• Validation of clinical/dosimetric/genetic risk factor models for late RT-induced rectal bleeding

      Rancati, T; Seibold, P; Webb, A; Chang-Claude, J; Cicchetti, A; Azria, D; De Ruysscher, D; Elliott, Rebecca M; Gutierrez-Enriquez, S; Rosenstein, BS; et al. (2019)
    • Validation of lysyl oxidase-like 2 (LOXL2) as prognostic marker for gastro-entero-pancreatic neuroendocrine tumours (GEP-NET) Using an independent cohort

      Barriuso, Jorge; Benavent, M; Lamarca, Angela; Bernal, E; Guerra-Pastrian, L; Heredia, V; Miguel, V; Garcia-Calderon, C; Alvarez-Escola, C; Castell, J; et al. (2016)
    • Validation of nomogram for disease free survival for colon cancer in UK population: A prospective cohort study.

      Kazem, M; Khan, A; Selvasekar, Chelliah; Surgery and Cancer Division, Leighton Hospital, Middlewich Road, Crewe CW1 4QJ, UK (2016-01-18)
      To externally validate the MSKCC nomogram in a UK population, and determine if it could be used in our practice here in the UK.
    • Validation of pharmacodynamic assays to evaluate the clinical efficacy of an antisense compound (AEG 35156) targeted to the X-linked inhibitor of apoptosis protein XIAP.

      Cummings, Jeffrey; Ward, Timothy H; Lacasse, Eric; Lefebvre, C; St-Jean, M; Durkin, J; Ranson, Malcolm R; Dive, Caroline; Clinical and Experimental Pharmacology, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, UK. jcummings@picr.man.ac.uk (2005-02-14)
      The inhibitor of apoptosis protein, XIAP, is frequently overexpressed in chemoresistant human tumours. An antisense oligonucleotide (AEG 35156/GEM 640) that targets XIAP has recently entered phase I trials in the UK. Method validation data are presented on three pharmacodynamic assays that will be utilised during this trial. Quantitative RT-PCR was based on a Taqman assay and was confirmed to be specific for XIAP. Assay linearity extended over four orders of magnitude. MDA-MB-231/U6-E1 cells and clone X-G4 stably expressing an RNAi vector against XIAP were chosen as high and low XIAP expression quality controls (QCs). Within-day and between-day coefficients of variation (CVs) in precision for cycle threshold (CT) and delta CT values (employing GAPDH and beta 2 microglobulin as housekeepers) were always less than 10%. A Western blotting technique was validated using a GST-XIAP fusion protein as a standard and HeLa cells and SF268 (human glioblastoma) cells as high and low XIAP expression QCs. Specificity of the final choice of antibody for XIAP was evaluated by analysing a panel of cell lines including clone X-G4. The assay was linear over a 29-fold range of protein concentration and between-day precision was 29% for the low QC and 23% for the high QC when normalised to GAPDH. XIAP protein was also shown to be stable at -80 degrees C for at least 60 days. M30-Apoptosense plasma Elisa detects a caspase-cleaved fragment of cytokeratin 18 (CK18), believed to be a surrogate marker for tumour cell apoptosis. Generation of an independent QC was achieved through the treatment of X-G4 cells with staurosporine and collection of media. Measurements on assay precision and kit-to-kit QC were always less than 10%. The M30 antigen (CK18-Asp396) was stable for 3 months at -80 degrees C, while at 37 degrees C it had a half-life of 80-100 h in healthy volunteer plasma. Results from the phase I trial are eagerly awaited.
    • Validation of ROS1 by immunohistochemistry against fluorescent in situ hybridisation on cytology and small biopsy samples in a large teaching hospital

      Narine, N.; Wallace, A. J.; Dore, J.; O'Leary-Jackson, S.; Al-Najjar, H.; Bailey, S.; Khan, K. A.; Teng, B.; Qasim, M.; Shelton, D.; et al. (2021)
      Objective: This is a prospective evaluation of ROS1 analysis by IHC against FISH on cytology and small biopsy samples in a routine diagnostic setting and demonstrates both technical and clinical validation. Methods: From 1st March to 31st December 2019, cytology cell blocks and small biopsy samples from a selected cohort of NSCLC patients were concurrently tested for ROS1 gene rearrangement by Vysis 6q22 Break Apart FISH probe and IHC using Cell Signalling D4D6 antibody. Mismatch cases were tested by an RNA fusion NGS panel. Results: In a prospective population of 95 cases, 91 were negative and 2 were positive by both FISH and IHC. Both dual positive cases were female never smokers and benefited from TKI treatment. Another 2 cases were positive by FISH but negative by IHC and repeat by NGS showed one to be negative but one failed. Turnaround time for IHC was 0 to 8 days from request to authorisation whilst that of FISH was 9 to 42 days at a cost of £51 and £159 respectively. Conclusion: IHC to assess for the protein product of ROS1 gene rearrangement on cytology cell blocks and small biopsy samples in a routine setting is a promising screening method to assess eligibility for TKI treatment with positive and indeterminate cases confirmed by FISH or NGS as it has good NPV, faster turnaround time and is cost effective with proven technical and clinical validation
    • Validation of the electron Monte Carlo (eMC) algorithm in Eclipse 13

      Kelly, D; Meara, Simon; Fogarty, K; Gately, L; The Clatterbridge Cancer Centre NHS Foundation Trust, Medical Physics, Wirral (2019)
    • Validation of the EORTC QLQ-BIL21 questionnaire for measuring quality of life in patients with cholangiocarcinoma and cancer of the gallbladder.

      Kaupp-Roberts, S; Yadegarfar, G; Friend, E; O'Donnell, C; Valle, Juan W; Byrne, C; Bahar, I; Finch-Jones, M; Gillmore, R; Johnson, C; et al. (2016-09-27)
      There is no specific quality of life (QoL) measurement tool to quantify QoL in patients with biliary tract cancer. Quality of life measurement is an increasingly crucial trial end point and is now being incorporated into clinical practice.
    • Validation of the EORTC QLQ-CAX24, a health-related quality of life (HRQOL) questionnaire for cancer patients with cachexia.

      Wheelwright, S; Madechangu, C; Hopkinson, J; Darlington, A; Fitzsimmons, D; Bahar, I; Balstad, T; Baracos, V; Bredart, A; Silva, J; et al. (2018)
    • Validation of the EPIPHANY index for predicting risk of serious complications in cancer patients with incidental pulmonary embolism.

      Ahn, S; Cooksley, Timothy J; Banala, S; Buffardi, L; Rice, T; Department of Emergency Medicine, Cancer Emergency Room, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea (2018-05-04)
      The EPIPHANY index was developed to classify cancer associated pulmonary embolism (PE) into different risk categories using decision tree modeling. In this study, we tried to externally validate this index in a distinct group of patients solely composed of incidental PE (IPE).
    • Validation of the impact of heart base dose on survival in NSCLC patients from the PET-Plan Trial

      Craddock, M.; Nestle, U.; Schimek-Jasch, T.; Kremp, S.; Lenz, S.; Price, G.; Salem, A.; Faivre-Finn, C.; van Herk, M.; McWilliam, A.; et al. (2021)
      Purpose or Objective Heart dose has emerged as an independent predictor of overall survival in non-small cell lung cancer patients. Several studies have identified the base of the heart as the most significant region and a potential target for cardiac sparing. This work aims to further validate the impact of heart base dose in the multicentre, randomised PET-plan trial data and for the first time, will determine whether the effect remains significant when baseline cardiac function is included in the analysis. Material and Methods 205 patients with inoperable UICC stage II/III non-small cell lung cancer treated with 60-72 Gy in 2 Gy fractions in the PET Plan randomised controlled trial (NCT00697333) were included in this study.  CT scans and dose distributions were spatially normalised to a reference patient using the “NiftyReg” deformable image registration package.  For a given time point, mean dose distributions were calculated for the alive and dead patients, censored for follow-up. Dose differences between the groups were calculated and tested for significance by comparison to the null hypothesis dose difference distribution approximated by permutation testing. An anatomical region of interest was defined at 95% of the maximum t-value in the dataset and the mean dose to the region was extracted for all patients. A uni-variable analysis tested the association of survival with dose to the identified region, clinical variables including age, gender, performance status, tumour volume and baseline ejection fraction measured prior to radiotherapy.  All variables were then included in a multivariable Cox proportional hazards model. Results 172 patients remained after processing and censoring for follow-up.  At 2-years post treatment, a highly significant region was identified within the base of the heart (p < 0.005), centred on the origin of the left coronary artery and the region of the atrioventricular node (Figure 1). The median dose to the region was 33.5 Gy. Uni-variable analyses determined worse performance status, ejection fraction less than 50%, tumour volume and mean dose to the defined cardiac region to be significant. In multi-variable analysis, performance status (p = 0.03, HR: 5.69, 95% CI: 1.21 – 26.71), ejection fraction (p = 0.008, HR: 2.91, 95% CI: 1.32-6.40) and mean dose to the cardiac sub-region (p = 0.01, HR: 1.02, 95% CI: 1.00-1.03), remained significant (Table 1). Conclusion This work validates previous image-based data mining studies in identifying a cardiac region within the base of the heart as strongly associated with overall survival.  Importantly, for the first-time baseline cardiac function was included with mean dose to the identified region in the multi-variable analysis. Poor ejection fraction did not negate the impact of dose to the base of the heart on survival. 
    • Validation of the IPF-specific version of St. George's Respiratory Questionnaire

      Prior, TS; Hoyer, N; Shaker, SB; Davidsen, JR; Yorke, Janelle; Hilberg, O; Bendstrup, E; Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus, Denmark. (2019)
      BACKGROUND: Patients with idiopathic pulmonary fibrosis (IPF) have impaired health-related quality of life (HRQL). To measure HRQL, an IPF-specific version of the St. George's Respiratory Questionnaire (SGRQ-I) was developed, but not sufficiently validated. This study aimed to assess the validity (i.a. known-groups validity and concurrent validity) and test-retest reliability of SGRQ-I in IPF patients with different disease durations. METHODS: Patients with IPF were consecutively recruited and completed SGRQ, SGRQ-I, King's Brief Interstitial Lung Disease questionnaire (K-BILD), University of California, San Diego Shortness of Breath Questionnaire (SOBQ) and Short Form-36 (SF-36) along with pulmonary function tests and a 6-min walk test (6MWT) at baseline. After two weeks, SGRQ-I and Global Rating of Change Scales (GRCS) were completed. RESULTS: At baseline and after two weeks, 150 and 134 patients completed the questionnaires, respectively. The internal consistency of SGRQ-I was high (Cronbach's ??=?0.92). Good concurrent validity was demonstrated by high intraclass correlation coefficients (ICC?=?0.97), Bland-Altman plots and moderate to strong correlations to K-BILD, SOBQ and SF-36 (r?=?-?0.46 to 0.80). High ICC (0.92) and a Bland-Altman plot indicated good test-retest reliability. SGRQ-I was good at discriminating between patients with different stages of disease (?score >?18.1, effect sizes >?0.10). Validity was similar across groups of different disease duration. CONCLUSIONS: SGRQ-I proved to be valid at distinguishing between different disease severities, valid compared to other HRQL instruments, applicable across different disease durations and reliable upon repetition. SGRQ-I is a valid option for measuring HRQL in patients with IPF. TRIAL REGISTRATION: The study was registered at clinicaltrials.org ( NCT02818712 ) on 15 June 2016.
    • Validation of the IPF-specific version of St. George's Respiratory Questionnaire in Danish

      Prior, TS; Hoyer, N; Shaker, S; Davidsen, JR; Yorke, Janelle; Hilberg, O; Bendstrup, E; Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus, Denmark (2019)
    • Validity of chemotherapy information derived from routinely collected healthcare data: A national cohort study of colon cancer patients

      Boyle, J. M.; Kuryba, A.; Braun, Michael S; Aggarwal, A.; van der Meulen, J.; Cowling, T; E.Walker, K.; Department of Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, UK; Clinical Effectiveness Unit, Royal College of Surgeons of England, London, UK. (2021)
      Background: We used a structured approach to validate chemotherapy information derived from a national routinely collected chemotherapy dataset and from national administrative hospital data. Methods: 10,280 patients who had surgical resection with stage III colon cancer were included. First, we compared information derived from the national chemotherapy dataset (SACT) and from the administrative hospital dataset (HES) in the English NHS with respect to receipt of adjuvant chemotherapy (ACT). Second, we compared regimen and number of cycles in linked patient-level records. Third, we carried out a sensitivity analysis to establish to what extent the impact of ACT receipt differed according to data source. Results: 6,012 patients (58 %) received ACT according to either dataset. Of these patients, 3,460 (58 %) had ACT records in both datasets, 1,649 (27 %) in SACT alone, and 903 (15 %) in HES alone. Of the 3,460 patients with records in both datasets, 3,320 (96 %) had matching regimens. There was good agreement on cycle number with similar proportions of patients recorded with a single cycle (6 % in SACT vs. 7 % in HES) and slightly fewer patients recorded with more than 8 cycles in SACT (32 % in SACT vs. 35 % in HES). 3-year cancer-specific mortality was similar for patients receiving ACT, regardless of whether a patient received ACT according to SACT alone (16.6 %), according to HES alone (16.8 %), or according to either SACT or HES (17.1 %). Conclusion: Routinely collected national chemotherapy data and administrative hospital data are highly accurate in recording regimen and number of chemotherapy cycles. However, chemotherapy information should ideally be captured from both datasets to avoid under-capture, particularly of oral chemotherapy from administrative hospital data, and to minimise bias.
    • The value of anticarcinoembryonic antigen, human milk factor globulin, and antikeratin antibodies in differentiating mesothelioma from lung carcinoma.

      Joglekar, V M; Oliver, D; Harris, Martin; Department of Histopathology, North Lonsdale Hospital, Barrow-in-Furness. (1991-01)
      Monoclonal anticarcinoembryonic antigen (antiCEA), human milk factor globulin (HMFG2), and antikeratin antibodies were assessed for their value in the differential diagnosis of pleural mesothelioma (53 cases) and carcinoma of the lung (60 cases) in material from necropsies. In 40 of the cases pleural biopsies were also studied in the same manner. AntiCEA was found to be the best discriminating antibody for most types of mesothelioma; HMFG2 was slightly less valuable but a useful additional tool. Antikeratin was the least useful. For both antiCEA and HMFG2 antibodies, however, the proportion of carcinomas staining was smaller than in previous studies and this, combined with the positive staining of some mesotheliomas, reduces the value of the reactions in the individual case. Medical panels adjudicating compensation claims should not use these reactions as the sole criteria in deciding the origin of the tumours in these cases.
    • The value of assessing and prescribing dosage in radiation therapy in simple terms

      Paterson, Ralston; Holt Radium Institute, Manchester (1939-02)
    • The value of bone marrow examination in the staging of Hodgkin's lymphoma: a review of 955 cases seen in a regional cancer centre.

      Howell, Sacha J; Grey, Mark; Chang, James; Morgenstern, Godfrey R; Cowan, Richard A; Deakin, David P; Radford, John A; Cancer Research UK Department of Medical Oncology, Christie Hospital NHS Trust, Manchester, UK. (2002-11)
      Bone marrow aspirates (BMA) and trephine biopsies (BMT) are commonly performed in the staging of patients with newly diagnosed Hodgkin's lymphoma (HL) but the value of these procedures is controversial. The purpose of this study was to evaluate the predictive value of the blood count and erythrocyte sedimentation rate (ESR) for bone marrow involvement (BMI) and the influence of BMI on stage and prognostic score. A retrospective analysis of 955 patients with newly diagnosed HL entered into clinical trials in a regional cancer centre between 1975 and 1999 was performed. BMI was identified by BMT in 50 patients (5.2%) but in only five of these by BMA. The negative predictive values of a normal full blood count (FBC) and ESR for absence of BMI were 98.8% and 97.3%, respectively, and the positive predictive value of an abnormal FBC and ESR for presence of BMI were both 6.7%. BMT did not alter initial patient management in a single case but provided valuable prognostic information in certain subgroups of patients. BMA gave no additional staging information over BMT and abnormalities of blood count and ESR were poor predictors of infiltration. We conclude that BMA should be abandoned for staging purposes in HL and BMT restricted to patients with stage IIB or III disease, for whom valuable prognostic information may be obtained.
    • The value of complementary therapies for carers witnessing patients' medical procedures

      Mackereth, Peter A; Mehrez, Anita; Hackman, Eileen; Knowles, Rebecca; Christie Hospital NHS FT. (2014)
    • Value of comprehensive genomic profiling in pre-screening patients for NTRK fusion in STARTRK2 trial: Single centre experience

      Ortega-Franco, Ana; Adamson-Raieste, A.; Rahman, Rozana A; Pihlak, Rille; Peters, N.; Scott, J. A.; Aruketty, Sreeja; Thomson, C.; Dransfield, Sarah; Henshaw, A.; et al. (2021)
      Background: Comprehensive genomic profiling (CGP) by next-generation sequencing (NGS) is increasingly used as a pre-screening tool for clinical trials. The aim of this project was to retrospectively determine the scope of alterations identified by CGP that could render patients suitable for alternative early phase clinical trials of genomically-matched (GM) / immunotherapy (IO) or ‘off-label’ drug use. Methods: Patients were pre-screened for the STARTRK2 study (Roche sponsored study of Entrectinib, NCT02568267) at The Christie NHS foundation Trust using FoundatioCDx. Testing is validated for NTRK, ROS1 and ALK fusion testing but all pathogenic alterations are reported on a clinical trial specific Foundation Medicine (FM) report. Results were scrutinised for actionable alterations that could direct patients to alternative clinical trials or off label drug use. Results: A total of 269 patients with were consented since FM testing was introduced in the trial in Jan’2019. FM yielded results in 229 patients (85.2%), mean age was 54, 58.4% were male and 45.8% had 1-2 prior systemic lines. Most prevalent tumour subtypes were colorectal (26.4%), head and neck (21.6%) and sarcomas (7.1%). Most prevalent alterations occurred in: TP53 (12.6%), APC (8.4%) and KRAS (4.6%). MSI High was 1.5%. No patients had NTRK/ROS1 fusions, 1 non-small cell lung cancer patient had ALK fusion. 104 (45.4%) patients were potentially eligible for matched clinical trials (101 for GM and 3 for IO) and 61 (26.6%) patients could have been considered for off-label drug use. The most prevalent actionable alterations found across common and rare disease types were PI3KCA (10%), ERBB2 (6.1%), PTEN (3.1%), tumour mutation burden 10 mut/Mb (2.6%) and HRAS (1.7%). The following alterations occurred in <1%: AKT1, KRAS G12C, BRAF V600E, BRCA, FGFR3 and IDH1. Conclusions: Our results highlight the relevance of CGP in identifying patients for GM or IO within clinical trials or off-label drug use. The retrospective nature of this work and the fact that FM results provided within STARTRK2 are not intended for clinical use precluded implementing these recommendations. NTRK fusions were not detected in our cohort which highlights the rarity of this event in our population
    • The value of dose intensification of standard chemotherapy for advanced breast cancer using colony-stimulating factors alone.

      Clemons, Mark; Gharif, R; Howell, Anthony; CRC Department of Medical Oncology, Christie Hospital, Manchester, U.K. (1998-06)
    • Value of early post-operative growth hormone testing in predicting long-term remission and residual disease after transsphenoidal surgery for acromegaly

      Wang, Y. Y.; Waqar, M.; Abou-Zeid, A.; Kearney, T.; Caputo, C.; Davis, J.; Trainer, Peter J; Higham, Claire E; Roncaroli, F.; Gnanalingham, K. K.; et al. (2021)
      Introduction: Surgical remission for acromegaly is dependent on a number of factors including tumour size, invasiveness, and surgical expertise. We studied the value of early post-operative growth hormone (GH) level as a predictor of outcome and to guide early surgical re-exploration for residual disease in patients with acromegaly. Methods: Patients with acromegaly undergoing first-time endoscopic transsphenoidal surgery between 2005 and 2015, in 2 regional neurosurgical centres, were studied. Insulin-like growth factor-1 (IGF-1), basal GH (i.e., sample before oral glucose), and GH nadir on oral glucose tolerance test (OGTT) were tested at various time points, including 2�5 days post-operatively. Definition of disease remission was according to the 2010 consensus statement (i.e., GH nadir <0.4 ?g/L during an OGTT and normalized population-matched IGF-1). Forward stepwise logistic regression was used to determine factors associated with remission. Results: We investigated 81 consecutive patients with acromegaly, 67 (83%) of which had macroadenomas and 22 (27%) were noted to be invasive at surgery. Mean follow-up was 44 � 25 months. Overall, surgical remission was achieved in 55 (68%) patients at final follow-up. On univariate analysis, the remission rates at the end of the study period for patients with early post-operative GH nadir on OGTT of <0.4 (N = 43), between 0.4 and 1 (N = 28), and >1 ?g/L (N = 8) were 88, 54, and 20%, respectively. Similar results were seen with basal GH on early post-operative OGTT. On multivariate regression analysis, pre-operative IGF-1 (odds ratio of 13.1) and early post-operative basal GH (odds ratio of 5.0) and GH nadir on OGTT (odds ratio of 6.8) were significant predictors of residual disease. Based on a raised early GH nadir and post-operative MR findings, 10 patients underwent early surgical re-exploration. There was reduction in post-operative GH levels in 9 cases, of which 5 (50%) achieved long-term remission. There was an increased risk of new pituitary hormone deficiencies in patients having surgical re-exploration compared to those having a single operation (60 vs. 14%). Conclusions: An early post-operative basal GH and GH nadir on OGTT are reliable predictors of long-term disease remission. It can be used to guide patients for early surgical re-exploration for residual disease, although there is increased risk of hypopituitarism.