• 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.
    • The value of exfoliative cytology in the diagnosis of rectal malignancy.

      Wilson, Malcolm S; El Teraifi, Hassan; Schofield, Philip F; Department of Surgery, Christie Hospital, Withington, Manchester, UK. (1993-07)
      This study has assessed the feasibility and reliability of cytology smears taken from patients with known rectal carcinomas without the use of any special instruments. In a pilot study of 23 patients who all had proved rectal cancer, 19 patients had satisfactory smears, one of which produced a false negative result. The remaining 18 displayed varying degrees of dysplasia (10) or frank malignancy (8). One of the patients with a smear containing severely dysplastic cells had a negative biopsy but had clear clinical and radiological evidence of a rectal tumour. Subsequently, a blind controlled study was undertaken on 29 patients with either carcinoma, proctitis or a normal rectum. All 29 sets of smears were of diagnostic quality and were correctly diagnosed as benign or malignant by the cytologist who had no knowledge of the clinical diagnosis. This is a rapid and simple diagnostic test which, if positive for malignancy, allows treatment to be planned at the first consultation. In combination with a forceps biopsy, the rate of positive diagnosis may be increased. A dysplastic smear adds to the level of clinical suspicion and confirms the need for biopsy of a lesion.
    • The value of FDG positron emission tomography/computerised tomography (PET/CT) in pre-operative staging of colorectal cancer: a systematic review and economic evaluation.

      Brush, J; Boyd, K; Chappell, F; Crawford, F; Dozier, M; Fenwick, E; Glanville, J; McIntosh, H; Renehan, Andrew G; Weller, D; et al. (2011-09)
      In the UK, colorectal cancer (CRC) is the third most common malignancy (behind lung and breast cancer) with 37,514 cases registered in 2006: around two-thirds (23,384) in the colon and one-third (14,130) in the rectum. Treatment of cancers of the colon can vary considerably, but surgical resection is the mainstay of treatment for curative intent. Following surgical resection, there is a comprehensive assessment of the tumour, it's invasion characteristics and spread (tumour staging). A number of imaging modalities are used in the pre-operative staging of CRCs including; computerised tomography (CT), magnetic resonance imaging, ultrasound imaging and positron emission tomography (PET). This report examines the role of CT in combination with PET scanning (PET/CT 'hybrid' scan). The research objectives are: to evaluate the diagnostic accuracy and therapeutic impact of fluorine-18-deoxyglucose (FDG) PET/CT for the pre-operative staging of primary, recurrent and metastatic cancer using systematic review methods; undertake probabilistic decision-analytic modelling (using Monte Carlo simulation); and conduct a value of information analysis to help inform whether or not there is potential worth in undertaking further research.
    • The value of hyoscine butylbromide in pelvic MRI.

      Johnson, Wendy; Taylor, Malcolm B; Carrington, Bernadette M; Bonington, Suzanne C; Swindell, Ric; Department of Diagnostic Radiology, Christie Hospital NHS Trust, Withington, Manchester, UK. (2007-11)
      AIM: To evaluate the effect of hyoscine butylbromide (HBB) on image quality and lesion and organ visualization in pelvic magnetic resonance imaging (MRI) MATERIALS AND METHODS: A prospective, ethically approved study was undertaken of 47 patients attending for pelvic MRI at a cancer centre. T2-weighted transverse and sagittal sequences were performed before and after intravenous injection of 20 mg HBB. Three radiologists independently scored anonymized image series for overall image quality, visualization of pelvic lesions and visualization of individual pelvic organs. Statistical analysis was performed to assess improvements in radiologists' scores post-HBB administration. Radiologists also assessed pre-HBB administration T1-weighted images for degree of bowel peristalsis to determine whether this could predict improvement in post-HBB T2-weighted image scores. Side effects of HBB were recorded using a patient questionnaire. RESULTS: Radiologists' scores for image quality and lesion visualization were significantly higher on the post-HBB administration T2-weighted series (p<0.0005). Scores for the visualization of the bladder, rectum, pelvic bowel, prostate, and seminal vesicles (all p<0.0005), cervix (p=0.019) and vagina (p=0.0001) were also significantly higher post-HBB administration. Scores for the degree of peristalsis on T1-weighted images were not related to improvement in image quality or lesion visualization on T2-weighted images post-HBB administration. Side effects of HBB were mild and self-limiting. CONCLUSION: Intravenous HBB administration improves image quality and lesion visualization in oncological pelvic MRI and is recommended for routine use.
    • The value of IGF1 estimation in adults with GH deficiency.

      Mukherjee, Annice; Shalet, Stephen M; Department of Endocrinology, Salford Royal NHS Foundation Trust, UK. annice.mukherjee@srft.nhs.uk (2009-11)
      The GH/IGF1 system, like other endocrine systems, is dynamic and its activity changes with age and sexual maturation, and is influenced by body composition and other factors. A normal level of IGF1 does not exclude a diagnosis of GH deficiency (GHD) in adults, and the usefulness of IGF1 in the diagnosis of adult GHD has historically been confusing and contentious. The regulation of IGF1 secretion in adults is complex, and is not solely dependent on GH status with factors recognized to influence IGF1 status in patients with GHD including age, gender, exogenous estrogen therapy, prolactin status, and severity of GHD. The usefulness of IGF1 for monitoring treatment of GH disorders in adulthood is now widely accepted, especially as GH-dosing regimens for GHD have evolved from weight-based dosing (associated with overtreatment and side effects) to individualized dose-titration strategies, which maintain IGF1 within target limits. Sub-optimal replacement therapy may be associated with morbidity and mortality risk from a continuing state of functional GHD. Conversely, avoiding iatrogenic biochemical acromegaly is clearly important and other potential safety issues may be associated with a persistently high IGF1. Analysis and interpretation of IGF1 status therefore represent a useful diagnostic tool especially in the younger adult patients with severe GHD and an essential measurement for monitoring GH replacement in all adults with GHD. High-quality, method-specific reference ranges for IGF1 and a high degree of methodological consistency in the assay are essential for reliable comparison of results.
    • The value of patient and public involvement in trial design and development.

      Gasson, S; Bliss, J; Jamal-Hanjani, M; Krebs, Matthew G; Swanton, C; Wilcox, M; Independent Cancer Patients' Voice, London, UK (2015-07-13)
    • Value of peer review of pathology in soft tissue sarcomas.

      Harris, Martin; Hartley, Ann L; Department of Pathology, Christie Hospital, Manchester, United Kingdom. (1997)
    • The value of radiotherapy for rectal cancer.

      James, Roger D; Schofield, Philip F (1989-07)
      Discrepancies in morbidity and local recurrence rates in published clinical trials of pelvic XRT for colorectal cancer are caused by a variety of complex factors. It is, however, clear that XRT is able to cure early rectal carcinomas and is particularly useful in alleviating the symptoms of advanced or recurrent disease. The selection of appropriate cases for combinations of XRT and surgery can be made on the basis of digital examination under anaesthetic. One aim of these combinations is to reduce the number of patients with mobile tumours of the lower two-thirds of the rectum who require a permanent colostomy. In the absence of effective chemotherapy for metastatic disease, liver XRT may have a place in controlling the growth rate of occult liver metastases in selected patients.
    • The value of rehabilitation interventions to address the needs of teenage and young adult oncology patients post haematology transplant

      Mackland, Anna; Chesman, Nicola; The Christie Hospital NHS Foundation Trust, Manchester (2019)
    • Value of routine serum-triiodothyronine estimation in diagnosis of thyrotoxicosis.

      Shalet, Stephen M; Beardwell, Colin G; Lamb, A; Gowland, E; Christie Hospital and Holt Radium Institute, Manchester (1975-11-22)
      Thyroid-stimulating hormone (T.S.H.), triiodothyronine (T3), and thyroxine (T4) concentrations were estimated on 432 blood specimens from patients with a provisional diagnosis of thyrotoxicosis. 59 patients had a raised serum T3 concentration with T.S.H. and T4 levels in the normal range. Further information was obtained in 41 of these patients, and T3 toxicosis was diagnosed in 17 cases, thus providing a projected total of 24 patients with T3 toxicosis. In addition, there were 56 patients, with more common biochemical features of thyrotoxicosis, having both a raised serum T3 and T4 concentration. Therefore 30% of the patients considered thyrotoxic in this retrospective survey were only diagnosed with the aid of a serum-T3 estimation.
    • The value of serial bone scanning in operable breast cancer.

      Monypenny, I J; Grieve, R J; Howell, Anthony; Morrison, J M; The Department of Oncology, Christie Hospital, Manchester, U.K. (1984-06)
      The value of initial and serial isotope bone scans was assessed in 685 patients with operable primary breast cancer. Nineteen (2.8 per cent) patients had a positive initial scan and negative skeletal radiographs; only nine of these developed other evidence of metastatic disease after a mean follow up of 21 months. Five hundred and ten patients had serial scans up to five years after simple mastectomy; 51 (10 per cent) had scan conversion, of whom 37 developed clinical or radiological confirmation of recurrent disease at a mean follow-up of 13 months. Compared with clinical or radiological methods for the detection of first metastases serial bone scans gave a mean lead time of five months in 15 patients and no lead time in the remaining 22 patients. Twelve of forty-five patients with radiologically proven bone metastases had negative scans. Neither initial or serial bone scanning is clinically useful or economically viable as a routine screening or follow-up procedure for patients with operable breast cancer.
    • The value of specialist oncological radiology review of cross-sectional imaging.

      Loughrey, Gareth J; Carrington, Bernadette M; Anderson, Heather; Dobson, M J; Lo Ying Ping, F; Department of Diagnostic Radiology, Christie Hospital NHS Trust, Withington, Manchester, UK. (1999-03)
      AIM: To determine whether specialist oncological radiology review of outside cross-sectional imaging affects patient management. MATERIALS AND METHODS: Five hundred and twenty-six patients attending a regional oncology centre had review of outside cross-sectional imaging over a 1-year period. The number of examinations per patient, time interval between examination and review request, and examination technical adequacy were recorded in each case. More detailed evaluation of 124 patients included comparison of outside and review reports for major differences in interpretation by a medical oncologist who also evaluated the effect of the review on patient management. Examinations resulting in major report discrepancies were subjected to independent radiological adjudication. RESULTS: Eighty-one percent of examinations were reviewed within 3 months of being performed and 94% were considered technically adequate. The hard copy images provided were incomplete in 33% of cases and a calibration rule was absent in 9%. There was a major difference in interpretation in 34% of examinations, the most common cause being differences in interpretation of lymphadenopathy (52%), particularly in the mediastinum (19%). Other problems identified were the failure to record disease dimensions and absence of specific information on key organs in the outside reports. Specialist radiology review changed radiological staging in 19% of patients, affected management in 7% of patients and resulted in a change in treatment in 4%. There was no correlation between management change and any particular tumour type. In 27% of cases, treatment decisions had been made before the review was requested. CONCLUSION: Specialist oncological radiology review of outside cross-sectional imaging changed radiological staging in 19% of cases but had little impact on patient management. Oncological cross-sectional imaging techniques in the North West of England are of high quality, probably helped by recent RCR guidelines.
    • Value of the Hospital Anxiety and Depression Scale in the follow up of head and neck cancer patients.

      Joseph, Lisa A; Routledge, Jacqueline A; Burns, Meriel P; Swindell, Ric; Sykes, Andrew J; Slevin, Nicholas J; Davidson, Susan E; Department of Clinical Oncology, The Christie NHS Foundation Trust, Manchester, UK. (2013-02-11)
      Background: Few studies have prospectively investigated psychological morbidity in UK head and neck cancer patients. This study aimed to explore changes in psychological symptoms over time, and associations with patients' tumour and treatment characteristics, including toxicity. Methods: Two hundred and twenty patients were recruited to complete the Hospital Anxiety and Depression Scale and the Late Effects on Normal Tissue (Subjective, Objective, Management and Analytic) ('LENT-SOMA') questionnaires, both pre- and post-treatment. Results: Anxiety was highest pre-treatment (38 per cent) and depressive symptoms peaked at the end of treatment (44 per cent). Anxiety significantly decreased and depression significantly increased, comparing pre- versus post-treatment responses (p < 0.001). Hospital Anxiety and Depression Scale scores were significantly correlated with toxicity, age and chemotherapy (p < 0.01 for all). Conclusion: This is the first study to analyse the relationship between Hospital Anxiety and Depression Scale scores and toxicity scores in head and neck cancer patients. It lends support for the use of the Hospital Anxiety and Depression Scale and the Late Effects on Normal Tissue (Subjective, Objective, Management and Analytic) questionnaire in routine clinical practice; furthermore, continued surveillance is required at multiple measurement points.
    • Value of tumor growth rate (TGR) as an early biomarker predictor of patients' outcome in neuroendocrine tumors (NET)-The GREPONET Study

      Lamarca, Angela; Crona, J; Ronot, M; Opalinska, M; Lopez, L; Pezzutti, D; Najran, Pavan; Carvhalo, L; Franca, Bezerra R; Borg, P; et al. (2019)
      INTRODUCTION: Tumor growth rate (TGR; percent size change per month [%/m]) is postulated to be an early radiological biomarker to overcome limitations of RECIST. This study aimed to assess the impact of TGR in neuroendocrine tumors (NETs) and potential clinical and therapeutic applications. MATERIALS AND METHODS: Patients (pts) with advanced grade (G) 1/2 NETs from the pancreas or small bowel initiating systemic treatment (ST) or watch and wait (WW) were eligible. Baseline and follow-up scans were retrospectively reviewed to calculate TGR at pretreatment (TGR0), first follow-up (TGRfirst), and 3(�1) months of study entry (TGR3m). RESULTS: Out of 905 pts screened, 222 were eligible. Best TGRfirst (222 pts) cutoff was 0.8 (area under the curve, 0.74). When applied to TGR3m (103 pts), pts with TGR3m <0.8 (66.9%) versus TGR3m ? 0.8 (33.1%) had longer median progression-free survival (PFS; 26.3 m; 95% confidence interval [CI] 19.5-32.4 vs. 9.3 m; 95% CI, 6.1-22.9) and lower progression rate at 12 months (7.3% vs. 56.8%; p = .001). WW (vs. ST) and TGR3m ? 0.8 (hazard ratio [HR], 3.75; 95% CI, 2.21-6.34; p < .001) were retained as factors associated with a shorter PFS in multivariable Cox regression. TGR3m (HR, 3.62; 95% CI, 1.97-6.64; p < .001) was also an independent factor related to shorter PFS when analysis was limited to pts with stable disease (81 pts). Out of the 60 pts with TGR0 data available, 60% of pts had TGR0 < 4%/month. TGR0 ? 4 %/month (HR, 2.22; 95% CI, 1.15-4.31; p = .018) was also an independent factor related to shorter PFS. CONCLUSION: TGR is an early radiological biomarker able to predict PFS and to identify patients with advanced NETs who may require closer radiological follow-up. IMPLICATIONS FOR PRACTICE: Tumor growth rate at 3 months (TGR3m) is an early radiological biomarker able to predict progression-free survival and to identify patients with advanced neuroendocrine tumors who may require closer radiological follow-up. It is feasible to calculate TGR3m in clinical practice and it could be a useful tool for guiding patient management. This biomarker could also be implemented in future clinical trials to assess response to therapy.
    • Value of tumor growth rate (TGR) as an early predictor of patients' outcome in patients diagnosed with well-differentiated neuroendocrine tumors (NETs): the GREPONET study.

      Lamarca, Angela; Crona, J; Ronot, M; Opalinska, M; Lopez, C; Pezzutti, D; Najran, Pavan; Franca, R; Scaefer, N; Sundin, A; et al. (2018)
    • The value of tumour markers in lung cancer.

      Gomm, S; Keevil, B; Thatcher, Nick; Hasleton, Philip S; Swindell, Ric; Department of Thoracic Medicine, Wynthenshawe Hospital, Manchester, UK. (1988-12)
      The pre-treatment serum levels of neuron-specific enolase (NSE), phosphohexose isomerase (PHI) and circulating immune complexes (CC) as tumour markers were compared to measurements of standard haematology and biochemical indices in 73 patients with lung cancer, as an aid to differentiation of tumour type, estimating disease extent, predicting response to therapy and prognosis. Elevated NSE greater than or equal to 12.5 ng ml-1, PHI greater than or equal to 55 mgl-1 levels were observed in 55% of cases for NSE, 90% for PHI and 49% for CC. NSE was significantly elevated in 61% (25/41) of patients with SCLC (P less than 0.005) compared to 41% (13/32) with NSCLC. CC levels were significantly raised in 72% (23/32) of patients with NSCLC (P less than 0.05) compared to 32% with SCLC. The levels of NSE and PHI were not related to tumour stage but CC was significantly raised in limited compared to extensive disease in SCLC (P less than 0.05). Serum albumin was significantly lower in NSCLC compared to SCLC, and median values of alkaline phosphatase, gamma-glutamyltranspeptidase and aminoaspartate transferase were significantly higher in patients with extensive disease. The pre-treatment serum values of NSE, PHI, and CC did not predict the response to therapy or prognosis in the 73 patients with lung cancer. The most important prognostic factor was the number of abnormal routine laboratory parameters (greater than 4) in this group of patients.
    • Vandetanib plus gemcitabine versus placebo plus gemcitabine in locally advanced or metastatic pancreatic carcinoma (ViP): a prospective, randomised, double-blind, multicentre phase 2 trial.

      Middleton, G; Palmer, D; Greenhalf, W; Ghaneh, P; Jackson, R; Cox, T; Evans, A; Shaw, V; Wadsley, J; Valle, Juan W; et al. (2017-03-01)
      Erlotinib is an EGFR tyrosine kinase inhibitor that has shown a significant but only marginally improved median overall survival when combined with gemcitabine in patients with locally advanced and metastatic pancreatic cancer. Vandetanib is a novel tyrosine kinase inhibitor of VEGFR2, RET, and EGFR, all of which are in involved in the pathogenesis of pancreatic cancer. We investigated the clinical efficacy of vandetanib when used in combination with gemcitabine in patients with advanced pancreatic cancer.