary consequences for their offspring. However, replacing procarbazine with dacarbazine appears to mitigate gonadal and stem-cell toxicity while maintaining similar clinical efficacy. FUNDING: Addenbrooke's Charitable Trust and Wellcome Trust
Identification and validation of a previously missed mutational signature in colorectal cancer
No full textMutational signature analysis has greatly enhanced our understanding of the mutagenic processes found in cancer and normal tissues. As part of a recent study, we analyzed 802 treatment-naïve, microsatellite-stable colorectal cancers (CRC) and identified a de novo signature, SBS_D, which was conservatively decomposed into SBS18, a signature associated with reactive oxygen species. Here, we re-evaluate this decomposition and provide evidence that SBS_D represents a distinct mutational process from that of SBS18. Through an independent analysis of 2,616 whole-genome sequenced microsatellite-stable CRCs across three distinct cohorts, we demonstrate that SBS_D is consistently present at a similar prevalence, suggesting that this signature may have been previously overlooked. Using a naïve decomposition approach, we demonstrate that the pattern of SBS_D better aligns with signatures previously associated with deficiencies in DNA polymerase delta (POLD1) proofreading and mismatch repair. However, multiple lines of evidence, including the absence of pathogenic mutations in the exonuclease domain of POLD1 or in mismatch repair-associated genes, indicate that SBS_D is not driven by canonical defects in these DNA repair pathways. Overall, this study identifies a previously unrecognized mutational signature in microsatellite-stable CRC and proposes that its etiology may be linked to DNA repair infidelity emerging late in tumor development in samples without canonical defects in DNA repair pathways
A scoping review of the reporting quality of reviews of commercially and publicly available mobile health apps
No full textOBJECTIVES: There is no guidance to support the reporting of systematic reviews of mobile health (mhealth) apps (app reviews), so authors attempt to use/modify the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). There is a need for reporting guidance, building on PRISMA where appropriate, tailored to app reviews. The objectives were to describe the reporting quality of published mHealth app reviews, identify the need for, and develop potential candidate items for a reporting guideline. MATERIALS AND METHODS: A scoping review following the Joanna Briggs Institute and Arksey and O'Malley approaches. App reviews were identified in January 2024 from SCOPUS, CINAHL, AMED, EMBASE, Medline, PsycINFO, ACM Digital Library, snowballing reference lists, and forward citation searches. Data were extracted into Excel and analyzed using descriptive statistics and content synthesis, using PRISMA items as a framework. RESULTS: One hundred and seventy-one app reviews were identified, published from 2013 to 2024. Protocols were developed for 11% of the reviews, and only 52% reported the geographical location of the app markets. Few reported the duplicate removal process (12%), device and operating system used (30%), or made clear recommendations for the best-rated apps (18%). Nineteen PRISMA items were not reported by most (>85%) reviews, and 4 were modified by >30% of the reviews. Involvement of patient/public contributors (4%) or other stakeholders (11%) was infrequent. Overall, 34 candidate items and 10 subitems were identified to be considered for a new guideline. DISCUSSION AND CONCLUSION: App reviews were inconsistently reported, and many PRISMA items were not deemed relevant. Consensus work is needed to revise and prioritize the candidate items for a reporting guideline for systematic app reviews
Evaluating cribriform pattern with clinical outcomes in the STAMPEDE cohort of primary advanced hormone sensitive prostate cancer
No full textSalvage brachytherapy for recurrent prostate cancer after radiotherapy: An expert-endorsed review by uroGEC
No full textRadiorecurrent prostate cancer remains a challenging clinical scenario. Salvage brachytherapy, either low-dose-rate (LDR) or high-dose-rate (HDR), offers a promising organ-preserving option in carefully selected patients. This narrative review, endorsed by the uroGEC (Urology - Groupe Européen de Curiethérapie), summarizes current evidence, indications, techniques, outcomes, and limitations of SBT in men with local recurrence after primary radiotherapy. Patient selection is critical and should be based on rigorous restaging, including multiparametric MRI and/or PSMA PET, as well as histological confirmation of local recurrence. Focal BT, guided by imaging and targeting only the recurrent lesion, has emerged as a feasible and less toxic alternative to whole-gland re-irradiation. Reported biochemical control rates range between 50-70 % at 5 years, with acceptable genitourinary and gastrointestinal toxicity profiles, particularly when advanced imaging and modern brachytherapy techniques are used. Despite promising results, the evidence remains limited by small, heterogeneous cohorts and lack of prospective randomized trials. The uroGEC expert panel advocates for multidisciplinary decision-making, standardized protocols, and patient inclusion in clinical trials to better define the role of BT. In conclusion, BT represents a valuable salvage option in well-selected patients with localized recurrence, and should be considered in the context of individualized, image-guided treatment strategies
Incidence of venous thromboembolic events (VTE) after penile cancer surgery in England: Analysis of hospital episode statistics (HES) data from 2015 to 2024
No full textRisks of Organ Preservation in Rectal Cancer: Data From Two International Registries on Rectal Cancer
No full textPURPOSEOrgan preservation has become an attractive alternative to surgery (total mesorectal excision [TME]) among patients with rectal cancer after neoadjuvant therapy who achieve a clinical complete response (cCR). Nearly 30% of these patients will develop local regrowth (LR). Although salvage resection is frequently feasible, there may be an increased risk for development of subsequent distant metastases (DM). The aim of this study is to compare the risk of DM between patients with LR after Watch and Wait (WW) and patients with near-complete pathologic response (nPCR) managed by TME at the time of reassessment of response.METHODSData from patients enrolled in the International Watch & Wait Database (IWWD) with cCR managed by WW and subsequent LR were compared with patients managed by TME (with <= 10% cancer cells-nPCR) from the Spanish Rectal Cancer Project (VIKINGO project). The primary end point was DM-free survival at 3 years from decision to WW or TME. The secondary end point was possible risk factors associated with DM.RESULTSFive hundred and eight patients with LR were compared with 893 patients with near-complete response after TME. Overall, DM rate was significantly higher among LRs (22.8% v 10.2%; P <= .001). Independent risk factors for DM included LR (v TME at reassessment; P = .001), ypT3-4 status (P = .016), and ypN+ status (P = .001) at the time of surgery. 3-year DM-free survival was significantly worse for patients with LR (75% v 87%; P = .001). When stratified for pathologic stage, patients with LR did significantly worse through all stages (P <= .009).CONCLUSIONPatients with LR appear to have a higher risk for subsequent DM development than patients with nPCR managed by TME at restaging irrespective of final pathology. Leaving the primary undetectable tumor in situ until development of LR may result in worse oncologic outcomes